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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 14 Nov 2022 at 02:04 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2022-11-09

Chen J, Zhang P, Zhao Y, et al (2022)

Nitroreductase-instructed supramolecular assemblies for microbiome regulation to enhance colorectal cancer treatments.

Science advances, 8(45):eadd2789.

The development of human microbiome has collectively correlated the sophisticated interactions between Fusobacterium nucleatum and colorectal cancers (CRCs). However, the treatment of CRC via disruption of gastrointestinal flora remains less explored. Aiming at the up-regulated activity of nitroreductase in F. nucleatum-infected tumors, here, we developed the nitroreductase-instructed supramolecular self-assembly. The designed assembly precursors underwent enzymatic transformation to form assemblies, which agglutinated F. nucleatum and eradicated the targeted bacteria. These assemblies with anti-F. nucleatum activity could further alleviate the bacteria-induced drug resistance effect, thus sensitizing CRC cells against chemo-drugs. Eventually, in mice bearing F. nucleatum-infected CRC, the local introduction of nitroreductase-instructed assemblies could efficiently inhibit the tumor growth. Overall, this study incorporated nitroreductase to broaden the toolbox of enzyme-instructed supramolecular self-assembly. The local introduction of nitroreductase-instructed assemblies could target F. nucleatum to eliminate its contribution to CRC drug resistance and ameliorate chemotherapy outcomes.

RevDate: 2022-11-08

Rasmussen N (2022)

René Dubos, the Autochthonous Flora, and the Discovery of the Microbiome.

Journal of the history of biology [Epub ahead of print].

Now characterised by high-throughput sequencing methods that enable the study of microbes without lab culture, the human "microbiome" (the microbial flora of the body) is said to have revolutionary implications for biology and medicine. According to many experts, we must now understand ourselves as "holobionts" like lichen or coral, multispecies superorganisms that consist of animal and symbiotic microbes in combination, because normal physiological function depends on them. Here I explore the 1960s research of biologist René Dubos, a forerunner figure mentioned in some historical accounts of the microbiome, and argue that he arrived at the superorganism concept 40 years before the Human Microbiome Project. This raises the question of why his contribution was not hailed as revolutionary at the time and why Dubos is not remembered for it.

RevDate: 2022-11-07

Mirabelli C, Santos-Ferreira N, Gillilland MG, et al (2022)

Human Norovirus Efficiently Replicates in Differentiated 3D-Human Intestinal Enteroids.

Journal of virology [Epub ahead of print].

Human norovirus (HNoV) accounts for one-fifth of all acute viral gastroenteritis worldwide and an economic burden of ~$60 billion globally. The lack of treatment options against HNoV is in part due to the lack of cultivation systems. Recently, a model of infection in biopsy-derived human intestinal enteroids (HIE) has been described: 3D-HIE are first dispersed in 2D-monolayers and differentiated prior to infection, resulting in a labor-intensive, time-consuming procedure. Here, we present an alternative protocol for HNoV infection of 3D-HIE. We found that 3D-HIE differentiated as efficiently as 2D-monolayers. In addition, immunofluorescence-based quantification of UEA-1, a lectin that stains the villus brush border, revealed that ~80% of differentiated 3D-HIE spontaneously undergo polarity inversion, allowing for viral infection without the need for microinjection. Infection with HNoV GII.4-positive stool samples attained a fold-increase over inoculum of ~2 Log10 at 2 days postinfection or up to 3.5 Log10 when ruxolitinib, a JAK1/2-inhibitor, was added. Treatment of GII.4-infected 3D-HIE with the polymerase inhibitor 2'-C-Methylcytidine (2CMC) and other antivirals showed a reduction in viral infection, suggesting that 3D-HIE are an excellent platform to test anti-infectives. The transcriptional host response to HNoV was then investigated by RNA sequencing in infected versus uninfected 3D-HIE in the presence of ruxolitinib to focus on virus-associated signatures while limiting interferon-stimulated gene signatures. The analysis revealed upregulated hormone and neurotransmitter signal transduction pathways and downregulated glycolysis and hypoxia-response pathways upon HNoV infection. Overall, 3D-HIE have proven to be a highly robust model to study HNoV infection, screen antivirals, and to investigate the host response to HNoV infection. IMPORTANCE The human norovirus (HNoV) clinical and socio-economic impact calls for immediate action in the development of anti-infectives. Physiologically relevant in vitro models are hence needed to study HNoV biology, tropism, and mechanisms of viral-associated disease, and also as a platform to identify antiviral agents. Biopsy-derived human intestinal enteroids are a biomimetic of the intestinal epithelium and were recently described as a model that supports HNoV infection. However, the established protocol is time-consuming and labor-intensive. Therefore, we sought to develop a simplified and robust alternative model of infection in 3D enteroids that undergoes differentiation and spontaneous polarity inversion. Advantages of this model are the shorter experimental time, better infection yield, and spatial integrity of the intestinal epithelium. This model is potentially suitable for the study of other pathogens that infect intestinal cells from the apical surface but also for unraveling the interactions between intestinal epithelium and indigenous bacteria of the human microbiome.

RevDate: 2022-11-07

Akimbekov NS, Digel I, Yerezhepov AY, et al (2022)

Nutritional factors influencing microbiota-mediated colonization resistance of the oral cavity: A literature review.

Frontiers in nutrition, 9:1029324.

The oral cavity is a key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems. The oral microbiota is a vital part of the human microbiome. It has been developed through mutual interactions among the environment, host physiological state, and microbial community composition. Indigenious microbiota of the oral cavity is one of the factors that prevent adhesion and invasion of pathogens on the mucous membrane, i.e., the development of the infectious process and thereby participating in the implementation of one of the mechanisms of local immunity-colonization resistance. The balance between bacterial symbiosis, microbial virulence, and host resistance ensures the integrity of the oral cavity. In this review we have tried to address how nutritional factors influence integrity of the oral indigenous microbiota and its involvement in colonization resistance.

RevDate: 2022-11-06

Cuozzo S, de Moreno de LeBlanc A, LeBlanc JG, et al (2022)

Streptomyces genus as a source of probiotics and its potential for its use in health.

Microbiological research, 266:127248 pii:S0944-5013(22)00288-9 [Epub ahead of print].

The effect of a probiotic on gut microbiota depends not only on the species of microorganism but specifically on the strain. In human beings, as in other animals, specific probiotics have been associated with numerous beneficial properties, which include weight modulation (gain or loss), immune modulation, and prevention of many disorders such as lactose intolerance, cardiovascular diseases, and antibiotic-associated diarrhoea. Streptomyces are an essential group of soil bacteria in the Actinomycetes family. They are related to producing a wide range of secondary metabolites known for their beneficial effects on human health. However, according to the human microbiome analysis, a lower prevalence of Streptomyces genus exists than in other non-human microbiomes. This difference can be associated with current lifestyles. In this article, we review the benefits associated with different compounds produced by Streptomyces, with a particular focus on the production of exopolysaccharides, antibiotics, and other secondary metabolites and the potential innovative use of Streptomyces spp. as probiotics.

RevDate: 2022-11-04

Clarke T, Brinkac L, Greco C, et al (2022)

Sampling from four geographically divergent young female populations demonstrates forensic geolocation potential in microbiomes.

Scientific reports, 12(1):18547.

Studies of human microbiomes using new sequencing techniques have increasingly demonstrated that their ecologies are partly determined by the lifestyle and habits of individuals. As such, significant forensic information could be obtained from high throughput sequencing of the human microbiome. This approach, combined with multiple analytical techniques demonstrates that bacterial DNA can be used to uniquely identify an individual and to provide information about their life and behavioral patterns. However, the transformation of these findings into actionable forensic information, including the geolocation of the samples, remains limited by incomplete understanding of the effects of confounding factors and the paucity of diverse sequences. We obtained 16S rRNA sequences of stool and oral microbiomes collected from 206 young and healthy females from four globally diverse populations, in addition to supporting metadata, including dietary and medical information. Analysis of these microbiomes revealed detectable geolocation signals between the populations, even for populations living within the same city. Accounting for other lifestyle variables, such as diet and smoking, lessened but does not remove the geolocation signal.

RevDate: 2022-11-02

Saleem A, Ikram A, Dikareva E, et al (2022)

Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus.

Gut microbes, 14(1):2142009.

Biogeographic variations in the gut microbiota are pivotal to understanding the global pattern of host-microbiota interactions in prevalent lifestyle-related diseases. Pakistani adults, having an exceptionally high prevalence of type 2 diabetes mellitus (T2D), are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by bacterial 16S ribosomal RNA gene and fungal internal transcribed spacer (ITS) region amplicon sequencing and eubacterial qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide-binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis of the bacterial microbiota. Overall, urbanized Pakistanis' gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations, e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for a more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.

RevDate: 2022-11-02

Stuivenberg GA, Chmiel JA, Akouris PP, et al (2022)

Probiotic Bifidobacteria Mitigate the Deleterious Effects of para-Cresol in a Drosophila melanogaster Toxicity Model.

mSphere [Epub ahead of print].

Renal impairment associated with chronic kidney disease (CKD) causes the buildup of uremic toxins that are deleterious to patient health. Current therapies that manage toxin accumulation in CKD offer an incomplete therapeutic effect against toxins such as para-cresol (p-cresol) and p-cresyl sulfate. Probiotic therapies can exploit the wealth of microbial diversity to reduce toxin accumulation. Using in vitro culture techniques, strains of lactobacilli and bifidobacteria from a 24-strain synbiotic were investigated for their ability to remove p-cresol. Four strains of bifidobacteria internalized p-cresol from the extracellular environment. The oral supplementation of these toxin-clearing probiotics was more protective than control strains in a Drosophila melanogaster toxicity model. Bifidobacterial supplementation was also associated with higher abundance of lactobacilli in the gut microbiota of p-cresol-exposed flies. The present findings suggest that these strains might reduce p-cresol in the gut in addition to increasing the prevalence of other beneficial bacteria, such as lactobacilli, and should be tested clinically to normalize the dysbiotic gut microbiota observed in CKD patients. IMPORTANCE Chronic kidney disease (CKD) affects approximately 10% of the global population and has limited treatment options. The accumulation of gut microbiota-derived uremic toxins, such as para-cresol (p-cresol) and p-cresyl sulfate, is associated with the onset of comorbidities (i.e., atherosclerosis and cognitive disorders) in CKD. Unfortunately, dialysis, the gold standard therapy is unable to remove these toxins from the bloodstream due to their highly protein-bound nature. Some strains of Bifidobacterium have metabolic properties that may be useful in managing uremic toxicity. Using a Drosophila model, the present work highlights why dosing with certain probiotic strains may be clinically useful in CKD management.

RevDate: 2022-11-02

Das BK (2022)

Altered Gut Microbiota in Hepatocellular Carcinoma: Insights into the Pathogenic Mechanism and Preclinical to Clinical Findings.

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica [Epub ahead of print].

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. It is usually the result of pre-existing liver damage caused by hepatitis B and/or C virus infection, alcohol consumption, non-alcoholic steatohepatitis (NASH), aflatoxin exposure, liver cirrhosis, obesity, and diabetes. A growing body of evidence suggests that gut microbes have a role in cancer genesis. More research into the microbiome gut-liver axis has recently contributed to understanding how the gut microbiome facilitates liver disease or even HCC progression. This review focuses on the preclinical results of gut-related hepatocarcinogenesis and probiotics, prebiotics, and antibiotics as therapeutic interventions to maintain gut microbial flora and minimize HCC-associated symptoms. Understanding the mechanistic link between the gut microbiota, host, and cancer progression could aid us in elucidating the cancer-related pathways and drive us toward preventing HCC-associated gut microbiota dysbiosis.

RevDate: 2022-11-02

Tierney BT, Versalovic J, Fasano A, et al (2022)

Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial.

Pediatric research [Epub ahead of print].

BACKGROUND: Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children.

METHODS: Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n = 31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo.

RESULTS: Treatment increased (p < 0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074).

CONCLUSIONS: These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children.

IMPACT: Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.

RevDate: 2022-11-01

Zhan Y, Liu Q, Zhang B, et al (2022)

Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside.

Frontiers of medicine [Epub ahead of print].

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease affecting multiple systems and organs. It is highly heterogeneous, and it preferentially affects women at childbearing age, causing worldwide social burden. The pathogenesis of SLE mostly involves genetic predisposition, epigenetic dysregulation, overactivation of the immune system, and environment factors. Human microbiome, which is mostly composed of microbiota colonized in the gut, skin, and oral cavity, provides a natural microbiome barrier against environmental risks. The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases. However, the role of microbiota in autoimmunity remains largely unknown until recently, when the technological and methodological progress facilitates further microbiota research in SLE. In this review, the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.

RevDate: 2022-11-01

Aggarwal N, Kitano S, Puah GRY, et al (2022)

Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies.

Chemical reviews [Epub ahead of print].

The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.

RevDate: 2022-10-31

Sadekov TS, Boyko AN, Omarova MA, et al (2022)

Evaluation of the structure of the human microbiome in multiple sclerosis by the concentrations of microbial markers in the blood.

Klinicheskaia laboratornaia diagnostika, 67(10):600-606.

The relationship between multiple sclerosis and the state of the human microbiome was studied, namely, the change in the representation of microbiota phylotypes, the proportion of coccal flora, the proportion of anaerobic, gram-negative, proteolytically active microflora, as well as the concentration of markers of bacterial plasmalogen and endotoxin in the blood. Microbiome studies were carried out by gas chromatography - mass spectrometry of microbial markers in the blood. A statistically significant increase in blood concentrations of the total level of microbial markers of bacterial plasmalogen and endotoxin was determined in multiple sclerosis, which may be associated with an increase in the permeability of the intestinal wall. In multiple sclerosis, the proportion of coccal, gram-negative, anaerobic microflora with a proteolytic type of metabolic activity increases. The correlations of the representation of microbiota phylotypes change due to the switching of the direct relationship Proteobacteria-Bacteroides to Proteobacteria-Firmicutes. In multiple sclerosis, Actinobacteria and Proteobacteria increase and Firmicutes decrease. Conclusion. The multiple sclerosis disease may be associated with pathological changes in the structure of the microbiome and the growth of endotoxemia, which may be one of the factors in the pathogenesis of the disease. New laboratory markers for diagnosing and predicting the course of MS have been proposed.

RevDate: 2022-10-28

Wang Y, C Jian (2022)

Sustainable plant-based ingredients as wheat flour substitutes in bread making.

NPJ science of food, 6(1):49.

Bread as a staple food has been predominantly prepared from refined wheat flour. The world's demand for food is rising with increased bread consumption in developing countries where climate conditions are unsuitable for wheat cultivation. This reliance on wheat increases the vulnerability to wheat supply shocks caused by force majeure or man-made events, in addition to negative environmental and health consequences. In this review, we discuss the contribution to the sustainability of food systems by partially replacing wheat flour with various types of plant ingredients in bread making, also known as composite bread. The sustainable sources of non-wheat flours, their example use in bread making and potential health and nutritional benefits are summarized. Non-wheat flours pose techno-functional challenges due to significantly different properties of their proteins compared to wheat gluten, and they often contain off-favor compounds that altogether limit the consumer acceptability of final bread products. Therefore, we detail recent advances in processing strategies to improve the sensory and nutritional profiles of composite bread. A special focus is laid on fermentation, for its accessibility and versatility to apply to different ingredients and scenarios. Finally, we outline research needs that require the synergism between sustainability science, human nutrition, microbiomics and food science.

RevDate: 2022-10-27

Armstrong D, Dregan A, Ashworth M, et al (2022)

Prior antibiotics and risk of subsequent Herpes zoster: A population-based case control study.

PloS one, 17(10):e0276807 pii:PONE-D-21-26046.

BACKGROUND: The effect of antibiotics on the human microbiome is now well established, but their indirect effect on the related immune response is less clear. The possible association of Herpes zoster, which involves a reactivation of a previous varicella zoster virus infection, with prior antibiotic exposure might indicate a potential link with the immune response.

METHODS: A case-control study was carried out using a clinical database, the UK's Clinical Practice Research Datalink. A total of 163,754 patients with varicella zoster virus infection and 331,559 age/sex matched controls were identified and their antibiotic exposure over the previous 10 years, and longer when data permitted, was identified. Conditional logistic regression was used to identify the association between antibiotic exposure and subsequent infection in terms of volume and timing.

RESULTS: The study found an association of antibiotic prescription and subsequent risk of varicella zoster virus infection (adjusted odds ratio of 1.50; 95%CIs: 1.42-1.58). The strongest association was with a first antibiotic over 10 years ago (aOR: 1.92; 95%CIs: 1.88-1.96) which was particularly pronounced in the younger age group of 18 to 50 (aOR 2.77; 95%CIs: 1.95-3.92).

CONCLUSIONS: By finding an association between prior antibiotics and Herpes zoster this study has shown that antibiotics may be involved in the reactivation of the varicella zoster virus. That effect, moreover, may be relatively long term. This indirect effect of antibiotics on viruses, possibly mediated through their effect on the microbiome and immune system, merits further study.

RevDate: 2022-10-27

Pereira GC (2023)

An Automated Strategy to Handle Antigenic Variability in Immunisation Protocols, Part I: Nanopore Sequencing of Infectious Agent Variants.

Methods in molecular biology (Clifton, N.J.), 2575:305-321.

Infectious agents often challenge therapeutics, from antibiotics resistance to antigenic variability affecting inoculation measures. Over the last decades, genome sequencing arose as an important ally to address such challenges. In bacterial infection, whole-genome-sequencing (WGS) supports tracking pathogenic alterations affecting the human microbiome. In viral infection, the analysis of the relevant sequence of nucleotides helps with determining historical variants of a virus and elucidates details about infection clusters and their distribution. Additionally, genome sequencing is now an important step in inoculation protocols, isolating target genes to design more robust immunisation assays. Ultimately, genetic engineering has empowered repurposing at scale, allowing long-lasting repeating clinical trials to be automated within a much shorter time-frame, by adjusting existing protocols. This is particularly important during sanitary emergencies as the ones caused by the 2014 West African Ebola outbreak, the Zika virus rapid spread in both South and North America in 2015, followed by Asia in 2016, and the pandemic caused by the SARS-CoV-2, which has infected more than 187 million people and caused more than 4 million deaths, worldwide, as per July 2021 statistics. In this scenery, this chapter presents a novel fully automated strategy to handle antigenic variability in immunisation protocols. The methodology comprises of two major steps (1) nanopore sequencing of infectious agent variants - the focus is on the SARS-CoV-2 and its variants; followed by (2) mRNA vector design for immunotherapy. This chapter presents the nanopore sequencing step and Chapter 17 introduces a protocol for mRNA vector design.

RevDate: 2022-10-26

France MT, Brown SE, Rompalo AM, et al (2022)

Identification of shared bacterial strains in the vaginal microbiota of related and unrelated reproductive-age mothers and daughters using genome-resolved metagenomics.

PloS one, 17(10):e0275908 pii:PONE-D-22-16695.

It has been suggested that the human microbiome might be vertically transmitted from mother to offspring and that early colonizers may play a critical role in development of the immune system. Studies have shown limited support for the vertical transmission of the intestinal microbiota but the derivation of the vaginal microbiota remains largely unknown. Although the vaginal microbiota of children and reproductive age women differ in composition, the vaginal microbiota could be vertically transmitted. To determine whether there was any support for this hypothesis, we examined the vaginal microbiota of daughter-mother pairs from the Baltimore metropolitan area (ages 14-27, 32-51; n = 39). We assessed whether the daughter's microbiota was similar in composition to their mother's using metataxonomics. Permutation tests revealed that while some pairs did have similar vaginal microbiota, the degree of similarity did not exceed that expected by chance. Genome-resolved metagenomics was used to identify shared bacterial strains in a subset of the families (n = 22). We found a small number of bacterial strains that were shared between mother-daughter pairs but identified more shared strains between individuals from different families, indicating that vaginal bacteria may display biogeographic patterns. Earlier-in-life studies are needed to demonstrate vertical transmission of the vaginal microbiota.

RevDate: 2022-10-26

Ponziani FR, Nesci A, Caputo C, et al (2022)

High Prevalence of Lower Limb Atherosclerosis is Linked with the Gut-Liver-Axis in Patients with Primary Biliary Cholangitis.

Liver international : official journal of the International Association for the Study of the Liver [Epub ahead of print].

BACKGROUND & AIMS: Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut-liver-axis and systemic inflammation.

METHODS: Thirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with nonalcoholic fatty liver disease (NAFLD), and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow mediated dilation, quantification of circulating cytokines and vasoactive mediators, characterization the compositional and functional profile of the gut microbiota.

RESULTS: PBC patients had higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p=0.01). Factors associated with LEAD at univariate analysis were VCAM-1 (p=0.002), ICAM-1 (p=0.003), and TNF-alpha (p=0.04), but only VCAM-1 (OR 1.1, 95% CI 1.0-1.1; p=0.04) and TNF-alpha (OR 1.12, 95%CI 0.99-1.26; p=0.04) were confirmed as independent predictors in the multivariate model. Gut microbiome analysis revealed that Acidaminococcus (FDR=0.0008), Bifidobacterium (FDR=0.001) and Oscillospira (FDR=0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha. Downregulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism, and branched chain amino acids degradation was found in the functional gut metagenome of PBC women.

CONCLUSIONS: LEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut-liver-axis.

RevDate: 2022-10-26

Jones RP, A Ponomarenko (2022)

Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths.

Infectious disease reports, 14(5):710-758 pii:idr14050076.

Pathogen interference is the ability of one pathogen to alter the course and clinical outcomes of infection by another. With up to 3000 species of human pathogens the potential combinations are vast. These combinations operate within further immune complexity induced by infection with multiple persistent pathogens, and by the role which the human microbiome plays in maintaining health, immune function, and resistance to infection. All the above are further complicated by malnutrition in children and the elderly. Influenza vaccination offers a measure of protection for elderly individuals subsequently infected with influenza. However, all vaccines induce both specific and non-specific effects. The specific effects involve stimulation of humoral and cellular immunity, while the nonspecific effects are far more nuanced including changes in gene expression patterns and production of small RNAs which contribute to pathogen interference. Little is known about the outcomes of vaccinated elderly not subsequently infected with influenza but infected with multiple other non-influenza winter pathogens. In this review we propose that in certain years the specific antigen mix in the seasonal influenza vaccine inadvertently increases the risk of infection from other non-influenza pathogens. The possibility that vaccination could upset the pathogen balance, and that the timing of vaccination relative to the pathogen balance was critical to success, was proposed in 2010 but was seemingly ignored. Persons vaccinated early in the winter are more likely to experience higher pathogen interference. Implications to the estimation of vaccine effectiveness and influenza deaths are discussed.

RevDate: 2022-10-26

Keren R, Méheust R, Santini JM, et al (2022)

Global genomic analysis of microbial biotransformation of arsenic highlights the importance of arsenic methylation in environmental and human microbiomes.

Computational and structural biotechnology journal, 20:559-572 pii:S2001-0370(22)00006-X.

Arsenic is a ubiquitous toxic element, the global cycle of which is highly affected by microbial redox reactions and assimilation into organoarsenic compounds through sequential methylation reactions. While microbial biotransformation of arsenic has been studied for decades, the past years have seen the discovery of multiple new genes related to arsenic metabolism. Still, most studies focus on a small set of key genes or a small set of cultured microorganisms. Here, we leveraged the recently greatly expanded availability of microbial genomes of diverse organisms from lineages lacking cultivated representatives, including those reconstructed from metagenomes, to investigate genetic repertoires of taxonomic and environmental controls on arsenic metabolic capacities. Based on the collection of arsenic-related genes, we identified thirteen distinct metabolic guilds, four of which combine the aio and ars operons. We found that the best studied phyla have very different combinations of capacities than less well-studied phyla, including phyla lacking isolated representatives. We identified a distinct arsenic gene signature in the microbiomes of humans exposed or likely exposed to drinking water contaminated by arsenic and that arsenic methylation is important in soil and in human microbiomes. Thus, the microbiomes of humans exposed to arsenic have the potential to exacerbate arsenic toxicity. Finally, we show that machine learning can predict bacterial arsenic metabolism capacities based on their taxonomy and the environment from which they were sampled.

RevDate: 2022-10-25

Yadav M, NS Chauhan (2022)

Role of gut-microbiota in disease severity and clinical outcomes.

Briefings in functional genomics pii:6770312 [Epub ahead of print].

A delicate balance of nutrients, antigens, metabolites and xenobiotics in body fluids, primarily managed by diet and host metabolism, governs human health. Human gut microbiota is a gatekeeper to nutrient bioavailability, pathogens exposure and xenobiotic metabolism. Human gut microbiota starts establishing during birth and evolves into a resilient structure by adolescence. It supplements the host's metabolic machinery and assists in many physiological processes to ensure health. Biotic and abiotic stressors could induce dysbiosis in gut microbiota composition leading to disease manifestations. Despite tremendous scientific advancements, a clear understanding of the involvement of gut microbiota dysbiosis during disease onset and clinical outcomes is still awaited. This would be important for developing an effective and sustainable therapeutic intervention. This review synthesizes the present scientific knowledge to present a comprehensive picture of the role of gut microbiota in the onset and severity of a disease.

RevDate: 2022-10-24

Gupta A, Singh V, I Mani (2022)

Dysbiosis of human microbiome and infectious diseases.

Progress in molecular biology and translational science, 192(1):33-51.

Since birth, the human body gets colonized by various communities of symbiotic or commensal microorganisms and they persist till the death of an individual. The human microbiome is comprised of the genomes of microorganisms such as viruses, archaea, eukaryotes, protozoa, and, most remarkably, bacteria. The development of "omics" technologies gave way to the Human Microbiome Project (HMP) which aimed at exploring the collection of microbial genes and genomes inhabiting the human body. Eubiosis, i.e., a healthy and balanced composition of such microbes contributes to the metabolic function, protection against pathogens and provides nutrients and energy to the host. Whereas, an imbalance in the diversity of microorganisms, termed dysbiosis, greatly influences the state of health and disease. This chapter summarizes the impact of gut bacteria on the well-being of humans and highlights the protective role played by the human microbiota during bacterial and viral infections. The condition of dysbiosis and how it plays a role in the establishment of various infections and metabolic disorders such as Clostridioides difficile infection (CFI), inflammatory bowel disease (IBD), cancer, periodontitis, and obesity are described in detail. Further, treatments such as fecal transplantation, probiotics, prebiotics, phage therapy, and CRISPR/Cas system, which target gut microbiota during digestive diseases are also discussed.

RevDate: 2022-10-24

Ahrodia T, Yodhaanjali JR, B Das (2022)

Vaginal microbiome dysbiosis in preterm birth.

Progress in molecular biology and translational science, 192(1):309-329.

All the environmentally exposed surfaces of the human body harbor ecologically distinct microbial communities with a mutualistic beneficial relationship. Depending on the body sites, microbes may provide metabolic functions, protection against pathogens, and signaling molecules to modulate host physiology and reduce disease susceptibility. Our recent understanding of the vaginal microbiome based on culture-independent 16S rRNA gene sequencing indicates that Lactobacillus-dominated microbial communities of healthy women play an important role in decreasing susceptibility to several urogenital diseases, including bacterial, fungal and viral infections. The findings of shotgun sequencing of the vaginal microbiome suggest that microbial-derived lactic acid, bacteriostatic, bactericidal molecules, and lower vaginal pH mediate such protections and regulations. Bacterial species, the dominant component of the vaginal microbiome, also play a key role in determining the gestation period and birth outcomes of reproductive-age women. The presence of Lactobacillus crispatus species in the vaginal milieu reduces the risk of preterm delivery in women of Asian ancestry. A deeper knowledge of the vaginal microbiota's role in the succession and development of newborn gut bacteria would also be beneficial. The microbiome of the mother changes throughout pregnancy and is linked to the microbiome of the newborn. This chapter highlights updated information and new opportunities for human microbiome research, focusing on the assessment of the risk of preterm birth.

RevDate: 2022-10-24

Alam MJ, Puppala V, Uppulapu SK, et al (2022)

Human microbiome and cardiovascular diseases.

Progress in molecular biology and translational science, 192(1):231-279.

A number of microorganisms are co-evolved with the host, among which bacteria are the predominant organisms in the colonic site. The human microbiota contributes to various physiological functions, including the digestion and degradation of food components, harvesting of inaccessible nutrients, immune system regulation, maintenance of gut barrier function, and regulation of brain function and behavior. Microbes in the gut produce a wealth of metabolites from the exogenous dietary substances or endogenous metabolic compounds produced by the host and the resident microorganisms. These microbial-derived metabolites are the major factors in the host-microbiota cross-talk and influence the host's cardiometabolic health directly or indirectly depending on the structure and function of the microbial community. Evidence suggests that the perturbation in the composition and function of gut microbiota (referred to as gut dysbiosis) is associated with the development of several diseased conditions such as that of the gastrointestinal tract or colorectal cancer, metabolic diseases such as obesity, diabetes, immune disorders e.g. asthma, allergies, depression, anxiety and cardiometabolic disease. Several pathological conditions in the gastrointestinal tract may impair the intestinal barrier that allows translocation of bacteria and their metabolites to a remote organ such as the heart, which may ultimately be associated with systemic inflammation and the development of CVDs. In this chapter, we will discuss various gut microbiota-dependent metabolites, which have a significant role in cardiovascular diseases' pathologic processes and their risk factors. Finally, we will discuss the therapeutic potential of the gut-metabolite-heart axis as a novel target for the treatment of CVD and highlight the current updates and exciting directions for future research.

RevDate: 2022-10-24

Nguyen NA, Huang X, Cabrera LE, et al (2022)

A comprehensive assessment of four whole blood stabilisers for flow-cytometric analysis of leukocyte populations.

Cytometry. Part A : the journal of the International Society for Analytical Cytology [Epub ahead of print].

Though cryopreservation of cell fractions is widely used in flow cytometry studies, whole blood cryopreservation is more challenging due to the presence of erythrocytes and effects of fixatives commonly used for preservation. Here, we evaluated and compared head-to-head the performance of four commercial whole blood cryopreservation kits; 1) Cytodelics, 2) Stable-Lyse V2 and Stable-Store V2 (SLSS-V2), 3) Proteomic stabiliser (PROT-1), and 4) Transfix. We found that PROT-1, Transfix and Cytodelics maintained the distribution of major leukocyte subsets - granulocytes, T cells, natural killer cells and B cells, on a comparable level to unpreserved samples, despite the attenuation of fluorescence intensities in flow cytometric assays. Moreover, these three stabilisers also maintained the activated phenotypes of neutrophils upon stimulation with N-Formylmethionyl-leucyl-phenylalanine and lipopolysaccharides. The upregulation of adhesion molecules (CD11b), Fc receptors (CD16) and granule proteins (CD66b), as well as the shedding of surface L-selectin (CD62L), was conserved most efficiently in PROT-1 and Cytodelics when compared to samples only treated with erythrocyte lysing. However, none of the stabilisers provided a reliable detection of CCR7 for accurate quantification of T cell maturation stages. We also evaluated the performance of Cytodelics in longitudinal clinical samples obtained from acute COVID-19 patients, where it allowed reliable detection of lymphopenia and granulocyte expansion. These results support the feasibility of whole blood cryopreservation for immunophenotyping by flow cytometry, particularly in longitudinal studies. In conclusion, the performance of different stabilizers is variable and therefore the choice of stabilisers should depend on cell type of interest, as well as antibody clones and experimental design of each study. This article is protected by copyright. All rights reserved.

RevDate: 2022-10-24

Suryaletha K, Savithri AV, Nayar SA, et al (2022)

Demystifying Bacteriocins of human microbiota by genome guided prospects: An impetus to rekindle the antimicrobial research.

Current protein & peptide science pii:CPPS-EPUB-127084 [Epub ahead of print].

The human microbiome is a reservoir of potential bacteriocins that can counteract with the multidrug resistant bacterial pathogens. Unlike antibiotics, bacteriocins selectively inhibit a spectrum of competent bacteria and are said to safeguard gut commensals, reducing the chance of dysbiosis. Bacteriocinogenic probiotics or bacteriocins of human origin will be more pertinent in human physiological conditions for therapeutic applications to act against invading pathogens. Recent advancement in the omics approach enables the mining of diverse and novel bacteriocins by identifying biosynthetic gene clusters from the human microbial genome, pangenome or shotgun metagenome, which is a breakthrough in the discovery line of novel bacteriocins. This review summarizes the most recent trends and therapeutic potential of bacteriocins of human microbial origin, and the advancement in the in silico algorithms and databases in the discovery of novel bacteriocin, and how to bridge the gap between the discovery of bacteriocin genes from big datasets and their in vitro production. Besides, the later part of the review discussed the various impediments in their clinical applications and possible solution to bring them in the frontline therapeutics to control infections, thereby meeting the challenges of global antimicrobial resistance.

RevDate: 2022-10-24

Matharu D, Ponsero AJ, Dikareva E, et al (2022)

Bacteroides abundance drives birth mode dependent infant gut microbiota developmental trajectories.

Frontiers in microbiology, 13:953475.

Background and aims: Birth mode and other early life factors affect a newborn's microbial colonization with potential long-term health effects. Individual variations in early life gut microbiota development, especially their effects on the functional repertoire of microbiota, are still poorly characterized. This study aims to provide new insights into the gut microbiome developmental trajectories during the first year of life.

Methods: Our study comprised 78 term infants sampled at 3 weeks, 3 months, 6 months, and 12 months (n = 280 total samples), and their mothers were sampled in late pregnancy (n = 50). Fecal DNA was subjected to shotgun metagenomic sequencing. Infant samples were studied for taxonomic and functional maturation, and maternal microbiota was used as a reference. Hierarchical clustering on taxonomic profiles was used to identify the main microbiota developmental trajectories in the infants, and their associations with perinatal and postnatal factors were assessed.

Results: In line with previous studies, infant microbiota composition showed increased alpha diversity and decreased beta diversity by age, converging toward an adult-like profile. However, we did not observe an increase in functional alpha diversity, which was stable and comparable with the mother samples throughout all the sampling points. Using a de novo clustering approach, two main infant microbiota clusters driven by Bacteroidaceae and Clostridiaceae emerged at each time point. The clusters were associated with birth mode and their functions differed mainly in terms of biosynthetic and carbohydrate degradation pathways, some of which consistently differed between the clusters for all the time points. The longitudinal analysis indicated three main microbiota developmental trajectories, with the majority of the infants retaining their characteristic cluster until 1 year. As many as 40% of vaginally delivered infants were grouped with infants delivered by C-section due to their clear and persistent depletion in Bacteroides. Intrapartum antibiotics, any perinatal or postnatal factors, maternal microbiota composition, or other maternal factors did not explain the depletion in Bacteroides in the subset of vaginally born infants.

Conclusion: Our study provides an enhanced understanding of the compositional and functional early life gut microbiota trajectories, opening avenues for investigating elusive causes that influence non-typical microbiota development.

RevDate: 2022-10-24

Zheng Y, Shi J, Chen Q, et al (2022)

Identifying individual-specific microbial DNA fingerprints from skin microbiomes.

Frontiers in microbiology, 13:960043.

Skin is an important ecosystem that links the human body and the external environment. Previous studies have shown that the skin microbial community could remain stable, even after long-term exposure to the external environment. In this study, we explore two questions: Do there exist strains or genetic variants in skin microorganisms that are individual-specific, temporally stable, and body site-independent? And if so, whether such microorganismal genetic variants could be used as markers, called "fingerprints" in our study, to identify donors? We proposed a framework to capture individual-specific DNA microbial fingerprints from skin metagenomic sequencing data. The fingerprints are identified on the frequency of 31-mers free from reference genomes and sequence alignments. The 616 metagenomic samples from 17 skin sites at 3-time points from 12 healthy individuals from Integrative Human Microbiome Project were adopted. Ultimately, one contig for each individual is assembled as a fingerprint. And results showed that 89.78% of the skin samples despite body sites could identify their donors correctly. It is observed that 10 out of 12 individual-specific fingerprints could be aligned to Cutibacterium acnes. Our study proves that the identified fingerprints are temporally stable, body site-independent, and individual-specific, and can identify their donors with enough accuracy. The source code of the genetic identification framework is freely available at

RevDate: 2022-10-21

Lau RI, Zhang F, Liu Q, et al (2022)

Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications.

Nature reviews. Gastroenterology & hepatology [Epub ahead of print].

The gastrointestinal tract is involved in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gut microbiota has important roles in viral entry receptor angiotensin-converting enzyme 2 (ACE2) expression, immune homeostasis, and crosstalk between the gut and lungs, the 'gut-lung axis'. Emerging preclinical and clinical studies indicate that the gut microbiota might contribute to COVID-19 pathogenesis and disease outcomes; SARS-CoV-2 infection was associated with altered intestinal microbiota and correlated with inflammatory and immune responses. Here, we discuss the cutting-edge evidence on the interactions between SARS-CoV-2 infection and the gut microbiota, key microbial changes in relation to COVID-19 severity and host immune dysregulations with the possible underlying mechanisms, and the conceivable consequences of the pandemic on the human microbiome and post-pandemic health. Finally, potential modulatory strategies of the gut microbiota are discussed. These insights could shed light on the development of microbiota-based interventions for COVID-19.

RevDate: 2022-10-21

Mahapatra S, Mohanty S, Mishra R, et al (2022)

An overview of cancer and the human microbiome.

Progress in molecular biology and translational science, 191(1):83-139.

Mutual beneficial associations with the microbial consortia are an essential requisite of human life. Microbial communities have both a symbiotic and a pathogenic standpoint, which portrays a context-dependent scenario of the human microbiome. The symbiotic assemblage works to develop indispensable functions of the human body such as immune system, digestive system, defense against colonization by pathobionts and their toxins, etc. Furthermore, any deviation in the resource utilization by the symbionts due to host factors comprising lifestyle changes, diet, drugs, immunocompromised states, and co-morbidities could perturb beneficial microbes communities and promote the invasion by opportunistic pathogens thus, disrupting the homeostatic state. Microbial infestations have proved to be carcinogenic but this does not spontaneously establish a cancer hallmark, rather they initiate a cascade of events that disturbs the normal cellular activities finally these defective machineries invade distant sites of the body, submitting to a devastative transformed internal milieu. Significant technological and system biology advances have been made in elucidating a lucid but complex basis of such microbe-associated malignancies. This chapter discusses the recent advances, without compromising the concepts of the inception studies, including a brief version of the microbial status in cancer generation, mechanistic approaches adapted, therapeutic interventions, system biology approaches with special mention on the study design gaps, challenges in addressing the drawbacks and finally with a perspective of the future targeted studies, has been a focus of this piece of work.

RevDate: 2022-10-21

Ahrodia T, Das S, Bakshi S, et al (2022)

Structure, functions, and diversity of the healthy human microbiome.

Progress in molecular biology and translational science, 191(1):53-82.

Taxonomic composition and functional potency of microbes associated with different parts of the human body have largely been explored by culture-independent metagenome sequencing. The diverse microbiota living throughout the human body is made up of thousands of microbial taxa from all three domains of life: Archaea, Bacteria, and Eukarya. Microbial load and functional potency in different body sites are well distinct and have minimal resemblance at higher taxonomic levels between the two habitats. The highest microbial load, diversity, and functional potency including biosynthesis of essential nutrients, chemical modifications of dietary components, and sources of immunomodulatory molecules, are found in the gut microbiome. However, the inter-individual diversity and dynamics of the human microbiome in a given body habitat vary greatly over time. Both environmental factors and host genetics contribute significantly to shaping microbial community structure and its stability. A basic understanding of native microbial compositions and their functional potency and stability in different parts of healthy humans living across geography will help us to identify disease-specific microbiota and develop potential microbiome-based therapeutics. Here, we updated our current understanding of the diversity, dynamics, and functional potency of microbiomes associated with different parts of the human body.

RevDate: 2022-10-21

Ghosh TS, M Das (2022)

Emerging tools for understanding the human microbiome.

Progress in molecular biology and translational science, 191(1):29-51.

Recent advances in sequencing technologies, experimental protocols and approaches in data generation and analysis have enabled us to investigate the human microbiome at an unprecedented level of resolution. The current chapter aims to provide an understanding of the different computational and bioinformatic strategies adopted to answer the different questions of a typical microbiome investigation and how the upstream DNA sequencing methodologies can affect this. The chapter enlist the state-of-the-art in metagenomic data analysis along with the available strategies to perform an integrated investigation of the human microbiome along with other data layers.

RevDate: 2022-10-21

Pant A, B Das (2022)

Microbiome-based therapeutics: Opportunity and challenges.

Progress in molecular biology and translational science, 191(1):229-262.

The autochthonous microbial communities comprising symbionts, commensals, and opportunistic pathogens living throughout the human body profoundly contribute to health by reducing disease susceptibility and maturing host immunity. The community compositions and functional repertoires of microbiomes present in the different body habitats are dynamic. The structural and functional balance of the human microbiome could be modulated by environmental factors, lifestyle, and host genetics. Several functions of the microbial community directly or indirectly modulate host cellular signaling pathways that are associated with energy assimilation, sensing and responding to environmental signals through the neuroendocrine pathways, and resistance against colonization of allochthonous microbiota with disease-causing potential. Both culture-dependent and independent characterizations of microbial community compositions and their functional attributes help us to recognize the importance of microbial diversity in individual's health and identify the microbes and their metabolites associated with health and diseases. Such an in-depth understanding of the human microbiome created avenues of microbiome-based translation research, which led to the discovery and development of large numbers of medical therapies. In this chapter, we discuss the current success of microbiome-based therapies for infectious and metabolic diseases, and the major bottleneck and challenges of translational research with the community of symbiotic microorganisms.

RevDate: 2022-10-21

Das B (2022)

An introduction to human microbiome.

Progress in molecular biology and translational science, 191(1):1-28.

The microbiome is an assemblage of a complex community of microbes (bacteria, archaea, fungi, algae, protists, and viruses) and their biomolecules occupying a well-defined habitat in or on a living or non-living object. All the environmentally exposed surfaces of the human body are colonized with trillions of microbes from all three major domains of life, including bacteria, archea, and microscopic eukarya. However, the richness, abundance, and functional potency of microbial taxa living in different parts of the human body are distinct. The Presence of common microbial taxa in different body habitats is also very rare. With the recent development of next generation sequencing technologies, it has been established that the indigenous microbial community in the human body and their functional attributes within a given body habitat vary over time, between ethnic groups and health status of the host. Perturbation of homeostasis in community structures or functions due to any extrinsic factors can alter mutualistic host-microbe interactions and may lead to disease. In addition, the dysbiotic state of the microbiome can also affect the efficacy of therapeutics, prolong treatment duration and lead to undesired treatment outcomes. In this chapter, structure, functions, diversity and dynamics of human microbiome in health and diseases, factors that alter microbial composition, interactions between microbial taxa and xenobiotics, and therapeutic efficacy of drugs in dysbiotic conditions are highlighted.

RevDate: 2022-10-21

Khorsand B, Asadzadeh Aghdaei H, Nazemalhosseini-Mojarad E, et al (2022)

Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn's disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets.

Frontiers in cellular and infection microbiology, 12:1015890.

Objectives: A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.

Methods: Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi'omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.

Results: Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.

Conclusions: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.

RevDate: 2022-10-20

Sauvaitre T, Van Landuyt J, Durif C, et al (2022)

Role of mucus-bacteria interactions in Enterotoxigenic Escherichia coli (ETEC) H10407 virulence and interplay with human microbiome.

NPJ biofilms and microbiomes, 8(1):86.

The intestinal mucus layer has a dual role in human health constituting a well-known microbial niche that supports gut microbiota maintenance but also acting as a physical barrier against enteric pathogens. Enterotoxigenic Escherichia coli (ETEC), the major agent responsible for traveler's diarrhea, is able to bind and degrade intestinal mucins, representing an important but understudied virulent trait of the pathogen. Using a set of complementary in vitro approaches simulating the human digestive environment, this study aimed to describe how the mucus microenvironment could shape different aspects of the human ETEC strain H10407 pathophysiology, namely its survival, adhesion, virulence gene expression, interleukin-8 induction and interactions with human fecal microbiota. Using the TNO gastrointestinal model (TIM-1) simulating the physicochemical conditions of the human upper gastrointestinal (GI) tract, we reported that mucus secretion and physical surface sustained ETEC survival, probably by helping it to face GI stresses. When integrating the host part in Caco2/HT29-MTX co-culture model, we demonstrated that mucus secreting-cells favored ETEC adhesion and virulence gene expression, but did not impede ETEC Interleukin-8 (IL-8) induction. Furthermore, we proved that mucosal surface did not favor ETEC colonization in a complex gut microbial background simulated in batch fecal experiments. However, the mucus-specific microbiota was widely modified upon the ETEC challenge suggesting its role in the pathogen infectious cycle. Using multi-targeted in vitro approaches, this study supports the major role played by mucus in ETEC pathophysiology, opening avenues in the design of new treatment strategies.

RevDate: 2022-10-20

Mäenpää K, Wang S, Ilves M, et al (2022)

Skin microbiota of oxazolone-induced contact hypersensitivity mouse model.

PloS one, 17(10):e0276071 pii:PONE-D-22-13700.

Contact allergy is a common skin allergy, which can be studied utilising contact hypersensitivity (CHS) animal model. However, it is not clear, whether CHS is a suitable model to investigate skin microbiota interactions. We characterised the effect of contact dermatitis on the skin microbiota and studied the biological effects of oxazolone (OXA) -induced inflammation on skin thickness, immune cell numbers and changes of the microbiota in CHS mouse model (n = 72) for 28 days. Through 16S rRNA gene sequencing we defined the composition of bacterial communities and associations of bacteria with inflammation. We observed that the vehicle solution of acetone and olive oil induced bacterial community changes on day 1, and OXA-induced changes were observed mainly on day 7. Many of the notably enriched bacteria present in the OXA-challenged positive group represented the genus Faecalibaculum which were most likely derived from the cage environment. Additionally, skin inflammation correlated negatively with Streptococcus, which is considered a native skin bacterium, and positively with Muribacter muris, which is typical in oral environment. Skin inflammation favoured colonisation of cage-derived faecal bacteria, and additionally mouse grooming transferred oral bacteria on the skin. Due to the observed changes, we conclude that CHS model could be used for certain skin microbiome-related research set-ups. However, since vehicle exposure can alter the skin microbiome as such, future studies should include considerations such as careful control sampling and statistical tests to account for potential confounding factors.

RevDate: 2022-10-19

Moitinho-Silva L, Degenhardt F, Rodriguez E, et al (2022)

Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota.

Nature communications, 13(1):6204.

Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across three different skin microenvironments through meta-analyses of genome-wide association studies (GWAS) of two population-based German cohorts. We identified 23 genome-wide significant loci harboring 30 candidate genes involved in innate immune signaling, environmental sensing, cell differentiation, proliferation and fibroblast activity. However, no locus passed the strict threshold for study-wide significance (P < 6.3 × 10-10 for 80 features included in the analysis). Mendelian randomization (MR) analysis indicated the influence of staphylococci on eczema/dermatitis and suggested modulating effects of the microbiota on other skin diseases. Finally, transcriptional profiles of keratinocytes significantly changed after in vitro co-culturing with Staphylococcus epidermidis, chosen as a representative of skin commensals. Seven candidate genes from the GWAS were found overlapping with differential expression in the co-culturing experiments, warranting further research of the skin commensal and host genetic makeup interaction.

RevDate: 2022-10-18

Vikramdeo KS, Anand S, Pierce JY, et al (2022)

Distribution of microbiota in cervical preneoplasia of racially disparate populations.

BMC cancer, 22(1):1074.

BACKGROUNDS: Microbiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women.

METHODS: Here, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n = 12), AA (n = 12), and CA (n = 12) women, who were screened for CC risk assessment. We employed a 16S rRNA gene sequencing approach adapted from the NIH-Human Microbiome Project to identify the microbial niche in all CIN lesions (n = 36).

RESULTS: We detected an appreciably decreased abundance of beneficial Lactobacillus in the CIN lesions of the AA and HIS women compared to the CA women. Differential abundance of potentially pathogenic Prevotella, Delftia, Gardnerella, and Fastidiosipila was also evident among the various racial groups. An increased abundance of Micrococcus was also evident in AA and HIS women compared to the CA women. The detection level of Rhizobium was higher among the AA ad CA women compared to the HIS women. In addition to the top 10 microbes, a unique niche of 27 microbes was identified exclusively in women with a histopathological diagnosis of CIN. Among these microbes, a group of 8 microbiota; Rubellimicrobium, Podobacter, Brevibacterium, Paracoccus, Atopobium, Brevundimonous, Comamonous, and Novospingobium was detected only in the CIN lesions obtained from AA and CA women.

CONCLUSIONS: Microbial dysbiosis in the cervical epithelium represented by an increased ratio of potentially pathogenic to beneficial microbes may be associated with increased CC risk disparities. Developing a race-specific reliable panel of microbial markers could be beneficial for CC risk assessment, disease prevention, and/or therapeutic guidance.

RevDate: 2022-10-17

Monshizadeh M, Zomorodi S, Mortensen K, et al (2022)

Revealing bacteria-phage interactions in human microbiome through the CRISPR-Cas immune systems.

Frontiers in cellular and infection microbiology, 12:933516.

The human gut microbiome is composed of a diverse consortium of microorganisms. Relatively little is known about the diversity of the bacteriophage population and their interactions with microbial organisms in the human microbiome. Due to the persistent rivalry between microbial organisms (hosts) and phages (invaders), genetic traces of phages are found in the hosts' CRISPR-Cas adaptive immune system. Mobile genetic elements (MGEs) found in bacteria include genetic material from phage and plasmids, often resultant from invasion events. We developed a computational pipeline (BacMGEnet), which can be used for inference and exploratory analysis of putative interactions between microbial organisms and MGEs (phages and plasmids) and their interaction network. Given a collection of genomes as the input, BacMGEnet utilizes computational tools we have previously developed to characterize CRISPR-Cas systems in the genomes, which are then used to identify putative invaders from publicly available collections of phage/prophage sequences. In addition, BacMGEnet uses a greedy algorithm to summarize identified putative interactions to produce a bacteria-MGE network in a standard network format. Inferred networks can be utilized to assist further examination of the putative interactions and for discovery of interaction patterns. Here we apply the BacMGEnet pipeline to a few collections of genomic/metagenomic datasets to demonstrate its utilities. BacMGEnet revealed a complex interaction network of the Phocaeicola vulgatus pangenome with its phage invaders, and the modularity analysis of the resulted network suggested differential activities of the different P. vulgatus' CRISPR-Cas systems (Type I-C and Type II-C) against some phages. Analysis of the phage-bacteria interaction network of human gut microbiome revealed a mixture of phages with a broad host range (resulting in large modules with many bacteria and phages), and phages with narrow host range. We also showed that BacMGEnet can be used to infer phages that invade bacteria and their interactions in wound microbiome. We anticipate that BacMGEnet will become an important tool for studying the interactions between bacteria and their invaders for microbiome research.

RevDate: 2022-10-14

Sánchez-Manubens J, Henares D, Muñoz-Almagro C, et al (2022)

Characterization of the nasopharyngeal microbiome in patients with Kawasaki disease.

Anales de pediatria pii:S2341-2879(22)00176-4 [Epub ahead of print].

INTRODUCTION: The aetiology of Kawasaki disease (KD) remains unknown. Several studies have linked the human microbiome with some diseases. However, there are limited studies on the role of the respiratory microbiome in KD. The aim of our study was to make a more thorough analysis of the causes and processes that increase the susceptibility to KD.

METHODS: Case-control study comparing the respiratory microbiome of KD patients with that of healthy children. The V3-V4 region of the 16S rRNA bacterial gene and 16 respiratory viruses were analysed by real-time polimerase-chain reaction. We used the Ribosomal Database Project (RDP) version 11.5 (taxonomic assignment).

RESULTS: The initial sample included 11 cases and 11 controls matched for age, sex and seasonality. One of the cases was excluded to poor sample quality. The final analysis included 10 cases and 10 controls. In the case group, the analysis detected Haemophilus, Moraxella, Streptococcus and Corynebacterium species (27.62%, 19.71%, 25.28%, 11.86%, respectively). In the control group, it found Haemophilus, Streptococcus, Moraxella, and Dolosigranulum species (38.59%, 23.71%, 16.08, 8.93%, respectively). We found a higher relative abundance of Corynebacterium in patients with KD (11.86% vs. 1.55%; P = 0.004).

CONCLUSIONS: To our knowledge, this is the first study that has found differences in the composition of the respiratory microbiome between patients with KD and healthy controls. The relative abundance of Corynebacterium spp. was greater in the KD group. This study shows differences in the microbiome between cases and controls, which suggests that the microbiome may play a role in facilitating the development of KD.

RevDate: 2022-10-14

Gauthier NPG, Locher K, MacDonald C, et al (2022)

Alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity.

PloS one, 17(10):e0275815 pii:PONE-D-22-19141.

OBJECTIVES: The COVID-19 pandemic and ensuing public health emergency has emphasized the need to study SARS-CoV-2 pathogenesis. The human microbiome has been shown to regulate the host immune system and may influence host susceptibility to viral infection, as well as disease severity. Several studies have assessed whether compositional alterations in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection. However, the results of these studies were varied, and many did not account for disease severity. This study aims to examine whether compositional differences in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection status and disease severity.

METHODS: We performed Nanopore full-length 16S rRNA sequencing on 194 nasopharyngeal swab specimens from hospitalized and community-dwelling SARS-CoV-2-infected and uninfected individuals. Sequence data analysis was performed using the BugSeq 16S analysis pipeline.

RESULTS: We found significant beta (PERMANOVA p < 0.05), but not alpha (Kruskal-Wallis p > 0.05) diversity differences in the nasopharyngeal microbiota among our study groups. We identified several differentially abundant taxa associated with SARS-CoV-2 infection status and disease severity using ALDEx2. Finally, we observed a trend towards higher abundance of Enterobacteriaceae in specimens from hospitalized SARS-CoV-2-infected patients.

CONCLUSIONS: This study identified several alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity. Understanding the role of the microbiome in infection susceptibility and severity may open new avenues of research for disease prevention and treatment.

RevDate: 2022-10-14

Merrill BD, Carter MM, Olm MR, et al (2022)

Ultra-deep Sequencing of Hadza Hunter-Gatherers Recovers Vanishing Gut Microbes.

bioRxiv : the preprint server for biology.

The gut microbiome is a key modulator of immune and metabolic health. Human microbiome data is biased towards industrialized populations, providing limited understanding of the distinct and diverse non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing and strain cultivation on 351 fecal samples from the Hadza, hunter-gatherers in Tanzania, and comparative populations in Nepal and California. We recover 94,971 total genomes of bacteria, archaea, bacteriophages, and eukaryotes, 43% of which are absent from existing unified datasets. Analysis of in situ growth rates, genetic pN/pS signatures, high-resolution strain tracking, and 124 gut-resident species vanishing in industrialized populations reveals differentiating dynamics of the Hadza gut microbiome. Industrialized gut microbes are enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource that expands our understanding of microbes capable of colonizing the human gut and clarifies the extensive perturbation brought on by the industrialized lifestyle.

RevDate: 2022-10-14

Uzelac M, Li Y, Chakladar J, et al (2022)

Archaea Microbiome Dysregulated Genes and Pathways as Molecular Targets for Lung Adenocarcinoma and Squamous Cell Carcinoma.

International journal of molecular sciences, 23(19): pii:ijms231911566.

The human microbiome is a vast collection of microbial species that exist throughout the human body and regulate various bodily functions and phenomena. Of the microbial species that exist in the human microbiome, those within the archaea domain have not been characterized to the extent of those in more common domains, despite their potential for unique metabolic interaction with host cells. Research has correlated tumoral presence of bacterial microbial species to the development and progression of lung cancer; however, the impacts and influences of archaea in the microbiome remain heavily unexplored. Within the United States lung cancer remains highly fatal, responsible for over 100,000 deaths every year with a 5-year survival rate of roughly 22.9%. This project attempts to investigate specific archaeal species' correlation to lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) incidence, patient staging, death rates across individuals of varying ages, races, genders, and smoking-statuses, and potential molecular targets associated with archaea microbiome. Archaeal species abundance was assessed across lung tissue samples of 527 LUAD patients, 479 LUSC patients, and 99 healthy individuals. Nine archaeal species were found to be of significantly altered abundance in cancerous samples as compared to normal counterparts, 6 of which are common to both LUAD and LUSC subgroups. Several of these species are of the taxonomic class Thermoprotei or the phylum Euryarchaeota, both known to contain metabolic processes distinct from most bacterial species. Host-microbe metabolic interactions may be responsible for the observed correlation of these species' abundance with cancer incidence. Significant microbes were correlated to patient gene expression to reveal genes of altered abundance with respect to high and low archaeal presence. With these genes, cellular oncogenic signaling pathways were analyzed for enrichment across cancer and normal samples. In comparing gene expression between LUAD and adjacent normal samples, 2 gene sets were found to be significantly enriched in cancers. In LUSC comparison, 6 sets were significantly enriched in cancer, and 34 were enriched in normals. Microbial counts across healthy and cancerous patients were then used to develop a machine-learning based predictive algorithm, capable of distinguishing lung cancer patients from healthy normal with 99% accuracy.

RevDate: 2022-10-14

Prakash A, Nourianpour M, Senok A, et al (2022)

Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota.

Cells, 11(19): pii:cells11193038.

Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the 'Human Microbiome Project' in 2016. We obtained 200 articles by inputting keywords such as 'gut microbiome', 'gut microbiota', 'gut dysbiosis', 'PCOS', and 'endometrial cancer' into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.

RevDate: 2022-10-11

Campana AM, Laue HE, Shen Y, et al (2022)

Assessing the role of the gut microbiome at the interface between environmental chemical exposures and human health: Current knowledge and challenges.

Environmental pollution (Barking, Essex : 1987) pii:S0269-7491(22)01594-9 [Epub ahead of print].

The explosion of microbiome research over the past decade has shed light on the various ways that external factors interact with the human microbiome to drive health and disease. Each individual is exposed to more than 300 environmental chemicals every day. Accumulating evidence indicates that the microbiome is involved in the early response to environmental toxicants and biologically mediates their adverse effects on human health. However, few review articles to date provided a comprehensive framework for research and translation of the role of the gut microbiome in environmental health science. This review summarizes current evidence on environmental compounds and their effect on the gut microbiome, discusses the involved compound metabolic pathways, and covers environmental pollution-induced gut microbiota disorders and their long-term outcomes on host health. We conclude that the gut microbiota may crucially mediate and modify the disease-causing effects of environmental chemicals. Consequently, gut microbiota needs to be further studied to assess the complete toxicity of environmental exposures. Future research in this field is required to delineate the key interactions between intestinal microbiota and environmental pollutants and further to elucidate the long-term human health effects.

RevDate: 2022-10-11

Zubeldia-Varela E, Barker-Tejeda TC, Obeso D, et al (2022)

Microbiome and Allergy: New Insights and Perspectives.

Journal of investigational allergology & clinical immunology, 32(5):327-344.

The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies are increasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immune response to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skin microbiota and atopic dermatitis, and between gut microbiota and food allergy. The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics are the techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerably in recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased. Thus, more and more studies are proposing mechanisms for intervention in the microbiota. In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous, and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases. Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy.

RevDate: 2022-10-10

Wishart DS, Oler E, Peters H, et al (2022)

MiMeDB: the Human Microbial Metabolome Database.

Nucleic acids research pii:6754917 [Epub ahead of print].

The Human Microbial Metabolome Database (MiMeDB) ( is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the human exposome and (iv) all of these 'omes' to human health. MiMeDB was established to consolidate the growing body of data connecting the human microbiome and the chemicals it produces to both health and disease. MiMeDB contains detailed taxonomic, microbiological and body-site location data on most known human microbes (bacteria and fungi). This microbial data is linked to extensive genomic and proteomic sequence data that is closely coupled to colourful interactive chromosomal maps. The database also houses detailed information about all the known metabolites generated by these microbes, their structural, chemical and spectral properties, the reactions and enzymes responsible for these metabolites and the primary exposome sources (food, drug, cosmetic, pollutant, etc.) that ultimately lead to the observed microbial metabolites in humans. Additional, extensively referenced data about the known or presumptive health effects, measured biosample concentrations and human protein targets for these compounds is provided. All of this information is housed in richly annotated, highly interactive, visually pleasing database that has been designed to be easy to search, easy to browse and easy to navigate. Currently MiMeDB contains data on 626 health effects or bioactivities, 1904 microbes, 3112 references, 22 054 reactions, 24 254 metabolites or exposure chemicals, 648 861 MS and NMR spectra, 6.4 million genes and 7.6 billion DNA bases. We believe that MiMeDB represents the kind of integrated, multi-omic or systems biology database that is needed to enable comprehensive multi-omic integration.

RevDate: 2022-10-08

Wang C, Zhang L, Jiang X, et al (2022)

Toward efficient and high-fidelity metagenomic data from sub-nanogram DNA: evaluation of library preparation and decontamination methods.

BMC biology, 20(1):225.

BACKGROUND: Shotgun metagenomic sequencing has greatly expanded the understanding of microbial communities in various biological niches. However, it is still challenging to efficiently convert sub-nanogram DNA to high-quality metagenomic libraries and obtain high-fidelity data, hindering the exploration of niches with low microbial biomass.

RESULTS: To cope with this challenge comprehensively, we evaluated the performance of various library preparation methods on 0.5 pg-5 ng synthetic microbial community DNA, characterized contaminants, and further applied different in silico decontamination methods. First, we discovered that whole genome amplification prior to library construction led to worse outcomes than preparing libraries directly. Among different non-WGA-based library preparation methods, we found the endonuclease-based method being generally good for different amounts of template and the tagmentation-based method showing specific advantages with 0.5 pg template, based on evaluation metrics including fidelity, proportion of designated reads, and reproducibility. The load of contaminating DNA introduced by library preparation varied from 0.01 to 15.59 pg for different kits and accounted for 0.05 to 45.97% of total reads. A considerable fraction of the contaminating reads were mapped to human commensal and pathogenic microbes, thus potentially leading to erroneous conclusions in human microbiome studies. Furthermore, the best performing in silico decontamination method in our evaluation, Decontam-either, was capable of recovering the real microbial community from libraries where contaminants accounted for less than 10% of total reads, but not from libraries with heavy and highly varied contaminants.

CONCLUSIONS: This study demonstrates that high-quality metagenomic data can be obtained from samples with sub-nanogram microbial DNA by combining appropriate library preparation and in silico decontamination methods and provides a general reference for method selection for samples with varying microbial biomass.

RevDate: 2022-10-07

Park HM, Park Y, Berani U, et al (2022)

In silico optimization of RNA-protein interactions for CRISPR-Cas13-based antimicrobials.

Biology direct, 17(1):27.

RNA-protein interactions are crucial for diverse biological processes. In prokaryotes, RNA-protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins. Thanks to the programmability and specificity of CRISPR-Cas systems, CRISPR-based antimicrobials have the potential to be repurposed as new types of antibiotics. Unlike traditional antibiotics, these CRISPR-based antimicrobials can be designed to target specific bacteria and minimize detrimental effects on the human microbiome during antibacterial therapy. In this study, we explore the potential of CRISPR-based antimicrobials by optimizing the RNA-protein interactions of crRNAs and Cas13 proteins. CRISPR-Cas13 systems are unique as they degrade specific foreign RNAs using the crRNA template, which leads to non-specific RNase activities and cell cycle arrest. We show that a high proportion of the Cas13 systems have no colocalized CRISPR arrays, and the lack of direct association between crRNAs and Cas proteins may result in suboptimal RNA-protein interactions in the current tools. Here, we investigate the RNA-protein interactions of the Cas13-based systems by curating the validation dataset of Cas13 protein and CRISPR repeat pairs that are experimentally validated to interact, and the candidate dataset of CRISPR repeats that reside on the same genome as the currently known Cas13 proteins. To find optimal CRISPR-Cas13 interactions, we first validate the 3-D structure prediction of crRNAs based on their experimental structures. Next, we test a number of RNA-protein interaction programs to optimize the in silico docking of crRNAs with the Cas13 proteins. From this optimized pipeline, we find a number of candidate crRNAs that have comparable or better in silico docking with the Cas13 proteins of the current tools. This study fully automatizes the in silico optimization of RNA-protein interactions as an efficient preliminary step for designing effective CRISPR-Cas13-based antimicrobials.

RevDate: 2022-10-06

Shetty SA, Kuipers B, Atashgahi S, et al (2022)

Author Correction: Inter-species metabolic interactions in an in-vitro minimal human gut microbiome of core bacteria.

NPJ biofilms and microbiomes, 8(1):76 pii:10.1038/s41522-022-00339-3.

RevDate: 2022-10-05

VanEvery H, Franzosa EA, Nguyen LH, et al (2022)

Microbiome epidemiology and association studies in human health.

Nature reviews. Genetics [Epub ahead of print].

Studies of the human microbiome share both technical and conceptual similarities with genome-wide association studies and genetic epidemiology. However, the microbiome has many features that differ from genomes, such as its temporal and spatial variability, highly distinct genetic architecture and person-to-person variation. Moreover, there are various potential mechanisms by which distinct aspects of the human microbiome can relate to health outcomes. Recent advances, including next-generation sequencing and the proliferation of multi-omic data types, have enabled the exploration of the mechanisms that connect microbial communities to human health. Here, we review the ways in which features of the microbiome at various body sites can influence health outcomes, and we describe emerging opportunities and future directions for advanced microbiome epidemiology.

RevDate: 2022-10-03

Poroyko V, Manuel ER, E Ilina (2022)

Editorial: The human microbiome: A new frontier in personalized cancer therapy.

Frontiers in cellular and infection microbiology, 12:1028120.

RevDate: 2022-10-03

Kasperkiewicz K, Świerzko AS, Michalski M, et al (2022)

Antibodies Recognizing Yersinia enterocolitica Lipopolysaccharides of Various Chemotypes in Synovial Fluids From Patients With Juvenile Idiopathic Arthritis.

Journal of immunology research, 2022:9627934.

Yersinia enterocolitica O:3 (YeO3) is considered to be associated with reactive arthritis (ReA), and its lipopolysaccharide (LPS) has been detected in synovial fluids from patients. Interestingly, YeO3 wild-type LPS was processed by host cells, resulting in truncated LPS molecules presenting the core region. Previously, we reported the immunogenicity but not adjuvanticity of YeO3 LPSs of wild (S) type, Ra, Rd, or Re chemotypes in mice. Here, we demonstrate the presence of YeO3 LPS chemotype-specific antibodies in all analyzed synovial fluids (SF) from patients with juvenile idiopathic arthritis (JIA). Interestingly, the high titer of antibodies specific for the Kdo-lipid A region was found in most tested SF. In contrast, only a few were positive for antibodies recognizing O-specific polysaccharides. Western blot analysis revealed the presence of antibodies reacting with fast-migrating LPS fractions and enterobacterial common antigen (ECA) in synovial fluid samples. Our data also suggest the importance of LPS-associated ECA for the antigenicity of endotoxin. Furthermore, we confirmed in vitro that Yersinia LPS processing leads to the exposure of its core region and enhanced potency of complement lectin pathway activation.

RevDate: 2022-09-30

Dohlman AB, Klug J, Mesko M, et al (2022)

A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors.

Cell, 185(20):3807-3822.e12.

Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-associated mycobiomes at up to 1 fungal cell per 104 tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of pro-inflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.

RevDate: 2022-09-29

Carpén N, Brodin P, de Vos WM, et al (2022)

Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial.

BMC pediatrics, 22(1):565.

BACKGROUND: A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life- a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system.

METHODS: Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother's stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4 weeks, then at the ages of 8 weeks, 3, 6, 12 and 24 months. The parents fill in questionnaires until the age of 24 months. Blood samples are taken at the age of 2-3 days and 3, 6, 12 and 24 months to assess development of major immune cell populations and plasma proteins throughout the first years of life.

DISCUSSION: This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS.

TRIAL REGISTRATION: NCT04173208 , registration date 21.11.2019.

RevDate: 2022-09-29

Peters SL, Borges AL, Giannone RJ, et al (2022)

Experimental validation that human microbiome phages use alternative genetic coding.

Nature communications, 13(1):5710.

Previous bioinformatic analyses of metagenomic data have indicated that bacteriophages can use genetic codes different from those of their host bacteria. In particular, reassignment of stop codon TAG to glutamine (a variation known as 'genetic code 15') has been predicted. Here, we use LC-MS/MS-based metaproteomics of human fecal samples to provide experimental evidence of the use of genetic code 15 in two crAss-like phages. Furthermore, the proteomic data from several phage structural proteins supports the reassignment of the TAG stop codon to glutamine late in the phage infection cycle. Thus, our work experimentally validates the expression of genetic code 15 in human microbiome phages.

RevDate: 2022-09-29

Jokela R, Korpela K, Jian C, et al (2022)

Quantitative insights into effects of intrapartum antibiotics and birth mode on infant gut microbiota in relation to well-being during the first year of life.

Gut microbes, 14(1):2095775.

Birth mode and maternal intrapartum (IP) antibiotics affect infants' gut microbiota development, but their relative contribution to absolute bacterial abundances and infant health has not been studied. We compared the effects of Cesarean section (CS) delivery and IP antibiotics on infant gut microbiota development and well-being over the first year. We focused on 92 healthy infants born between gestational weeks 37-42 vaginally without antibiotics (N = 26), with IP penicillin (N = 13) or cephalosporin (N = 7) or by CS with IP cephalosporin (N = 33) or other antibiotics (N = 13). Composition and temporal development analysis of the gut microbiota concentrated on 5 time points during the first year of life using 16S rRNA gene amplicon sequencing, integrated with qPCR to obtain absolute abundance estimates. A mediation analysis was carried out to identify taxa linked to gastrointestinal function and discomfort (crying, defecation frequency, and signs of gastrointestinal symptoms), and birth interventions. Based on absolute abundance estimates, the depletion of Bacteroides spp. was found specifically in CS birth, while decreased bifidobacteria and increased Bacilli were common in CS birth and exposure to IP antibiotics in vaginal delivery. The abundances of numerous taxa differed between the birth modes among cephalosporin-exposed infants. Penicillin had a milder impact on the infant gut microbiota than cephalosporin. CS birth and maternal IP antibiotics had both specific and overlapping effects on infants' gut microbiota development. The resulting deviations in the gut microbiota are associated with increased defecation rate, flatulence, perceived stomach pain, and intensity of crying in infancy.

RevDate: 2022-09-29

Mousa WK (2022)

The microbiome-product colibactin hits unique cellular targets mediating host-microbe interaction.

Frontiers in pharmacology, 13:958012 pii:958012.

The human microbiota produces molecules that are evolved to interact with the diverse cellular machinery of both the host and microbes, mediating health and diseases. One of the most puzzling microbiome molecules is colibactin, a genotoxin encoded in some commensal and extraintestinal microbes and is implicated in initiating colorectal cancer. The colibactin cluster was discovered more than 15 years ago, and most of the research studies have been focused on revealing the biosynthesis and precise structure of the cryptic encoded molecule(s) and the mechanism of carcinogenesis. In 2022, the Balskus group revealed that colibactin not only hits targets in the eukaryotic cell machinery but also in the prokaryotic cell. To that end, colibactin crosslinks the DNA resulting in activation of the SOS signaling pathway, leading to prophage induction from bacterial lysogens and modulation of virulence genes in pathogenic species. These unique activities of colibactin highlight its ecological role in shaping gut microbial communities and further consequences that impact human health. This review dives in-depth into the molecular mechanisms underpinning colibactin cellular targets in eukaryotic and prokaryotic cells, aiming to understand the fine details of the role of secreted microbiome chemistry in mediating host-microbe and microbe-microbe interactions. This understanding translates into a better realization of microbiome potential and how this could be advanced to future microbiome-based therapeutics or diagnostic biomarkers.

RevDate: 2022-09-28

Oduaran OH, AS Bhatt (2022)

Equitable partnerships and the path to inclusive, innovative and impactful human microbiome research.

Nature reviews. Gastroenterology & hepatology [Epub ahead of print].

RevDate: 2022-09-28

Jalanka J, Gunn D, Singh G, et al (2022)

Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery.

Gut pii:gutjnl-2021-326828 [Epub ahead of print].

OBJECTIVES: Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics.

DESIGN: A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40 days) as well as 40-60 days and >80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing.

RESULTS: PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria.

CONCLUSION: The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD.


RevDate: 2022-09-28

Sheldon JM, N Alonso (2022)

The Therapeutic Benefits of Single and Multi-Strain Probiotics on Mean Daily Crying Time and Key Inflammatory Markers in Infantile Colic.

Cureus, 14(8):e28363.

Infantile colic is a functional gastrointestinal disorder in which a healthy infant displays paroxysms of intense crying or fussiness. Although this condition is self-limited, it causes significant distress for parents and may be linked to long-term health concerns for children. The microbiome of infants with colic has been correlated with increased dysbiosis or imbalance of commensal bacteria. This dysbiosis may ultimately lead to changes in infants' immunological profiles, favoring markers linked to inflammation, including specific cytokines, calprotectin, and genetic markers. Therapeutic regimens such as probiotics may be helpful in modifying the gut microbial composition, thereby influencing the presence of inflammatory markers and potentially reducing colic symptoms in infants. This review provides a summary of the findings from 10 randomized, placebo-controlled, double-blinded studies conducted in the past five years with the aim of examining the potential therapeutic benefits of probiotics in infantile colic. The articles were selected through PubMed and Google Scholar using the keywords infantile colic, microbiome, probiotics, cytokines, dysbiosis, inflammatory markers, and lactobacilli. We summarize the results of these studies to explore the potential anti-inflammatory therapeutic benefits of single and multi-strain probiotic formulations on daily crying time and key inflammatory markers in infants with colic. The research largely shows the beneficial role of probiotics, largely of the lactobacillus genus, in the reduction of colic symptoms and the reduction of key inflammatory markers. However, some studies demonstrated an insignificant effect of certain probiotic strains in symptom management. Further research is necessary to better understand the anti-inflammatory properties of probiotics and determine the role this could have on the manifestation of colic in infants.

RevDate: 2022-09-28
CmpDate: 2022-09-28

Yang Q, Van Haute M, Korth N, et al (2022)

Genetic analysis of seed traits in Sorghum bicolor that affect the human gut microbiome.

Nature communications, 13(1):5641.

Prebiotic fibers, polyphenols and other molecular components of food crops significantly affect the composition and function of the human gut microbiome and human health. The abundance of these, frequently uncharacterized, microbiome-active components vary within individual crop species. Here, we employ high throughput in vitro fermentations of pre-digested grain using a human microbiome to identify segregating genetic loci in a food crop, sorghum, that alter the composition and function of human gut microbes. Evaluating grain produced by 294 sorghum recombinant inbreds identifies 10 loci in the sorghum genome associated with variation in the abundance of microbial taxa and/or microbial metabolites. Two loci co-localize with sorghum genes regulating the biosynthesis of condensed tannins. We validate that condensed tannins stimulate the growth of microbes associated with these two loci. Our work illustrates the potential for genetic analysis to systematically discover and characterize molecular components of food crops that influence the human gut microbiome.

RevDate: 2022-09-28

Aboul Naga SH, Hassan LM, El Zanaty RT, et al (2022)

Behçet uveitis: Current practice and future perspectives.

Frontiers in medicine, 9:968345.

Described as early as Hippocrates in his "Third Book of Endemic Diseases," Behçet's Disease (BD), also known as "The Silk Road Disease" following its initial demographics, consists of a triad of recurrent oro-genital ulcers and associated uveitis. Current demographics and rising percentages of patients seen far beyond the Silk Road in Ocular Inflammatory Disease and Uveitis Clinics list BD uveitis as one of the frontliners of non-infectious autoinflammatory eye diseases. Clinical features of BD and juvenile-onset BD are detailed alongside various approaches in classification and suggested algorithms for diagnosis that are outlined in this review. With the ongoing Human Microbiome Project and studies such as the MAMBA study, the role of the human microbiome in BD is highlighted in the pathophysiology of BD to include the current research and literature perspective. Furthermore, with the advancement of recent diagnostic and investigative techniques, especially in the field of Optical Coherence Tomography (OCT), disease-related characteristics are updated to encompass SD, EDI and OCT-angiography characteristics of BD. Having entered the era of biologic therapy, the role of various specific cytokine-blocking biologic drugs, such as TNF-α inhibitors (e.g., adalimumab, infliximab), interferon α-2a inhibitors, IL-6 and IL-1 inhibitors are presented and contrasted alongside the conventional immunosuppressant drugs and the classic old gold standard: corticosteroids (systemic or local). Finally, with the ongoing SARS-CoV-2 pandemic, it was not possible to conclude the review without reviewing the latest evidence-based literature reporting BD morbidity in this era, the observed pattern and treatment recommendations as well as those related to reported post-vaccine complications and emergence of BD.

RevDate: 2022-09-28

Maslennikov R, Efremova I, Ivashkin V, et al (2022)

Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial.

World journal of hepatology, 14(8):1667-1677.

BACKGROUND: Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.

AIM: To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial.

METHODS: This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis; 24 patients received probiotics (Saccharomyces boulardii) for 3 mo, and 16 patients received a placebo over the same period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated.

RESULTS: Following a 3-mo course of probiotics in comparison to the control group, we observed amelioration of hyperdynamic circulation [a decrease in cardiac output (P = 0.026) and an increase in systemic vascular resistance (P = 0.026)] and systemic inflammation [a decrease in serum C-reactive protein levels (P = 0.044)], with improved liver function [an increase in serum albumin (P = 0.001) and a decrease in the value of Child-Pugh score (P = 0.001)] as well as a reduction in the severity of ascites (P = 0.022), hepatic encephalopathy (P = 0.048), and cholestasis [a decrease in serum alkaline phosphatase (P = 0.016) and serum gamma-glutamyl transpeptidase (P = 0.039) activity] and an increase in platelet counts (P < 0.001) and serum sodium level (P = 0.048).

CONCLUSION: Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.

RevDate: 2022-09-28

Kumari P, Prakash P, Yadav S, et al (2022)

Microbiome analysis: An emerging forensic investigative tool.

Forensic science international, 340:111462 pii:S0379-0738(22)00292-4 [Epub ahead of print].

Microbial diversity's potential has been investigated in medical and therapeutic studies throughout the last few decades. However, its usage in forensics is increasing due to its effectiveness in circumstances when traditional approaches fail to provide a decisive opinion or are insufficient in forming a concrete opinion. The application of human microbiome may serve in detecting the type of stains of saliva and vaginal fluid, as well as in attributing the stains to the individual. Similarly, the microbiome makeup of a soil sample may be utilised to establish geographic origin or to associate humans, animals, or things with a specific area, additionally microorganisms influence the decay process which may be used in depicting the Time Since death. Further in detecting the traces of the amount and concentration of alcohol, narcotics, and other forensically relevant compounds in human body or visceral tissues as they also affect the microbial community within human body. Beside these, there is much more scope of microbiomes to be explored in terms of forensic investigation, this review focuses on multidimensional approaches to human microbiomes from a forensic standpoint, implying the potential of microbiomes as an emerging tool for forensic investigations such as individual variability via skin microbiomes, reconstructing crime scene, and linking evidence to individual.

RevDate: 2022-09-26

Saha UB, SD Saroj (2022)

Lactic acid bacteria: prominent player in the fight against human pathogens.

Expert review of anti-infective therapy [Epub ahead of print].

INTRODUCTION: The human microbiome is a unique repository of diverse bacteria. Over 1000 microbial species reside in the human gut, which predominantly influences the host's internal environment and plays a significant role in host health. Lactic acid bacteria have long been employed for multiple purposes, ranging from food to medicines. Lactobacilli, which are often used in commercial food fermentation, have improved to the point that they might be helpful in medical applications.

AREAS COVERED: This review summarises various clinical and experimental evidence on efficacy of lactobacilli in treating a wide range of infections. Both laboratory based and clinical studies have been discussed.

EXPERT OPINION: Lactobacilli are widely accepted as safe biological treatments and host immune modulators (GRAS- Generally regarded as safe) by the US Food and Drug Administration and Qualified Presumption of Safety. Understanding the molecular mechanisms of lactobacilli in the treatment and pathogenicity of bacterial infections can help with the prediction and development of innovative therapeutics aimed at pathogens which have gained resistance to antimicrobials. To formulate effective lactobacilli based therapy significant research on the effectiveness of different lactobacilli strains and its association with demographic distribution is required. Also, the side effects of such therapy needs to be evaluated.

RevDate: 2022-09-24

White MG, JA Wargo (2022)

The Microbiome in Gastrointestinal Cancers.

Gastroenterology clinics of North America, 51(3):667-680.

The human microbiome has been recognized as increasingly important to health and disease. This is especially prescient in the development of various cancers, their progression, and the microbiome's modulation of various anticancer therapeutics. Mechanisms behind these interactions have been increasingly well described through modulation of the host immune system as well as induction of genetic changes and local inactivation of cancer therapeutics. Here, we review these associations for a variety of gastrointestinal malignancies as well as contemporary strategies proposed to leverage these associations to improve cancer treatment outcomes.

RevDate: 2022-09-24

Pedro N, Brucato N, Cavadas B, et al (2022)

First insight into oral microbiome diversity in Papua New Guineans reveals a specific regional signature.

Molecular ecology [Epub ahead of print].

The oral microbiota is a highly complex and diversified part of the human microbiome. Being located at the interface between the human body and the exterior environment, this microbiota can deepen our understanding of the environmental impacts on the global status of human health. This research topic has been well addressed in Westernized populations, but these populations only represent a fraction of human diversity. Papua New Guinea hosts very diverse environments and one of the most unique human biological diversities worldwide. In this work we performed the first known characterization of the oral microbiome in 85 Papua New Guinean individuals living in different environments, using a qualitative and quantitative approach. We found a significant geographical structure of the Papua New Guineans oral microbiome, especially in the groups most isolated from urban spaces. In comparison to other global populations, two bacterial genera related to iron absorption were significantly more abundant in Papua New Guineans and Aboriginal Australians, which suggests a shared oral microbiome signature. Further studies will be needed to confirm and explore this possible regional-specific oral microbiome profile.

RevDate: 2022-09-24

Begum N, Harzandi A, Lee S, et al (2022)

Host-mycobiome metabolic interactions in health and disease.

Gut microbes, 14(1):2121576.

Fungal communities (mycobiome) have an important role in sustaining the resilience of complex microbial communities and maintenance of homeostasis. The mycobiome remains relatively unexplored compared to the bacteriome despite increasing evidence highlighting their contribution to host-microbiome interactions in health and disease. Despite being a small proportion of the total species, fungi constitute a large proportion of the biomass within the human microbiome and thus serve as a potential target for metabolic reprogramming in pathogenesis and disease mechanism. Metabolites produced by fungi shape host niches, induce immune tolerance and changes in their levels prelude changes associated with metabolic diseases and cancer. Given the complexity of microbial interactions, studying the metabolic interplay of the mycobiome with both host and microbiome is a demanding but crucial task. However, genome-scale modelling and synthetic biology can provide an integrative platform that allows elucidation of the multifaceted interactions between mycobiome, microbiome and host. The inferences gained from understanding mycobiome interplay with other organisms can delineate the key role of the mycobiome in pathophysiology and reveal its role in human disease.

RevDate: 2022-09-23

Yutin N, Rayko M, Antipov D, et al (2022)

Varidnaviruses in the Human Gut: A Major Expansion of the Order Vinavirales.

Viruses, 14(9): pii:v14091842.

Bacteriophages play key roles in the dynamics of the human microbiome. By far the most abundant components of the human gut virome are tailed bacteriophages of the realm Duplodnaviria, in particular, crAss-like phages. However, apart from duplodnaviruses, the gut virome has not been dissected in detail. Here we report a comprehensive census of a minor component of the gut virome, the tailless bacteriophages of the realm Varidnaviria. Tailless phages are primarily represented in the gut by prophages, that are mostly integrated in genomes of Alphaproteobacteria and Verrucomicrobia and belong to the order Vinavirales, which currently consists of the families Corticoviridae and Autolykiviridae. Phylogenetic analysis of the major capsid proteins (MCP) suggests that at least three new families should be established within Vinavirales to accommodate the diversity of prophages from the human gut virome. Previously, only the MCP and packaging ATPase genes were reported as conserved core genes of Vinavirales. Here we report an extended core set of 12 proteins, including MCP, packaging ATPase, and previously undetected lysis enzymes, that are shared by most of these viruses. We further demonstrate that replication system components are frequently replaced in the genomes of Vinavirales, suggestive of selective pressure for escape from yet unknown host defenses or avoidance of incompatibility with coinfecting related viruses. The results of this analysis show that, in a sharp contrast to marine viromes, varidnaviruses are a minor component of the human gut virome. Moreover, they are primarily represented by prophages, as indicated by the analysis of the flanking genes, suggesting that there are few, if any, lytic varidnavirus infections in the gut at any given time. These findings complement the existing knowledge of the human gut virome by exploring a group of viruses that has been virtually overlooked in previous work.

RevDate: 2022-09-23

Liu M, Nieuwdorp M, de Vos WM, et al (2022)

Microbial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders.

Metabolites, 12(9): pii:metabo12090834.

The trillions of commensal microorganisms comprising the gut microbiota have received growing attention owing to their impact on host physiology. Recent advances in our understandings of the host-microbiota crosstalk support a pivotal role of microbiota-derived metabolites in various physiological processes, as they serve as messengers in the complex dialogue between commensals and host immune and endocrine cells. In this review, we highlight the importance of tryptophan-derived metabolites in host physiology, and summarize the recent findings on the role of tryptophan catabolites in preserving intestinal homeostasis and fine-tuning immune and metabolic responses. Furthermore, we discuss the latest evidence on the effects of microbial tryptophan catabolites, describe their mechanisms of action, and discuss how perturbations of microbial tryptophan metabolism may affect the course of intestinal and extraintestinal disorders, including inflammatory bowel diseases, metabolic disorders, chronic kidney diseases, and cardiovascular diseases.

RevDate: 2022-09-23

Olunoiki E, Rehner J, Bischoff M, et al (2022)

Characteristics of the Skin Microbiome in Selected Dermatological Conditions: A Narrative Review.

Life (Basel, Switzerland), 12(9): pii:life12091420.

The skin is the largest and outermost organ of the human body. The microbial diversity of the skin can be influenced by several variable factors such as physiological state, lifestyle, and geographical locations. Recent years have seen increased interest in research aiming at an improved understanding of the relationship between the human microbiota and several diseases. Albeit understudied, interesting correlations between the skin microbiota and several dermatological conditions have been observed. Studies have shown that a decrease or increase in the abundance of certain microbial communities can be implicated in several dermatological pathologies. This narrative review (i) examines the role of the skin microbiota in the maintenance of skin homeostasis and health, (ii) provides examples on how some common skin diseases (acne inversa, candidiasis, psoriasis) are associated with the dysbiosis of microbial communities, and (iii) describes how recent research approaches used in skin microbiome studies may lead to improved, more sensitive diagnostics and individual therapeutics in the foreseeable future.

RevDate: 2022-09-23

Del Chierico F, Conta G, Matteoli MC, et al (2022)

Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset.

International journal of molecular sciences, 23(18): pii:ijms231810256.

Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and 1H-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA1c levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D.

RevDate: 2022-09-23

Riva V, Patania G, Riva F, et al (2022)

Acinetobacter baylyi Strain BD413 Can Acquire an Antibiotic Resistance Gene by Natural Transformation on Lettuce Phylloplane and Enter the Endosphere.

Antibiotics (Basel, Switzerland), 11(9): pii:antibiotics11091231.

Antibiotic resistance spread must be considered in a holistic framework which comprises the agri-food ecosystems, where plants can be considered a bridge connecting water and soil habitats with the human microbiome. However, the study of horizontal gene transfer events within the plant microbiome is still overlooked. Here, the environmental strain Acinetobacter baylyi BD413 was used to study the acquisition of extracellular DNA (exDNA) carrying an antibiotic resistance gene (ARG) on lettuce phylloplane, performing experiments at conditions (i.e., plasmid quantities) mimicking those that can be found in a water reuse scenario. Moreover, we assessed how the presence of a surfactant, a co-formulant widely used in agriculture, affected exDNA entry in bacteria and plant tissues, besides the penetration and survival of bacteria into the leaf endosphere. Natural transformation frequency in planta was comparable to that occurring under optimal conditions (i.e., temperature, nutrient provision, and absence of microbial competitors), representing an entrance pathway of ARGs into an epiphytic bacterium able to penetrate the endosphere of a leafy vegetable. The presence of the surfactant determined a higher presence of culturable transformant cells in the leaf tissues but did not significantly increase exDNA entry in A. baylyi BD413 cells and lettuce leaves. More research on HGT (Horizontal Gene Transfer) mechanisms in planta should be performed to obtain experimental data on produce safety in terms of antibiotic resistance.

RevDate: 2022-09-21

Smith C, Van Haute MJ, Xian Y, et al (2022)

Carbohydrate utilization by the gut microbiome determines host health responsiveness to whole grain type and processing methods.

Gut microbes, 14(1):2126275.

Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains - brown rice and whole wheat - and two processing methods - boiling (porridge) and extrusion - were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health.Abbreviations: CU- carbohydrate utilization; SCFA- short-chain fatty acids; GF- germ-free; HMA, human-microbiome associated; ipGTT- intraperitoneal glucose tolerance test; HOMA-IR- Homeostatic Model Assessment for Insulin Resistance; AUC- area under the glycemia curve; ASV- amplicon sequence variant; lf- low-fat; wd- Western diet; wd_wwp- Western diet containing whole wheat porridge; wd_wwe- Western diet containing whole wheat extrudate; wd_bre- Western diet containing brown rice extrudate; wd_extr- Western diet containing either whole wheat or brown rice extrudate.

RevDate: 2022-09-21

Mao J, LI Ma (2022)


The annals of applied statistics, 16(3):1476-1499.

Studying the human microbiome has gained substantial interest in recent years, and a common task in the analysis of these data is to cluster microbiome compositions into subtypes. This subdivision of samples into subgroups serves as an intermediary step in achieving personalized diagnosis and treatment. In applying existing clustering methods to modern microbiome studies including the American Gut Project (AGP) data, we found that this seemingly standard task, however, is very challenging in the microbiome composition context due to several key features of such data. Standard distance-based clustering algorithms generally do not produce reliable results as they do not take into account the heterogeneity of the cross-sample variability among the bacterial taxa, while existing model-based approaches do not allow sufficient flexibility for the identification of complex within-cluster variation from cross-cluster variation. Direct applications of such methods generally lead to overly dispersed clusters in the AGP data and such phenomenon is common for other microbiome data. To overcome these challenges, we introduce Dirichlet-tree multinomial mixtures (DTMM) as a Bayesian generative model for clustering amplicon sequencing data in microbiome studies. DTMM models the microbiome population with a mixture of Dirichlet-tree kernels that utilizes the phylogenetic tree to offer a more flexible covariance structure in characterizing within-cluster variation, and it provides a means for identifying a subset of signature taxa that distinguish the clusters. We perform extensive simulation studies to evaluate the performance of DTMM and compare it to state-of-the-art model-based and distance-based clustering methods in the microbiome context, and carry out a validation study on a publicly available longitudinal data set to confirm the biological relevance of the clusters. Finally, we report a case study on the fecal data from the AGP to identify compositional clusters among individuals with inflammatory bowel disease and diabetes. Among our most interesting findings is that enterotypes (i.e., gut microbiome clusters) are not always defined by the most dominant species as previous analyses had assumed, but can involve a number of less abundant OTUs, which cannot be identified with existing distance-based and method-based approaches.

RevDate: 2022-09-20

Darling KW, Boyce AM, Cho MK, et al (2015)

"What is the FDA Going to Think?": Negotiating Values through Reflective and Strategic Category Work in Microbiome Science.

Science, technology & human values, 40(1):71-95.

The US National Institute of Health's Human Microbiome Project aims to use genomic techniques to understand the microbial communities that live on the human body. The emergent field of microbiome science brought together diverse disciplinary perspectives and technologies, thus facilitating the negotiation of differing values. Here, we describe how values are conceptualized and negotiated within microbiome research. Analyzing discussions from a series of interdisciplinary workshops conducted with microbiome researchers, we argue that negotiations of epistemic, social, and institutional values were inextricable from the reflective and strategic category work (i.e., the work of anticipating and strategizing around divergent sets of institutional categories) that defined and organized the microbiome as an object of study and a potential future site of biomedical intervention. Negotiating the divergence or tension between emerging scientific and regulatory classifications also activated "values levers" and opened up reflective discussions of how classifications embody values and how these values might differ across domains. These data suggest that scholars at the intersections of science and technology studies, ethics, and policy could leverage such openings to identify and intervene in the ways that ethical/regulatory and scientific/technical practices are coproduced within unfolding research.

RevDate: 2022-09-16

Askari H, Shojaei-Zarghani S, Raeis-Abdollahi E, et al (2022)

The Role of Gut Microbiota in Inflammatory Bowel Disease-Current State of the Art.

Mini reviews in medicinal chemistry pii:MRMC-EPUB-126304 [Epub ahead of print].

The human microbiome comprises the genomes of the microbiota that live on and within humans, such as protozoa, archaea, eukaryotes, viruses, and most bacteria. Gastrointestinal disorders such as inflammatory bowel disease, colon cancer, celiac disease, and irritable bowel syndrome can all be triggered by a change in gut flora. The alteration of the gut microbiota (also known as "gut dysbiosis") is affected by host genetics, nutrition, antibiotics, and inflammation, and it is associated with the development of inflammatory bowel disease (IBD). Also, intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation are frequently detected in individuals with severe IBD, which may be attributed to impaired miRNA expression functions. While the exact mechanisms of how Gut Microbiota may cause IBD and intestinal epithelial dysfunction are still debated, recent data point toward the possibility that hormones, gender and miRNAs expression are modifiable contributors to IBD. This review summarizes the current evidence for an association between hormones, gender and miRNAs and Gut Microbiota in IBD and discusses potential mechanisms by which gut microbiota may impact IBD. The study also outlines critical unanswered topics that need to be solved to enhance IBD prevention and treatment in people with gut dysbiosis.

RevDate: 2022-09-19
CmpDate: 2022-09-19

Roussel C, Anunciação Braga Guebara S, Plante PL, et al (2022)

Short-term supplementation with ω-3 polyunsaturated fatty acids modulates primarily mucolytic species from the gut luminal mucin niche in a human fermentation system.

Gut microbes, 14(1):2120344.

Consumption of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provides multifaceted health benefits. Recent studies suggest that ω-3 PUFAs modulate the gut microbiota by enhancing health-promoting bacteria, such as the mucin specialist Akkermansia muciniphila. However, these prebiotic properties have been poorly investigated and direct effects on the gut microbiome have never been explored dynamically across gut regions and niches (lumen vs. mucus-associated microbiota). Thus, we studied the effects of 1 week EPA- and DHA-enriched ω-3 fish-oil supplementation on the composition and functionality of the human microbiome in a Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME®). Gut microbial communities derived from one individual harvested in two different seasons were tested in duplicate. Luminal and outer mucus-associated microbiota of the ileum, ascending, transverse and descending colons were cultivated over 28 d from fecal inoculates and supplemented with ω-3 PUFAs for the last 7 d. We show that ω-3 PUFA supplementation modulates the microbiota in a gut region- and niche-dependent fashion. The outer mucus-associated microbiota displayed a higher resilience than the luminal mucin habitat to ω-3 PUFAs, with a remarkable blooming of Akkermansia muciniphila in opposition to a decrease of Firmicutes-mucolytic bacteria. The ω-3 PUFAs also induced a gradual and significant depletion of non-mucolytic Clostridia members in luminal habitats. Finally, increased concentrations of the short chain fatty acids (SCFA) propionate in colon regions at the end of the supplementation was associated positively with the bloom of Akkermansia muciniphila and members of the Desulfovibrionia class.

RevDate: 2022-09-15

Ianiro G, Punčochář M, Karcher N, et al (2022)

Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases.

Nature medicine [Epub ahead of print].

Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.

RevDate: 2022-09-15

Schmidt TSB, Li SS, Maistrenko OM, et al (2022)

Drivers and determinants of strain dynamics following fecal microbiota transplantation.

Nature medicine [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor-recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.

RevDate: 2022-09-15

Nidhi S, Tripathi P, V Tripathi (2022)

Phylogenetic Analysis of Anti-CRISPR and Member Addition in the Families.

Molecular biotechnology [Epub ahead of print].

CRISPR-Cas is a widespread anti-viral adaptive immune system in the microorganisms. Viruses living in bacteria or some phages carry anti-CRISPR proteins to evade immunity by CRISPR-Cas. The anti-CRISPR proteins are prevalent in phages capable of lying dormant in a CRISPR-carrying host, while their orthologs frequently found in virulent phages. Here, we propose a probabilistic strategy of ancestral sequence reconstruction (ASR) and Hidden Markov Model (HMM) profile search to fish out sequences of anti-CRISPR proteins from environmental metagenomic, human microbiome metagenomic, human microbiome reference genome, and NCBI's non-redundant databases. Our results revealed that the metagenome database dark matter might contain anti-CRISPR encoding genes.

RevDate: 2022-09-19
CmpDate: 2022-09-19

Schul M, Mason A, Ushijima B, et al (2022)

Microbiome and Metabolome Contributions to Coral Health and Disease.

The Biological bulletin, 243(1):76-83.

AbstractCoral populations are declining worldwide as a result of increased environmental stressors, including disease. Coral health is greatly dependent on complex interactions between the host animal and its associated microbial symbionts. While relatively understudied, there is growing evidence that the coral microbiome contributes to the health and resilience of corals in a variety of ways, similar to more well-studied systems, such as the human microbiome. Many of these interactions are dependent upon the production and exchange of natural products, including antibacterial compounds, quorum-sensing molecules, internal signaling molecules, nutrients, and so on. While advances in sequencing, culturing, and metabolomic techniques have aided in moving forward the understanding of coral microbiome interactions, current sequence and metabolite databases are lacking, hindering detailed descriptions of the microbes and metabolites involved. This review focuses on the roles of coral microbiomes in health and disease processes of coral hosts, with special attention to the coral metabolome. We discuss what is currently known about the relationship between the coral microbiome and disease, of beneficial microbial products or services, and how the manipulation of the coral microbiome may chemically benefit the coral host against disease. Understanding coral microbiome-metabolome interactions is critical to assisting management, conservation, and restoration strategies.

RevDate: 2022-09-16
CmpDate: 2022-09-16

Wang X, Pang K, Wang J, et al (2022)

Microbiota dysbiosis in primary Sjögren's syndrome and the ameliorative effect of hydroxychloroquine.

Cell reports, 40(11):111352.

The human microbiome plays an important role in autoimmune diseases. However, there is limited knowledge regarding the microbiota in individuals with primary Sjögren's syndrome (pSS). Here, we perform 16S ribosomal RNA gene sequencing of fecal, oral, and vaginal samples from a cohort of 133 individuals with pSS, 56 with non-pSS, and 40 healthy control (HC) individuals. Dysbiosis in the gut, oral, and vaginal microbiome is evident in patients with pSS, and oral samples demonstrate the greatest extent of microbial variation. Multiple key indicator bacteria and clinical characteristics are identified across different body sites, implying that microbial dysbiosis has important roles in the pathogenesis of pSS. Furthermore, we observe pSS-like dysbiosis in individuals with pre-clinical pSS or non-pSS-related disease, revealing that microbial shifts could appear prior to pSS. After hydroxychloroquine (HCQ) treatment, microbial dysbiosis in individuals with pSS is partially resolved, although the microbiota composition remain disordered. These results contribute to the overall understanding of the relationship between the microbiome and pSS.

RevDate: 2022-09-16
CmpDate: 2022-09-16

Wikström T, Abrahamsson S, Bengtsson-Palme J, et al (2022)

Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery.

Clinical and translational medicine, 12(9):e1023.

BACKGROUND: Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term.

METHODS: Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery <37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses.

RESULTS: We found 17 human genes to be differentially expressed (false discovery rate, FDR < 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR < 0.05). We found 11 individual bacterial species to be differentially expressed (FDR < 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups.

CONCLUSIONS: In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.

RevDate: 2022-09-17

Loiko N, Kanunnikov O, Gannesen A, et al (2022)

Brain Natriuretic Peptide (BNP) Affects Growth and Stress Tolerance of Representatives of the Human Microbiome, Micrococcus luteus C01 and Alcaligenes faecalis DOS7.

Biology, 11(7):.

Brain natriuretic peptide (BNP) is secreted by the ventricles of the heart during overload to signal heart failure. Slight bilateral skin itching induced by BNP has been associated with response activity of the skin microbiota. In this work, we studied the effect of 25-250,000 pg BNP/mL on the growth, long-term survival, and stress (H2O2, antibiotics, salinity, heat and pH shock) resistance of human symbiont bacteria: Gram-positive Micrococcus luteus C01 and Gram-negative Alcaligenes faecalis DOS7. The effect of BNP turned out to be dose-dependent. Up to 250 pg BNP/mL made bacteria more stress resistant. At 2500 pg BNP/mL (heart failure) the thermosensitivity of the bacteria increased. Almost all considered BNP concentrations increased the resistance of bacteria to the action of tetracycline and ciprofloxacin. Both bacteria survived 1.3-1.7 times better during long-term (up to 4 months) storage. Our findings are important both for clinical medical practice and for practical application in other areas. For example, BNP can be used to obtain stress-resistant bacteria, which is important in the collection of microorganisms, as well as for the production of bacterial preparations and probiotics for cosmetology, agriculture, and waste management.

RevDate: 2022-09-15
CmpDate: 2022-09-15

Mangutov EO, Alieva AA, Kharseeva GG, et al (2022)

Corynebacterium spp.: relationship of pathogenic properties and antimicrobial resistance.

Klinicheskaia laboratornaia diagnostika, 67(9):519-524.

Corynebacterium spp. are part of the human microbiome, but can cause the development of inflammatory diseases of various localization. Purpose - to evaluate the relationship between pathogenic properties and resistance to antimicrobial drugs (AMD) of Corynebacterium spp. from patients with inflammatory diseases of the respiratory tract. Strains of Corynebacterium spp. isolated from patients with inflammatory diseases of the respiratory tract (99 pcs.) and practically healthy individuals (33 pcs.). Isolates were identified by mass spectrometric method (MALDI-ToFMS), their adhesive and invasive activity on Hep-2 cells, cytopathic effect (CPE) in CHO-K1 cell culture, and resistance to antimicrobial drugs (AMD) were determined. Indicators of adhesion (3.65±0.679(CFU±m)x102/ml), invasion (1.72±0.230 (CFU±m)x102/ml), cytotoxicity (69.1±3.8% of dead CHO-K1 cells) Corynebasterium spp. strains isolated from patients are higher (p≤0.05) than similar indicators in practically healthy people. 90.9% of isolates from patients had resistance to AMD, in most cases (57.6±4.9%) resistance to only one AMP was noted, less often to two (25.2±4.3%), three or more (8.08±2.7%). According to the results of correlation-regression analysis, pathogenic properties (adhesiveness, invasiveness, cytotoxicity) of Corynebacterium spp. strains isolated from patients are in close direct relationship with resistance to AMD. This indicates the importance of identifying strains of non-diphtheria corynebacteria resistant to AMDs, which, under the influence of developing resistance to AMDs, can increase their pathogenic potential, moving from commensalism to parasitism.

RevDate: 2022-09-13

Wang Y, Guo A, Liu Z, et al (2022)

Expansion of Opportunistic Enteric Fungal Pathogens and Occurrence of Gut Inflammation in Human Liver Echinococcosis.

Microbiology spectrum [Epub ahead of print].

Increasing evidence shows that the gut fungal mycobiota is implicated in human disease. However, its relationship with chronic helminth infections, which cause immunosuppression and affect over 1 billion people worldwide, remains unexplored. In this study, we investigated the gut mycobiome and its associations with gut homeostasis in a severe helminth disease worldwide: liver echinococcosis. Fecal samples from 63 patients and 42 healthy controls were collected to characterize the fungal signatures using ITS1 sequencing, QIIME pipeline, and machine learning analysis. The levels of fecal calprotectin and serological anti-Saccharomyces cerevisiae antibodies (ASCA) in these subjects were experimentally measured. We found that fungal microbiota was significantly skewed in disease, with an overrepresentation of Aspergillus, Candida, Geotrichum, Kazachstania, and Penicillium and a decrease of Fusarium. Machine learning analysis revealed that the altered fungal features could efficiently predict infection with high sensitivity and specificity (area under the curve [AUC] = 0.93). The dysbiosis was characterized by expansions of multiple opportunistic pathogens (Aspergillus spp. and Candida spp.). Clinical association analysis revealed that host immunity might link to the expansions of the invasive fungi. Accompanying the opportunistic pathogen expansion, the levels of fungi-associated fecal calprotectin and serological ASCA in the patients were elevated, suggesting that gut inflammation and microbiota translocation occurred in this generally assumed extraintestinal disease. This study highlights enteric fungal pathogen expansions and increased levels of markers for fungi-associated mucosal inflammation and intestinal permeability as hallmarks of liver echinococcosis. IMPORTANCE Helminth infection affects over 1 billion people worldwide. However, its relationship with the gut mycobiome remains unknown. Among the most prevalent helminth diseases, human hydatid disease (echinococcosis) is highlighted as one of the most important (second/third for alveolar/cystic echinococcosis) foodborne parasitic diseases at the global level. Herein, we investigated the mycobiome and gut homeostasis (i.e., inflammation and permeability) in human echinococcosis. Our results revealed that fungal dysbiosis with an expansion of opportunistic pathogens and increased levels of fecal calprotectin and serum ASCA are hallmarks of human liver echinococcosis. Host immunity is associated with enteric fungal expansions. These findings suggest that an extraintestinal helminth infection is able to alter gut fungal microbiota and impair gut homeostasis, which resembles concomitant gut symptoms in inflammatory gut-related diseases (e.g., AIDS). In clinical practice, physicians need to take cautious medical consideration of gut health for nonintestinal helminth diseases.

RevDate: 2022-09-12

Baky MH, Salah M, Ezzelarab N, et al (2022)

Insoluble dietary fibers: structure, metabolism, interactions with human microbiome, and role in gut homeostasis.

Critical reviews in food science and nutrition [Epub ahead of print].

Consumption of food rich in dietary fibers (DFs) has been long recognized to exert an overall beneficial effect on human health. This review aims to provide a holistic overview on how IDFs impact human gut health either directly, or through modulation of the gut microbiome. Several databases were searched for collecting papers such as PubMed, Google Scholar, Web of Science, Scopus and Reaxys from 2000 till 2022. Firstly, an overview of the chemical structure of the various IDFs and the pathways employed by gut microbiota for their degradation is provided. The impact of IDFs on microbial community structure and pathogens colonization inside the human gut was discussed. Finally, the impact of IDFs on gut homeostasis and systemic effects at the cellular level, as well as the overall immunological benefits of IDFs consumption were analyzed. IDFs viz., cellulose, hemicellulose, resistant starch, and lignin found enriched in food are discussed for these effects. IDFs were found to induce gut immunity, improve intestinal integrity and mucosal proliferation, and favor adhesion of probiotics and hence improve human health. Also, IDFs were concluded to improve the bioavailability of plant polyphenols and improve their health-related functional roles. Ultimately, dietary fibers processing by modification shows potential to enhance fibers-based functional food production, in addition to increase the economic value and usage of food-rich fibers and their by-products.

RevDate: 2022-09-15
CmpDate: 2022-09-13

Korpela K, WM de Vos (2022)

Infant gut microbiota restoration: state of the art.

Gut microbes, 14(1):2118811.

The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. Recent years have witnessed an accumulation of understanding of the process of the colonization and development of the gut microbiota in infants. The natural gut microbiota colonization during birth is frequently disrupted due to C-section birth or intrapartum or postpartum antibiotic exposure, and consequently aberrant gut microbiota development is common. On a positive note, research has shown that restoration of normal gut microbiota development is feasible. We discuss here the current understanding of the infant microbiota, provide an overview of the sources of disturbances, and critically evaluate the evidence on early life gut microbiota restoration for improved health outcomes by analyzing published data from infant gut microbiota restoration studies.

RevDate: 2022-09-10

Czibulka A (2022)

Probiotics for Otolaryngologic Disorders.

Otolaryngologic clinics of North America pii:S0030-6665(22)00067-6 [Epub ahead of print].

Chronic low-level inflammation is a causative factor in many of our common diseases. Switching to an anti-inflammatory diet is an important step that patients can take in for rectifying this risk factor. In this review, the author discusses the essential components of an anti-inflammatory diet and its contribution not only to the overall well-being but also to the body's defense against disease. The human microbiome is reviewed in detail and dietary connections and recommendations are explained for several otolaryngologic conditions.

RevDate: 2022-09-20

Wang S, Kang X, Alenius H, et al (2022)

Oral exposure to Ag or TiO2 nanoparticles perturbed gut transcriptome and microbiota in a mouse model of ulcerative colitis.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 169:113368 pii:S0278-6915(22)00566-X [Epub ahead of print].

Silver (nAg) and titanium dioxide (nTiO2) nanoparticles improve texture, flavour or anti-microbial properties of various food products and packaging materials. Despite their increased oral exposure, their potential toxicities in the dysfunctional intestine are unclear. Here, the effects of ingested nAg or nTiO2 on inflamed colon were revealed in a mouse model of chemical-induced acute ulcerative colitis. Mice (eight/group) were exposed to nAg or nTiO2 by oral gavage for 10 consecutive days. We characterized disease phenotypes, histology, and alterations in colonic transcriptome (RNA sequencing) and gut microbiome (16S sequencing). Oral exposure to nAg caused only minor changes in phenotypic hallmarks of colitic mice but induced extensive responses in gene expression enriching processes of apoptotic cell death and RNA metabolism. Instead, ingested nTiO2 yielded shorter colon, aggravated epithelial hyperplasia and deeper infiltration of inflammatory cells. Both nanoparticles significantly changed the gut microbiota composition, resulting in loss of diversity and increase of potential pathobionts. They also increased colonic mucus and abundance of Akkermansia muciniphila. Overall, nAg and nTiO2 induce dissimilar immunotoxicological changes at the molecular and microbiome level in the context of colon inflammation. The results provide valuable information for evaluation of utilizing metallic nanoparticles in food products for the vulnerable population.

RevDate: 2022-09-09

Pinto S, Benincà E, van Nes EH, et al (2022)

Species abundance correlations carry limited information about microbial network interactions.

PLoS computational biology, 18(9):e1010491 pii:PCOMPBIOL-D-22-00053 [Epub ahead of print].

Unraveling the network of interactions in ecological communities is a daunting task. Common methods to infer interspecific interactions from cross-sectional data are based on co-occurrence measures. For instance, interactions in the human microbiome are often inferred from correlations between the abundance of bacterial phylogenetic groups across subjects. We tested whether such correlation-based methods are indeed reliable for inferring interaction networks. For this purpose, we simulated bacterial communities by means of the generalized Lotka-Volterra model, with variation in model parameters representing variability among hosts. Our results show that correlations can be indicative for presence of bacterial interactions, but only when measurement noise is low relative to the variation in interaction strengths between hosts. Indication of interaction was affected by type of interaction network, process noise and sampling under non-equilibrium conditions. The sign of a correlation mostly coincided with the nature of the strongest pairwise interaction, but this is not necessarily the case. For instance, under rare conditions of identical interaction strength, we found that competitive and exploitative interactions can result in positive as well as negative correlations. Thus, cross-sectional abundance data carry limited information on specific interaction types. Correlations in abundance may hint at interactions but require independent validation.

RevDate: 2022-09-13
CmpDate: 2022-09-13

Bachmann R, Van Hul M, Baldin P, et al (2022)

Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism.

Cells, 11(17):.

Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.

RevDate: 2022-09-08

Wang YR, Zhu T, Kong FQ, et al (2022)

Infant Mode of Delivery Shapes the Skin Mycobiome of Prepubescent Children.

Microbiology spectrum [Epub ahead of print].

Characterizing the skin mycobiome is necessary to define its association with the host immune system, particularly in children. In this study, we describe the skin mycobiome on the face, ventral forearm, and calf of 72 prepubescent children (aged 1 to 10 years) and their mothers, based on internal transcribed spacer (ITS) amplicon sequencing. The age and delivery mode at birth are the most influential factors shaping the skin mycobiome. Compared with that of the vaginally born children, the skin mycobiome of caesarean-born children is assembled by predominantly deterministic niche-based processes and exhibits a more fragile microbial network at all three sampling sites. Moreover, vaginal delivery leads to clearer intra- and interindividual specialization of fungal structures with increasing age; this phenomenon is not observed in caesarean-born children. The maternal correlation with children also differs based on the mode of delivery; specifically, the mycobiomes of vaginally born children at younger ages are more strongly correlated with vagina-associated fungal genera (Candida and Rhodotorula), whereas those of caesarean-delivered children at elder age include more skin-associated and airborne fungal genera (Malassezia and Alternaria). Based on this ecological framework, our results suggest that the delivery mode is significantly associated with maturation of the skin fungal community in children. IMPORTANCE Human skin is permanently colonized by microbes starting at birth. The hygiene hypothesis suggests that a lack of early-life immune imprinting weakens the body's resilience against atopic disorders later in life. To better understand fungal colonization following early-life periods affected by interruption, we studied the skin mycobiomes of 73 children and their mothers. Our results suggest a differentiation of the skin mycobiomes between caesarean-born and vaginally born children. Caesarean-born children exhibit a mycobiome structure with more fitted deterministic niche-based processes, a fragile network, and an unchanged microbial dissimilarity over time. In vaginally born children, this dissimilarity increases with age. The results indicate that initial microbial colonization has a long-term impact on a child's skin mycobiome. We believe that these findings will inspire further investigations of the "hygiene hypothesis" in the human microbiome, especially in providing novel insights into influences on the development of the early-life microbiome.

RevDate: 2022-09-10

Piazzesi A, L Putignani (2022)

Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention.

Frontiers in microbiology, 13:958346.

Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.

RevDate: 2022-09-07

Maringanti VS, Bucci V, GK Gerber (2022)

MDITRE: Scalable and Interpretable Machine Learning for Predicting Host Status from Temporal Microbiome Dynamics.

mSystems [Epub ahead of print].

Longitudinal microbiome data sets are being generated with increasing regularity, and there is broad recognition that these studies are critical for unlocking the mechanisms through which the microbiome impacts human health and disease. However, there is a dearth of computational tools for analyzing microbiome time-series data. To address this gap, we developed an open-source software package, Microbiome Differentiable Interpretable Temporal Rule Engine (MDITRE), which implements a new highly efficient method leveraging deep-learning technologies to derive human-interpretable rules that predict host status from longitudinal microbiome data. Using semi-synthetic and a large compendium of publicly available 16S rRNA amplicon and metagenomics sequencing data sets, we demonstrate that in almost all cases, MDITRE performs on par with or better than popular uninterpretable machine learning methods, and orders-of-magnitude faster than the prior interpretable technique. MDITRE also provides a graphical user interface, which we show through case studies can be used to derive biologically meaningful interpretations linking patterns of microbiome changes over time with host phenotypes. IMPORTANCE The human microbiome, or collection of microbes living on and within us, changes over time. Linking these changes to the status of the human host is crucial to understanding how the microbiome influences a variety of human diseases. Due to the large scale and complexity of microbiome data, computational methods are essential. Existing computational methods for linking changes in the microbiome to the status of the human host are either unable to scale to large and complex microbiome data sets or cannot produce human-interpretable outputs. We present a new computational method and software package that overcomes the limitations of previous methods, allowing researchers to analyze larger and more complex data sets while producing easily interpretable outputs. Our method has the potential to enable new insights into how changes in the microbiome over time maintain health or lead to disease in humans and facilitate the development of diagnostic tests based on the microbiome.

RevDate: 2022-09-10
CmpDate: 2022-09-08

Kaiyrlykyzy A, Kozhakhmetov S, Babenko D, et al (2022)

Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan.

Scientific reports, 12(1):15115.

We have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals. Relative abundance analysis has revealed increased amount of taxa belonging to Acidobacteriota, Verrucomicrobiota, Planctomycetota and Synergistota phyla in AD patients. Among bacterial genera, microbiotas of AD participants were characterized by a decreased amount of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus. Differential abundance analysis determined enriched genera of Christensenellaceae R-7 group, Prevotella, Alloprevotella, Eubacterium coprostanoligenes group, Ruminococcus, Flavobacterium, Ohtaekwangia, Akkermansia, Bacteroides sp. Marseille-P3166 in AD patients, whereas Levilactobacillus, Lactiplantibacillus, Tyzzerella, Eubacterium siraeum group, Monoglobus, Bacteroides, Erysipelotrichaceae UCG-003, Veillonella, Faecalibacterium, Roseburia, Haemophilus were depleted. We have also found correlations between some bacteria taxa and blood serum biochemical parameters. Adiponectin was correlated with Acidimicrobiia, Faecalibacterium, Actinobacteria, Oscillospiraceae, Prevotella and Christensenellaceae R-7. The Christensenellaceae R-7 group and Acidobacteriota were correlated with total bilirubin, while Firmicutes, Acidobacteriales bacterium, Castellaniella alcaligenes, Lachnospiraceae, Christensenellaceae and Klebsiella pneumoniae were correlated with the level of CRP in the blood of AD patients. In addition, we report the correlations found between disease severity and certain fecal bacteria. This is the first reported study demonstrating gut microbiota alterations in AD in the Central Asian region.

RevDate: 2022-09-10
CmpDate: 2022-09-08

Ke S, Weiss ST, YY Liu (2022)

Dissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes.

Nature communications, 13(1):5235.

Coronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that most previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from 514 COVID-19 related nasopharyngeal and fecal samples in six independent cohorts. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that there is a significant reduction of strain richness for many species in the gut microbiome of COVID-19 patients. The gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. Finally, we demonstrated that the main findings of our study can be largely validated in three independent cohorts. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )