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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 04 Feb 2025 at 01:56 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®)

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RevDate: 2025-02-01
CmpDate: 2025-02-01

McGann C, Phyu R, Bittinger K, et al (2025)

Role of the Microbiome in Neonatal Infection: Pathogenesis and Implications for Management.

Clinics in perinatology, 52(1):147-166.

The human microbiome refers to the collective genome of microorganisms, including bacteria, fungi, and viruses residing on human body surfaces that are in contact with the environment. Together these communities protect against invasive infections. Conversely, when disrupted, the microbiome can be the source of pathogens causing invasive infection. Interventions to manipulate it via probiotics, antibiotics, and fecal transplantation are available. The risk benefit of these interventions remains unclear. In this review, the authors discuss evidence linking the gut microbiome to neonatal sepsis and also discuss the challenges for translating this knowledge into better clinical care.

RevDate: 2025-01-31
CmpDate: 2025-01-31

Nissilä E, Starck L, Aho E, et al (2025)

The COVID-19 vaccine ChAdOx1 is opsonized by anti-vector antibodies that activate complement and promote viral vector phagocytosis.

Scandinavian journal of immunology, 101(2):e70000.

The ChAdOx1 nCoV-19 vaccine has been in large-scale use during the COVID-19 pandemic. Limited efficacy compared to mRNA vaccines and certain potential side effects raise the question of whether anti-adenoviral vector antibodies influence immune responses against the vaccine. Complement activation by ChAdOx1 and leukocyte phagocytosis of ChAdOx1 in vitro were studied. Plasma IgG levels against ChAdOx1 and human adenovirus 2 (hAdV2) hexon protein were determined (n = 20) and IgGs from high- and low-titre plasmas were isolated (n = 3). Complement activation was measured as cleavage of C3 by immunoblotting and generation of C3a and sC5b-9 by ELISA. pHrodo-labelled ChAdOx1 was opsonized with complement and IgG, and phagocytosis by isolated blood PMNs in vitro was studied by flow cytometry. The transcriptomic profile of PMN cells exposed to ChAdOx1 was analysed by RNA-seq. ChAdOx1 activated the classical complement pathway in an anti-adenovirus antibody-dependent manner. Generation of the terminal complement complex sC5b-9 in individual sera correlated with anti-hAdV2 hexon and anti-ChAdOx1 IgG levels. Phagocytosis of ChAdOx1 also correlated significantly with anti-hAdV2 hexon IgG, anti-ChAdOx1 IgG and serum sC5b-9 levels. High-titre anti-hAdv2 hexon IgG increased phagocytosis in the presence of normal serum. Anti-vector antibodies induced rapid complement activation and promoted phagocytosis of the ChAdOx1 vaccine by neutrophils. Moreover, transcriptomic analysis revealed upregulation of complement-related genes induced by the ChAdOx1 vaccine in vitro. Anti-adenovirus vector antibodies and complement activation may thus influence the efficacy of the ChAdOx1 vaccine against SARS-CoV-2 and be also involved in vaccine-related side effects.

RevDate: 2025-01-31
CmpDate: 2025-01-31

Pitkänen HH, Helin T, Khawaja T, et al (2025)

Coagulation Profile of Convalescent Plasma Donors and Recipients.

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 31:10760296251317522.

Convalescent plasma (CP) therapy for COVID-19 infection may have favorable safety but varying efficacy, with concerns about its procoagulant impact. We investigated whether administration of CP to hospitalized patients affects their coagulation profile. Fifty-four patients randomized in a double-blinded fashion received either placebo, low-titer CP (LCP) or high-titer CP (HCP). Donor blood samples were obtained at the time of the plasmapheresis, while recipient blood samples were collected before infusion, one day post-infusion and between two and six days after infusion. Routine laboratory follow-up, coagulation biomarkers, antiphospholipid antibodies, and thrombin generation (TG) were assessed. CP donors had normal blood cell counts and coagulation profiles, without differences between LCP and HCP donors at the baseline. All CP recipients were on low-molecular-weight heparin thromboprophylaxis at the time of the infusion. Despite randomization, the HCP group had lower baseline (p = 0.004) and Day 1 platelet counts (p = 0.019) than the LCP group. Von Willebrand antigen (VWF:Ag) levels clearly exceeded normal without differences at baseline. At Day 1, LCP recipients had higher VWF:Ag (mean ± SD 224 ± 15%) than HCP recipients (210 ± 8%) (p = 0.012). In all groups, overall 80% lupus anticoagulant was positive. Baseline TG variables were comparable, but again LCP recipients exhibited higher endogenous thrombin potential (ETP) (1313 ± 535 nM.min) (p = 0.038) and peak TG (184 ± 106 nM) (p = 0.037) than the HCP group (870 ± 425 nM.min and 86 ± 54 nM). Our findings show that LCP increases VWF:Ag levels and enhances TG despite the thromboprophylaxis. These results suggest that HCP induces less hypercoagulability than LCP, which may contribute to the variability in CP efficacy.

RevDate: 2025-01-30

Koh H, Kim J, H Jang (2025)

MiCML: a causal machine learning cloud platform for the analysis of treatment effects using microbiome profiles.

BioData mining, 18(1):10.

BACKGROUND: The treatment effects are heterogenous across patients due to the differences in their microbiomes, which in turn implies that we can enhance the treatment effect by manipulating the patient's microbiome profile. Then, the coadministration of microbiome-based dietary supplements/therapeutics along with the primary treatment has been the subject of intensive investigation. However, for this, we first need to comprehend which microbes help (or prevent) the treatment to cure the patient's disease.

RESULTS: In this paper, we introduce a cloud platform, named microbiome causal machine learning (MiCML), for the analysis of treatment effects using microbiome profiles on user-friendly web environments. MiCML is in particular unique with the up-to-date features of (i) batch effect correction to mitigate systematic variation in collective large-scale microbiome data due to the differences in their underlying batches, and (ii) causal machine learning to estimate treatment effects with consistency and then discern microbial taxa that enhance (or lower) the efficacy of the primary treatment. We also stress that MiCML can handle the data from either randomized controlled trials or observational studies.

CONCLUSION: We describe MiCML as a useful analytic tool for microbiome-based personalized medicine. MiCML is freely available on our web server (http://micml.micloud.kr). MiCML can also be implemented locally on the user's computer through our GitHub repository (https://github.com/hk1785/micml).

RevDate: 2025-01-29

Nandwana D, Zhang Y, N Feng (2025)

Contribution of the Microbiome to Interstitial Cystitis/Bladder Pain Syndrome: A Mini Review.

European urology focus pii:S2405-4569(25)00008-2 [Epub ahead of print].

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by pelvic pain and urinary urgency and frequency with an unclear etiology. Emerging evidence implicates microbiome dysbiosis-disruptions in the microbial communities inhabiting the body-in IC/BPS pathophysiology. This review synthesizes the literature on microbial alterations in IC/BPS, including urinary, vaginal, and gastrointestinal microbiota, and their interactions with host inflammatory and metabolic pathways. PATIENT SUMMARY: We reviewed studies from the past 10 years on microbial communities in the body for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Studies have revealed significant changes in microbial species for these patients, especially in urine. However, research on whether IC/BPS can be treated with interventions to modify microbial communities in the body is still needed.

RevDate: 2025-01-29
CmpDate: 2025-01-29

Slater AS, Hickey RM, GP Davey (2024)

Interactions of human milk oligosaccharides with the immune system.

Frontiers in immunology, 15:1523829.

Human milk oligosaccharides (HMOs) are abundant, diverse and complex sugars present in human breast milk. HMOs are well-characterized barriers to microbial infection and by modulating the human microbiome they are also thought to be nutritionally beneficial to the infant. The structural variety of over 200 HMOs, including neutral, fucosylated and sialylated forms, allows them to interact with the immune system in various ways. Clinically, HMOs impact allergic diseases, reducing autoimmune and inflammatory responses, and offer beneficial support to the preterm infant immune health. This review examines the HMO composition and associated immunomodulatory effects, including interactions with immune cell receptors and gut-associated immune responses. These immunomodulatory properties highlight the potential for HMO use in early stage immune development and for use as novel immunotherapeutics. HMO research is rapidly evolving and promises innovative treatments for immune-related conditions and improved health outcomes.

RevDate: 2025-01-29

Fehringer M, T Vogl (2025)

Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases.

Journal of translational autoimmunity, 10:100269.

Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes). This similarity can lead to cross-reactive antibodies and T-cell receptors, resulting in an immune response against autoantigens. Both commensal microbes in the human microbiome and pathogens can trigger molecular mimicry, thereby potentially contributing to the onset of ARDs. In this review, we focus on the role of molecular mimicry in the onset of rheumatoid arthritis and systemic lupus erythematosus. Moreover, implications of molecular mimicry are also briefly discussed for ankylosing spondylitis, systemic sclerosis and myositis.

RevDate: 2025-01-28

Tiwari S, V Paramanik (2025)

Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase.

Molecular neurobiology [Epub ahead of print].

Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.

RevDate: 2025-01-27

Britton GJ, Mogno I, Chen-Liaw A, et al (2025)

Inflammatory disease microbiomes share a functional pathogenicity predicted by C-reactive protein.

bioRxiv : the preprint server for biology pii:2025.01.14.633015.

We examine disease-specific and cross-disease functions of the human gut microbiome by colonizing germ-free mice, at risk for inflammatory arthritis, colitis, or neuroinflammation, with over 100 human fecal microbiomes from subjects with rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, ulcerative colitis, Crohn's disease, or colorectal cancer. We find common inflammatory phenotypes driven by microbiomes from individuals with intestinal inflammation or inflammatory arthritis, as well as distinct functions specific to microbiomes from multiple sclerosis patients. Inflammatory disease in mice colonized with human microbiomes correlated with systemic inflammation, measured by C-reactive protein, in the human donors. These cross-disease patterns of human microbiome pathogenicity mirror features of the inflammatory diseases, including therapeutic targets and the presence or absence of systemic inflammation, suggesting shared and disease-specific mechanisms by which the microbiome is shaped and drives pathogenic inflammatory responses.

RevDate: 2025-01-27

Freibauer A, Pai N, R RamachandranNair (2025)

Characterizing the fecal microbiome in patients on the ketogenic diet for drug resistant epilepsy.

Heliyon, 11(1):e41631.

BACKGROUND: The ketogenic diet is a dietary therapy with anti-seizure effects. The efficacy of the diet is variable, with initial animal studies suggesting the intestinal microbiome may have a modulating effect. Initial research on the role of the human microbiome in pediatric epilepsy management has been inconclusive.

METHODS: In this single-center prospective cohort study, stool samples were collected from 4 patients with drug resistant epilepsy on the ketogenic diet and 9 with drug resistant epilepsy as controls. The samples were analyzed by 16S RNA sequencing.

RESULTS: A trend towards increased alpha diversity was noted among patients on the ketogenic diet compared to the control group. Patients on the ketogenic diet also trended towards a higher relative abundance of Bacteroidaceae, Ruminococcaceae, and Prevotellaceae species. A subset of the control group had a high relative abundance of Bifidobacterium, which may make them a candidate for a trial of the ketogenic diet as a therapeutic option.

CONCLUSION: These findings add to the growing field of research of how the ketogenic diet modulates the intestinal microbiome in pediatric epilepsy patients. Future emphasis on multi-centre trials, consistent stool collection practices and the establishment of standardized stool biobanking protocols are needed further to validate these novel findings in a pediatric population.

RevDate: 2025-01-27

Hao T, Li Y, Ren Q, et al (2025)

circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer.

Molecular therapy. Oncology, 33(1):200919.

Pancreatic cancer is among the most challenging tumors to treat, and due to its immune tolerance characteristics, existing immunotherapy methods are not effective in alleviating the disease. Oncolytic virus therapy, a potential new strategy for treating pancreatic cancer, also faces the limitation of being ineffective when used alone. Elucidating the key host endogenous circular RNAs (circRNAs) involved in M1 virus-mediated killing of pancreatic ductal adenocarcinoma (PDAC) cells may help overcome this limitation. Here, we report that the oncolytic virus M1, a nonpathogenic alphavirus, exhibits different cell viability-inhibitory effects on different pancreatic cancer cells in the clinical stage. Through high-throughput circRNA sequencing, we found that circRNA expression varies among these cells. Further gain-of-function and loss-of-function experiments have shown that circ-1584 can selectively enhance the anti-pancreatic cancer effects of the M1 virus in vitro and in vivo. Additionally, circ-1584 may negatively regulate miR-578 to modulate the anti-pancreatic cancer effects of the M1 virus. Our findings lay the foundation for using circRNA as an adjuvant to enhance the M1 virus efficacy against pancreatic cancer.

RevDate: 2025-01-26

Hong X, Chen T, Liu Y, et al (2025)

Design, Current States, and Challenges of Nanomaterials in Anti-Neuroinflammation: A Perspective on Alzheimer's Disease.

Ageing research reviews pii:S1568-1637(25)00015-7 [Epub ahead of print].

Alzheimer's disease (AD), an age-related neurodegenerative disease, brings huge damage to the society, to the whole family and even to the patient himself. However, until now, the etiological factor of AD is still unknown and there is no effective treatment for it. Massive deposition of amyloid-beta peptide(Aβ) and hyperphosphorylation of Tau proteins are acknowledged pathological features of AD. Recent studies have revealed that neuroinflammation plays a pivotal role in the pathology of AD. With the rise of nanomaterials in the biomedical field, researchers are exploring how the unique properties of these materials can be leveraged to develop effective treatments for AD. This article has summarized the influence of neuroinflammation in AD, the design of nanoplatforms, and the current research status and inadequacy of nanomaterials in improving neuroinflammation in AD.

RevDate: 2025-01-27

Carter MM, Zeng X, Ward CP, et al (2025)

A gut pathobiont regulates circulating glycine and host metabolism in a twin study comparing vegan and omnivorous diets.

medRxiv : the preprint server for health sciences.

Metabolic diseases such as type 2 diabetes and obesity pose a significant global health burden. Plant-based diets, including vegan diets, are linked to favorable metabolic outcomes, yet the underlying mechanisms remain unclear. In a randomized trial involving 21 pairs of identical twins, we investigated the effects of vegan and omnivorous diets on the host metabolome, immune system, and gut microbiome. Vegan diets induced significant shifts in serum and stool metabolomes, cytokine profiles, and gut microbial composition. Notably, vegan diet subjects exhibited elevated serum glycine levels despite lower dietary glycine intake, linked to reduced abundance of the gut pathobiont Bilophila wadsworthia. Functional studies demonstrated that B. wadsworthia metabolizes glycine via the glycine reductase pathway and modulates host glycine availability. Removing B. wadsworthia from gnotobiotic mice elevated glycine levels and improved metabolic markers. These findings reveal a previously underappreciated mechanism by which the gut microbiota regulates host metabolic status through diet.

RevDate: 2025-01-25
CmpDate: 2025-01-25

Toivonen E, Sikkinen J, Salonen A, et al (2025)

Metabolic profiles of meconium in preeclamptic and normotensive pregnancies.

Metabolomics : Official journal of the Metabolomic Society, 21(1):21.

INTRODUCTION: Preeclampsia (PE) is a common vascular pregnancy disorder affecting maternal and fetal metabolism with severe immediate and long-term consequences in mothers and infants. During pregnancy, metabolites in the maternal circulation pass through the placenta to the fetus. Meconium, a first stool of the neonate, offers a view to maternal and fetoplacental unit metabolism and could add to knowledge on the effects of PE on the fetus and newborn.

OBJECTIVES: To compare meconium metabolome of infants from PE and normotensive pregnancies.

METHODS: A cohort of preeclamptic parturients and normotensive controls were recruited in Tampere University Hospital during 2019-2022. Meconium was sampled and its metabolome analyzed using liquid chromatography- mass spectrometry in 48 subjects in each group.

RESULTS: Differences in abundances of 1263 compounds, of which 19 could be annotated, were detected between the two groups. Several acylcarnitines, androsterone sulfate, three bile acids, amino acid derivatives (phenylacetylglutamine, epsilon-(gamma-glutamyl)lysine and N-(phenylacetyl)glutamic acid), as well as caffeine and paraxanthine were lower in the PE group compared to the control group. Urea and progesterone were higher in the PE group.

CONCLUSION: PE is associated with alterations in the meconium metabolome of infants. The differing abundances of several metabolites show alterations in the interaction between the fetoplacental unit and mother in PE, but whether they are a cause or an effect of the disorder remains to be further investigated.

RevDate: 2025-01-25

Amir S, Kumar M, Kumar V, et al (2025)

HgutMgene-Miner: In silico genome mining tool for deciphering the drug-metabolizing potential of human gut microbiome.

Computers in biology and medicine, 186:109679 pii:S0010-4825(25)00029-0 [Epub ahead of print].

The biotransformation of drugs by enzymes from the human microbiome can produce active or inactive products, impacting the bioactivity and function of these drugs inside the human host. However, understanding the biotransformation reactions of drug molecules catalyzed by bacterial enzymes in human microbiota is still limited. Hence, to characterize drug utilization capabilities across all the microbial phyla inside the human gut, we have used a knowledge-based approach to develop HgutMgene-Miner software which predicts xenobiotic metabolizing enzymes (XMEs) through genome mining. HgutMgene-Miner derives its predictive power from the MicrobiomeMetDB database, which systematically catalogs all known biotransformation reactions of xenobiotics and primary metabolites mediated by host-associated microbial enzymes. Over 10,000 isolate genomes from 830 different bacterial species found in the Unified Human Gastrointestinal Genome (UHGG) collection have been analyzed by HgutMgene-Miner. This led to the identification of 89,377 xenobiotic metabolizing enzymes (XMEs) across 13 phyla, with the greatest diversity in Bacteroidota, Firmicutes_A, Firmicutes, and Proteobacteria. Bacteroides, Clostridium, and Alitsipes were found to be the richest genera, while Actinomyces were found to encode the fewest XMEs, primarily metabolizing Diclofenac, a nonsteroidal anti-inflammatory drug. Overall, we discovered XMEs in 220 genera, exceeding the number experimentally reported in fewer than 10 genera. Notably, Eggerthella lenta's cgr2 involved in Digoxin inactivation was identified in very distant Holdemania genera, likewise Clostridium leptum's nitroreductase, involved in Nitrazepam metabolism, was found in Fusobacterium. These findings highlight the extensive and diverse distribution of XMEs across microbial taxa.

RevDate: 2025-01-25
CmpDate: 2025-01-25

Tahmasebi H, Arjmand N, Monemi M, et al (2025)

From Cure to Crisis: Understanding the Evolution of Antibiotic-Resistant Bacteria in Human Microbiota.

Biomolecules, 15(1): pii:biom15010093.

The growing prevalence of antibiotic-resistant bacteria within the human microbiome has become a pressing global health crisis. While antibiotics have revolutionized medicine by significantly reducing mortality and enabling advanced medical interventions, their misuse and overuse have led to the emergence of resistant bacterial strains. Key resistance mechanisms include genetic mutations, horizontal gene transfer, and biofilm formation, with the human microbiota acting as a reservoir for antibiotic resistance genes (ARGs). Industrialization and environmental factors have exacerbated this issue, contributing to a rise in infections with multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae. These resistant pathogens compromise the effectiveness of essential treatments like surgical prophylaxis and chemotherapy, increase healthcare costs, and prolong hospital stays. This crisis highlights the need for a global One-Health approach, particularly in regions with weak regulatory frameworks. Innovative strategies, including next-generation sequencing (NGS) technologies, offer promising avenues for mitigating resistance. Addressing this challenge requires coordinated efforts, encompassing research, policymaking, public education, and antibiotic stewardship, to safeguard current antibiotics and foster the development of new therapeutic solutions. An integrated, multidimensional strategy is essential to tackle this escalating problem and ensure the sustainability of effective antimicrobial treatments.

RevDate: 2025-01-25

Al-Matouq J, Al-Ghafli H, Alibrahim NN, et al (2025)

Unveiling the Interplay Between the Human Microbiome and Gastric Cancer: A Review of the Complex Relationships and Therapeutic Avenues.

Cancers, 17(2): pii:cancers17020226.

The human microbiota plays a crucial role in maintaining overall health and well-being. The gut microbiota has been implicated in developing and progressing various diseases, including cancer. This review highlights the related mechanisms and the compositions that influence cancer pathogenesis with a highlight on gastric cancer. We provide a comprehensive overview of the mechanisms by which the microbiome influences cancer development, progression, and response to treatment, with a focus on identifying potential biomarkers for early detection, prevention strategies, and novel therapeutic interventions that leverage microbiome modulation. This comprehensive review can guide future research and clinical practices in understanding and harnessing the microbiome to optimize gastric cancer therapies.

RevDate: 2025-01-25

Jaimez-Alvarado S, LĂ³pez-Tenorio II, BarragĂ¡n-De Los Santos J, et al (2025)

Gut-Heart Axis: Microbiome Involvement in Restrictive Cardiomyopathies.

Biomedicines, 13(1): pii:biomedicines13010144.

An intriguing aspect of restrictive cardiomyopathies (RCM) is the microbiome role in the natural history of the disease. These cardiomyopathies are often difficult to diagnose and so result in significant morbidity and mortality. The human microbiome, composed of billions of microorganisms, influences various physiological and pathological processes, including cardiovascular health. Studies have shown that gut dysbiosis, an imbalance in the composition of intestinal bacteria, can contribute to systemic inflammation, a key factor in many cardiovascular conditions. An increase in gut permeability, frequently caused by dysbiosis, allows bacterial endotoxins to enter the bloodstream, activating inflammatory pathways that exacerbate cardiac dysfunction. Recent reports highlight the potential role of microbiome in amyloidogenesis, as certain bacteria produce proteins that accelerate the formation of amyloid fibrils. Concurrently, advancements in amyloidosis treatments have sparked renewed hopes, marking a promising era for managing these kinds of diseases. These findings suggest that the gut-heart axis may be a potential factor in the development and progression of cardiovascular disease like RCM, opening new paths for therapeutic intervention. The aim of this review is to provide a detailed overview of the gut-heart axis, focusing on RCM.

RevDate: 2025-01-24

Tisza MJ, Lloyd RE, Hoffman K, et al (2025)

Longitudinal phage-bacteria dynamics in the early life gut microbiome.

Nature microbiology [Epub ahead of print].

Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We developed an extensive metagenome-assembled genome catalogue using the Marker-MAGu pipeline, which comprised 49,111 phage taxa from existing human microbiome datasets. This was used to identify phage marker genes and their integration into the MetaPhlAn 4 bacterial marker gene database enabled simultaneous assessment of phage and bacterial dynamics. We found that individual children are colonized by hundreds of different phages, which are more transitory than bacteria, accumulating a more diverse phage community over time. Type 1 diabetes correlated with a decreased rate of change in bacterial and viral communities in children aged one and two. The addition of phage data improved the ability of machine learning models to discriminate samples by country. Finally, although phage populations were specific to individuals, we observed trends of phage ecological succession that correlated well with putative host bacteria. This resource improves our understanding of phage-bacteria interactions in the developing early life microbiome.

RevDate: 2025-01-24

Sutanto H, Elisa E, Rachma B, et al (2025)

Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.

The American journal of medicine pii:S0002-9343(25)00033-6 [Epub ahead of print].

The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.

RevDate: 2025-01-24
CmpDate: 2025-01-24

Li L, Geng Y, Chen T, et al (2025)

Deep learning model targeting cancer surrounding tissues for accurate cancer diagnosis based on histopathological images.

Journal of translational medicine, 23(1):110.

Accurate and fast histological diagnosis of cancers is crucial for successful treatment. The deep learning-based approaches have assisted pathologists in efficient cancer diagnosis. The remodeled microenvironment and field cancerization may enable the cancer-specific features in the image of non-cancer regions surrounding cancer, which may provide additional information not available in the cancer region to improve cancer diagnosis. Here, we proposed a deep learning framework with fine-tuning target proportion towards cancer surrounding tissues in histological images for gastric cancer diagnosis. Through employing six deep learning-based models targeting region-of-interest (ROI) with different proportions of no-cancer and cancer regions, we uncovered the diagnostic value of non-cancer ROI, and the model performance for cancer diagnosis depended on the proportion. Then, we constructed a model based on MobileNetV2 with the optimized weights targeting non-cancer and cancer ROI to diagnose gastric cancer (DeepNCCNet). In the external validation, the optimized DeepNCCNet demonstrated excellent generalization abilities with an accuracy of 93.96%. In conclusion, we discovered a non-cancer ROI weight-dependent model performance, indicating the diagnostic value of non-cancer regions with potential remodeled microenvironment and field cancerization, which provides a promising image resource for cancer diagnosis. The DeepNCCNet could be readily applied to clinical diagnosis for gastric cancer, which is useful for some clinical settings such as the absence or minimum amount of tumor tissues in the insufficient biopsy.

RevDate: 2025-01-23

Abdill RJ, Graham SP, Rubinetti V, et al (2025)

Integration of 168,000 samples reveals global patterns of the human gut microbiome.

Cell pii:S0092-8674(24)01430-2 [Epub ahead of print].

The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline. We use this compendium to evaluate geographic and technical effects on microbiome variation. We find that regions such as Central and Southern Asia differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America and that composition alone can be used to predict a sample's region of origin. We also find strong associations between microbiome variation and technical factors such as primers and DNA extraction. We anticipate this growing work, the Human Microbiome Compendium, will enable advanced applied and methodological research.

RevDate: 2025-01-23

Liu B, Xie Y, Zhang Y, et al (2025)

Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity.

Cell & bioscience, 15(1):7.

BACKGROUND: Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. However, the lack of a quick and convenient approach to determine the intratumoral epigenetic heterogeneity (eITH) limit the application of eITH in clinical settings. Here, we aimed to develop a tool that can evaluate the eITH using the DNA methylation profiles from bulk tumors.

METHODS: Genomic DNA of three laser micro-dissected tumor regions, including digestive tract surface, central bulk, and invasive front, was extracted from formalin-fixed paraffin-embedded sections of colorectal cancer patients. The genome-wide methylation profiles were generated with methylation array. The most variable methylated probes were selected to construct a DNA methylation-based heterogeneity (MeHEG) estimation tool that can deconvolve the proportion of each reference tumor region with the support vector machine model-based method. A PCR-based assay for quantitative analysis of DNA methylation (QASM) was developed to specifically determine the methylation status of each CpG in MeHEG assay at single-base resolution to realize fast evaluation of epigenetic heterogeneity.

RESULTS: In the discovery set with 79 patients, the differentially methylated CpGs among the three tumor regions were found. The 7 most representative CpGs were identified and subsequently selected to develop the MeHEG algorithm. We validated its performance of deconvolution of tumor regions in an independent cohort. In addition, we showed the significant association of MeHEG-based epigenetic heterogeneity with the genomic heterogeneity in mutation and copy number variation in our in-house and TCGA cohorts. Besides, we found that the patients with higher MeHEG score had worse disease-free and overall survival outcomes. Finally, we found dynamic change of epigenetic heterogeneity based on MeHEG score in cancer cells under the treatment of therapeutic drugs.

CONCLUSION: By developing a 7-loci panel using a machine learning approach combined with the QASM assay for PCR-based application, we present a valuable method for evaluating intratumoral heterogeneity. The MeHEG algorithm offers novel insights into tumor heterogeneity from an epigenetic perspective, potentially enriching current knowledge of tumor complexity and providing a new tool for clinical and research applications in cancer biology.

RevDate: 2025-01-22

Pitashny M, Kesten I, Shlon D, et al (2025)

The Future of Microbiome Therapeutics.

Drugs [Epub ahead of print].

The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.

RevDate: 2025-01-22

Dufresne K, Al KF, Craig HC, et al (2025)

TSST-1 promotes colonization of Staphylococcus aureus within the vaginal tract by activation of CD8[+] T cells.

Infection and immunity [Epub ahead of print].

Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus and is the determinant of menstrual toxic shock syndrome (mTSS); however, the impact of TSST-1 on the vaginal environment beyond mTSS is not understood. Herein, we assessed how TSST-1 affects vaginal colonization by S. aureus, host inflammatory responses, and changes in microbial communities within the murine vagina. We demonstrated that TSST-1 induced a CD8[+] T-cell-dependent inflammatory response in 24 h that correlated with S. aureus persistence within the vaginal tract. This increase was due to superantigen-dependent T-cell activation that triggered a change in microbial composition within the vaginal tract. Altogether, this study demonstrates that within the vaginal tract, TSST-1 modulates the vaginal microbiota to favor the survival of S. aureus in the absence of mTSS.IMPORTANCEToxic shock syndrome toxin-1 (TSST-1) is a superantigen toxin produced from Staphylococcus aureus that causes the menstrual form of toxic shock syndrome. This research demonstrates that TSST-1 also has a wider function within the vaginal tract than previously expected. We show that TSST-1, by activating CD8[+] T cells, induces an inflammatory environment that modifies the vaginal microbiota to favor colonization by S. aureus. These are important findings as S. aureus can colonize the human vaginal tract efficiently and subsequently trigger dysbiosis within the microbial communities leading to several adverse outcomes such as decreased fertility, increased risks for sexually transmitted diseases, and issues related to pregnancy and birth.

RevDate: 2025-01-23
CmpDate: 2025-01-23

Trepka KR, Olson CA, Upadhyay V, et al (2025)

Pharma[e]cology: How the Gut Microbiome Contributes to Variations in Drug Response.

Annual review of pharmacology and toxicology, 65(1):355-373.

Drugs represent our first, and sometimes last, line of defense for many diseases, yet despite decades of research we still do not fully understand why a given drug works in one patient and fails in the next. The human gut microbiome is one of the missing puzzle pieces, due to its ability to parallel and extend host pathways for drug metabolism, along with more complex host-microbiome interactions. Herein, we focus on the well-established links between the gut microbiome and drugs for heart disease and cancer, plus emerging data on neurological disease. We highlight the interdisciplinary methods that are available and how they can be used to address major remaining knowledge gaps, including the consequences of microbial drug metabolism for treatment outcomes. Continued progress in this area promises fundamental biological insights into humans and their associated microbial communities and strategies for leveraging the microbiome to improve the practice of medicine.

RevDate: 2025-01-22

Griffin EF, MG Owens (2025)

Dopaminergic neurodegeneration in C. elegans cultivated with Porphorymonas gingivalis.

microPublication biology, 2025:.

Disruption of the human microbiome has emerged as a major contributing factor in the etiology of neurodegenerative disease. Previous work suggests a positive correlation between periodontal inflammation and Parkinson's disease. Here, we show that feeding C. elegans animals Porphorymonas gingivalis causes neurodegeneration that is not additive with neurodegeneration induced by the Parkinson's-associated protein, α-synuclein. In contrast, α-synuclein-expressing animals fed P. gingivalis show additional disruption in basal slowing, suggesting that P. gingivalis induces neurodegeneration while altering neuronal function of extant neurons. Though the mechanism is unclear, these results suggest a relationship between P. gingivalis and neurodegeneration that warrants further investigation.

RevDate: 2025-01-22

Modha S, Hughes J, Orton RJ, et al (2025)

Expanding the genomic diversity of human anelloviruses.

Virus evolution, 11(1):veaf002.

Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera: Alphatorquevirus, Betatorquevirus, and Gammatorquevirus, while we also present new genomes of the under-sampled Hetorquevirus, Memtorquevirus, and Samektorquevirus genera. We performed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same genus and only 15 inter-genus recombination events were detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, while a recombination coldspot was detected within the gene. Our analysis suggests that anellovirus evolution is governed by homologous recombination; however, events between distant viruses or ones producing chimaeric ORF1s likely lead to nonviable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses' rolling-circle replication. A subset of the genomes assembled in both this and previous studies are completely lacking these essential elements, opening up the possibility that anellovirus intracellular populations contain nonstandard viral genomes. However, low-read depth of the metagenomically assembled contigs may partly explain the lack of some features. Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.

RevDate: 2025-01-21
CmpDate: 2025-01-21

Gill B, Wessels JM, Hayes CL, et al (2025)

Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial.

PloS one, 20(1):e0315576 pii:PONE-D-23-43948.

BACKGROUND: A dysbiotic vaginal microbiome (VMB) is associated with clinical conditions such as bacterial vaginosis (BV) and an increased risk of human immunodeficiency virus (HIV-1) infection. Considering the high prevalence of BV among African, Caribbean and Black (ACB) women, we conducted a prospective, randomized, open-label phase 1 clinical trial to determine the feasibility, safety and tolerability of administering low-dose estrogen, probiotics or both in combination to improve vaginal health and decrease HIV-1 susceptibility.

METHODS: ACB women aged 18-49 from the Greater Toronto Area (GTA) were randomized to one of four study arms: intravaginal estradiol (Estring©; 7.5mg/day); a vaginal probiotic (RepHresh™ Pro-B™) administered twice daily; a combination of Estring© and vaginal RepHresh™ Pro-B™ (twice daily); or the Estring© and oral RepHresh™ Pro-B™ (twice daily), for a duration of 30 days. Feasibility was evaluated through enrolment, retention, and adherence rates, while safety and tolerability were determined by a pre- and post-treatment blood panel and reported adverse events (AEs).

RESULTS: Overall, 63 ACB women were screened, 50 were enrolled and received the intervention while 41 completed the study, resulting in 80% enrollment and 82% retention rates. Overall adherence to the study protocol was high at 93%, with an adherence of 92% for RepHresh™ Pro-B™ and 97% for Estring©. A total of 88 AEs were reported by 29 participants which were mild (66/88; 75%) and largely resolved (82/88;93%) by the end of the study, with no serious AEs (SAEs) noted. In addition, a panel of safety blood markers measured pre- and post-intervention confirmed no clinically significant changes in blood chemistry or blood cell count.

CONCLUSION: Overall, the administration of intravaginal estrogen and/or probiotics in pre-menopausal ACB women is feasible, safe, and well tolerated.

TRIAL REGISTRATION: The trial was registered with Clinicaltrials.gov (NCT03837015) and CIHR HIV Clinical Trials (CTN308).

RevDate: 2025-01-20

Ni M, Fan Y, Liu Y, et al (2025)

Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.

bioRxiv : the preprint server for biology pii:2025.01.11.632565.

The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A central strategy for genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePV have been well characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting the ones associated with antibiotics or fecal microbiota transplantation. Second, we analyzed an extensive collection of public short-read metagenomic sequencing datasets, uncovering a greater prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variations associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePV can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common and broad strategy used by bacteria in the human gut to adapt to their environment.

RevDate: 2025-01-17
CmpDate: 2025-01-17

Jeyaram K, Lahti L, Tims S, et al (2025)

Fermented foods affect the seasonal stability of gut bacteria in an Indian rural population.

Nature communications, 16(1):771.

The effect of fermented foods on healthy human gut microbiota structure and function, particularly its seasonal preference and frequent long-term consumption, has been largely uncharacterised. Here, we assess the gut microbiota and metabolite composition of 78 healthy Indian agrarian individuals who differ in the intake of fermented milk and soybean products by seasonal sampling during hot-humid summer, autumn and dry winter. Here we show that, seasonal shifts between the Prevotella- and Bifidobacterium/Ruminococcus-driven community types, or ecological states, and associated fatty acid derivatives, with a bimodal change in Bacteroidota community structure during summer, particularly in fermented milk consumers. Our results associate long-term fermented food consumption with reduced gut microbiota diversity and bacterial load. We identify taxonomic groups that drive the seasonal fluctuation and associated shifts between the two ecological states in gut microbiota. This understanding may pave the way towards developing strategies to sustain a healthy and resilient gut microbiota through dietary interventions.

RevDate: 2025-01-17

Sfanos KS (2025)

Clinical translation of the interconnected role of the microbiome and diet in genitourinary malignancies.

Urologic oncology pii:S1078-1439(24)01049-4 [Epub ahead of print].

A complex and often under-appreciated relationship exists between the human microbiome, diet, and the development or progression of cancer. There is likewise an emerging appreciation for the role that the human-associated microbiota play in mediating cancer treatment response. This seminar series covers our current understanding of the interplay between the microbiome and cancer in genitourinary malignancies inclusive of bladder, kidney, and prostate cancers.

RevDate: 2025-01-16

Amari Y, Hosonuma M, Mizukami T, et al (2025)

Association between the ABCC11 gene polymorphism-determined earwax properties and external auditory canal microbiota in healthy adults.

Microbiology spectrum [Epub ahead of print].

UNLABELLED: The concept of genome-microbiome interactions, in which the microenvironment determined by host genetic polymorphisms regulates the local microbiota, is important in the pathogenesis of human disease. In otolaryngology, the resident bacterial microbiota is reportedly altered in non-infectious ear diseases, such as otitis media pearls and exudative otitis media. We hypothesized that a single-nucleotide polymorphism in the ATP-binding cassette sub-family C member 11 (ABCC11) gene, which determines earwax properties, regulates the ear canal microbiota. We analyzed ABCC11 gene polymorphisms and ear canal microbiota in healthy individuals to understand the relationship between genome-microbiome interactions in the ear canal. The study included 21 subjects who were divided into two groups: 538GA (9) and 538AA (12). Staphylococcus auricularis and Corynebacterium spp. were observed in the 538GA group, whereas Methylocella spp. was observed in the 538AA group. PICRUSt analysis revealed significant enrichment of certain pathways, such as superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation, chlorosalicylate degradation, mycothiol biosynthesis, and enterobactin biosynthesis in the GA group, whereas allantoin degradation IV (anaerobic), nitrifier denitrification, starch degradation III, L-valine degradation I, and nicotinate degradation I were significantly enriched in the AA group. The ABCC11 gene polymorphism regulates the composition of the ear canal microbiota and its metabolic pathways. This study revealed a genome-microbiome interaction within the resident microbiota of the external auditory canal that may help to elucidate the pathogenesis of ear diseases and develop novel therapies.

IMPORTANCE: The ABCC11 gene polymorphism, which determines earwax characteristics, regulates the composition of the ear canal microbiota and its metabolic pathways. We determined the presence of genome-microbiome interactions in the resident microbiota of the ear canal. Future studies should focus on ABCC11 gene polymorphisms to elucidate the pathogenesis of ear diseases and develop therapeutic methods.

RevDate: 2025-01-16

Bao Z, Zhang B, Yao J, et al (2025)

MultiTax-human: an extensive and high-resolution human-related full-length 16S rRNA reference database and taxonomy.

Microbiology spectrum [Epub ahead of print].

Considering that the human microbiota plays a critical role in health and disease, an accurate and high-resolution taxonomic classification is thus essential for meaningful microbiome analysis. In this study, we developed an automatic system, named MultiTax pipeline, for generating de novo taxonomy from full-length 16S rRNA sequences using the Genome Taxonomy Database and other existing reference databases. We first constructed the MultiTax-human database, a high-resolution resource specifically designed for human microbiome research and clinical applications. The database includes 842,649 high-quality full-length 16S rRNA sequences, extracted from multiple public repositories and human-related studies, offering a comprehensive and accurate portrayal of the human microbiome. To validate the MultiTax-human database, we profiled the human microbiome across various body sites, identified core microbial taxa, and tested its performance using an independent data set. Additionally, the database is equipped with a user-friendly web interface for easy querying and data exploration. The MultiTax-human database is poised to serve as a valuable tool for researchers, enhancing the precision of human microbiome studies and advancing our understanding of its impact on human health and diseases.IMPORTANCEUnderstanding the human microbiome, the collection of microorganisms in and on our bodies, is essential for advancing health research. Current methods often lack precision and consistency, hindering our ability to study these microorganisms effectively. Our study presents the MultiTax-human database, a high-resolution reference tool specifically designed for human microbiome research. By integrating data from multiple sources and employing advanced classification techniques, this database offers an accurate and detailed map of the human microbiome. This resource enhances the ability of researchers and clinicians to explore the roles of microorganisms in health and disease, potentially leading to improved diagnostics, treatments, and insights into various medical conditions.

RevDate: 2025-01-14

Galeota-Sprung B, Bhatt AS, C de la Fuente-Nunez (2025)

Microproteins: emerging roles as antibiotics.

Trends in genetics : TIG pii:S0168-9525(24)00297-X [Epub ahead of print].

Recent advances in computational prediction and experimental techniques have detected previously unknown microproteins, particularly in the human microbiome. These small proteins, produced by diverse microbial species, are emerging as promising candidates for new antibiotics.

RevDate: 2025-01-14

Liu X, Meng L, Song W, et al (2025)

Efficacy of Toothpaste Containing Polylysine and Funme Peptide on Oral Microbiome and Oral Health.

International dental journal pii:S0020-6539(24)01612-5 [Epub ahead of print].

OBJECTIVE: To evaluate the effect of the toothpaste containing ε-poly-L-lysine (ε-PL) and funme peptide (FP) as key components on oral microbial composition and oral health.

METHODS: An oral microbiome study was initially carried out to analyze the variation in the oral microbiota before and after use of antimicrobial peptide (AMP) toothpaste. Subsequently, a clinical trial was independently performed to assess the efficacy of AMP toothpaste by measuring the dental plaque index (PLI), volatile sulfur compounds (VSCs) levels, modified bleeding index (mBI), and bleeding on probing rate (BOP%).

RESULTS: The application of AMP toothpaste increased the α diversity and modified β diversity of oral microbiome across 3 oral niches. AMP toothpaste increased the relative abundance of the commensal oral microbes, and attenuated the abundance of pathogenic bacteria in gingivitis patients to normal levels. The clinical trial showed 44.33% and 12.29% reductions of PLI scores in the test and control groups, respectively, and the test group exhibited a more pronounced decrease in VSC levels. The test group recorded significant reductions in mBI and BOP% by 39.09% and 24.59%, respectively, exceeding the control group's reductions of 4.63% and -0.97% (P < .05).

CONCLUSION: The formulation of toothpaste with ε-PL and FP recalibrated the oral microbiome's diversity and abundance, and mitigated common oral health issues such as plaque, halitosis, and gingivitis while maintaining well safety.

CLINICAL RELEVANCE: Oral care products containing ε-PL and FP can be used as a new treatment for improving oral microbiota and oral diseases.

RevDate: 2025-01-14

KolĂ¡Å™ M (2023)

[Selected aspects of the human microbiome].

Klinicka mikrobiologie a infekcni lekarstvi, 29(2):46-51.

This review briefly defines the term microbiome and characterizes its importance in health and disease.

RevDate: 2025-01-13
CmpDate: 2025-01-13

Puller V, Plaza Oñate F, Prifti E, et al (2025)

Impact of simulation and reference catalogues on the evaluation of taxonomic profiling pipelines.

Microbial genomics, 11(1):.

Microbiome profiling tools rely on reference catalogues, which significantly affect their performance. Comparing them is, however, challenging, mainly due to differences in their native catalogues. In this study, we present a novel standardized benchmarking framework that makes such comparisons more accurate. We decided not to customize databases but to translate results to a common reference to use the tools with their native environment. Specifically, we conducted two realistic simulations of gut microbiome samples, each based on a specific taxonomic profiler, and used two different taxonomic references to project their results, namely the Genome Taxonomy Database and the Unified Human Gastrointestinal Genome. To demonstrate the importance of using such a framework, we evaluated four established profilers as well as the impact of the simulations and that of the common taxonomic references on the perceived performance of these profilers. Finally, we provide guidelines to enhance future profiler comparisons for human microbiome ecosystems: (i) use or create realistic simulations tailored to your biological context (BC), (ii) identify a common feature space suited to your BC and independent of the catalogues used by the profilers and (iii) apply a comprehensive set of metrics covering accuracy (sensitivity/precision), overall representativity (richness/Shannon) and quantification (UniFrac and/or Aitchison distance).

RevDate: 2025-01-13

Li D, Wu R, Yu Q, et al (2024)

Microbiota and urinary tumor immunity: Mechanisms, therapeutic implications, and future perspectives.

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, 36(6):596-615.

RevDate: 2025-01-12

Zhang H, Chen A, Li S, et al (2025)

Spatio-Temporal Change of Skin and Oral Microbiota: A Longitudinal Study of Microbial Diversity and Stability.

Electrophoresis [Epub ahead of print].

The human skin and oral cavity harbor complex microbial communities, which exist in dynamic equilibrium with the host's physiological state and the external environment. This study investigates the microbial atlas of human skin and oral cavities using samples collected over a 10-month period, aiming to assess how both internal and external factors influence the human microbiome. We examined bacterial community diversity and stability across various body sites, including palm and nasal skin, saliva, and oral epithelial cells, during environmental changes and a COVID-19 pandemic. The skin microbiome was confirmed to display spatial and temporal stability compared to the oral microbiome, particularly the oral epithelium, which was susceptible to changes in the host's physiological state and immune response. Moreover, significant differences in the microbial community structure among the 4 sample types were observed, and 87 distinct bacteria biomarkers were identified. The random forest prediction model achieved an overall prediction accuracy of 95.24% across the four types of samples studied. Additionally, nasal skin samples showed significant promise for individual identification through profiling the skin microbiota. These findings highlight the potential of skin and oral microbiota as forensic markers for inferring body sites and identifying individuals. In summary, despite facing limitations such as a small cohort size and the need for broader validation, this research provides an overall perspective and initial insights for refining experimental designs and conducting in-depth research in various microbial research fields.

RevDate: 2025-01-11

Heckmann ND, Culler M, Mont MA, et al (2025)

Emerging Concepts in Periprosthetic Joint Infection Research: The Human Microbiome.

The Journal of arthroplasty pii:S0883-5403(25)00001-4 [Epub ahead of print].

Microorganisms, including bacteria, fungi, and viruses, that reside on and within the human body are collectively known as the human microbiome. Dysbiosis, or disruption in the microbiome, has been implicated in several disease processes, including asthma, obesity, autoimmune diseases, and numerous other conditions. While the Human Microbiome Project (HMP) and the generation of descriptive studies it inspired established correlations between characteristic patterns in the composition of the microbiome and specific disease phenotypes, current research has begun to focus on elucidating the causal role of the microbiome in disease pathogenesis. Within the field of orthopaedic surgery, researchers have proposed the concept of a "gut-joint axis" by which the intestinal microbiome influences joint health and the development of diseases such as osteoarthritis and periprosthetic joint infection (PJI). It is theorized that intestinal dysbiosis increases gut permeability, leading to the translocation of bacteria and their metabolic products into the systemic circulation and the stimulation of proinflammatory response cascades throughout the body, including within the joints. While correlative studies have identified patterns of dysbiotic derangement associated with osteoarthritis and PJI, translational research is needed to clarify the precise mechanisms by which these changes influence disease processes. Additionally, an emerging body of literature has challenged the previously held belief that certain body sites are sterile and do not possess a microbiome, with studies identifying distinct microbial genomic signatures and a core microbiome that varies between anatomic sites. A more thorough characterization of the joint microbiome may have profound implications for our understanding of PJI pathogenesis and our ability to stratify patients based on risk. The purpose of this review was to outline our current understanding of the human microbiome, to describe the gut-joint axis and its role in specific pathologies, including PJI, and to highlight the potential of microbiome-based therapeutic interventions in the field of orthopaedics.

RevDate: 2025-01-11

Chong-Nguyen C, Yilmaz B, Coles B, et al (2025)

A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology.

European journal of clinical investigation [Epub ahead of print].

BACKGROUND: The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.

METHODS: Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes.

RESULTS: Thirteen studies were included in the review: five human, three animal and five in vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E. coli.

CONCLUSIONS: TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.

RevDate: 2025-01-11
CmpDate: 2025-01-11

Wu F, Guo Y, Wang Y, et al (2024)

Effects of Long-Term Fasting on Gut Microbiota, Serum Metabolome, and Their Association in Male Adults.

Nutrients, 17(1): pii:nu17010035.

BACKGROUND: Long-term fasting demonstrates greater therapeutic potential and broader application prospects in extreme environments than intermittent fasting.

METHOD: This pilot study of 10-day complete fasting (CF), with a small sample size of 13 volunteers, aimed to investigate the time-series impacts on gut microbiome, serum metabolome, and their interrelationships with biochemical indices.

RESULTS: The results show CF significantly affected gut microbiota diversity, composition, and interspecies interactions, characterized by an expansion of the Proteobacteria phylum (about six-fold) and a decrease in Bacteroidetes (about 50%) and Firmicutes (about 34%) populations. Notably, certain bacteria taxa exhibited complex interactions and strong correlations with serum metabolites implicated in energy and amino acid metabolism, with a particular focus on fatty acylcarnitines and tryptophan derivatives. A key focus of our study was the effect of Ruthenibacterium lactatiformans, which was highly increased during CF and exhibited a strong correlation with fat metabolic indicators. This bacterium was found to mitigate high-fat diet-induced obesity, glucose intolerance, dyslipidemia, and intestinal barrier dysfunction in animal experiments. These effects suggest its potential as a probiotic candidate for the amelioration of dyslipidemia and for mediating the benefits of fasting on fat metabolism.

CONCLUSIONS: Our pilot study suggests that alterations in gut microbiota during CF contribute to the shift of energy metabolic substrate and the establishment of a novel homeostatic state during prolonged fasting.

RevDate: 2025-01-11

Galazka S, Vigl V, Kuffner M, et al (2024)

Prevalence of Antibiotic Resistance Genes in Differently Processed Smoothies and Fresh Produce from Austria.

Foods (Basel, Switzerland), 14(1): pii:foods14010011.

Plant-derived foods are potential vehicles for microbial antibiotic resistance genes (ARGs), which can be transferred to the human microbiome if consumed raw or minimally processed. The aim of this study was to determine the prevalence and the amount of clinically relevant ARGs and mobile genetic elements (MGEs) in differently processed smoothies (freshly prepared, cold-pressed, pasteurized and high-pressure processed) and fresh produce samples (organically and conventionally cultivated) to assess potential health hazards associated with their consumption. The MGE ISPps and the class 1 integron-integrase gene intI1 were detected by probe-based qPCR in concentrations up to 10[4] copies/mL in all smoothies, lettuce, carrots and a single tomato sample. The highest total (2.2 × 10[5] copies/mL) and the most diverse ARG and MGE loads (16/26 targets) were observed in freshly prepared and the lowest prevalences (5/26) and concentrations (4.1 × 10[3] copies/mL) in high-pressure-processed (HPP) smoothies. BlaCTX-M-1-15 (1.2 × 10[5] c/mL) and strB (6.3 × 10[4] c/mL) were the most abundant, and qacEΔ1 (95%), blaTEM1 (85%), ermB and sul1 (75%, each) were the most prevalent ARGs. QnrS, vanA, sat-4, blaKPC, blaNDM-1 and blaOXA-10 were never detected. HPP treatment reduced the microbial loads by ca. 5 logs, also destroying extracellular DNA potentially encoding ARGs that could otherwise be transferred by bacterial transformation. The bacterial microbiome, potential pathogens, bacterial ARG carriers and competent bacteria able to take up ARGs were identified by Illumina 16S rRNA gene sequencing. To reduce the risk of AMR spread from smoothies, our data endorse the application of DNA-disintegrating processing techniques such as HPP.

RevDate: 2025-01-10

Lan P, Zhang ZJ, Z He (2025)

[Progress in the study of the surgical management of Crohn disease based on the mesenteric concept].

Zhonghua wai ke za zhi [Chinese journal of surgery], 63(2):107-113 [Epub ahead of print].

In recent years, with the deepening of mesentery research, it is found that its blood vessels, nerves, lymphoid tissue, adipose tissue and other structures play an important role in the occurrence and development of Crohn disease, and the degree of lesion is related with the disease process, surgical difficulty, the occurrence of intraoperative complications and postoperative recurrence. The optimal surgical strategy of Crohn disease based on mesenteric involvement has received great attention. Multiple retrospective studies found that extended mesenteric resection and Kono-S anastomosis potentially could reduce the rate of postoperative recurrence. However, the latest prospective randomized controlled studies did not achieve the expected results, and the evidence for the surgical strategy based on mesentery is still weak. This review summarises the findings of basic and clinical investigations of the mesentery in Crohn disease so far and explores its role in surgical treatment optimization, and provides new thinking and insights for the further research and surgical options for Crohn disease.

RevDate: 2025-01-10
CmpDate: 2025-01-10

Putumbaka S, Schut GJ, Thorgersen MP, et al (2025)

Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe Eubacterium limosum.

Proceedings of the National Academy of Sciences of the United States of America, 122(1):e2411809121.

Eubacterium limosum is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by E. limosum has not been explored. We show that E. limosum growing on lactate takes up added tungstate rather than molybdate and produces the SCFAs acetate and butyrate, but not propionate. The genes encoding an electron bifurcating, tungsten-containing oxidoreductase (WOR1) and a tungsten-containing formate dehydrogenase (FDH), along with an electron bifurcating lactate dehydrogenase (LCT), lactate permease, and enzymes of the propanediol pathway, are all up-regulated on lactate compared to growth on glucose. Lactate metabolism is controlled by a GntR-family repressor (LctR) and two global regulators, Rex and CcpA, where Rex in part controls W storage and tungstopyranopterin (Tuco) biosynthesis. Tuco-dependent riboswitches, along with CcpA, also control two iron transporters, consistent with the increased iron demand for many iron-containing enzymes, including WOR1 and FDH, involved in SCFA production. From intracellular aldehyde concentrations and the substrate specificity of WOR1, we propose that WOR1 is involved in detoxifying acetaldehyde produced during lactate degradation. Lactate to SCFA conversion by E. limosum is clearly highly tungstocentric and tungsten might be an overlooked micronutrient in the human microbiome and in overall human health.

RevDate: 2025-01-10

Wang P, Xia P, Gao S, et al (2025)

Critical Structures of Bisphenol Analogues on Embryonic Toxicity Identified by a Computational Approach.

Environmental science & technology [Epub ahead of print].

Safer chemical alternatives to bisphenol (BP) have been a major pursuit of modern green chemistry and toxicology. Using a chemical similarity-based approach, it is difficult to identify minor structural differences that contribute to the significant changes of toxicity. Here, we used omics and computational toxicology to identify chemical features associated with BP analogue-induced embryonic toxicity, offering valuable insights to inform the design of safer chemical alternatives. The zebrafish embryonic acute toxicity, behavioral effects, and concentration-dependent transcriptome analysis of 17 BP analogues were tested, and the chemical structure characteristics and key biological activities-induced embryonic toxicity were explored. BPE, BPF, BPP, BPBP, and BPS induced lower embryonic lethality than BPA. And, 8 BP analogues triggered hyperactive behavior at environmentally and human relevant concentrations. BP analogues with phenol rings linked via hydrophobic segments ("chain:alkaneBranch_neopentyl_C5") disturbed stress response, leading to embryonic lethality, and introducing hydrophobic groups on the meta position of bisphenol structure augmented their embryonic lethality effects. "3DACorr_TotChg_3" of BP analogues is a key physicochemical feature for behavioral disorders, and BP analogues with 3DACorr_TotChg_3 value < 0.11 could induce hyperactive behavior by perturbing neurodevelopment relevant biological pathways. This study provides an integrated strategy, combining data-driven profiling and mechanism-based analysis for safer chemical alternatives.

RevDate: 2025-01-10

Soborowski AL, Hackley RK, Hwang S, et al (2025)

Genomic re-sequencing reveals mutational divergence across genetically engineered strains of model archaea.

mSystems [Epub ahead of print].

UNLABELLED: Archaeal molecular biology has been a topic of intense research in recent decades as their role in global ecosystems, nutrient cycles, and eukaryotic evolution comes to light. The hypersaline-adapted archaeal species Halobacterium salinarum and Haloferax volcanii serve as important model organisms for understanding archaeal genomics, genetics, and biochemistry, in part because efficient tools enable genetic manipulation. As a result, the number of strains in circulation among the haloarchaeal research community has increased in recent decades. However, the degree of genetic divergence and effects on genetic integrity resulting from the creation and inter-lab transfer of novel lab stock strains remain unclear. To address this, we performed whole-genome re-sequencing on a cross-section of wild-type, parental, and knockout strains in both model species. Integrating these data with existing repositories of re-sequencing data, we identify mutations that have arisen in a collection of 60 strains, sampled from two species across eight different labs. Independent of sequencing, we construct strain lineages, identifying branch points and significant genetic events in strain history. Combining this with our sequencing data, we identify small clusters of mutations that definitively separate lab strains. Additionally, an analysis of gene knockout strains suggests that roughly one in three strains currently in use harbors second-site mutations of potential phenotypic impact. Overall, we find that divergence among lab strains is thus far minimal, though as the archaeal research community continues to grow, careful strain provenance and genomic re-sequencing are required to keep inter-lab divergence to a minimum, prevent the compounding of mutations into fully independent lineages, and maintain the current high degree of reproducible research between lab groups.

IMPORTANCE: Archaea are a domain of microbial life whose member species play a critical role in the global carbon cycle, climate regulation, the human microbiome, and persistence in extreme habitats. In particular, hypersaline-adapted archaea are important, genetically tractable model organisms for studying archaeal genetics, genomics, and biochemistry. As the archaeal research community grows, keeping track of the genetic integrity of strains of interest is necessary. In particular, routine genetic manipulations and the common practice of sharing strains between labs allow mutations to arise in lab stocks. If these mutations affect cellular processes, they may jeopardize the reproducibility of work between research groups and confound the results of future studies. In this work, we examine DNA sequences from 60 strains across two species of archaea. We identify shared and unique mutations occurring between and within strains. Independently, we trace the lineage of each strain, identifying which genetic manipulations lead to observed off-target mutations. While overall divergence across labs is minimal so far, our work highlights the need for labs to continue proper strain husbandry.

RevDate: 2025-01-09
CmpDate: 2025-01-09

Barman I, Seo H, Kim S, et al (2025)

Isolation of New Strains of Lactic Acid Bacteria from the Vaginal Microbiome of Postmenopausal Women and their Probiotic Characteristics.

Current microbiology, 82(2):76.

Lactic acid bacteria (LAB), traditionally consumed as fermented foods, are now being applied to the medical field beyond health-functional food as probiotics. Therefore, it is necessary to continuously discover and evaluate new strains with suitable probiotic characteristics, mainly focusing on safety. In this study, we isolated eight new strains from postmenopausal vaginal fluid using culturomics approaches, an emerging area of interest. Data showed that most strains possessed significant cell surface hydrophobicity (≥ 76%), auto-aggregation capacity (17 to 61%), strong adhesion activity (8 to 34%), and excellent resistance to gastric acid, bile salt, and digestive enzyme, enhancing their survival in the gastrointestinal tract. Moreover, the strains exhibited functional characteristics, including substantial antibacterial activity with a minimal inhibitory concentration (MIC) ranging from 12.5 to 50%. They also harbored bacteriocins genes, produced short-chain fatty acids (acetate and propionate), exhibited significant phagocytic activity, possessed high antioxidative properties, rapidly depleted sodium nitrite, and exhibited proteolysis and β-glucosidase activity. In addition, heat-killed LAB strains significantly reduced the gene expressions of proinflammatory cytokines such as IL-β, IL-6, and iNOS in macrophages. Safety assessment revealed no cytotoxicity in macrophage cell lines. All strains tested negative for biogenic amine or H2O2 production, displayed no gelatinase or hemolytic activity, lacked virulence genes or detrimental enzymes, and displayed antibiotic susceptibility. In summary, these newly isolated strains demonstrate excellent probiotic functionality with a strong focus on safety, making them promising candidates for future drug development in the relevant fields.

RevDate: 2025-01-09

Xu B, Luo Z, Niu X, et al (2025)

Fungi, immunosenescence and cancer.

Seminars in cancer biology pii:S1044-579X(25)00002-1 [Epub ahead of print].

Fungal microbes are a small but immunoreactive component of the human microbiome, which may influence cancer development, progression and therapeutic response. Immunosenescence is a process of immune dysfunction that occurs with aging, including lymphoid organ remodeling, contributing to alterations in the immune system in the elderly, which plays a critical role in many aspects of cancer. There is evidence for the interactions between fungi and immunosenescence in potentially regulating cancer progression and remodeling the tumor microenvironment (TME). In this review, we summarize potential roles of commensal and pathogenic fungi in modulating cancer-associated processes and provide more-detailed discussions on the mechanisms of which fungi affect tumor biology, including local and distant regulation of the TME, modulating antitumor immune responses and interactions with neighboring bacterial commensals. We also delineate the features of immunosenescence and its influence on cancer development and treatment, and highlight the interactions between fungi and immunosenescence in cancer. We discuss the prospects and challenges for harnessing fungi and immunosenescence in cancer diagnosis and/or treatment. Considering the limited understanding and techniques in conducting such research, we also provide our view on how to overcome challenges faced by the exploration of fungi, immunosenescence and their interactions on tumor biology.

RevDate: 2025-01-09

Theodosiou AA, Fady PE, Bennett N, et al (2025)

Microbiotoxicity: a call to arms for cross-sector protection of the human microbiome.

RevDate: 2025-01-08

Xu Y, Wang Z, Li C, et al (2025)

Droplet microfluidics: unveiling the hidden complexity of the human microbiome.

Lab on a chip [Epub ahead of print].

The human body harbors diverse microbial communities essential for maintaining health and influencing disease processes. Droplet microfluidics, a precise and high-throughput platform for manipulating microscale droplets, has become vital in advancing microbiome research. This review introduces the foundational principles of droplet microfluidics, its operational capabilities, and wide-ranging applications. We emphasize its role in enhancing single-cell sequencing technologies, particularly genome and RNA sequencing, transforming our understanding of microbial diversity, gene expression, and community dynamics. We explore its critical function in isolating and cultivating traditionally unculturable microbes and investigating microbial activity and interactions, facilitating deeper insight into community behavior and metabolic functions. Lastly, we highlight its broader applications in microbial analysis and its potential to revolutionize human health research by driving innovations in diagnostics, therapeutic development, and personalized medicine. This review provides a comprehensive overview of droplet microfluidics' impact on microbiome research, underscoring its potential to transform our understanding of microbial dynamics and their relevance to health and disease.

RevDate: 2025-01-08

Enderlin D, Bieri U, Gadient J, et al (2024)

Towards Reliable Methodology: Microbiome Analysis of Fresh Frozen vs. Formalin-Fixed Paraffin-Embedded Bladder Tissue Samples: A Feasibility Study.

Microorganisms, 12(12): pii:microorganisms12122594.

Studies have shown that the human microbiome influences the response to systemic immunotherapy. However, only scarce data exist on the impact of the urinary microbiome on the response rates of bladder cancer (BC) to local Bacillus Calmette-Guérin instillation therapy. We launched the prospective SILENT-EMPIRE study in 2022 to address this question. We report the results of the pilot study of SILENT-EMPIRE, which aimed to compare the microbiome between fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) samples in the cancerous tissue and adjacent healthy tissue of BC patients. Our results show that alpha diversity is increased in FF samples compared to FFPE (coverage index p = 0.041, core abundance index p = 0.008). No significant differences concerning alpha diversity could be detected between cancerous and non-cancerous tissue in the same BC patients. This study demonstrates that microbiome analysis from both FF and FFPE samples is feasible. Implementing this finding could aid in the translation of research findings into clinical practice.

RevDate: 2025-01-08

Ricchezze G, Buratti E, De Micco F, et al (2024)

Medico-Legal Applications of the Human Microbiome and Critical Issues Due to Environmental Transfer: A Review.

Microorganisms, 12(12): pii:microorganisms12122424.

Microbiome has recently seen an increase in its forensic applications. It could be employed to identify a suspect when DNA is not available; it can be used to establish postmortem interval (PMI). Furthermore, it could prove to be fundamental in cases of sexual assault. One of the most interesting aspects to study is how microbiomes are transferred. The aim of this review is to analyze the existing literature focusing on the potential transfer of microbiome from humans to environment. Searches on PubMed, Scopus, and Web of Science identified a total of 348 articles. Furthermore, from the bibliographies of the included articles, an additional publication was selected, in accordance with the established inclusion and exclusion criteria. This study has shown the potential of utilizing microbiomes as trace evidence, particularly in connecting individuals to specific environments or objects. However, the variability and dynamics of microbial transfer and persistence need to be carefully addressed.

RevDate: 2025-01-07

Glowacki RWP, Engelhart MJ, Till JM, et al (2024)

Identification of strain-specific cues that regulate biofilm formation in Bacteroides thetaiotaomicron.

bioRxiv : the preprint server for biology pii:2024.12.20.629428.

UNLABELLED: Members of the gut microbiome encounter a barrage of host- and microbe-derived microbiocidal factors that must be overcome to maintain fitness in the intestine. The long-term stability of many gut microbiome strains within the microbiome suggests the existence of strain-specific strategies that have evolved to foster resilience to such insults. Despite this, little is known about the mechanisms that mediate this resistance. Biofilm formation represents one commonly employed defense strategy against stressors like those found in the intestine. Here, we demonstrate strain-level variation in the capacity of the gut symbiont Bacteroides thetaiotaomicron to form biofilms. Despite the potent induction of biofilm formation by purified bile in most strains, we show that the specific bile acid species driving biofilm formation differ among strains, and uncover that a secondary bile-acid, lithocholic acid, and its conjugated forms, potently induce biofilm formation in a strain-specific manner. Additionally, we found that the short-chain fatty acid, acetic acid, could suppress biofilm formation. Thus, our data defines the molecular components of bile that promote biofilm formation in B. thetaiotaomicron and reveals that distinct molecular cues trigger the induction or inhibition of this process. Moreover, we uncover strain-level variation in these responses, thus identifying that both shared and strain-specific determinants govern biofilm formation in this species.

IMPORTANCE: In order to thrive within the intestine, it is imperative that gut microbes resist the multitude of insults derived from the host immune system and other microbiome members. As such, they have evolved strategies that ensure their survival within the intestine. We investigated one such strategy, biofilm formation, in Bacteroides thetaiotaomicron , a common member of the human microbiome. We uncovered significant variation in natural biofilm formation in the absence of an overt stimulus among different Bacteroides thetaiotaomicron strains, and revealed that different strains adopted a biofilm lifestyle in response to distinct molecular stimuli. Thus our studies provide novel insights into factors mediating gut symbiont resiliency, revealing strain-specific and shared strategies in these responses. Collectively, our findings underscore the prevalence of strain-level differences that should be factored into our understanding of gut microbiome functions.

RevDate: 2025-01-05

Cruz-LebrĂ³n A, Faiez TS, Hess MM, et al (2025)

Diet and the microbiome as mediators of prostate cancer risk, progression, and therapy response.

Urologic oncology pii:S1078-1439(24)00781-6 [Epub ahead of print].

Complex relationships between the human microbiome and cancer are increasingly recognized for cancer sites that harbor commensal microbial communities such as the gut, genitourinary tract, and skin. For organ sites that likely do not contain commensal microbiota, there is still a substantial capacity for the human-associated microbiota to influence disease etiology across the cancer spectrum. We propose such a relationship for prostate cancer, the most commonly diagnosed cancer in males in the United States. This review explores the current evidence for a role for the urinary and gut microbiota in prostate cancer risk, via both direct interactions (prostate infections) and long-distance interactions such as via the metabolism of procarcinogenic or anticarcinogenic dietary metabolites. We further explore a newly recognized role of the gut microbiota in mediating cancer treatment response or resistance either via production of androgens and/or procarcinogenic metabolites or via direct metabolism of anticancer drugs that are used to treat advanced disease. Overall, we present the current state of knowledge relating to how the human microbiome mediates prostate cancer risk, progression, and therapy response, as well as suggest future research directions for the field.

RevDate: 2025-01-04

Peng S, Wu M, Yan Q, et al (2025)

Disrupting EDEM3-induced M2-like macrophage trafficking by glucose restriction overcomes resistance to PD-1/PD-L1 blockade.

Clinical and translational medicine, 15(1):e70161.

BACKGROUND: Immunotherapy is beneficial for some colorectal cancer (CRC) patients, but immunosuppressive networks limit its effectiveness. Cancer-associatedfibroblasts (CAFs) are significant in immune escape and resistance toimmunotherapy, emphasizing the urgent need for new treatment strategies.

METHODS: Flow cytometric, Western blotting, proteomics analysis, analysis of public database data, genetically modified cell line models, T cell coculture, crystal violetstaining, ELISA, metabonomic and clinical tumour samples were conducted to assess the role of EDEM3 in immune escape and itsmolecular mechanisms. We evaluated theeffects of FMD plus 2-DG on antitumour immunity using multipleximmunofluorescence, flow cytometry, cytokine profiling, TUNEL assays, xenografttumours, and in vivo studies.

RESULTS: We show thatCAFs upregulate PD-L1 glycosylation and contribute to immune evasion byglycosyltransferase EDEM3. Additionally, EDEM3 plays a role in tumour immunityduring tumour progression. However, the EDEM3-mediated upregulation of PD-L1 expression underpins PD-1/PD-L1 blockade resistance in vivo. This finding contradictsthe previous trend that positive PD-L1 expression indicates a strong responseto PD-1/PD-L1 blockade. Mechanistically, high-EDEM3 expression facilitates M2-like This finding contradictsthe previous trend that positive PD-L1 expression indicates a strong responseto PD-1/PD-L1 blockade.Mechanistically, polarizationand chemotactic migration of macrophages, which are enriched in theperipheral region of tumours compared to thecore region, precluding access of CD8+ T cells to tumourfoci. Furthermore, we EDEM3 predominantly activates the recruited M2-like macrophagesvia a glucose metabolism-dependent mechanism. Manipulationof glucose utilization by a fasting-mimicking diet(FMD) plus 2-DG treatmentsynergistically with PD-1 antibody elicits potent antitumour activity byeffectively decreasing tumour glycosylated PD-L1 expression, augmenting the CD8+effector T cell infiltration and activation while concurrently reducing the infiltration.TheCAFs-EDEM3-M2-like macrophage axis plays a critical role in promotingimmunotherapy resistance. infiltration.TheCAFs-EDEM3-M2-like macrophage axis plays a critical role in promotingimmunotherapy resistance.

CONCLUSIONS: Our study suggests that blocking EDEM3-induced M2-like macro phage trafficking by FMD plus 2-DG is a promising and effective strategy to overcomeresistance to checkpoint blockade therapy offeringhope for improved treatment outcomes.

KEY POINTS: Cancer-associated fibroblasts (CAFs) can enhance PD-L1 glycosylation through the glycosyltransferase EDEM3, contributing to immune evasion during tumour progression. EDEM3 predominantly activates the recruit M2-like macrophages via a glucose metabolism-dependent mechanism. Blocking glucose utilization antagonizes recruiting and polarizing M2-like macrophages synergistically with PD-1 antibody to improve anticancer immunity.

RevDate: 2025-01-03
CmpDate: 2025-01-03

Wu W, Zhao Y, Cheng X, et al (2025)

Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer's disease.

Nature communications, 16(1):63.

Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer's disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy.

RevDate: 2025-01-03

Hsu TY, Nzabarushimana E, Wong D, et al (2025)

Profiling lateral gene transfer events in the human microbiome using WAAFLE.

Nature microbiology [Epub ahead of print].

Lateral gene transfer (LGT), also known as horizontal gene transfer, facilitates genomic diversification in microbial populations. While previous work has surveyed LGT in human-associated microbial isolate genomes, the landscape of LGT arising in personal microbiomes is not well understood, as there are no widely adopted methods to characterize LGT from complex communities. Here we developed, benchmarked and validated a computational algorithm (WAAFLE or Workflow to Annotate Assemblies and Find LGT Events) to profile LGT from assembled metagenomes. WAAFLE prioritizes specificity while maintaining high sensitivity for intergenus LGT. Applying WAAFLE to >2,000 human metagenomes from diverse body sites, we identified >100,000 high-confidence previously uncharacterized LGT (~2 per microbial genome-equivalent). These were enriched for mobile elements, as well as restriction-modification functions associated with the destruction of foreign DNA. LGT frequency was influenced by biogeography, phylogenetic similarity of involved pairs (for example, Fusobacterium periodonticum and F. nucleatum) and donor abundance. These forces manifest as networks in which hub taxa donate unequally with phylogenetic neighbours. Our findings suggest that human microbiome LGT may be more ubiquitous than previously described.

RevDate: 2025-01-03

Olm MR, Spencer SP, Takeuchi T, et al (2025)

Metagenomic immunoglobulin sequencing reveals IgA coating of microbial strains in the healthy human gut.

Nature microbiology [Epub ahead of print].

IgA, the primary human antibody secreted from the gut mucosa, shapes the intestinal microbiota. Methodological limitations have hindered defining which microbial strains are targeted by IgA and the implications of binding. Here we develop a technique, metagenomic immunoglobulin sequencing (MIg-seq), that provides strain-level resolution of microbes coated by IgA and use it to determine IgA coating levels for 3,520 gut microbiome strains in healthy human faeces. We find that both health and disease-associated bacteria are targeted by IgA. Microbial genes are highly predictive of IgA binding levels; in particular, mucus degradation genes are correlated with high binding, and replication rates are significantly reduced for microbes bound by IgA. We demonstrate that IgA binding is more correlated with host immune status than traditional relative abundance measures of microbial community composition. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host-microbe interactions.

RevDate: 2025-01-02

Goldhawk DE, Al KF, Donnelly SC, et al (2025)

Assessing microbiota in vivo: debugging with medical imaging.

Trends in microbiology pii:S0966-842X(24)00317-2 [Epub ahead of print].

The microbiota is integral to human health and has been mostly characterized through various ex vivo 'omic'-based approaches. To better understand the real-time function and impact of the microbiota, in vivo molecular imaging is required. With technologies such as positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), insight into microbiological processes may be coupled to in vivo information. Noninvasive imaging enables longitudinal tracking of microbes and their components in real time; mapping of microbiota biodistribution, persistence and migration; and simultaneous monitoring of host physiological responses. The development of molecular imaging for clinical translation is an interdisciplinary science, with broad implications for deeper understanding of host-microbe interactions and the role(s) of the microbiome in health and disease.

RevDate: 2024-12-31
CmpDate: 2024-12-31

Palkovsky M, Modrackova N, Neuzil-Bunesova V, et al (2025)

The Bidirectional Impact of Cancer Radiotherapy and Human Microbiome: Microbiome as Potential Anti-tumor Treatment Efficacy and Toxicity Modulator.

In vivo (Athens, Greece), 39(1):37-54.

Microbiome and radiotherapy represent bidirectionally interacting entities. The human microbiome has emerged as a pivotal modulator of the efficacy and toxicity of radiotherapy; however, a reciprocal effect of radiotherapy on microbiome composition alterations has also been observed. This review explores the relationship between the microbiome and extracranial solid tumors, particularly focusing on the bidirectional impact of radiotherapy on organ-specific microbiome. This article aims to provide a systematic review on the radiotherapy-induced microbial alteration in-field as well as in distant microbiomes. In this review, particular focus is directed to the oral and gut microbiome, its role in the development and progression of cancer, and how it is altered throughout radiotherapy. This review concludes with recommendations for future research, such as exploring microbiome modification to optimize radiotherapy-induced toxicities or enhance its anti-cancer effects.

RevDate: 2024-12-31
CmpDate: 2024-12-31

Ecklu-Mensah G, Miller R, Maseng MG, et al (2024)

Modulating the human gut microbiome and health markers through kombucha consumption: a controlled clinical study.

Scientific reports, 14(1):31647.

Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. We did not observe significant changes in either biochemical parameters or levels of circulating markers of inflammation across the entire cohort. However, paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance of Weizmannia, a kombucha-enriched probiotic and several SCFA producing taxa to be overrepresented in consumers at the end of the intervention. Collectively, in our healthy cohort consuming a Western diet, a short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters, which may be attributed to relatively small number of participants and the extensive inter-participant variability.

RevDate: 2024-12-31

Fagnano A, Capocasa G, Frateloreto F, et al (2024)

Deciphering the Role of Crown-ether Receptor Orientation in C-H Oxidation Catalyzed by Supramolecular Nonheme FeIV(O) Complexes.

Chemistry (Weinheim an der Bergstrasse, Germany) [Epub ahead of print].

The outstanding efficiency and selectivity of enzymatic reactions, such as C-H oxidation by nonheme iron oxygenases, stems from a precise control of substrate positioning inside the active site. The resulting proximity between a specific moiety (a certain C-H bond) to the reactant (a FeIV(O) active species) translates into higher rates and selectivity, that can be in part replicated also with artificial supramolecular catalysts. However, structural modification of the position and orientation of the binding site both in enzymes and in artificial catalysts often leads to significant variations in reactivity that can be difficult to rationalize due to the system's complexity. Herein, we quantitatively analyzed the impact of such a structural modification (namely receptor orientation) on the C-H oxidation reactivity (kinetics, Effective Molarity) and selectivity by comparing simple supramolecular FeIV(O) models. Overall, we did not observe significant differences in reaction rates, but we noticed slight changes in the selectivity profile. These results indicate that, when a crown-ether is employed as a recognition site, the key ingredient for enhanced reactivity is the presence of the supramolecular receptor itself rather than its exact orientation, providing a guide for the rational design of supramolecular catalysts.

RevDate: 2024-12-30

Monshizadeh M, Hong Y, Y Ye (2025)

Multitask knowledge-primed neural network for predicting missing metadata and host phenotype based on human microbiome.

Bioinformatics advances, 5(1):vbae203.

MOTIVATION: Microbial signatures in the human microbiome are closely associated with various human diseases, driving the development of machine learning models for microbiome-based disease prediction. Despite progress, challenges remain in enhancing prediction accuracy, generalizability, and interpretability. Confounding factors, such as host's gender, age, and body mass index, significantly influence the human microbiome, complicating microbiome-based predictions.

RESULTS: To address these challenges, we developed MicroKPNN-MT, a unified model for predicting human phenotype based on microbiome data, as well as additional metadata like age and gender. This model builds on our earlier MicroKPNN framework, which incorporates prior knowledge of microbial species into neural networks to enhance prediction accuracy and interpretability. In MicroKPNN-MT, metadata, when available, serves as additional input features for prediction. Otherwise, the model predicts metadata from microbiome data using additional decoders. We applied MicroKPNN-MT to microbiome data collected in mBodyMap, covering healthy individuals and 25 different diseases, and demonstrated its potential as a predictive tool for multiple diseases, which at the same time provided predictions for the missing metadata. Our results showed that incorporating real or predicted metadata helped improve the accuracy of disease predictions, and more importantly, helped improve the generalizability of the predictive models.

https://github.com/mgtools/MicroKPNN-MT.

RevDate: 2024-12-28

Tegegne HA, TC Savidge (2024)

Leveraging human microbiomes for disease prediction and treatment.

Trends in pharmacological sciences pii:S0165-6147(24)00248-7 [Epub ahead of print].

The human microbiome consists of diverse microorganisms that inhabit various body sites. As these microbes are increasingly recognized as key determinants of health, there is significant interest in leveraging individual microbiome profiles for early disease detection, prevention, and drug efficacy prediction. However, the complexity of microbiome data, coupled with conflicting study outcomes, has hindered its integration into clinical practice. This challenge is partially due to demographic and technological biases that impede the development of reliable disease classifiers. Here, we examine recent advances in 16S rRNA and shotgun-metagenomics sequencing, along with bioinformatics tools designed to enhance microbiome data integration for precision diagnostics and personalized treatments. We also highlight progress in microbiome-based therapies and address the challenges of establishing causality to ensure robust diagnostics and effective treatments for complex diseases.

RevDate: 2024-12-28
CmpDate: 2024-12-28

Virtanen S, Saqib S, Kanerva T, et al (2024)

Metagenome-validated combined amplicon sequencing and text mining-based annotations for simultaneous profiling of bacteria and fungi: vaginal microbiota and mycobiota in healthy women.

Microbiome, 12(1):273.

BACKGROUND: Amplicon sequencing of kingdom-specific tags such as 16S rRNA gene for bacteria and internal transcribed spacer (ITS) region for fungi are widely used for investigating microbial communities. So far most human studies have focused on bacteria while studies on host-associated fungi in health and disease have only recently started to accumulate. To enable cost-effective parallel analysis of bacterial and fungal communities in human and environmental samples, we developed a method where 16S rRNA gene and ITS1 amplicons were pooled together for a single Illumina MiSeq or HiSeq run and analysed after primer-based segregation. Taxonomic assignments were performed with Blast in combination with an iterative text-extraction-based filtration approach, which uses extensive literature records from public databases to select the most probable hits that were further validated by shotgun metagenomic sequencing.

RESULTS: Using 50 vaginal samples, we show that the combined run provides comparable results on bacterial composition and diversity to conventional 16S rRNA gene amplicon sequencing. The text-extraction-based taxonomic assignment-guided tool provided ecosystem-specific bacterial annotations that were confirmed by shotgun metagenomic sequencing (VIRGO, MetaPhlAn, Kraken2). Fungi were identified in 39/50 samples with ITS sequencing while in the metagenome data fungi largely remained undetected due to their low abundance and database issues. Co-abundance analysis of bacteria and fungi did not show strong between-kingdom correlations within the vaginal ecosystem of healthy women.

CONCLUSION: Combined amplicon sequencing for bacteria and fungi provides a simple and cost-effective method for simultaneous analysis of microbiota and mycobiota within the same samples. Conventional metagenomic sequencing does not provide sufficient fungal genome coverage for their reliable detection in vaginal samples. Text extraction-based annotation tool facilitates ecosystem-specific characterization and interpretation of microbial communities by coupling sequence homology to microbe metadata readily available through public databases. Video Abstract.

RevDate: 2024-12-26

Ma X, Zhang J, Jiang Q, et al (2024)

Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicry.

EBioMedicine, 111:105516 pii:S2352-3964(24)00552-8 [Epub ahead of print].

BACKGROUND: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction.

METHODS: We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens. Subsequently, we conducted a range of in vitro and in vivo assays to assess the encephalitogenic potential of these microbial-derived peptides.

FINDINGS: We analyzed 304,246 human microbiome genomes and 103 metagenomes collected from the MS cohort and identified 731 nonredundant analogs of myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Of note, half of these analogs could bind to MHC II and interact with TCR through structural modeling of the interaction using fine-tuned AlphaFold. Among the 8 selected peptides, the peptide (P3) shows the ability to activate MOG35-55-specific CD4[+] T cells in vitro. Furthermore, P3 shows encephalitogenic capacity and has the potential to induce EAE in some animals. Notably, mice immunized with a combination of P3 and MOG35-55 develop severe EAE. Additionally, dendritic cells could process and present P3 to MOG35-55-specific CD4[+] T cells and activate these cells.

INTERPRETATION: Our data suggests the potential involvement of a MOG35-55-mimic peptide derived from the gut microbiota as a molecular trigger of EAE pathogenesis. Our findings offer direct evidence of how microbes can initiate the development of EAE, suggesting a potential explanation for the correlation between certain gut microorganisms and MS prevalence.

FUNDING: National Natural Science Foundation of China (82371350 to GY).

RevDate: 2024-12-26

Ma J, Palmer DJ, Geddes D, et al (2024)

Maternal Allergic Disease Phenotype and Infant Birth Season Influence the Human Milk Microbiome.

Allergy [Epub ahead of print].

Early infancy is a critical period for immune development. In addition to being the primary food source during early infancy, human milk also provides multiple bioactive components that shape the infant gut microbiome and immune system and provides a constant source of exposure to maternal microbiota. Given the potential interplay between allergic diseases and the human microbiome, this study aimed to characterise the milk microbiome of allergic mothers. Full-length 16S rRNA gene sequencing was performed on milk samples collected at 3 and 6 months postpartum from 196 women with allergic disease. Multivariate linear mixed models were constructed to identify the maternal, infant, and environmental determinants of the milk microbiome. Human milk microbiome composition and beta diversity varied over time (PERMANOVA R[2] = 0.011, p = 0.011). The season of infant birth emerged as the strongest determinant of the microbiome community structure (PERMANOVA R[2] = 0.014, p = 0.011) with impacts on five of the most abundant taxa. The milk microbiome also varied according to the type of maternal allergic disease (allergic rhinitis, asthma, atopic dermatitis, and food allergy). Additionally, infant formula exposure reduced the relative abundance of several typical oral taxa in milk. In conclusion, the milk microbiome of allergic mothers was strongly shaped by the season of infant birth, maternal allergic disease phenotype, and infant feeding mode. Maternal allergic disease history and infant season of birth should therefore be considered in future studies of infant and maternal microbiota. Trial Registration: ClinicalTrials.gov identifier: ACTRN12606000281594.

RevDate: 2024-12-25
CmpDate: 2024-12-25

Guha SK, S Niyogi (2024)

Microbial Dynamics in COVID-19: Unraveling the Impact of Human Microbiome on Disease Susceptibility and Therapeutic Strategies.

Current microbiology, 82(1):59.

This review explores the bidirectional relationship between the human microbiome and SARS-CoV-2 infection, elucidating its implications for COVID-19 susceptibility, severity, and therapeutic strategies. Metagenomic analyses reveal notable alterations in microbiome composition associated with SARS-CoV-2 infection, impacting disease severity and clinical outcomes. Dysbiosis within the respiratory, gastrointestinal, oral, and skin microbiomes exacerbates COVID-19 pathology through immune dysregulation and inflammatory pathways. Understanding these microbial shifts is pivotal for devising targeted therapeutic interventions. Notably, co-infection of oral pathogens with SARS-CoV-2 worsens lung pathology, while gut microbiome dysbiosis influences viral susceptibility and severity. Potential therapeutic approaches targeting the microbiome include probiotics, antimicrobial agents, and immunomodulatory strategies. This review underscores the importance of elucidating host-microbiota interactions to advance precision medicine and public health initiatives in combating COVID-19 and other infectious diseases.

RevDate: 2024-12-24

Zhou Y, Jiang M, Li X, et al (2024)

Bibliometric and visual analysis of human microbiome-breast cancer interactions: current insights and future directions.

Frontiers in microbiology, 15:1490007.

The composition of the gut microbiome differs from that of healthy individuals and is closely linked to the progression and development of breast cancer. Recent studies have increasingly examined the relationship between microbial communities and breast cancer. This study analyzed the research landscape of microbiome and breast cancer, focusing on 736 qualified publications from the Web of Science Core Collection (WoSCC). Publications in this field are on the rise, with the United States leading in contributions, followed by China and Italy. Despite this strong output, the centrality value of China in this field is comparatively low at ninth, highlighting a gap between the quantity of research and its global impact. This pattern is repetitively observed in institutional contributions, with a predominance of Western institutes among the top contributors, underscoring a potential research quality gap in China. Keyword analysis reveals that research hotspots are focused on the effect of microbiome on breast cancer pathogenesis and tumor metabolism, with risk factors and metabolic pathways being the most interesting areas. Publications point to a shift toward anti-tumor therapies and personalized medicine, with clusters such as "anti-tumor" and "potential regulatory agent" gaining prominence. Additionally, intratumor bacteria studies have emerged as a new area of significant interest, reflecting a new direction in research. The University of Helsinki and Adlercreutz H are influential institutions and researchers in this field. Current trends in microbiome and breast cancer research indicate a significant shift toward therapeutic applications and personalized medicine. Strengthening international collaborations and focusing on research quality is crucial for advancing microbiome and breast cancer research.

RevDate: 2024-12-24

Fallah A, Sedighian H, Kachuei R, et al (2025)

Human microbiome in post-acute COVID-19 syndrome (PACS).

Current research in microbial sciences, 8:100324.

The global COVID-19 pandemic, which began in 2019, is still ongoing. SARS-CoV-2, also known as the severe acute respiratory syndrome coronavirus 2, is the causative agent. Diarrhea, nausea, and vomiting are common GI symptoms observed in a significant number of COVID-19 patients. Additionally, the respiratory and GI tracts express high level of transmembrane protease serine 2 (TMPRSS2) and angiotensin-converting enzyme-2 (ACE2), making them primary sites for human microbiota and targets for SARS-CoV-2 infection. A growing body of research indicates that individuals with COVID-19 and post-acute COVID-19 syndrome (PACS) exhibit considerable alterations in their microbiome. In various human disorders, including diabetes, obesity, cancer, ulcerative colitis, Crohn's disease, and several viral infections, the microbiota play a significant immunomodulatory role. In this review, we investigate the potential therapeutic implications of the interactions between host microbiota and COVID-19. Microbiota-derived metabolites and components serve as primary mediators of microbiota-host interactions, influencing host immunity. We discuss the various mechanisms through which these metabolites or components produced by the microbiota impact the host's immune response to SARS-CoV-2 infection. Additionally, we address confounding factors in microbiome studies. Finally, we examine and discuss about a range of potential microbiota-based prophylactic measures and treatments for COVID-19 and PACS, as well as their effects on clinical outcomes and disease severity.

RevDate: 2024-12-23

Neumann CJ, Mohammadzadeh R, Woh PY, et al (2024)

First-year dynamics of the anaerobic microbiome and archaeome in infants' oral and gastrointestinal systems.

mSystems [Epub ahead of print].

UNLABELLED: Recent research provides new insights into the early establishment of the infant gut microbiome, emphasizing the influence of breastfeeding on the development of gastrointestinal microbiomes. In our study, we longitudinally examined the taxonomic and functional dynamics of the oral and gastrointestinal tract (GIT) microbiomes of healthy infants (n = 30) in their first year, focusing on the often-over-looked aspects, the development of archaeal and anaerobic microbiomes. Breastfed (BF) infants exhibit a more defined transitional phase in their oral microbiome compared to non-breastfed (NBF) infants, marked by a decrease in Streptococcus and the emergence of anaerobic genera such as Granulicatella. This phase, characterized by increased alpha-diversity and significant changes in beta-diversity, occurs earlier in NBF infants (months 1-3) than in BF infants (months 4-6), suggesting that breastfeeding supports later, more defined microbiome maturation. We demonstrated the presence of archaea in the infant oral cavity and GIT microbiome from early infancy, with Methanobrevibacter being the predominant genus. Still, transient patterns show that no stable archaeome is formed. The GIT microbiome exhibited gradual development, with BF infants showing increased diversity and complexity between the third and eighth months, marked by anaerobic microbial networks. NBF infants showed complex microbial co-occurrence patterns from the start. These strong differences between BF and NBF infants' GIT microbiomes are less pronounced on functional levels than on taxonomic levels. Overall, the infant microbiome differentiates and stabilizes over the first year, with breastfeeding playing a crucial role in shaping anaerobic microbial networks and overall microbiome maturation.

IMPORTANCE: The first year of life is a crucial period for establishing a healthy human microbiome. Our study analyses the role of archaea and obligate anaerobes in the development of the human oral and gut microbiome, with a specific focus on the impact of breastfeeding in this process. Our findings demonstrated that the oral and gut microbiomes of breastfed infants undergo distinct phases of increased dynamics within the first year of life. In contrast, the microbiomes of non-breastfed infants are more mature from the first month, leading to a steadier development without distinct transitional phases in the first year. Additionally, we found that archaeal signatures are present in infants under 1 year of age, but they do not form a stable archaeome. In contrast to this, we could track specific bacterial strains transitioning from oral to gut or persisting in the gut over time.

RevDate: 2024-12-20

Kaur S, Patel BCK, Collen A, et al (2024)

The microbiome and the eye: a new era in ophthalmology.

Eye (London, England) [Epub ahead of print].

The human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.

RevDate: 2024-12-19

Evans SE, Valentine ME, Gallimore F, et al (2024)

Perturbations in the Gut Microbiome of C57BL/6J Mice by the Sobriety Aid Antabuse® (Disulfiram).

Journal of applied microbiology pii:7929021 [Epub ahead of print].

AIMS: Disulfiram (Antabuse®) is an oral alcohol sobriety medication that exhibits antimicrobial activity against Gram-positive facultative anaerobes. The aims of this study were to measure the antimicrobial activity against anaerobic bacteria of the gut human microbiome and establish the extent that disulfiram alters the microbial composition of the ileum, cecum, and feces using C57BL/6 mice.

METHODS AND RESULTS: Antimicrobial susceptibility testing by the microdilution method revealed that disulfiram inhibits the in vitro growth of gut anaerobic species of Bacteroides, Clostridium, Peptostreptococcus, and Porphyromonas. Differential sequencing of 16S rRNA isolated from the ileum, cecum, and feces contents of treated vs. untreated mice showed disulfiram enriches the Gram-negative enteric population. In female mice, the enrichment was greatest in the ileum whereas the feces composition in male mice was the most heavily altered.

CONCLUSIONS: Daily administration of oral disulfiram depletes the enteric Gram-positive anaerobe population as predicted by the MIC data for isolates from the human gut microbiota.

RevDate: 2024-12-19

Lei Y, Li M, Zhang H, et al (2024)

Comparative analysis of the human microbiome from four different regions of China and machine learning-based geographical inference.

mSphere [Epub ahead of print].

The human microbiome, the community of microorganisms that reside on and inside the human body, is critically important for health and disease. However, it is influenced by various factors and may vary among individuals residing in distinct geographic regions. In this study, 220 samples, consisting of sterile swabs from palmar skin and oral and nasal cavities were collected from Chinese Han individuals living in Shanghai, Chifeng, Kunming, and Urumqi, representing the geographic regions of east, northeast, southwest, and northwest China. The full-length 16S rRNA gene of the microbiota in each sample was sequenced using the PacBio single-molecule real-time sequencing platform, followed by clustering the sequences into operational taxonomic units (OTUs). The analysis revealed significant differences in microbial communities among the four regions. Cutibacterium was the most abundant bacterium in palmar samples from Shanghai and Kunming, Psychrobacter in Chifeng samples, and Psychrobacillus in Urumqi samples. Additionally, Streptococcus and Staphylococcus were the dominant bacteria in the oral and nasal cavities. Individuals from the four regions could be distinguished and predicted based on a model constructed using the random forest algorithm, with the predictive effect of palmar microbiota being better than that of oral and nasal cavities. The prediction accuracy using hypervariable regions (V3-V4 and V4-V5) was comparable with that of using the entire 16S rRNA. Overall, our study highlights the distinctiveness of the human microbiome in individuals living in these four regions. Furthermore, the microbiome can serve as a biomarker for geographic origin inference, which has immense application value in forensic science.IMPORTANCEMicrobial communities in human hosts play a significant role in health and disease, varying in species, quantity, and composition due to factors such as gender, ethnicity, health status, lifestyle, and living environment. The characteristics of microbial composition at various body sites of individuals from different regions remain largely unexplored. This study utilized single-molecule real-time sequencing technology to detect the entire 16S rRNA gene of bacteria residing in the palmar skin, oral, and nasal cavities of Han individuals from four regions in China. The composition and structure of the bacteria at these three body sites were well characterized and found to differ regionally. The results elucidate the differences in bacterial communities colonizing these body sites across different regions and reveal the influence of geographical factors on human bacteria. These findings not only contribute to a deeper understanding of the diversity and geographical distribution of human bacteria but also enrich the microbiome data of the Asian population for further studies.

RevDate: 2024-12-19

Aluthge N, Adams S, Davila CA, et al (2024)

Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico.

Frontiers in microbiology, 15:1470037.

INTRODUCTION: The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use.

METHODS: Using amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use.

RESULTS AND DISCUSSION: Our findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.

RevDate: 2024-12-19
CmpDate: 2024-12-19

Rodriguez J, Cordaillat-Simmons M, Badalato N, et al (2024)

Microbiome testing in Europe: navigating analytical, ethical and regulatory challenges.

Microbiome, 12(1):258.

BACKGROUND: In recent years, human microbiome research has flourished and has drawn attention from both healthcare professionals and general consumers as the human microbiome is now recognized as having a significant influence on human health. This has led to the emergence of companies offering microbiome testing services. Some of these services are sold directly to the consumer via companies' websites or via medical laboratory websites.

METHODOLOGY: In order to provide an overview of the consumer experience proposed by these microbiome testing services, one single faecal sample was sent to six different companies (five based in Europe and one based in the USA). Two out of the six testing kits were commercialized by medical laboratories, but without any requirement for a medical prescription. The analyses and reports received were discussed with a panel of experts (21 experts from 8 countries) during an online workshop.

RESULTS: This workshop led to the identification of several limitations and challenges related to these kits, including over-promising messages from the companies, a lack of transparency in the methodology used for the analysis and a lack of reliability of the results. The experts considered the interpretations and recommendations provided in the different reports to be premature due to the lack of robust scientific evidence and the analyses associated with the reports to be of limited clinical utility. The experts also discussed the grey areas surrounding the regulatory status of these test kits, including their positioning in the European market. The experts recommended a distinction between regulatory requirements based on the intended use or purpose of the kit: on the one hand, test kits developed to satisfy consumer curiosity, with a clear mention of this objective, and no mention of any disease or risk of disease, and on the other hand, in vitro diagnostic (IVD) CE-marked test kits, which could go deeper into the analysis and interpretation of samples, as such a report would be intended for trained healthcare professionals.

CONCLUSIONS: Recommendations or actions, specific to the context of use of microbiome testing kits, are listed to improve the quality and the robustness of these test kits to meet expectations of end users (consumers, patients and healthcare professionals). The need for standardization, robust scientific evidence, qualification of microbiome-based biomarkers and a clear regulatory status in Europe are the main issues that will require attention in the near future to align laboratory development with societal needs and thus foster translation into daily health practice.

RevDate: 2024-12-18
CmpDate: 2024-12-18

Moore M, Whittington HD, Knickmeyer R, et al (2025)

Non-stochastic reassembly of a metabolically cohesive gut consortium shaped by N-acetyl-lactosamine-enriched fibers.

Gut microbes, 17(1):2440120.

Diet is one of the main factors shaping the human microbiome, yet our understanding of how specific dietary components influence microbial consortia assembly and subsequent stability in response to press disturbances - such as increasing resource availability (feeding rate) - is still incomplete. This study explores the reproducible re-assembly, metabolic interplay, and compositional stability within microbial consortia derived from pooled stool samples of three healthy infants. Using a single-step packed-bed reactor (PBR) system, we assessed the reassembly and metabolic output of consortia exposed to lactose, glucose, galacto-oligosaccharides (GOS), and humanized GOS (hGOS). Our findings reveal that complex carbohydrates, especially those containing low inclusion (~1.25 gL[-1]) components present in human milk, such as N-acetyl-lactosamine (LacNAc), promote taxonomic, and metabolic stability under varying feeding rates, as shown by diversity metrics and network analysis. Targeted metabolomics highlighted distinct metabolic responses to different carbohydrates: GOS was linked to increased lactate, lactose to propionate, sucrose to butyrate, and CO2, and the introduction of bile salts with GOS or hGOS resulted in butyrate reduction and increased hydrogen production. This study validates the use of single-step PBRs for reliably studying microbial consortium stability and functionality in response to nutritional press disturbances, offering insights into the dietary modulation of microbial consortia and their ecological dynamics.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Ullah H, Hassan SHA, Yang Q, et al (2024)

Dynamic interaction of antibiotic resistance between plant microbiome and organic fertilizers: sources, dissemination, and health risks.

World journal of microbiology & biotechnology, 41(1):4.

Antibiotic resistance is a global health problem driven by the irrational use of antibiotics in different areas (such as agriculture, animal farming, and human healthcare). Sub-lethal concentrations of antibiotic residues impose selective pressure on environmental, plant-associated, and human microbiome leading to the emergence of antibiotic-resistant bacteria (ARB). This review summarizes all sources of antibiotic resistance in agricultural soils (including manure, sewage sludge, wastewater, hospitals/pharmaceutical industry, and bioinoculants). The factors (such as the physicochemical properties of soil, root exudates, concentration of antibiotic exposure, and heavy metals) that facilitate the transmission of resistance in plant microbiomes are discussed. Potential solutions for effective measures and control of antibiotic resistance in the environment are also hypothesized. Manure exhibits the highest antibiotics load, followed by hospital and municipal WW. Chlortetracycline, tetracycline, and sulfadiazine have the highest concentrations in the manure. Antibiotic resistance from organic fertilizers is transmitted to the plant microbiome via horizontal gene transfer (HGT). Plant microbiomes serve as transmission routes of ARB and ARGS to humans. The ingestion of ARB leads to human health risks (such as ineffectiveness of medication, increased morbidity, and mortality).

RevDate: 2024-12-17
CmpDate: 2024-12-17

Tsuchida S, Umemura H, Iizuka K, et al (2024)

Recent findings on metabolomics and the microbiome of oral bacteria involved in dental caries and periodontal disease.

World journal of microbiology & biotechnology, 41(1):11.

Periodontal disease is characterized by bacterial toxins within the oral biofilm surrounding the teeth, leading to gingivitis and the gradual dissolution of the alveolar bone, which supports the teeth. Notably, symptoms in the early stages of the disease are often absent. Similarly, dental caries occurs when oral bacteria metabolize dietary sugars, producing acids that dissolve tooth enamel and dentin. These bacteria are commonly present in the oral cavity of most individuals. Metabolomics, a relatively recent addition to the "omics" research landscape, involves the comprehensive analysis of metabolites in vivo to elucidate pathological mechanisms and accelerate drug discovery. Meanwhile, the term "microbiome" refers to the collection of microorganisms within a specific environmental niche or their collective genomes. The human microbiome plays a critical role in health and disease, influencing a wide array of physiological and pathological processes. Recent advances in microbiome research have identified numerous bacteria implicated in dental caries and periodontal disease. Additionally, studies have uncovered various pathogenic factors associated with these microorganisms. This review focuses on recent findings in metabolomics and the microbiome, specifically targeting oral bacteria linked to dental caries and periodontal disease. We acknowledge the limitation of relying exclusively on the MEDLINE database via PubMed, while excluding other sources such as gray literature, conference proceedings, and clinical practice guidelines.

RevDate: 2024-12-17

Chircop O, Jaggers C, Spiteri M, et al (2024)

DOXY do, or DOXY Don't? Syphilis and doxycycline post-exposure prophylaxis: A case report.

International journal of STD & AIDS [Epub ahead of print].

The resurgence of syphilis across Europe has led to a growing number of atypical cases, often characterised by varied symptoms that can delay diagnosis. We report the case of a young man who has sex with men (MSM), presenting with persistent headaches and swelling of the forehead suggestive of giant cell arteritis (GCA). Despite a recent negative syphilis test, further investigations confirmed the diagnosis of neurosyphilis. The patient had been using doxycycline post-exposure prophylaxis (DoxyPEP), which is suspected to have delayed the diagnosis by masking the typical antibody response. This case highlights concerns about DoxyPEP's impact on syphilis detection and disease progression. Further research is warranted to explore its effects on antimicrobial resistance, the human microbiome, and clinical outcomes.

RevDate: 2024-12-17

Jiang H, Miao X, Thairu MW, et al (2024)

Multimedia: multimodal mediation analysis of microbiome data.

Microbiology spectrum [Epub ahead of print].

UNLABELLED: Mediation analysis has emerged as a versatile tool for answering mechanistic questions in microbiome research because it provides a statistical framework for attributing treatment effects to alternative causal pathways. Using a series of linked regressions, this analysis quantifies how complementary data relate to one another and respond to treatments. Despite these advances, existing software's rigid assumptions often result in users viewing mediation analysis as a black box. We designed the multimedia R package to make advanced mediation analysis techniques accessible, ensuring that statistical components are interpretable and adaptable. The package provides a uniform interface to direct and indirect effect estimation, synthetic null hypothesis testing, bootstrap confidence interval construction, and sensitivity analysis, enabling experimentation with various mediator and outcome models while maintaining a simple overall workflow. The software includes modules for regularized linear, compositional, random forest, hierarchical, and hurdle modeling, making it well-suited to microbiome data. We illustrate the package through two case studies. The first re-analyzes a study of the microbiome and metabolome of Inflammatory Bowel Disease patients, uncovering potential mechanistic interactions between the microbiome and disease-associated metabolites, not found in the original study. The second analyzes new data about the influence of mindfulness practice on the microbiome. The mediation analysis highlights shifts in taxa previously associated with depression that cannot be explained indirectly by diet or sleep behaviors alone. A gallery of examples and further documentation can be found at https://go.wisc.edu/830110.

IMPORTANCE: Microbiome studies routinely gather complementary data to capture different aspects of a microbiome's response to a change, such as the introduction of a therapeutic. Mediation analysis clarifies the extent to which responses occur sequentially via mediators, thereby supporting causal, rather than purely descriptive, interpretation. Multimedia is a modular R package with close ties to the wider microbiome software ecosystem that makes statistically rigorous, flexible mediation analysis easily accessible, setting the stage for precise and causally informed microbiome engineering.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Balla B, IllĂ©s A, TobiĂ¡s B, et al (2024)

The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature.

International journal of molecular sciences, 25(23): pii:ijms252313227.

The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Cominelli G, Lonati C, Pinto D, et al (2024)

Melatonin Attenuates Ferritinophagy/Ferroptosis by Acting on Autophagy in the Liver of an Autistic Mouse Model BTBR T[+]Itpr3[tf]/J.

International journal of molecular sciences, 25(23): pii:ijms252312598.

Autism spectrum disorders (ASDs) are a pool of neurodevelopment disorders in which social impairment is the main symptom. Presently, there are no definitive medications to cure the symptoms but the therapeutic strategies that are taken ameliorate them. The purpose of this study was to investigate the effects of melatonin (MLT) in treating ASDs using an autistic mouse model BTBR T[+]Itpr3[tf]/J (BTBR). We evaluated the hepatic cytoarchitecture and some markers of autophagy, ferritinophagy/ferroptosis, in BTBR mice treated and not-treated with MLT. The hepatic morphology and the autophagy and ferritinophagy/ferroptosis pathways were analyzed by histological, immunohistochemical, and Western blotting techniques. We studied p62 and microtubule-associated protein 1 light chain 3 B (LC3B) for evaluating the autophagy; nuclear receptor co-activator 4 (NCOA4) and long-chain-coenzyme synthase (ACSL4) for monitoring ferritinophagy/ferroptosis. The liver of BTBR mice revealed that the hepatocytes showed many cytoplasmic inclusions recognized as Mallory-Denk bodies (MDBs); the expression and levels of p62 and LC3B were downregulated, whereas ACSL4 and NCOA4 were upregulated, as compared to control animals. MLT administration to BTBR mice ameliorated liver damage and reduced the impairment of autophagy and ferritinophagy/ferroptosis. In conclusion, we observed that MLT alleviates liver damage in BTBR mice by improving the degradation of intracellular MDBs, promoting autophagy, and suppressing ferritinophagy/ferroptosis.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Ouédraogo LO, Deng L, Ouattara CA, et al (2024)

Describing Biological Vulnerability in Small, Vulnerable Newborns in Urban Burkina Faso (DenBalo): Gut Microbiota, Immune System, and Breastmilk Assembly.

Nutrients, 16(23): pii:nu16234242.

Background: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. Objectives: The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants. Methods: This prospective cohort observational study will recruit 141 mother-infant pairs (70 SVNs and 71 healthy controls) from four health centers in Bobo-Dioulasso, Burkina Faso. The mother-infant pairs will be followed for six months with anthropometric measurements and biospecimen collections, including blood, breast milk, saliva, stool, vaginal swabs, and placental biopsies. Multi-omics approaches, encompassing metagenomics, metabolomics, proteomics, and immune profiling, will be used to assess vaginal and gut microbiota composition and functionality, immune cell maturation, and cytokine levels at critical developmental stages. Conclusions: This study will generate comprehensive data on how microbiota, metabolomic, and proteomic profiles, along with immune system development, differ between SVNs and healthy infants. These findings will guide targeted interventions to improve neonatal health outcomes and reduce mortality, particularly in vulnerable populations.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Kim S, Rahim MA, Tajdozian H, et al (2024)

Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index.

Cells, 13(23): pii:cells13232029.

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Seo H, Kim S, Beck S, et al (2024)

Perspectives on Microbiome Therapeutics in Infectious Diseases: A Comprehensive Approach Beyond Immunology and Microbiology.

Cells, 13(23): pii:cells13232003.

Although global life expectancy has increased over the past 20 years due to advancements in managing infectious diseases, one-fifth of people still die from infections. In response to this ongoing threat, significant efforts are underway to develop vaccines and antimicrobial agents. However, pathogens evolve resistance mechanisms, complicating their control. The COVID-19 pandemic has underscored the limitations of focusing solely on the pathogen-killing strategies of immunology and microbiology to address complex, multisystemic infectious diseases. This highlights the urgent need for practical advancements, such as microbiome therapeutics, that address these limitations while complementing traditional approaches. Our review emphasizes key outcomes in the field, including evidence of probiotics reducing disease severity and insights into host-microbiome crosstalk that have informed novel therapeutic strategies. These findings underscore the potential of microbiome-based interventions to promote physiological function alongside existing strategies aimed at enhancing host immune responses and pathogen destruction. This narrative review explores microbiome therapeutics as next-generation treatments for infectious diseases, focusing on the application of probiotics and their role in host-microbiome interactions. While offering a novel perspective grounded in a cooperative defense system, this review also addresses the practical challenges and limitations in translating these advancements into clinical settings.

RevDate: 2024-12-17

Morales C, Ballestero L, Del RĂ­o P, et al (2024)

Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.

Diagnostics (Basel, Switzerland), 14(23): pii:diagnostics14232635.

BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.

METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.

RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.

RevDate: 2024-12-16

Joos R, Boucher K, Lavelle A, et al (2024)

Author Correction: Examining the healthy human microbiome concept.

RevDate: 2024-12-16
CmpDate: 2024-12-16

Bhatnagar K, Jha K, Dalal N, et al (2024)

Exploring micronutrients and microbiome synergy: pioneering new paths in cancer therapy.

Frontiers in immunology, 15:1442788.

The human microbiome is the complex ecosystem consisting of trillions of microorganisms that play a key role in developing the immune system and nutrient metabolism. Alterations in the gut microbiome have been linked to cancer initiation, progression, metastasis, and response to treatment. Accumulating evidence suggests that levels of vitamins and minerals influence the gut environment and may have implications for cancer risk and progression. Bifidobacterium has been reported to reduce the colorectal cancer risk by binding to free iron. Additionally, zinc ions have been shown to activate the immune cells and enhance the effectiveness of immunotherapy. Higher selenium levels have been associated with a reduced risk of several cancers, including colorectal cancer. In contrast, enhanced copper uptake has been implicated in promoting cancer progression, including colon cancer. The interaction between cancer and gut bacteria, as well as dysbiosis impact has been studied in animal models. The interplay between prebiotics, probiotics, synbiotics, postbiotics and gut bacteria in cancer offers the diverse physiological benefits. We also explored the particular probiotic formulations like VSL#3, Prohep, Lactobacillus rhamnosus GG (LGG), etc., for their ability to modulate immune responses and reduce tumor burden in preclinical models. Targeting the gut microbiome through antibiotics, bacteriophage, microbiome transplantation-based therapies will offer a new perspective in cancer research. Hence, to understand this interplay, we outline the importance of micronutrients with an emphasis on the immunomodulatory function of the microbiome and highlight the microbiome's potential as a target for precision medicine in cancer treatment.

RevDate: 2024-12-15

Skurnik M (2024)

Scholarly discussion on the classification and electron microscopy analysis of lytic phage EC BD.

RevDate: 2024-12-11

Hodgkiss R, A Acharjee (2024)

Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling.

Biochimica et biophysica acta. Molecular basis of disease pii:S0925-4439(24)00612-4 [Epub ahead of print].

Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.

RevDate: 2024-12-10

Sinkko H, Olah P, Yang Y, et al (2024)

Taxonomic and functional profiling of skin microbiome in psoriasis.

The British journal of dermatology pii:7919383 [Epub ahead of print].

RevDate: 2024-12-10

Yang W, Wu K, Chen H, et al (2024)

Emerging role of rare earth elements in biomolecular functions.

The ISME journal pii:7918809 [Epub ahead of print].

The importance of rare earth elements is increasingly recognized due to the increased demand for their mining and separation. This demand is driving research on the biology of rare earth elements. Biomolecules associated with rare earth elements include rare earth element-dependent enzymes (methanol dehydrogenase XoxF, ethanol dehydrogenase ExaF/PedH), rare earth element-binding proteins, and the relevant metallophores. Traditional (chemical) separation methods for rare earth elements harvesting and separation are typically inefficient, while causing environmental problems, whereas bioharvesting, potentially, offers more efficient, more green platforms. Here, we review the current state of research on the biological functions of rare earth element-dependent biomolecules, and the characteristics of the relevant proteins, including the specific amino acids involved in rare earth metal binding. We also provide an outlook at strategies for further understanding of biological processes and the potential applications of rare earth element-dependent enzymes and other biomolecules.

RevDate: 2024-12-10

Han H, Choi YH, Kim SY, et al (2024)

Optimizing microbiome reference databases with PacBio full-length 16S rRNA sequencing for enhanced taxonomic classification and biomarker discovery.

Frontiers in microbiology, 15:1485073.

BACKGROUND: The study of the human microbiome is crucial for understanding disease mechanisms, identifying biomarkers, and guiding preventive measures. Advances in sequencing platforms, particularly 16S rRNA sequencing, have revolutionized microbiome research. Despite the benefits, large microbiome reference databases (DBs) pose challenges, including computational demands and potential inaccuracies. This study aimed to determine if full-length 16S rRNA sequencing data produced by PacBio could be used to optimize reference DBs and be applied to Illumina V3-V4 targeted sequencing data for microbial study.

METHODS: Oral and gut microbiome data (PRJNA1049979) were retrieved from NCBI. DADA2 was applied to full-length 16S rRNA PacBio data to obtain amplicon sequencing variants (ASVs). The RDP reference DB was used to assign the ASVs, which were then used as a reference DB to train the classifier. QIIME2 was used for V3-V4 targeted Illumina data analysis. BLAST was used to analyze alignment statistics. Linear discriminant analysis Effect Size (LEfSe) was employed for discriminant analysis.

RESULTS: ASVs produced by PacBio showed coverage of the oral microbiome similar to the Human Oral Microbiome Database. A phylogenetic tree was trimmed at various thresholds to obtain an optimized reference DB. This established method was then applied to gut microbiome data, and the optimized gut microbiome reference DB provided improved taxa classification and biomarker discovery efficiency.

CONCLUSION: Full-length 16S rRNA sequencing data produced by PacBio can be used to construct a microbiome reference DB. Utilizing an optimized reference DB can increase the accuracy of microbiome classification and enhance biomarker discovery.

RevDate: 2024-12-09

Poncet R, O Gargominy (2024)

In the Shadow of Medicine: The Glaring Absence of Occurrence Records of Human-Hosted Biodiversity.

Online journal of public health informatics, 16:e60140 pii:v16i1e60140.

Microbial diversity is vast, with bacteria playing a crucial role in human health. However, occurrence records (location, date, observer, and host interaction of human-associated bacteria) remain scarce. This lack of information hinders our understanding of human-microbe relationships and disease prevention. In this study, we show that existing solutions such as France's Système d'Information sur le Patrimoine Naturel framework, can be used to efficiently collect and manage occurrence data on human-associated bacteria. This user-friendly system allows medical personnel to easily share and access data on bacterial pathogens. By adopting similar national infrastructures and treating human-associated bacteria as biodiversity data, we can significantly improve public health management and research, and our understanding of the One Health concept, which emphasizes the interconnectedness of human, animal, and environmental health.

RevDate: 2024-12-09

Burton JP, Kofoed RH, R Rust (2024)

Science around the world.

Trends in molecular medicine, 30(3):197-199.

RevDate: 2024-12-08

Porcari S, Mullish BH, Asnicar F, et al (2024)

International consensus statement on microbiome testing in clinical practice.

The lancet. Gastroenterology & hepatology pii:S2468-1253(24)00311-X [Epub ahead of print].

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.

RevDate: 2024-12-05
CmpDate: 2024-12-06

Ma ZS (2024)

Revisiting microgenderome: detecting and cataloguing sexually unique and enriched species in human microbiomes.

BMC biology, 22(1):284.

BACKGROUND: Microgenderome or arguably more accurately microsexome refers to studies on sexual dimorphism of human microbiomes aimed at investigating bidirectional interactions between human microbiomes, sex hormones, and immune systems. It is important because of its implications to disease susceptibility and therapy, in which men and women demonstrate divergence in many diseases especially autoimmune diseases. In a previous report [1], we presented analyses of several key ecological aspects of microgenderome by leveraging the large datasets of the HMP (human microbiome project) but failed to offer species-level composition differences such as sexually unique species (US) and enriched species (ES). Existing approaches, for such tasks, including differential species relative abundance analysis and differential network analysis, possess certain limitations given that virtually all rely on species abundance alone or are univariate, while ignoring species distribution information across samples. Obviously, it is both species abundance and distribution that shape/drive the structure and dynamics of human microbiomes, and both should be equally responsible for the universal heterogeneity of microbiomes including the sexual dimorphism.

RESULTS: Here, we fill the gap by taking advantages of a recently developed computational algorithm, species specificity, and specificity diversity (SSD) framework (refer to the companion article) to reanalyze the HMP and complementary seminovaginal microbiome datasets. The SSD framework can randomly search and catalogue the sexually specific unique/enriched species with statistical rigor, guided by species specificity (a synthetic metric of abundance and distribution) and specificity diversity (SD). The SSD framework reveals that men seem to have more unique species than women in their gut and reproductive system microbiomes, but women seem to have more unique species than men in the airway, oral, and skin microbiomes, which is likely due to sexual dimorphism in the hormone and immune systems. We further investigate co-dependency and heterogeneity of those sexually unique/enriched species across 15 body sites, with core/periphery network analyses.

CONCLUSIONS: This study not only produced sexually unique/enriched species in the human microbiomes and analyzed their codependency and heterogeneity but also further validated the robustness of the SSD framework presented in the companion article, by performing all negative control tests based on the HMP gut microbiome samples.

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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.

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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.

Timelines

ESP now offers a large collection of user-selected side-by-side timelines (e.g., all science vs. all other categories, or arts and culture vs. world history), designed to provide a comparative context for appreciating world events.

Biographies

Biographical information about many key scientists (e.g., Walter Sutton).

Selected Bibliographies

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

ESP Picks from Around the Web (updated 28 JUL 2024 )