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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 17 Jun 2019 at 01:37 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-06-15

Baron SA, Cassir N, Mékidèche T, et al (2019)

Successful treatment and digestive decolonization of a patient with osteitis caused by a Carbapenemase-producing Klebsiella pneumoniae isolate harboring both NDM-1 and OXA-48 enzymes.

Journal of global antimicrobial resistance pii:S2213-7165(19)30144-4 [Epub ahead of print].

OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae (CRKP) is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. Here we reported the case of a patient from Romania hospitalized in Bulgaria after an accident trauma that came in France for the treatment of an osteitis caused by a K. pneumoniae carrying both blaNDM-1 and blaOXA-48.

METHOD: The resistome of this extremely-drug-resistant bacterium was analyzed both with phenotypic (large antibiotic susceptibility testing) and genomic method (genome sequencing). The genetic environment of the two carbapenemases was studied.

RESULTS: K. pneumoniae ST307 carrying both a blaNDM-1 gene and a blaOXA-48 gene located on two different plasmids, an Inc L/M and an IncFII. Patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI 2 times/day), intravenous fosfomycin (4 g 3 times/day) and oral doxycycline (100 mg 2 times/day) for 3 months. Fecal microbiota transplantation was successfully conducted for a stool carriage.

CONCLUSION: The ST307 type is becoming endemic in hospital environment and is frequently associated with carbapenem resistance. Treatment of infection caused by multi-drug resistant bacteria are a clinical challenge and the use of old antibiotics associated with a screening and decolonization of the reservoirs can be an efficient therapeutic alternative.

RevDate: 2019-06-15

Wortelboer K, Nieuwdorp M, H Herrema (2019)

Fecal microbiota transplantation beyond Clostridioides difficile infections.

EBioMedicine pii:S2352-3964(19)30375-5 [Epub ahead of print].

The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.

RevDate: 2019-06-14

Wang JW, Wang YK, Zhang F, et al (2019)

Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series.

The Kaohsiung journal of medical sciences [Epub ahead of print].

Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well-tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.

RevDate: 2019-06-13

Na SY, W Moon (2019)

Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.

Gut and liver pii:gnl19019 [Epub ahead of print].

New therapeutic strategies in inflammatory bowel disease (IBD) have shifted from symptom control towards treat-totarget algorithms in order to optimize treatment results. The treatment of IBD has evolved with the development of tumor necrosis factor-α inhibitors beyond the conventional therapies. In spite of their long-term effectiveness, many patients do not respond to or cannot sustain treatment with these drugs, which have various side effects. Therefore, the development of new drugs targeting specific pathways in the pathogenesis of IBD has become necessary. Some novel biologics and small molecule drugs have shown potential in IBD clinical trials, providing safe and effective results. In addition, clinicians are now trying to target the dysbiotic microbiome of patients with IBD using fecal microbiota transplantation. New tools such as stem cells have also been developed. The available therapeutic options for IBD are expanding rapidly. In the next few years, physicians will face an unprecedented number of options when choosing the best treatments for patients with IBD. This review provides an overview of recent advances in IBD treatment options.

RevDate: 2019-06-13

Ilan Y (2019)

Why targeting the microbiome is not so successful: can randomness overcome the adaptation that occurs following gut manipulation?.

Clinical and experimental gastroenterology, 12:209-217 pii:203823.

The microbiome is explored as a potential target for therapy of bowel and systemic diseases. Fecal microbiota transplantation (FMT) has demonstrated efficacy in Clostridium difficile infection. However, clinical results regarding other diseases are modest, despite the abundant research on the microbiome over the last decade. Both high rate variability of the microbiome and adaptation to gut manipulations may underlie the lack of ultimate effects of FMT, probiotics, prebiotics, synbiotics, and antibiotics, which are aimed at restoring a healthier microbiome. The present review discusses the inherent variability of the microbiome and multiple factors that affect its diversity, as possible causes of the adaptation of the gut microbiome to chronic manipulation. The potential use of randomness is proposed, as a means of overcoming the adaptation and of restoring some of the inherent variability, with the goal of improving the long-term efficacy of these therapies.

RevDate: 2019-06-13

Mazzawi T, Hausken T, Hov JR, et al (2019)

Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.

Scandinavian journal of gastroenterology [Epub ahead of print].

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ID: NCT03333291.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Zare A, Johansson AM, Karlsson E, et al (2018)

The gut microbiome participates in transgenerational inheritance of low-temperature responses in Drosophila melanogaster.

FEBS letters, 592(24):4078-4086.

Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germline although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature, while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Joshi T, Elderd BD, KC Abbott (2018)

No appendix necessary: Fecal transplants and antibiotics can resolve Clostridium difficile infection.

Journal of theoretical biology, 442:139-148.

The appendix has been hypothesized to protect the colon against Clostridium difficile infection (CDI) by providing a continuous source of commensal bacteria that crowd out the potentially unhealthy bacteria and/or by contributing to defensive immune dynamics. Here, a series of deterministic systems comprised of ordinary differential equations, which treat the system as an ecological community of microorganisms, model the dynamics of colon microbiome. The first model includes migration of commensal bacteria from the appendix to the gut, while the second model expands this to also include immune dynamics. Simulations and simple analytic techniques are used to explore dynamics under biologically relevant parameters values. Both models exhibited bistability with steady states of a healthy state and of fulminant CDI. However, we find that the appendix size was much too small for migration to affect the stability of the system. Both models affirm the use of fecal transplants in conjunction with antibiotic use for CDI treatment, while the second model also suggests that anti-inflammatory drugs may protect against CDI. Ultimately, in general neither the appendiceal migration rate of commensal microbiota nor the boost to antibody production could exert an appreciable impact on the stability of the system, thus failing to support the proposed protective role of the appendix against CDI.

RevDate: 2019-06-11

Costello SP, Conlon MA, JM Andrews (2019)

Fecal Microbiota Transplantation for Ulcerative Colitis-Reply.

JAMA, 321(22):2240-2241.

RevDate: 2019-06-11

Benech N, Kapel N, H Sokol (2019)

Fecal Microbiota Transplantation for Ulcerative Colitis.

JAMA, 321(22):2240.

RevDate: 2019-06-11

Smibert O, Satlin MJ, Nellore A, et al (2019)

Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles.

Current infectious disease reports, 21(7):26 pii:10.1007/s11908-019-0679-4.

PURPOSE OF REVIEW: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles.

RECENT FINDINGS: CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future. As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.

RevDate: 2019-06-10

Lam WC, Zhao C, Ma WJ, et al (2019)

The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis.

Gastroenterology research and practice, 2019:1287493.

Background and Purpose: Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation.

Methods: We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses.

Key Results: A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P < 0.001; I2 = 0%) and clinical response (OR, 2.75 [1.33, 5.67]; P = 0.006; I2 = 49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P = 0.37; I2 = 69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P = 0.44; I2 = 0%).

Conclusions and Inferences: Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.

RevDate: 2019-06-10

Lui RN, Wong SH, Lau LHS, et al (2019)

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

Hong Kong medical journal = Xianggang yi xue za zhi [Epub ahead of print].

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong.

METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected.

RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported.

CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

RevDate: 2019-06-07

Borody TJ, Eslick GD, RL Clancy (2019)

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer.

Current opinion in pharmacology, 49:43-51 pii:S1471-4892(19)30022-0 [Epub ahead of print].

Fecal microbiota transplantation (FMT) represents the most effective means of therapeutically manipulating the gastrointestinal microbiome. Originally employed as a treatment of last-resort in patients with life-threatening Clostridioides difficile infection (CDI), FMT gained widespread acceptance during the CDI epidemic, where it achieved resolution rates approaching 100%. Following our newfound appreciation for the role of the gut microbiome in both health and disease and owing to FMT's unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. We review the role of FMT from its beginnings in CDI to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer.

RevDate: 2019-06-10

Herfarth H, Barnes EL, Long MD, et al (2019)

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment.

Inflammatory intestinal diseases, 4(1):1-6.

Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP.

Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene.

Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response.

Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.

RevDate: 2019-06-07

Martínez N, Hidalgo-Cantabrana C, Delgado S, et al (2019)

Filling the gap between collection, transport and storage of the human gut microbiota.

Scientific reports, 9(1):8327 pii:10.1038/s41598-019-44888-8.

Stool collection devices minimizing the exposure of gut bacteria to oxygen are critical for the standardization of further microbiota-based studies, analysis and developments. The aim of this work was to evidence that keeping anaerobiosis has a deep impact on the viability and diversity of the fecal microbiota that is recovered in the laboratory. Recovering certain microbial populations, such as obligate anaerobic bacteria, is particularly critical if the purpose of the study is to envisage personalized therapeutic purposes, such as autologous Fecal Microbiota Transplant. In this study the same fecal specimens were sampled in conventional stool containers and GutAlive, a disposable device that minimizes exposure of the gut microbiota to oxygen. Samples from five healthy donors were analysed and 150 differential colonies were recovered and identified by 16S rRNA gene sequencing. Globally, GutAlive maintained extremely oxygen sensitive (EOS) populations that were lost in conventional stool containers, and thus viability of species such as as Akkermansia muciniphila, Faecalibacterium prausnitzii and a novel member of the Clostridiales order was kept. These obligate anaerobes were not recovered using the conventional stool collection device. In conclusion, the use of GutAlive for stool collection and transport optimized the viability and recovery of EOS bacteria in the lab by diminishing oxygen toxicity.

RevDate: 2019-06-06

Gurram B, PK Sue (2019)

Fecal microbiota transplantation in children: current concepts.

Current opinion in pediatrics [Epub ahead of print].

PURPOSE OF REVIEW: Administration of fecal material into the gastrointestinal tract, termed fecal microbiota transplantation (FMT), is increasingly recognized as an effective treatment option for recurrent Clostridium difficile infection (RCDI). The impact of FMT on host microbial communities and subsequent disease states has also been explored in recent years for conditions as varied as inflammatory bowel disease especially ulcerative colitis, metabolic diseases, such as diabetes, graft-versus-host disease in hematopoietic stem cell transplant recipients, and autism and autism spectrum disorders. The purpose of this article is to review the evidence for FMT as a treatment option in various pediatric illnesses.

RECENT FINDINGS: The rate of C. difficile infection is rising among children, and is associated with significant morbidity and disease, with recurrence in up to 20% of pediatric patients. Several randomized controlled trials evaluating the utility of FMT in RCDI in comparison to vancomycin have been published and demonstrate high rates of efficacy between 70 and 100%. In addition, the safety of FMT in the treatment of RCDI has been well described in the adult population, with several pediatric case series demonstrating similar rates of tolerability and adverse events. FMT in ulcerative colitis appears promising, especially with multiple infusions administered via the lower gastrointestinal tract. However, there are several limitations, including the lack of uniformity of protocols used, source of FMT, route of administration and the lack of standardization of concomitant therapies. The data on usage of FMT for other indications are preliminary and limited.

SUMMARY: FMT is recognized as an effective treatment option for RCDI and is increasing sought by parents. Although limited, pediatric studies to date on the use of FMT for RCDI demonstrate similar efficacy rates as in the adult population. FMT has been proposed as a treatment option for an increasing number of pediatric conditions, and additional studies are needed to delineate the efficacy of FMT outside of RCDI, as well as its short and long-term impacts on human health.

RevDate: 2019-06-05

Lee CH, Chai J, Hammond K, et al (2019)

Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-019-03602-2 [Epub ahead of print].

Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered "much better" in 17 patients (73.9%); "somewhat better" in 3 patients (13.0%); and "about the same" in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48-96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported "much better" overall health following FMT.

RevDate: 2019-06-03

Yin GF, Li B, XM Fan (2019)

[Effects and mechanism of fecal transplantation on acute lung injury induced by lipopolysaccharide in rats].

Zhonghua yi xue za zhi, 99(20):1582-1587.

Objective: To investigate the effect of fecal microbiota transplantation (FMT) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its regulatory mechanism. Methods: Fifteen rats were divided into control group, LPS group and LPS+FMT group by random number table method. LPS group and LPS+FMT group were intraperitoneally injected with LPS to generate rat ALI model. After 24 h of modeling, feces (10 ml/kg) were given to the LPS+FMT group twice a day, and the control group and LPS group were given the same amount of normal saline. The intervention lasted for 2 days. After 24 h of the last fecal microbiota transplantation, arterial blood gas analysis was performed in each group. Then rats were sacrificed and enzyme-linked immunosorbent (ELISA) method was used to detect intercellular adhesion molecule 1 (ICAM-1) content in the serum and bronchoalveolar lavage fluid (BALF). The lung wet-dry weight ratio (W/D) was evaluated; HE staining and lung tissue pathology scoring, immunohistochemical detection of nuclear factor-kappa B (NF-κB) predominate nuclear expression and expression of ICAM-1 of alveolar epithelial cells were conducted; Western blot was used to detect the expression of proteins related to the intracellular phosphatidylinositol kinase (PI3K)/protein kinase (AKT) signaling pathway. Samples of rat feces were collected and DNA was extracted. Polymerase chain reaction (PCR) products of the V3 and V4 regions of the 16S ribosomal RNA gene (16SrDNA) were sequenced at high throughput, and bioinformatics analysis was conducted on the microbial community based on the operational classification unit. Results: The lung W/D and lung histopathological score of the LPS group were significantly higher than those of the control group, while the arterial partial oxygen pressure (PaO(2)) of the LPS group was significantly lower than that of the control group [(79.2±5.89 vs 95.2±2.77) mmHg, 1 mmHg=0.133 kPa](all P<0.05). The results of intestinal flora sequencing revealed that the diversity index of LPS group was significantly higher than that of the control group, while the lactobacillus of LPS group rats was significantly lower than that of the control group. The content of ICAM-1 in serum, BALF and its relative expression on the cell membrane in the LPS group was significantly higher than that in the control group [(8.64±0.87) vs (7.40±0.32) ng/L; (0.941±0.035) vs (0.739±0.079) ng/L; (0.250±0.010) vs (0.076±0.010)] (all P<0.05). Moreover, the relative expression levels of phosphorylated P65 (p-P65), p-PI3K and p-AKT nucleoprotein in the LPS group were significantly higher than those in the control group (4.89±0.27 vs 3.28±0.13, 0.265±0.030 vs 0.036±0.013 and 0.444±0.040 vs 0.109±0.016) (all P<0.05). The above injury effect was reduced after fecal fungus transplantation. The lung W/D and lung pathological score of LPS+FMT group were significantly lower than those of LPS group, and PaO(2) of LPS+FMT group was significantly higher than that of LPS group [(88.0±3.53) mmHg]. The results of intestinal flora sequencing revealed that the diversity index of LPS+FMT group was significantly lower than that of LPS group, and the lactobacillus genus of LPS+FMT group was significantly higher than that of LPS group. ICAM-1 in the blood serum ((7.44±0.46) ng/L), BALF (0.834±0.040) ng/L) and its relative expression on alveolar epithelial cell membrane (0.173±0.030), the relative expression of p-P65, p-PI3K and p-AKT protein of NF-κB in alveolar epithelial cells was down-regulated ((2.99±0.28, 0.090±0.013 and 0.206±0.018) in LPS+FMT group than those of LPS group, the differences were statistically significant (all P<0.05). Conclusion: Fecal transplantation can alleviate lipopolysaccharide-induced acute lung injury in rats, and its regulatory effect may be related to inhibiting the activation of PI3K/AKT/NF-κB signaling pathway and reducing the expression of inflammatory factor ICAM-1.

RevDate: 2019-06-02

Kim KO, Schwartz MA, Lin OST, et al (2019)

Reducing Cost and Complexity of Fecal Microbiota Transplantation Using Universal Donors for Recurrent Clostridium difficile Infection.

Advances in therapy pii:10.1007/s12325-019-00974-x [Epub ahead of print].

INTRODUCTION: Fecal microbiota transplantation resolves recurrent Clostridium difficile infections in greater than 82% of patients. Highly screened, processed universal donor fecal material is available. We compared cost and scheduling efficiency of fecal microbiota transplantation by universal donors to patient-directed donors.

METHODS: Medical records from a prospectively maintained database of recurrent C. difficile patients who underwent fecal microbiota transplantation between 2012 and 2017 were reviewed retrospectively. Patient-directed donor stool was prepared in our microbiology laboratory using protocol-based screening. We transitioned to purchasing and using universal donor fecal material in 2015. Clinical outcomes, adverse events, time between consult to infusion, consultation fees, and material costs were compared. This was a retrospective comparison of two historical cohorts.

RESULTS: A total of 111 fecal microbiota transplantations were performed on 105 patients (56 from patient-directed donors and 55 from universal donors). Median recipient age was 66 years (18-96) with male to female ratio of 1:2.7, equivalent in both cohorts. Total consultation fees were significantly lower in the universal donor group owing to fewer infectious disease consultations. Costs for donor screening and stool preparation were lower in the universal donor cohort ($485.0 vs. $1189.90 ± 541.4, p < 0.001, 95% CI 559.9-849.9). Time from consultations to infusion was shorter in the universal donor cohort (18.9 ± 19.1 vs. 36.4 ± 23.3 days, p < 0.001, 95% CI 9.521-25.591). Recurrences within 8 weeks after fecal microbiota transplantation were equivalent (p = 0.354). Adverse events were equivalent.

CONCLUSIONS: Fecal microbiota transplantation using universal donors versus patient-directed donors for recurrent C. difficile showed comparable efficacy and short-term complications. The use of universal donors resulted in significant cost savings and scheduling efficiency.

RevDate: 2019-05-30

Ji J, Ge X, Chen Y, et al (2019)

Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [Epub ahead of print].

Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti-inflammatory and immune-regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium-treated mice. In particular, this agent significantly elevated the abundance of short-chain fatty acid (SCFA)-producing gut microbiota, causatively related with the enhanced development of Treg cells and the reduced proinflammatory Th17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA-producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.-Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.

RevDate: 2019-06-10

Zeng W, Shen J, Bo T, et al (2019)

Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation.

Journal of immunology research, 2019:1603758.

Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient's intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.

RevDate: 2019-05-30

Burrello C, Giuffrè MR, Macandog AD, et al (2019)

Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition.

Cells, 8(6): pii:cells8060517.

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

RevDate: 2019-05-25

Alagna L, Haak BW, A Gori (2019)

Fecal microbiota transplantation in the ICU: perspectives on future implementations.

Intensive care medicine pii:10.1007/s00134-019-05645-7 [Epub ahead of print].

RevDate: 2019-06-10

Cavuoto KM, Banerjee S, A Galor (2019)

Relationship between the microbiome and ocular health.

The ocular surface pii:S1542-0124(19)30028-X [Epub ahead of print].

The microbiome is important to the host as a whole, both in maintenance of health and in the pathophysiology of disease. The purpose of this review is to explore the relationship between the gut, ocular microbiome, and ocular disease states. We will also discuss how the microbiome can serve as a potential target for treatment, by methods such as modulation of diet, probiotics and fecal microbiota transplantation. The information discussed in the review has been gathered using literature published from 2004 to November 2018, as indexed in PubMed.

RevDate: 2019-05-24

Sharpton SR, Maraj B, Harding-Theobald E, et al (2019)

Gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression.

The American journal of clinical nutrition pii:5498099 [Epub ahead of print].

BACKGROUND: Preclinical evidence suggests that modulation of the gut microbiome could represent a new therapeutic target in nonalcoholic fatty liver disease (NAFLD).

OBJECTIVES: The aim of this study was to evaluate the most current evidence for liver-specific and metabolic effects of microbiome-targeted therapies (MTTs) in persons with NAFLD.

METHODS: We searched multiple electronic databases for randomized controlled trials (RCTs) published from January 1, 2005 to December 1, 2018 that enrolled persons with NAFLD who received MTT rather than placebo or usual care. MTT was defined as antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). Clinical outcomes were pooled with the use of random-effects models and heterogeneity was assessed with the I2 statistic. A random-effects meta-regression was performed to determine sources of heterogeneity in prevalence estimates between studies.

RESULTS: Twenty-one RCTs (1252 participants) were included; 9 evaluated probiotics and 12 evaluated synbiotics, with treatment duration ranging from 8 to 28 wk. No RCTs examined the efficacy of antibiotics or FMT. Probiotics/synbiotics were associated with a significant reduction in alanine aminotransferase activity [ALT, weighted mean difference (WMD): -11.23 IU/L; 95% CI: -15.02, -7.44 IU/L] and liver stiffness measurement (LSM) by elastography (reflecting inflammation and fibrosis) (WMD: -0.70 kPa; 95% CI: -1.00, -0.40 kPa), although analyses showed heterogeneity (I2 = 90.6% and I2 = 93.4%, respectively). Probiotics/synbiotics were also associated with increased odds of improvement in hepatic steatosis, as graded by ultrasound (OR: 2.40; 95% CI: 1.50, 3.84; I2 = 22.4%). No RCTs examined sequential liver biopsy findings. Probiotics (WMD: -1.84; 95% CI: -3.30, -0.38; I2 = 23.6%), but not synbiotics (WMD: -0.85; 95% CI: -2.17, 0.47; I2 = 96.6%), were associated with a significant reduction in body mass index.

CONCLUSIONS: The use of probiotics/synbiotics was associated with improvement in liver-specific markers of hepatic inflammation, LSM, and steatosis in persons with NAFLD. Although promising, given the heterogeneity in pooled analyses, additional well-designed RCTs are needed to define the efficacy of probiotics/synbiotics for treatment of NAFLD. This study was registered with PROSPERO as CRD42018091455.

RevDate: 2019-05-24

Li N, Wang Q, Wang Y, et al (2019)

Fecal microbiota transplantation from chronic unpredictable mild stress mice donors affects anxiety-like and depression-like behavior in recipient mice via the gut microbiota-inflammation-brain axis.

Stress (Amsterdam, Netherlands) [Epub ahead of print].

Recent studies have demonstrated that there are significant changes in the gut microbiota (GM) of humans with depression and animal models of depression and chronic stress. In our present study, we determined whether an alteration in GM is a decisive factor in anxiety-like and depression-like behavior and its impact on brain neurochemistry. An antibiotic cocktail was used to deplete the GM of mice before they were colonized, via fecal microbiota transplantation (FMT), by the GM of control mice or mice that had been exposed to chronic unpredictable mild stress (CUMS donors). The CUMS-donor group of mice and the mice that were colonized by their microbiota (the CUMS-recipient group) both showed higher levels of anxiety- and depression-like behavior compared to the controls. The GM community of the CUMS-donor and CUMS-recipient was distinctively different from the controls, with the CUMS group characterized by a lower relative abundance of Lactobacillus and a higher relative abundance of Akkermansia. Interestingly, FMT affected both behavior and neuroinflammation. Mice given the CUMS microbiota had significant elevations of interferon-γ (IFN-γ) and the tumor necrosis factor-alpha (TNF-α) in the hippocampus, which were accompanied by upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in the hippocampus. These results suggest that GM modulates pro-inflammatory cytokines in the hippocampus through dysfunctional microbiota-gut-brain axis, exacerbating anxiety- and depression-like phenotypes. Key Points Chronic unpredictable mild stress increased anxiety- and depression-like behavior in mice. Mice colonized with gut microbiota (GM) from stressed mice showed similar behaviors. The GM composition of the donor and recipient mice was also comparable. Their relative pattern of two bacteria has been tied to neuroinflammatory activity. The results suggest a link between GM, brain function, and anxiety and depression.

RevDate: 2019-06-10

Yousi F, Kainan C, Junnan Z, et al (2019)

Evaluation of the effects of four media on human intestinal microbiota culture in vitro.

AMB Express, 9(1):69 pii:10.1186/s13568-019-0790-9.

The human intestinal microbiota has an important role in the maintenance of human health and disease pathogenesis. The aim of this research was to investigate the impact of four media on human intestinal microbiota metabolite and composition changes, we performed in vitro batch culture using intestinal microbiota samples from three fecal microbiota transplantation (FMT) donors. After 48 h culture, gut microbiota medium (GMM) had the highest production of acetic acid (73.00 ± 7.56 mM) and propionic acid (16.79 ± 1.59 mM), bacterial growth media (BGM) had the highest production of butyric acid (13.39 ± 0.56 mM). In addition, brain heart infusion (BHI) promoted (p < 0.05) the growth of Bacteroidetes, especially Bacteroides after 48 h, GMM resulted in a significant increase (p < 0.05) in Actinobacteria and increased the beneficial genus Bifidobacterium, fastidious anaerobe broth (FAB) increased Firmicutes population, and BGM promoted the growth of Escherichia-Shigella and Akkermansia. The results suggest that four media had different effects on the human intestinal microbiota metabolism and composition in vitro. These results may facilitate the culture of bacteria from the human intestinal microbiota.

RevDate: 2019-06-05

Yu F, Han W, Zhan G, et al (2019)

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice.

Aging, 11(10):3262-3279.

Both diabetes and Alzheimer's disease are age-related disorders, and numerous studies have demonstrated that patients with diabetes are at an increased risk of cognitive dysfunction (CD) and Alzheimer's disease, suggesting shared or interacting pathomechanisms. The present study investigated the role of abnormal gut microbiota in diabetes-induced CD and the potential underlying mechanisms. An intraperitoneal injection of streptozotocin administered for 5 consecutive days was used for establishing a diabetic animal model. Hierarchical cluster analysis of Morris water maze (MWM) performance indices (escape latency and target quadrant crossing) was adopted to classify the diabetic model mice into CD and Non-CD phenotypes. Both β-diversity and relative abundance of several gut bacteria significantly differed between the CD and Non-CD groups. Further, fecal bacteria transplantation from Non-CD mice, but not from CD mice, into the gut of pseudo-germ-free mice significantly improved host MWM performance, an effect associated with alterations in β-diversity and relative abundance of host gut bacteria. Collectively, these findings suggest that abnormal gut microbiota composition contributes to the onset of diabetes-induced CD and that improving gut microbiota composition is a potential therapeutic strategy for diabetes and related comorbidities.

RevDate: 2019-05-24

McSweeney B, Allegretti JR, Fischer M, et al (2019)

In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation.

Gut microbes [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

RevDate: 2019-06-10

Contreras GA, Munita JM, CA Arias (2019)

Novel Strategies for the Management of Vancomycin-Resistant Enterococcal Infections.

Current infectious disease reports, 21(7):22 pii:10.1007/s11908-019-0680-y.

PURPOSE OF REVIEW: Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens that commonly affect critically ill patients. VRE have a remarkable genetic plasticity allowing them to acquire genes associated with antimicrobial resistance. Therefore, the treatment of deep-seated infections due to VRE has become a challenge for the clinician. The purpose of this review is to assess the current and future strategies for the management of recalcitrant deep-seated VRE infections and efforts for infection control in the hospital setting.

RECENT FINDINGS: Preventing colonization and decolonization of multidrug-resistant bacteria are becoming the most promising novel strategies to control and eradicate VRE from the hospital environment. Fecal microbiota transplantation (FMT) has shown remarkable results on treating colonization and infection due to Clostridiodes difficille and VRE, as well as to recover the integrity of the gut microbiota under antibiotic pressure. Initial reports have shown the efficacy of FMT on reestablishing patient microbiota diversity in the gut and reducing the dominance of VRE in the gastrointestinal tract. In addition, the use of bacteriophages may be a promising strategy in eradicating VRE from the gut of patients. Until these strategies become widely available in the hospital setting, the implementation of infection control measures and stewardship programs are paramount for the control of this pathogen and each program should provide recommendations for the proper use of antibiotics and develop strategies that help to detect populations at risk of VRE colonization, prevent and control nosocomial transmission of VRE, and develop educational programs for all healthcare workers addressing the epidemiology of VRE and the potential impact of these pathogens on the cost and outcomes of patients. In terms of antibiotic strategies, daptomycin has become the standard of care for the management of deep-seated infections due to VRE. However, recent evidence indicates that the efficacy of this antibiotic is limited, and higher (10-12 mg/kg) doses and/or combination with β-lactams is needed for therapeutic success. Clinical data to support the best use of daptomycin against VRE are urgently needed. This review provides an overview of recent developments regarding the prevention, treatment, control, and eradication of VRE in the hospital setting. We aim to provide an update of the most recent therapeutic strategies to treat deep-seated infections due to VRE.

RevDate: 2019-05-23

Cho JM, Pestana L, Pardi R, et al (2019)

Fecal microbiota transplant via colonoscopy may be preferred due to intraprocedure findings.

Intestinal research pii:ir.2019.00056 [Epub ahead of print].

RevDate: 2019-05-22

Revolinski SL, LS Munoz-Price (2019)

Clostridioides difficile in transplant patients: early diagnosis, treatment, and prevention.

Current opinion in infectious diseases [Epub ahead of print].

PURPOSE OF REVIEW: Clostridioides difficile infection is common in solid organ transplant and hematopoietic stem-cell transplant recipients and is associated with significant morbidity and mortality. These populations are also underrepresented in clinical trials, making optimal management difficult. Because of this, management of these populations follows national guideline recommendations. This review aims to summarize the recent relevant literature pertaining to the clinical management of C. difficile infection in transplant patients, with a particular focus on diagnosis, treatment, and prevention.

RECENT FINDINGS: Early diagnosis of C. difficile colonization may mitigate both horizontal and vertical transmission (progression from colonization to colitis) of infection. Once diagnosed, recent literature suggests antibiotic treatment should align with that recommended by national guidelines. Fecal microbiota transplant is an emerging therapy for recurrent C. difficile infection, and recent data have demonstrated safety and efficacy. Prevention strategies including antimicrobial stewardship, probiotic administration, antibiotic administration, and bezlotoxumab may be beneficial in transplant populations, but more data are needed to confirm recent findings.

SUMMARY: Studies evaluating C. difficile infection in transplant patients are only recently starting to emerge. Further research is needed to identify optimal treatment and prevention strategies, and to examine novel strategies such as microbiome manipulation.

RevDate: 2019-05-22

Krensky C, Poutanen SM, SS Hota (2019)

Diarrhea after fecal microbiota transplantation for recurrent Clostridioides difficile infection.

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 191(20):E559-E561.

RevDate: 2019-05-22

Saha S, S Khanna (2019)

Management of Clostridioides difficile colitis: insights for the gastroenterologist.

Therapeutic advances in gastroenterology, 12:1756284819847651 pii:10.1177_1756284819847651.

Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases.

RevDate: 2019-05-22

Wang J, Lang T, Shen J, et al (2019)

Core Gut Bacteria Analysis of Healthy Mice.

Frontiers in microbiology, 10:887.

Previous studies revealed that there existed great individual variations of gut microbiota in mice, and the gut bacteria of mice were changed with the occurrence and development of diseases. To identify the core gut bacteria in healthy mice and explore their relationships with the host phenotypes would help to understand the underlying mechanisms. In this study, we identified 37 genus-level core bacteria from feces of 101 healthy mice with different ages, sexes, and mouse strains in three previous studies. They collectively represented nearly half of the total sequences, and predominantly included carbohydrate- and amino acids-metabolizing bacteria and immunomodulatory bacteria. Among them, Anaerostipes indwelt the gut of all healthy mice. Co-abundance analysis showed that these core genera were clustered into five groups (Group C1-C5), which were ecologically related. For example, the abundances of Group C2 including probiotics Bifidobacterium and Lactobacillus slightly positively correlated with those of Group C1. Principal component analysis (PCA) and multivariate analysis of variance test revealed that these core gut genera were distinguished with age and sex, and also associated with their health/disease state. Linear discriminant analysis effect size (LEfSe) method showed that bacteria in Group C1 and C2/C3 increased with the age in infancy and early adulthood, and were more abundant in female mice than in male ones. The metabolic syndrome (MS) induced by high fat diet (HFD) and accelerated postnatal growth would decrease Group C2 genera, whereas probiotics intervention would reverse HFD-induced reduction of Group C2. Spearman correlation analysis indicated that the principal components based on the abundance of the 37 core genera were significantly correlated with host characteristic parameters of MS. These results demonstrated that the 37 core genera in five co-abundance groups from healthy mice were related to host phenotypes. It was indicated that these prevalent gut bacterial genera could be representative of the healthy gut microbiome in gnotobiotic animal models, and might also be candidates of probiotics and fecal microbiota transplantation.

RevDate: 2019-06-10

Dailey FE, Turse EP, Daglilar E, et al (2019)

The dirty aspects of fecal microbiota transplantation: a review of its adverse effects and complications.

Current opinion in pharmacology, 49:29-33 pii:S1471-4892(18)30155-3 [Epub ahead of print].

Fecal microbiota transplantation is becoming a growing therapy for a variety of indications, including recurrent or refractory Clostridium difficile infection (CDI), as well as many other gastrointestinal and extra-intestinal diseases. In fact, fecal microbiota transplantation is now strongly recommended as the treatment of choice for multiple recurrences of CDI, given its strong efficacy and a favorable short-term side effect profile. As the application of this therapy expands, awareness of its adverse events has also developed. The purpose of this review is to bring to light the side effects and complications associated with fecal microbiota transplantation, with an emphasis on findings from recently published studies.

RevDate: 2019-05-16

Sasmita AO (2019)

Modification of the gut microbiome to combat neurodegeneration.

Reviews in the neurosciences pii:/j/revneuro.ahead-of-print/revneuro-2019-0005/revneuro-2019-0005.xml [Epub ahead of print].

The gut microbiome was extensively researched for its biological variety and its potential role in propagating diseases outside of the gastrointestinal (GI) tract. Recently, a lot of effort was focused on comprehending the gut-brain axis and the bizarre communication between the GI system and the nervous system. Ample amount of studies being carried out also revealed the involvement of the gut microbiome in enhancing the degree of many neurological disorders, including neurodegenerative diseases. It was widely observed that there were distinct microbiome profiles and dysbiosis within patients suffering from Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Various approaches to re-establish the balance of the gut microbiome, from antibiotic therapy, fecal microbiota transplant, or ingestion of psychobiotics, are discussed within this review within the specific context of combating neurodegenerative diseases. Present studies and clinical trials indicate that although there is an immense potential of gut microbiome modification to be preventive or therapeutic, there are still many intercalated components of the gut-brain axis at play and thus, more research needs to be carried out to delineate microbiome factors that may potentially alleviate symptoms of neurodegeneration.

RevDate: 2019-05-16

Noce A, Marrone G, Di Daniele F, et al (2019)

Impact of Gut Microbiota Composition on Onset and Progression of Chronic Non-Communicable Diseases.

Nutrients, 11(5): pii:nu11051073.

In recent years, mounting scientific evidence has emerged regarding the evaluation of the putative correlation between the gut microbiota composition and the presence of chronic non-communicable diseases (NCDs), such as diabetes mellitus, chronic kidney disease, and arterial hypertension. The aim of this narrative review is to examine the current literature with respect to the relationship between intestinal dysbiosis and the insurgence/progression of chronic NCDs, analyzing the physiopathological mechanisms that can induce microbiota modification in the course of these pathologies, and the possible effect induced by microbiota alteration upon disease onset. Therapy based on probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplant can represent a useful therapeutic tool, as has been highlighted on animal studies. To this moment, clinical studies that intended to demonstrate the beneficial effect induced by this kind of oral supplementation on the gut microbiota composition, and subsequent amelioration of signs and symptoms of chronic NCDs have been conducted on limited sample populations for a limited follow-up period. Therefore, to fully evaluate the therapeutic value of this kind of intervention, it would be ideal to design ample population; randomized clinical trials with a lengthy follow up period.

RevDate: 2019-05-22

Prevel R, Boyer A, M'Zali F, et al (2019)

Is systematic fecal carriage screening of extended-spectrum beta-lactamase-producing Enterobacteriaceae still useful in intensive care unit: a systematic review.

Critical care (London, England), 23(1):170 pii:10.1186/s13054-019-2460-3.

BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are disseminating worldwide leading to increased hospital length of stay and mortality in intensive care units (ICU). ESBL-E dissemination was first due to outbreaks in hospital settings which led to the implementation of systematic fecal carriage screening to improve hygiene procedures by contact precautions. ESBLs have since spread in the community, and the relevance of contact precautions is questioned. ESBL-E dissemination led to an overuse of carbapenems triggering the emergence of carbapenem-resistant Enterobacteriaceae. Empirical antimicrobial therapy based on ESBL-E fecal carriage has been proposed but is debated as it could increase the consumption of carbapenems among ESBL-E carriers without any clinical benefit. Finally, selective decontamination among ESBL-E fecal carriers is evoked to decrease the risk for subsequent ESBL-E infection, but its efficacy remains debated. We propose to systematically review the evidence to recommend or not such systematic ESBL-E fecal carriage screening in adult ICU.

METHODS: Every article focusing on ESBL-E and ICU available on the MEDLINE database was assessed. Articles were included if focusing on cross-transmission, efficacy of hygiene procedures, link between ESBL-E colonization and infection or guidance of empirical therapy or selective decontamination efficacy.

RESULTS: Among 330 articles referenced on PubMed, 39 abstracts were selected for full-text assessment and 25 studies were included. Systematic screening of ESBL-E fecal carriage to guide contact precautions do not seem to decrease the rate of ESBL-E cross-transmission. It has a very good negative predictive value for subsequent ESBL-E infections but a positive predictive value between 40 and 50% and so does not help to spare carbapenems. Cessation of ESBL-E carriage systematic screening could decrease the use of carbapenems in ICU without any clinical harm. Nevertheless, further studies are needed to validate these results from monocentric before-after study. Selective decontamination strategy applied to ESBL-E fecal carriers could be helpful, but available data are conflicting.

CONCLUSION: Current knowledge lacks of high-quality evidence to strongly recommend in favor of or against a systematic ESBL-E fecal carriage screening policy for ICU patients in a non-outbreak situation. Further evaluation of selective decontamination or fecal microbiota transplantation among ESBL-E fecal carriers is needed.

RevDate: 2019-06-10

Turse EP, Dailey FE, Ghouri YA, et al (2019)

Fecal microbiota transplantation donation: the gift that keeps on giving.

Current opinion in pharmacology, 49:24-28 pii:S1471-4892(18)30156-5 [Epub ahead of print].

Fecal microbiota transplantation (FMT) is being studied and utilized for various medical conditions including Clostridium difficile colitis, inflammatory bowel diseases (IBD), obesity, myasthenia gravis, and so on. Yet, FMT donation, whether from an individual or a stool bank, can be challenging given the numerous requirements and donor costs. Furthermore, data outcomes on recipients of FMT regarding donor's health co-morbidities, age, and weight are limited but emerging. The purpose of this review is to evaluate cost, safety, and accessibility in FMT donation.

RevDate: 2019-05-14

Shaukat A, DM Brenner (2019)

Fecal Microbiota Transplant for Irritable Bowel Syndrome: Panacea or Placebo?.

The American journal of gastroenterology [Epub ahead of print].

Irritable bowel syndrome (IBS) is a common disorder of heterogeneous pathogenesis, and alterations in the gut microbiome/dysbiosis play a role in the development of symptoms in a subset of individuals with IBS. Consequently, it stands to reason that modulation of the microbiome via fecal microbial transplant (FMT) may serve as an effective treatment strategy because this has proven effective for treating other illnesses such as Clostridium difficile colitis. Small studies completed to date have offered conflicting results and the strains used, route of administration, and IBS subtypes may all play a role in treatment outcomes. A better understanding of the altered microbiome of patients with IBS and more rigorous trials are warranted before the utility of fecal microbial transplant for IBS symptoms can be determined.

RevDate: 2019-06-10

Lin C, Wan J, Lu Y, et al (2019)

Active bacterial communities of pig fecal microbiota transplantation suspension prepared and preserved under different conditions.

AMB Express, 9(1):63 pii:10.1186/s13568-019-0787-4.

Although fecal microbiota transplantation (FMT) has become a research hotspot, studies on comparison of the active fecal bacteria suspension under different preparation conditions are limited. This study investigated the abundances of active bacterial community in pig FMT suspension that produced under different oxygen concentrations or cryopreservation conditions. Fecal samples from a Landrace × Yorkshire sow were used to prepare fecal bacteria suspension under the anaerobic (AN group) and aerobic conditions (AE group), respectively. And then half of the anaerobic fecal bacteria suspension was cryopreservation in - 80 °C (AN-CR group) for 1 week. The microbial RNA in the fecal bacteria suspension was extracted before and after cryopreservation, and reverse transcribed into cDNA. MiSeq sequencing 16S rRNA gene of bacterial cDNA showed that the bacterial diversity in the AN group was significantly higher than that in the AE group. Comparing with the sows' fecal sample, the relative abundances of Lactobacillus johnsonii, Lactobacillus coleohominis and Parabacteroides merdae in AN, AE and AN-CR groups were reduced. The short-term cryopreservation had low impact on the structure of the active bacterial community in the fecal bacterial suspension. These results suggest that fecal bacteria suspension can be better prepared under strict anaerobic condition, and that fecal bacteria suspension can be cryopreserved in - 80 °C for a short time.

RevDate: 2019-05-12

Jia Q, Zhang L, Zhang J, et al (2019)

Fecal Microbiota of Diarrhea-Predominant Irritable Bowel Syndrome Patients Causes Hepatic Inflammation of Germ-Free Rats and Berberine Reverses It Partially.

BioMed research international, 2019:4530203.

Effects of the microbiome associated with diarrhea-predominant irritable bowel syndrome (IBS-D) on the gut have been reported, but no study has reported the effects of the IBS-D gut microbiome on the liver. We transplanted the fecal microbiota from an IBS-D patient and from a healthy volunteer to GF rats. The hepatic inflammation, serum biochemical parameters and metabolome, fecal microbiota profile, fecal short-chain fatty acids (SCFAs), and correlations among them before and after berberine intervention were assessed. Compared with the healthy control fecal microbiome transplantation (FMT) rats, the fecal microbiota of IBS-D patients induces significant Kupffer cell hyperplasia, hepatic sinusoid hypertrophy, and elevated levels of hepatic tumor necrosis factor-α and interferon-γ and decreases the synthesis of ALB in GF rats. This is possibly related to Faecalibacterium and Bifidobacterium attributable to fecal formate, acetate, and propionate levels, which are associated with the host linoleic acid pathway. Berberine can partially reverse the Kupffer cell hyperplasia, Faecalibacterium, fecal formate, acetate, and propionate by modulating the gut microbiome composition. These results may imply that IBS-D not only is an intestinal functional disorder but can cause liver inflammation, thus providing some implications regarding the clinical cognition and treatment of IBS-D.

RevDate: 2019-05-09

Huang HL, Chen HT, Luo QL, et al (2019)

Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota.

Journal of digestive diseases [Epub ahead of print].

AIM: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for refractory irritable bowel syndrome (IBS).

METHODS: Microbiota suspensions from feces donors were injected into the intestines of 30 Chinese patients with IBS. Microbiota composition analysis and genomic DNA extraction were performed on fecal samples obtained from these patients at baseline and 1 month after FMT. FMT's clinical efficacy and safety were assessed using questionnaires covering four aspects of IBS therapeutic efficacy and assessment of adverse effects during a 6-month follow-up.

RESULTS: Analytical data showed that FMT could change the gut microbiota composition, improve gastrointestinal symptoms, and alleviate depression and anxiety by restoring microbial diversity. The questionnaire scores confirmed that the maintained clinical response is 3-6 months after the first FMT.

CONCLUSIONS: FMT could be an effective and safe therapeutic strategy for IBS treatment, warranting comprehensive investigation.

RevDate: 2019-05-12

Xia GH, You C, Gao XX, et al (2019)

Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke.

Frontiers in neurology, 10:397.

Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome. Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0-2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome. Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17+ γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05). Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.

RevDate: 2019-05-08

Gilbert B, J Schrenzel (2019)

[Fecal microbiota transplantation : current status and prospects].

Revue medicale suisse, 15(650):976-983.

Fecal microbiota transplantation (FMT) is approved as a safe and effective treatment of recurrent Clostridium difficile infections. The technique is now being studied for other indications, usually involving chronic inflammation, metabolic disorders, or autoimmunity, for which the gut microbiota appears to play a key role. We detail thereafter, according to their degree of evidence, the potential future indications, in which FMT has already been tried on Humans. Except for ulcerative colitis and metabolic syndrome, the methodology of the published trials is often insufficiently described and inhomogeneous. Further randomized placebo-controlled trials and standardization of practice will be needed to confirm these preliminary but encouraging results.

RevDate: 2019-05-11

Galloway-Peña JR, Peterson CB, Malik F, et al (2019)

Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study.

Open forum infectious diseases, 6(5):ofz173 pii:ofz173.

Background: Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers.

Methods: Longitudinal fecal specimens (n = 451) were collected from 44 patients before HSCT through 100 days after transplantation, as well as 1-time samples from healthy volunteers (n = 18) as controls. Microbiota composition was determined using 16S ribosomal RNA V4 sequencing. Fecal indole and butyrate levels were determined using liquid chromatography tandem mass spectrometry.

Results: Among HSCT recipients, both fecal indole and butyrate levels correlated with the Shannon diversity index at baseline (P = .02 and P = .002, respectively) and directly after transplantation (P = .006 and P < .001, respectively). Samples with high butyrate levels were enriched for Clostridiales, whereas samples containing high indole were also enriched for Bacteroidales. A lower Shannon diversity index at the time of engraftment was associated with increased incidence of acute intestinal graft-vs-host disease (iGVHD) (P = .02) and transplant-related deaths (P = .03). Although fecal metabolites were not associated with acute iGVHD or overall survival, patients contracting bloodstream infections within 30 days after transplantation had significantly lower levels of fecal butyrate (P = .03).

Conclusions: Longitudinal analysis of fecal microbiome and metabolites after HSCT identified butyrate and indole as potential surrogate markers for microbial diversity and specific taxa. Further studies are needed to ascertain whether fecal metabolites can be used as biomarkers of acute iGVHD or bacteremia after HSCT.

RevDate: 2019-05-08

Buchta Rosean C, Bostic RR, Ferey JCM, et al (2019)

Pre-existing commensal dysbiosis is a host-intrinsic regulator of tissue inflammation and tumor cell dissemination in hormone receptor-positive breast cancer.

Cancer research pii:0008-5472.CAN-18-3464 [Epub ahead of print].

It is unknown why some patients with hormone receptor-positive (HR+) breast cancer present with more aggressive and invasive disease. Metastatic dissemination occurs early in disease and is facilitated by crosstalk between the tumor and tissue environment, suggesting that undefined host-intrinsic factors enhance early dissemination and the probability of developing metastatic disease. Here we have identified commensal dysbiosis as a host-intrinsic factor associated with metastatic dissemination. Using a mouse model of HR+ mammary cancer, we demonstrate that a pre-established disruption of commensal homeostasis results in enhanced circulating tumor cells and subsequent dissemination to the tumor-draining lymph nodes and lungs. Commensal dysbiosis promoted early inflammation within the mammary gland that was sustained during HR+ mammary tumor progression. Furthermore, dysbiosis enhanced fibrosis and collagen deposition both systemically and locally within the tumor microenvironment and induced significant myeloid infiltration into the mammary gland and breast tumor. These effects were recapitulated both by directly targeting gut microbes using non-absorbable antibiotics and by fecal microbiota transplantation of dysbiotic cecal contents, demonstrating the direct impact of gut dysbiosis on mammary tumor dissemination. This study identifies dysbiosis as a pre-existing, host-intrinsic regulator of tissue inflammation, myeloid recruitment, fibrosis, and dissemination of tumor cells in HR+ breast cancer.

RevDate: 2019-06-10

Zhang F, Zhang T, Zhu H, et al (2019)

Evolution of fecal microbiota transplantation in methodology and ethical issues.

Current opinion in pharmacology, 49:11-16 pii:S1471-4892(18)30149-8 [Epub ahead of print].

Fecal microbiota transplantation (FMT), the core therapy for remodeling the gut microbiota with a long medical history, has gained great attention worldwide in recent years. Increasing studies have explored its indications, methodology, efficacy, safety, and ethics. Purified forms of FMT, using an automated method for the purification of fecal microbiota from stool, has become a reality. Colonic transendoscopic enteral tubing makes frequent FMT delivery into the whole colon feasible. This review focuses on the recent progress in laboratory preparation, updated clinical strategies, novel delivery methods, and ethical issues surrounding FMT in clinical studies.

RevDate: 2019-05-08

Fiedorová K, Radvanský M, Němcová E, et al (2019)

The Impact of DNA Extraction Methods on Stool Bacterial and Fungal Microbiota Community Recovery.

Frontiers in microbiology, 10:821.

Our understanding of human gut microbiota in health and disease depends on accurate and reproducible microbial data acquisition. The critical step in this process is to apply an appropriate methodology to extract microbial DNA, since biases introduced during the DNA extraction process may result in inaccurate microbial representation. In this study, we attempted to find a DNA extraction protocol which could be effectively used to analyze both the bacterial and fungal community. We evaluated the effect of five DNA extraction methods (QIAamp DNA Stool Mini Kit, PureLinkTM Microbiome DNA Purification Kit, ZR Fecal DNA MiniPrepTM Kit, NucleoSpin® DNA Stool Kit, and IHMS protocol Q) on bacterial and fungal gut microbiome recovery using (i) a defined system of germ-free mice feces spiked with bacterial or fungal strains, and (ii) non-spiked human feces. In our experimental setup, we confirmed that the examined methods significantly differed in efficiency and quality, which affected the identified stool microbiome composition. In addition, our results indicated that fungal DNA extraction might be prone to be affected by reagent/kit contamination, and thus an appropriate blank control should be included in mycobiome research. Overall, standardized IHMS protocol Q, recommended by the International Human Microbiome Consortium, performed the best when considering all the parameters analyzed, and thus could be applied not only in bacterial, but also in fungal microbiome research.

RevDate: 2019-05-05

Lynch SM, Mu J, Grady JJ, et al (2019)

Fecal Microbiota Transplantation for Clostridium difficile Infection: A One-Center Experience.

Digestive diseases (Basel, Switzerland) pii:000499873 [Epub ahead of print].

BACKGROUND: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis.

OBJECTIVE: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut.

METHODS: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review.

RESULTS: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female.

CONCLUSIONS: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none.

RevDate: 2019-05-12

Khanna S, DN Gerding (2019)

Current and future trends in clostridioides (clostridium) difficile infection management.

Anaerobe pii:S1075-9964(19)30077-0 [Epub ahead of print].

Current and future management of Clostridioides difficile infection (CDI) including antibiotic treatment is increasingly focused on preventive strategies, either prevention of recurrent CDI (rCDI) or primary prevention of CDI. In addition to newer narrow spectrum antibiotics and pulse dosing of antibiotic treatment, multiple widely differing approaches to prevention of CDI and rCDI are under clinical development or recently approved for clinical use. They include immunologics, both passive monoclonal antibodies and active vaccines targeted at C. difficile toxins, approaches to reduce antibiotic dysbiosis in the gut, microbiome restoration using fecal microbiome transplants (FMT) or biotherapeutic bacterial derivatives, and substitution of non-toxigenic C. difficile (NTCD) for toxigenic C. difficile. Newer antibiotics, monoclonal antibodies, and FMT are targeted at reducing rCDI whereas vaccines and reduction of antibiotic dysbiosis in the gut are targeted at prevention of primary CDI. Biotherapeutics may be used for prevention of either primary CDI or rCDI. Approaches such as monoclonal antibodies, FMT, and biotherapeutics provide rapid but transient preventive benefits, whereas vaccines require weeks to months to be effective, but will presumably provide long term prevention. More rapid but transient prevention strategies such as FMT and biotherapeutics could be used in combination with vaccines to provide both rapid and durable CDI prevention.

RevDate: 2019-05-05

Zhang J, Ren G, Li M, et al (2019)

The Effects of Fecal Donors with Different Feeding Patterns on Diarrhea in a Patient Undergoing Hematopoietic Stem Cell Transplantation.

Case reports in hematology, 2019:4505238.

Almost 90% of patients undergoing hematopoietic stem cell transplantation (HSCT) experience diarrheal episodes, which represent a severe, often life-threatening complication for these patients. Although fecal microbiota transplantation (FMT) represents an alternative treatment option for infection-related diarrhea, the application of FMT in HSCT patients is greatly restricted for safety reasons. Furthermore, the therapeutic outcomes of FMT as a diarrhea treatment are somewhat related to the choice of the FMT donor. Here, we comprehensively profiled the dynamic changes in the intestinal microbiota after FMT from two donors with different feeding patterns and the same severely diarrheal recipient undergoing HSCT via a 45-day clinical observation. Importantly, no adverse events attributed to FMT were observed. The stool volume and frequency of the patient were reduced when we used feces from donor #1 (mixed feeding), but these changes were not observed after FMT from donor #2 (exclusive breastfeeding). Interestingly, no obvious differences in overall diversity (Shannon) or richness (Chao1) between the two donors were observed. Additionally, Bifidobacterium accounted for 29.9% and 18.1% of OTUs in the stools of donors #1 and #2, respectively. Lactobacillus accounted for 16.3% and 2.9% of the stools of donors #1 and #2, respectively. Furthermore, through longitudinal monitoring of the patient, we identified 6 OTUs that were particularly sensitive to the different FMT complements. Together, we present a case report suggesting that the overall diversity of the intestinal microbiota may not be the only important element in the selection of an effective FMT donor.

RevDate: 2019-05-03

Lavelle A, C Hill (2019)

Gut Microbiome in Health and Disease: Emerging Diagnostic Opportunities.

Gastroenterology clinics of North America, 48(2):221-235.

The gut microbiome is fundamental to human health and development. Altered microbiomes have been associated with many diseases. However, variation between individuals, environmental effects, and a lack of standardization across studies makes differentiation between health and disease challenging. Large-scale population cohorts in different countries will be required to match disease subjects with healthy controls, whereas standardized, reproducible pipelines for analysis are required to compare findings between studies. Despite this, several conditions have already demonstrated great promise for developing microbiome-based biomarkers as well as providing a gateway into integrated personalized medicine.

RevDate: 2019-04-30

Vujkovic-Cvijin I, M Somsouk (2019)

HIV and the Gut Microbiota: Composition, Consequences, and Avenues for Amelioration.

Current HIV/AIDS reports pii:10.1007/s11904-019-00441-w [Epub ahead of print].

PURPOSE OF REVIEW: We discuss recent advances in understanding of gut bacterial microbiota composition in HIV-infected subjects and comment on controversies. We discuss the putative effects of microbiota shifts on systemic inflammation and HIV disease progression and potential mechanisms, as well as ongoing strategies being developed to modulate the gut microbiota in humans for amelioration of infectious and inflammatory diseases.

RECENT FINDINGS: Lifestyle and behavioral factors relevant to HIV infection studies have independent effects on the microbiota. Microbial metabolism of immunomodulatory compounds and direct immune stimulation by translocation of microbes are putative mechanisms contributing to HIV disease. Fecal microbiota transplantation, microbial enzyme inhibition, phage therapy, and rationally selected probiotic cocktails have emerged as promising strategies for microbiota modulation. Numerous surveys of the HIV gut microbiota matched for lifestyle factors suggest consistent shifts in gut microbiota composition among HIV-infected subjects. Evidence exists for a complex pathogenic role of the gut microbiota in HIV disease progression, warranting further study.

RevDate: 2019-04-28

Campbell CT, Poisson MO, EO Hand (2019)

An Updated Review of Clostridium difficile Treatment in Pediatrics.

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 24(2):90-98.

Clostridium difficile infection (CDI) continues to have clinical and economic impact across all health care settings. Pediatrics accounts for a small percentage of worldwide infection; however, screening and diagnosis are confounded by asymptomatic colonization in young infants. Metronidazole and oral vancomycin have historically been the agents used to manage CDI in both pediatrics and adults. Newer agents and alternative therapies, such as fecal microbiota transplantation, may offer additional benefit. Recent guidelines updates from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America separate pediatric and adult recommendations for epidemiology, diagnosis, and treatment. This review will discuss the risk factors, management, prevention, and updated guideline recommendations for CDI in the pediatric population.

RevDate: 2019-06-07

Hsu WH, Wang JY, CH Kuo (2019)

Current applications of fecal microbiota transplantation in intestinal disorders.

The Kaohsiung journal of medical sciences, 35(6):327-331.

Fecal microbiota transplantation (FMT) had been an ancient remedy for severe illness several centuries ago. Under modern medical analysis and evidence-based research, it has been proved as an alternative treatment for recurrent Clostridium difficile infection and recent randomized control study also showed that FMT could be an adjuvant treatment for inflammatory bowel disease. As we get a better understanding of the relationship between gut microbiota and systemic disease, FMT became a potential treatment to explore. This article summarized procedures such as donor selection, fecal material preparation, transplantation delivery methods, and adverse events. We also review the present evidence about FMT in clinical practice.

RevDate: 2019-05-27

Nicholson MR, Mitchell PD, Alexander E, et al (2019)

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(19)30427-6 [Epub ahead of print].

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.

METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMTs at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.

RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.

CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.

RevDate: 2019-04-21

Misch EA, N Safdar (2019)

Clostridioides difficile Infection in the Stem Cell Transplant and Hematologic Malignancy Population.

Infectious disease clinics of North America, 33(2):447-466.

Clostridioides difficile infection (CDI) is common in the stem cell transplant (SCT) and hematologic malignancy (HM) population and mostly occurs in the early posttransplant period. Treatment of CDI in SCT/HM is the same as for the general population, with the exception that fecal microbiota transplant (FMT) has not been widely adopted because of safety concerns. Several case reports, small series, and retrospective studies have shown that FMT is effective and safe. A randomized controlled trial of FMT for prophylaxis of CDI in SCT patients is underway. In addition, an abundance of novel therapeutics for CDI is currently in development.

RevDate: 2019-06-10

Xie Y, Matsumoto H, Kennedy S, et al (2019)

Impaired Chylomicron Assembly Modifies Hepatic Metabolism Through Bile Acid-Dependent and Transmissible Microbial Adaptations.

Hepatology (Baltimore, Md.) [Epub ahead of print].

The mechanisms by which alterations in intestinal bile acid (BA) metabolism improve systemic glucose tolerance and hepatic metabolic homeostasis are incompletely understood. We examined metabolic adaptations in mice with conditional intestinal deletion of the abetalipoproteinemia (ABL) gene microsomal triglyceride transfer protein (Mttp-IKO), which blocks chylomicron assembly and impairs intestinal lipid transport. Mttp-IKO mice exhibit improved hepatic glucose metabolism and augmented insulin signaling, without weight loss. These adaptations included decreased BA excretion, increased pool size, altered BA composition, and increased fibroblast growth factor 15 production. Mttp-IKO mice absorb fructose normally but are protected against dietary fructose-induced hepatic steatosis, without weight loss or changes in energy expenditure. In addition, Mttp-IKO mice exhibit altered cecal microbial communities, both at baseline and following fructose feeding, including increased abundance of Bacteroides and Lactobacillus genera. Transplantation of cecal microbiota from chow-fed Mttp-IKO mice into antibiotic-treated wild-type recipients conferred transmissible protection against fructose-induced hepatic steatosis in association with a bloom in Akkermansia and increased Clostridium XIVa genera, whose abundance was positively correlated with fecal coprostanol and total neutral sterol excretion in recipient mice. However, antibiotic-treated Mttp-IKO mice were still protected against fructose-induced hepatic steatosis, suggesting that changes in microbiota are not required for this phenotype. Nevertheless, we found increased abundance of fecal Akkermansia from two adult ABL subjects with MTTP mutations compared to their heterozygous parents and within the range noted in six healthy control subjects. Furthermore, Akkermansia abundance across all subjects was positively correlated with fecal coprostanol excretion. Conclusion: The findings collectively suggest multiple adaptive pathways of metabolic regulation following blocked chylomicron assembly, including shifts in BA signaling and altered microbial composition that confer a transmissible phenotype.

RevDate: 2019-04-19

Jones EW, JM Carlson (2019)

Steady-state reduction of generalized Lotka-Volterra systems in the microbiome.

Physical review. E, 99(3-1):032403.

The generalized Lotka-Volterra (gLV) equations, a classic model from theoretical ecology, describe the population dynamics of a set of interacting species. As the number of species in these systems grow in number, their dynamics become increasingly complex and intractable. We introduce steady-state reduction (SSR), a method that reduces a gLV system of many ecological species into two-dimensional subsystems that each obey gLV dynamics and whose basis vectors are steady states of the high-dimensional model. We apply this method to an experimentally-derived model of the gut microbiome in order to observe the transition between "healthy" and "diseased" microbial states. Specifically, we use SSR to investigate how fecal microbiota transplantation, a promising clinical treatment for dysbiosis, can revert a diseased microbial state to health.

RevDate: 2019-04-21

Nishida A, Imaeda H, Inatomi O, et al (2019)

The efficacy of fecal microbiota transplantation for patients with chronic pouchitis: A case series.

Clinical case reports, 7(4):782-788 pii:CCR32096.

Pouchitis is one of the most common complications that develop after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Single fecal microbiota transplantation (FMT) by colonoscopy was performed safely on three patients with pouchitis. However, the efficacy of FMT on pouchitis was limited.

RevDate: 2019-06-05

Abreu Y Abreu AT, Velarde-Ruiz Velasco JA, Zavala-Solares MR, et al (2019)

Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection.

Revista de gastroenterologia de Mexico, 84(2):204-219.

In recent decades, Clostridium difficile infection (CDI) has become a worldwide health problem. Mexico is no exception, and therefore the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, endoscopists, internists, infectious disease specialists, and microbiologists) to carry out the "Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection", establishing useful recommendations (in relation to the adult population) for the medical community. Said recommendations are presented herein. Among them, it was recognized that CDI should be suspected in subjects with diarrhea that have a history of antibiotic and/or immunosuppressant use, but that it can also be a community-acquired infection. A 2-step diagnostic algorithm was proposed, in which a highly sensitive test, such as glutamate dehydrogenase (GDH), is first utilized, and if positive, confirmed by the detection of toxins through immunoassay or nucleic acid detection tests. Another recommendation was that CDI based on clinical evaluation be categorized as mild-moderate, severe, and complicated severe, given that such a classification enables better therapeutic decisions to be made. In mild-moderate CDI, oral vancomycin is the medication of choice, and metronidazole is recommended as an alternative treatment. In addition, fecal microbiota transplantation was recognized as an efficacious option in patients with recurrence or in the more severe cases of infection, and surgery should be reserved for patients with severe colitis (toxic megacolon), in whom all medical treatment has failed.

RevDate: 2019-04-15

Stallmach A, Grunert P, Pieper D, et al (2019)

[Ulcerative colitis: Does the modulation of gut microbiota induce long-lasting remission?].

Zeitschrift fur Gastroenterologie [Epub ahead of print].

Although the pathogenesis of ulcerative colitis (UC) remains elusive, substantial progress in understanding its development and progression has been achieved in the past decades, and novel effective treatment strategies have been developed. Changes in gut microbiota, environmental triggers, deregulation of immunological responses, and genetic predisposition have been identified as pathogenic key factors. There are several lines of clinical observations, which support a close connection of altered gut microbiota with the development and course of UC. Despite a plethora of microbiota alterations in UC, it is currently unclear whether the observed changes in inflammation are cause or effect of the altered microbiota state.Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore gut microbial diversity, bacterial richness, and microbial homeostasis in UC. FMT is an already established treatment option for recurrent Clostridioides difficile infection, and several case series and randomized controlled trials have described its use in UC. In this review, we evaluate recent efficacy and safety data on FMT for UC, discuss possible pitfalls and show possible areas of future development. Although FMT could become a promising treatment modality for UC, based on currently available data, FMT should be only performed in clinical trials as controlled studies focusing on long-term outcomes and safety are warranted.

RevDate: 2019-05-24

Belga S, Chiang D, Kabbani D, et al (2019)

The direct and indirect effects of vancomycin-resistant enterococci colonization in liver transplant candidates and recipients.

Expert review of anti-infective therapy, 17(5):363-373.

Introduction: Vancomycin-resistant enterococci (VRE) colonization and subsequent infection results in increased morbidity, mortality and use of health-care resources. The burden of VRE colonization in liver transplant candidates and recipients is significant. VRE colonization is a marker of gut dysbiosis and its impact on the microbiota-liver axis, may negatively affect graft function and result in negative outcomes pre- and post-transplantation. Areas covered: In this article we describe the epidemiology of VRE colonization, risk factors for VRE infection, health-care costs associated with VRE, with a focus on the impact of VRE colonization on liver transplant recipients' fecal microbiota, the therapeutic strategies for VRE decolonization and proposed pathophysiologic mechanisms of VRE colonization in liver transplant recipients. Expert opinion: VRE colonization results in a significant loss of bacterial microbiome diversity. This may have metabolic consequences, with low production of short-chain fatty acids which may, in turn, result in immune dysregulation. As antibiotics have failed to decolonize the gut, alternative strategies such as fecal microbiota transplantation (FMT), stimulation of intestinal antimicrobial peptides and phage therapy warrants future studies.

RevDate: 2019-04-11

Ding X, Li Q, Li P, et al (2019)

Long-Term Safety and Efficacy of Fecal Microbiota Transplant in Active Ulcerative Colitis.

Drug safety pii:10.1007/s40264-019-00809-2 [Epub ahead of print].

INTRODUCTION AND OBJECTIVE: The therapeutic role of fecal microbiota transplantation in ulcerative colitis varies across different reports. This study aims to evaluate the long-term safety and efficacy of a strategy called step-up fecal microbiota transplantation for ulcerative colitis.

METHODS: Two clinical trials (NCT01790061, NCT02560727) for moderate-to-severe ulcerative colitis (Mayo score range 6-12) were performed from November 2012 to July 2017. Both studies were pooled for analysis on the safety and efficacy of fecal microbiota transplantation in patients with ulcerative colitis over a 1-year follow-up. The step-up fecal microbiota transplantation strategy included step 1: single fecal microbiota transplantation; step 2: two or more fecal microbiota transplantations; and step 3: fecal microbiota transplantations followed by immunosuppressants. Long-term clinical efficacy and adverse events were assessed, and multiple factors related to fecal microbiota transplantation were evaluated.

RESULTS: Of 134 eligible patients in this real-word study, 81.3% (109/134) were included for analysis. The follow-up ranged from 1 to 5 years. Fecal microbiota transplantation-related adverse events were observed in 17.4% (43/247) of fecal microbiota transplantation procedures including one serious adverse event (myasthenia gravis) and 56 non-serious adverse events. Multivariable logistic regression analysis showed that both the method of preparation of microbiota from stool using the automatic system and the delivery method of colonic transendoscopic enteral tubing were associated with a lower rate of fecal microbiota transplantation-related adverse events (p = 0.023, p = 0.017, respectively). In total, 74.3% (81/109) and 51.4% (56/109) of patients achieved clinical response at 1 month and 3 months after step-up fecal microbiota transplantation, respectively.

CONCLUSIONS: Fecal microbiota transplantation should be a safe and promising therapy for ulcerative colitis. The improved fecal microbiota preparation and colonic transendoscopic enteral tubing might reduce the rate of adverse events in ulcerative colitis.


RevDate: 2019-04-29
CmpDate: 2019-04-29

Galperine TK, B Guery (2019)

[Customised infectiology - Fecal microbiota transplantation : following the Clostridioides difficile pathway].

Revue medicale suisse, 15(646):776-779.

Fecal microbiota transplantation (FMT) raised, in the recent years, a growing interest, mostly in Clostridioides difficile infections (CDI). The concept of FMT is quite simple based on the administration of fecal matter from a healthy donor to a patient with a disease related to the gut microbiota imbalance (dysbiosis). Although the theory seems straightforward, the fine mechanisms are multiple and not yet completely understood. In Switzerland, FMT is considered as a drug under the pharmacist responsibility. The only official indication for FMT is multi-recurrent CDI. For practical reasons, most of the FMT are performed with fresh stools, but development of frozen forms and capsules should considerably enhance treatment delivery. Other indications are currently investigated but not yet in the clinical routine.

RevDate: 2019-06-04

Alukal J, Dutta SK, Surapaneni BK, et al (2019)

Safety and efficacy of fecal microbiota transplant in 9 critically ill patients with severe and complicated Clostridium difficile infection with impending colectomy.

Journal of digestive diseases [Epub ahead of print].

OBJECTIVE: Significant data support the efficacy and safety of fecal microbiota transplant (FMT) in recurrent Clostridium difficile infection (CDI). The objective of our study was to determine the success rate of FMT in patients diagnosed with severe and complicated CDI with impending colectomy in the intensive care setting.

METHODS: This was a 2-center study of 9 patients who met the criteria for severe and complicated CDI and had an impending colectomy. All 9 patients had failed conventional antibiotic therapy and were deemed too unstable to undergo a colectomy. Hence, FMT was considered to be the next step in managing their condition.

RESULTS: Following FMT there was marked improvement in the patients' clinical status, with the resolution of diarrhea, reduced requirement for vasopressor, and the reduction in abdominal distention and pain. The primary cure rate of our study after a single round of FMT was 78% (7/9). Of the 9 patients 8 (88.88%) avoided a colectomy during the same hospital admission. the CDI-related death rate was 12.5% (1/9) and that of non-CDI was 12.5% (1/9).

CONCLUSION: Our success with FMT in fulminant CDI shows that this therapeutic modality is a promising alternative to a colectomy and could be a potential bowel-saving intervention.

RevDate: 2019-04-12

Mrazek K, Bereswill S, MM Heimesaat (2019)

Fecal Microbiota Transplantation Decreases Intestinal Loads of Multi-Drug Resistant Pseudomonas aeruginosa in Murine Carriers.

European journal of microbiology & immunology, 9(1):14-22.

Intestinal carriage of multi-drug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Psae) constitutes a pivotal prerequisite for subsequent fatal endogenous infections in patients at risk. We here addressed whether fecal microbiota transplantation (FMT) could effectively combat MDR-Psae carriage. Therefore, secondary abiotic mice were challenged with MDR-Psae by gavage. One week later, mice were subjected to peroral FMT from either murine or human donors on 3 consecutive days. Irrespective of murine or human origin of fecal transplant, intestinal MDR-Psae loads decreased as early as 24 h after the initial FMT. Remarkably, the murine FMT could lower intestinal MDR-Psae burdens by approximately 4 log orders of magnitude within 1 week. In another intervention study, mice harboring a human gut microbiota were perorally challenged with MDR-Psae and subjected to murine FMT on 3 consecutive days, 1 week later. Strikingly, within 5 days, murine FMT resulted in lower loads and carrier rates of MDR-Psae in mice with a human gut microbiota. In conclusion, FMT might be a promising antibiotics-independent option to combat intestinal MDR-Psae carriage and thus prevent from future endogenous infections of patients at risk.

RevDate: 2019-04-12

Bereswill S, Escher U, Grunau A, et al (2019)

Pituitary Adenylate Cyclase-Activating Polypeptide-A Neuropeptide as Novel Treatment Option for Subacute Ileitis in Mice Harboring a Human Gut Microbiota.

Frontiers in immunology, 10:554.

The neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its important functions in immunity and inflammation. Data regarding anti-inflammatory properties of PACAP in the intestinal tract are limited, however. In our present preclinical intervention study we addressed whether PACAP treatment could alleviate experimental subacute ileitis mimicking human gut microbiota conditions. Therefore, secondary abioitic mice were subjected to human fecal microbiota transplantation (FMT) and perorally infected with low-dose Toxoplasma gondii to induce subacute ileitis on day 0. From day 3 until day 8 post-infection, mice were either treated with synthetic PACAP38 or placebo. At day 9 post-infection, placebo, but not PACAP treated mice exhibited overt macroscopic sequelae of intestinal immunopathology. PACAP treatment further resulted in less distinct apoptotic responses in ileal and colonic epithelia that were accompanied by lower T cell numbers in the mucosa and lamina propria and less secretion of pro-inflammatory cytokines in intestinal ex vivo biopsies. Notably, ileitis-associated gut microbiota shifts were less distinct in PACAP as compared to placebo treated mice. Inflammation-ameliorating effects of PACAP were not restricted to the intestines, but could also be observed in extra-intestinal including systemic compartments as indicated by lower apoptotic cell counts and less pro-inflammatory cytokine secretion in liver and lungs taken from PACAP treated as compared to placebo control mice, which also held true for markedly lower serum TNF and IL-6 concentrations in the former as compared to the latter. Our preclinical intervention study provides strong evidence that synthetic PACAP alleviates subacute ileitis and extra-intestinal including systemic sequelae of T cell-driven immunopathology. These findings further support PACAP as a novel treatment option for intestinal inflammation including inflammatory bowel diseases (IBD).

RevDate: 2019-04-14

Kang DW, Adams JB, Coleman DM, et al (2019)

Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota.

Scientific reports, 9(1):5821 pii:10.1038/s41598-019-42183-0.

Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.

RevDate: 2019-04-27

He Y, Yu H, Ge Y, et al (2019)

Bacterial β-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease.

Biochemical and biophysical research communications, 513(2):426-433.

OBJECTIVE: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial β-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD.

METHODS: We first analyzed β-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of β-glucuronidase on experimental colitis was investigated in detail by administration of β-glucuronidase (from E. coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days.

RESULTS: Mice with colitis showed unchanged activity of β-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial β-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-α, IL-1β, TLR-4 and MyD88, and increase in IL-10 and IκBα in gut, restored fecal β-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with β-glucuronidase.

CONCLUSIONS: Bacterial β-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD.

RevDate: 2019-04-08

Tariq R, Pardi DS, Bartlett MG, et al (2019)

Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 68(8):1351-1358.

BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridium difficile infection (CDI) in observational studies (>90%), but cure rates in clinical trials are lower. We performed a systematic review and meta-analysis to assess the efficacy of FMT for recurrent CDI in open-label studies and clinical trials .

METHODS: A systematic search from January 1978 to March 2017 was performed to include clinical trials of FMT for CDI. We analyzed CDI resolution by calculating weighted pooled rates (WPRs).

RESULTS: Thirteen trials were included, comprising 610 patients with CDI treated with single FMT. Overall, 439 patients had clinical cure (WPR, 76.1%; 95% confidence interval (CI), 66.4%-85.7%). There was significant heterogeneity among studies (I2 = 91.35%). Cure rates were lower in randomized trials (139/216 patients; WPR, 67.7%; 95% CI, 54.2%-81.3%) than in open-label studies (300/394 patients; WPR, 82.7%; 71.1%-94.3%) (P < .001). Subgroup analysis by FMT delivery modality showed lower cure rates with enema than colonoscopy (WPR, 66.3% vs 87.4%; P < .001) but no difference between colonoscopy and oral delivery (WPR, 87.4% vs 81.4%; P = .17). Lower rates were seen for studies including both recurrent and refractory CDI than for those including only recurrent CDI (WPR, 63.9% vs 79%; P < .001).

CONCLUSIONS: FMT was associated with lower cure rates in randomized trials than in open-label and in observational studies. Colonoscopy and oral route are more effective than enema for stool delivery. The efficacy also seems to be higher for recurrent than for refractory CDI.

RevDate: 2019-05-22

Cold F, Browne PD, Günther S, et al (2019)

Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated - an open-label pilot study.

Scandinavian journal of gastroenterology, 54(3):289-296.

Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules. Methods: Seven patients with active UC, aged 27-50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months. Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p = .001) and 6 (p = .001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800 mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported. Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.

RevDate: 2019-04-04

Czepiel J, Dróżdż M, Pituch H, et al (2019)

Clostridium difficile infection: review.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-019-03539-6 [Epub ahead of print].

Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.

RevDate: 2019-04-03

Wardill HR, Secombe KR, Bryant RV, et al (2019)

Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients.

EBioMedicine pii:S2352-3964(19)30215-4 [Epub ahead of print].

FMT has gained enormous momentum in the treatment of acute inflammatory and infectious diseases. Despite an encouraging safety profile, FMT has been met with caution in the oncological setting due to perceived infectious risks in immunocompromised patients. Theoretical risks aside, the application of FMT in oncology may stand to benefit patients, via modulation of treatment efficacy and the mitigation of treatment complications. Here, we summarize most recent safety data of FMT in immunocompromised cohorts, including people with cancer, highlighting that FMT may actually provide protection against bacterial translocation via introduction of a diverse microbiome and restoration of epithelial defenses. We also discuss the emerging translational applications of FMT within supportive oncology, including the prevention and treatment of graft vs. host disease and sepsis, treatment of immunotherapy-induced colitis and restoration of the gut microbiome in survivors of childhood cancer.

RevDate: 2019-04-06

Ingle H, Lee S, Ai T, et al (2019)

Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ.

Nature microbiology pii:10.1038/s41564-019-0416-7 [Epub ahead of print].

Commensal microbes profoundly impact host immunity to enteric viral infections1. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut2,3. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.

RevDate: 2019-04-03

Toral M, Robles-Vera I, de la Visitación N, et al (2019)

Critical Role of the Interaction Gut Microbiota - Sympathetic Nervous System in the Regulation of Blood Pressure.

Frontiers in physiology, 10:231.

Association between gut dysbiosis and neurogenic diseases, such as hypertension, has been described. The aim of this study was to investigate whether changes in the gut microbiota alter gut-brain interactions inducing changes in blood pressure (BP). Recipient normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were orally gavaged with donor fecal contents from SHR and WKY. We divided the animals into four groups: WKY transplanted with WKY microbiota (W-W), SHR with SHR (S-S), WKY with SHR (W-S) and SHR with WKY (S-W). Basal systolic BP (SBP) and diastolic BP (DBP) were reduced with no change in heart rate as a result of fecal microbiota transplantation (FMT) from WKY rats to SHR. Similarly, FMT from SHR to WKY increased basal SBP and DBP. Increases in both NADPH oxidase-driven reactive oxygen species production and proinflammatory cytokines in brain paraventricular nucleus linked to higher BP drop with pentolinium and plasmatic noradrenaline (NA) levels were found in the S-S group as compared to the W-W group. These parameters were reduced by FMT from WKY to SHR. Increased levels of pro-inflammatory cytokines, tyrosine hydroxylase mRNA levels and NA content in the proximal colon, whereas reduced mRNA levels of gap junction proteins, were found in the S-S group as compared to the W-W group. These changes were inhibited by FMT from WKY to SHR. According to our correlation analyses, the abundance of Blautia and Odoribacter showed a negative correlation with high SBP. In conclusion, in SHR gut microbiota is an important factor involved in BP control, at least in part, as consequence of its effect on neuroinflammation and the sympathetic nervous system activity.

RevDate: 2019-04-01

Caesar R (2019)

Pharmacologic and Nonpharmacologic Therapies for the Gut Microbiota in Type 2 Diabetes.

Canadian journal of diabetes, 43(3):224-231.

The gut microbiota is an important regulator of host metabolism. Metagenome analyses have demonstrated that the gut microbiota differs between patients with type 2 diabetes and healthy subjects, and several studies have shown that impaired glucose metabolism is associated with decreased levels of butyrate-producing bacteria. Gut microbiota-produced metabolites, such as short-chain fatty acids, amino acid derivatives and secondary bile acids, participate in metabolic and immunologic processes and, hence, pose putative links between the gut microbiota and glucose homeostasis. Strategies to prevent and treat type 2 diabetes through manipulation of the gut microbiota are being developed. These include replacement of the gut microbiota by fecal transplantation, consumption of fibres to promote the function and growth of beneficial bacteria and treatment with probiotic bacterial strains. Furthermore, it has been shown that many drugs, including drugs used for treatment of diabetes, have major impacts on gut microbiota and, thereby, potentially on glucose metabolism. In particular, the commonly used drug metformin has been shown to influence the functional capacity of the gut microbiota, and recent evidence indicates that this may contribute to the antidiabetes effect of metformin.

RevDate: 2019-03-29

Suzumura EA, Bersch-Ferreira ÂC, Torreglosa CR, et al (2019)

Effects of oral supplementation with probiotics or synbiotics in overweight and obese adults: a systematic review and meta-analyses of randomized trials.

Nutrition reviews pii:5423210 [Epub ahead of print].

CONTEXT: Recent evidence suggests that modulation of the gut microbiota may contribute to body weight control.

OBJECTIVE: This systematic review aimed to assess the effects of oral supplementation with probiotics or synbiotics on body weight, body mass index (BMI), and waist circumference in overweight and obese adults (BMI ≥ 25 kg/m2).

DATA SOURCES: Five electronic databases-PubMed, Embase, Cochrane Library/CENTRAL, LILACS, and Web of Science-were searched from inception to August 2017. No language restrictions were applied.

STUDY SELECTION: Randomized and quasi-randomized parallel trials that assessed the effects of oral supplementation with probiotics or synbiotics vs any other intervention but bariatric surgery or fecal transplantation in overweight or obese adults were selected.

DATA EXTRACTION: Three teams of 2 authors independently assessed risk of bias and extracted data from the included trials. Data were pooled using inverse-variance random-effects meta-analyses. The quality of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

RESULTS: Nineteen randomized trials (28 publications, 1412 participants) were included. There were no differences in mean body weight change [mean difference (MD), -0.54 kg; 95%CI, -1.09 to 0.01; I2 = 0%; moderate quality of evidence) or mean BMI change (MD, -0.19 kg/m2; 95%CI, -0.43 to 0.04; I2 = 51%; low quality of evidence) between groups who received probiotics or synbiotics and control groups. Oral supplementation with probiotics or synbiotics reduced mean waist circumference compared with control (MD, -0.82 cm; 95%CI, -1.43 to -0.21; I2 = 46%; low quality of evidence).

CONCLUSIONS: The findings suggest that oral supplementation with probiotics or synbiotics has a small effect to reduce waist circumference but no effect on body weight or BMI, although the quality of evidence is low to moderate. Therefore, the current evidence is not definitive. Large-scale trials are needed and may help to better inform clinical practice.

PROSPERO registration number CRD42018075126.

RevDate: 2019-03-29

Liao X, Song L, Zeng B, et al (2019)

Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis.

EBioMedicine pii:S2352-3964(19)30202-6 [Epub ahead of print].

BACKGROUND: Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and α-glucosidase inhibitor in modulating the gut microbiota.

METHODS: 16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC-MS systems.

FINDINGS: Although DPP-4i and α-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HFD were rescued by DPP-4i. FMT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover, DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate.

INTERPRETATION: Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis. FUND: This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518).

RevDate: 2019-03-28

Bajaj JS, RA Hays (2019)

Manipulation of the Gut-Liver Axis Using Microbiome Restoration Therapy in Primary Sclerosing Cholangitis.

The American journal of gastroenterology [Epub ahead of print].

Alteration of the normal gut-liver axis is important in primary sclerosing cholangitis (PSC). Lack of effective medical therapy for PSC makes microbiome restoration an alluring therapeutic target. Allegretti et al. performed an open-label safety trial of fecal microbiota transplant (FMT) in noncirrhotic PSC patients with inflammatory bowel disease in remission on minimal therapy. FMT was safe in this population, and after FMT, there was a stable, early increase in microbial diversity and donor engraftment with mixed effects on alkaline phosphatase but no significant change in fecal bile acid profile. Further trials are needed to find whether FMT has a role to play in PSC therapy.

RevDate: 2019-05-15

Matsuo K, Haku A, Bi B, et al (2019)

Fecal microbiota transplantation prevents Candida albicans from colonizing the gastrointestinal tract.

Microbiology and immunology [Epub ahead of print].

Gut microbes symbiotically colonize the gastrointestinal (GI) tract, interacting with each other and their host to maintain GI tract homeostasis. Recent reports have shown that gut microbes help protect the gut from colonization by pathogenic microbes. Here, we report that commensal microbes prevent colonization of the GI tract by the pathogenic fungus, Candida albicans. Wild-type specific pathogen-free (SPF) mice are resistant to C. albicans colonization of the GI tract. However, administering certain antibiotics to SPF mice enables C. albicans colonization. Quantitative kinetics of commensal bacteria are inversely correlated with the number of C. albicans in the gut. Here, we provide further evidence that transplantation of fecal microbiota is effective in preventing Candida colonization of the GI tract. These data demonstrate the importance of commensal bacteria as a barrier for the GI tract surface and highlight the potential clinical applications of commensal bacteria in preventing pathogenic fungal infections.

RevDate: 2019-03-28

Adler E, Tabaa A, Kassam Z, et al (2019)

Capsule-Delivered Fecal Microbiota Transplant Is Safe and Well Tolerated in Patients with Ulcerative Colitis.

Digestive diseases and sciences pii:10.1007/s10620-019-05596-5 [Epub ahead of print].

RevDate: 2019-04-21

Kim KO, M Gluck (2019)

Fecal Microbiota Transplantation: An Update on Clinical Practice.

Clinical endoscopy, 52(2):137-143.

Fecal microbiota transplantation (FMT) is an infusion in the colon, or the delivery through the upper gastrointestinal tract, of stool from a healthy donor to a recipient with a disease believed to be related to an unhealthy gut microbiome. FMT has been successfully used to treat recurrent Clostridium difficile infection (rCDI). The short-term success of FMT in rCDI has led to investigations of its application to other gastrointestinal disorders and extra-intestinal diseases with presumed gut dysbiosis. Despite the promising results of FMT in these conditions, several barriers remain, including determining the characteristics of a healthy microbiome, ensuring the safety of the recipient with respect to long-term outcomes, adequate monitoring of the recipient of fecal material, achieving high-quality control, and maintaining reasonable costs. For these reasons, establishing uniform protocols for stool preparation, finding the best modes of FMT administration, maintaining large databases of donors and recipients, and assuring that oral ingestion is equivalent to the more widely accepted colonoscopic infusion are issues that need to be addressed.

RevDate: 2019-03-25

Xu D, Chen VL, Steiner CA, et al (2019)

Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

The American journal of gastroenterology [Epub ahead of print].

OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS.

METHODS: We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement.

RESULTS: Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met eligibility. No significant difference in global improvement of IBS symptoms was observed at 12 weeks in FMT vs placebo (RR = 0.93; 95% CI 0.48-1.79). Heterogeneity among studies was significant (I = 79%). Subgroup analyses revealed benefits of single-dose FMT using colonoscopy and nasojejunal tubes in comparison with autologous FMT for placebo treatment (number needed to treat = 5, RR = 1.59; 95% CI 1.06-2.39; I = 0%) and a reduction in likelihood of improvement of multiple-dose capsule FMT RCTs (number needed to harm = 3, RR = 0.54; 95% CI 0.34-0.85; I = 13%). Placebo response was 33.7% in nonoral FMT RCTs and 67.8% in capsule FMT RCTs. The Grading of Recommendations Assessment, Development and Evaluation quality of the body of evidence was very low.

CONCLUSIONS: Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms. There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.

RevDate: 2019-03-29

Zhou J, Zhou Z, Ji P, et al (2019)

Effect of fecal microbiota transplantation on experimental colitis in mice.

Experimental and therapeutic medicine, 17(4):2581-2586.

The aim of the present study was to investigate the effect of fecal microbiota transplantation (FMT) on the acute inflammatory response in a murine model of dextran sulfate sodium (DSS)-induced colitis, and to delineate the putative underlying mechanism(s). Mice were divided into four groups, namely the normal control, DSS, 5-aminosalicylic acid (5-ASA) and FMT group. Mice in the DSS, 5-ASA and FMT groups were orally administered 3% DSS (w/v) solution for 7 days to induce colitis. On days 1, 3, 5 and 7, mice in the DSS, 5-ASA and FMT groups were respectively administered 0.5% carboxymethylcellulose sodium, 5-ASA suspension and fecal suspension by enema. The disease activity index of each mouse was calculated on a daily basis. All mice were sacrificed on day 8, and the length of their colons was measured. Myeloperoxidase (MPO) activity, and the levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-10 in the colon tissues of each group were also measured. Compared with that in the DSS group, FMT ameliorated the severity of inflammation due to ulcerative colitis in mice, which was accompanied by a significantly decreased MPO activity, reduced levels of TNF-α and IL-1β, and an increased level of IL-10 in colon tissue (all P<0.05). Taken together, these results demonstrated that FMT exerted a therapeutic effect on experimental colitis in mice, and the associated mechanism is likely to involve the remodeling of the intestinal flora and regulation of intestinal T-cell immunity homeostasis.

RevDate: 2019-03-29

Levy AN, JR Allegretti (2019)

Insights into the role of fecal microbiota transplantation for the treatment of inflammatory bowel disease.

Therapeutic advances in gastroenterology, 12:1756284819836893 pii:10.1177_1756284819836893.

Fecal microbiota transplantation (FMT) has changed the treatment landscape of Clostridium difficile infection (CDI). Emerging evidence has shown that FMT can also be an effective and safe treatment strategy in CDI with underlying inflammatory bowel disease (IBD). Recently, randomized controlled trials of FMT in ulcerative colitis support its expanding role in restoring gut homeostasis in this disease. However, heterogeneous study designs leave several questions yet to be answered, including how to best position this novel therapy in the treatment approach of Crohn's disease and pouchitis. Additional studies are needed to validate whether FMT can assume a complementary role in the standard treatment of IBD.

RevDate: 2019-04-09

Wu X, Zhang T, Chen X, et al (2019)

Microbiota transplantation: Targeting cancer treatment.

Cancer letters, 452:144-151.

Mounting evidence have demonstrated that gut microbiota plays a critical role in cancer patients' therapeutic responses to chemotherapy, radiotherapy and immunotherapy, including clinical efficacy and sensitivity to toxicity. These fascinating findings evoke a possibility of manipulating gut microbiota to optimize anti-cancer treatment from bench to beside. Microbiota transplantation (MT), including fecal microbiota transplantation (FMT) and selective microbiota transplantation (SMT), may improve the effect of anti-cancer treatment and/or reduce the related side effects. The safety and efficacy of MT in cancer treatment are the core of translational research in this promising field, which inspire us to focus on the MT technology and mechanism of MT targeting anti-cancer treatment. To perform clean FMT based on automatic methods by machine in exclusive laboratory has become true. Colonic transendoscopic enteral tubing as a novel delivering way for MT should bring convenience for frequent delivering in practice and feasible tool for confirming the therapeutic effect in research. The present review focuses on the recent findings on role of microbiota on chemotherapy, radiotherapy and immunotherapy, and the methodology, feasibility and challenges of MT in anti-cancer treatment.

RevDate: 2019-03-29

Fischer M (2019)

Recent Research on Fecal Microbiota Transplantation in Inflammatory Bowel Disease Patients.

Gastroenterology & hepatology, 15(1):44-47.

RevDate: 2019-04-04
CmpDate: 2019-04-04

Wang W, Lin L, Du Y, et al (2019)

Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes.

Nature communications, 10(1):1317 pii:10.1038/s41467-019-09267-x.

Currently, there are more than 200 fecal microbiota transplantation (FMT) clinical trials worldwide. However, our knowledge of this microbial therapy is still limited. Here we develop a strategy using sequential tagging with D-amino acid-based metabolic probes (STAMP) for assessing the viabilities of transplanted microbiotas. A fluorescent D-amino acid (FDAA) is first administered to donor mice to metabolically label the gut microbiotas in vivo. The labeled microbiotas are transplanted to recipient mice, which receive a second FDAA with a different color. The surviving transplants should incorporate both FDAAs and can be readily distinguished by presenting two colors simultaneously. Isolation of surviving bacteria and 16S rDNA sequencing identify several enriched genera, suggesting the importance of specific bacteria in FMT. In addition, using STAMP, we evaluate the effects on transplant survival of pre-treating recipients using different antibiotics. We propose STAMP as a versatile tool for deciphering the complex biology of FMT, and potentially improving its treatment efficacy.

RevDate: 2019-04-05

Alsahhar JS, RS Rahimi (2019)

Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy.

Current opinion in gastroenterology, 35(3):145-154.

PURPOSE OF REVIEW: Hepatic encephalopathy is one of the most debilitating clinical manifestations of cirrhosis and associated with increased morbidity and mortality. Treatment modalities available include the nonabsorbable disaccharides (lactulose) and the nonabsorbable antibiotics (rifaximin).

RECENT FINDINGS: Newer therapeutic targets under evaluation include ammonia scavengers (ornithine phenylacetate) and modulation of gut microbiota (fecal microbiota transplantation).

SUMMARY: This review will focus on the pathophysiology of hepatic encephalopathy along with an update on therapeutic targets under investigation.

RevDate: 2019-03-29

Wan JJ, Lin CH, Ren ED, et al (2019)

Effects of Early Intervention With Maternal Fecal Bacteria and Antibiotics on Liver Metabolome and Transcription in Neonatal Pigs.

Frontiers in physiology, 10:171.

The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (>109/mL), respectively, on days 1-6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of arachidonate 12-lipoxygenase (ALOX12), acetyl-CoA acyltransferase 2 (ACAA2), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), glutamic-pyruvic transaminase 2 (GPT2) and argininosuccinate synthase 1 (ASS1) were downregulated (P < 0.05) by AM on day 7, and that the mRNA expressions of arachidonate 15-lipoxygenase (ALOX15), CYP1A2 and GPT2 were downregulated (P < 0.05) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (P < 0.05) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced (P < 0.05) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health.

RevDate: 2019-04-02

Ohara T (2019)

Identification of the microbial diversity after fecal microbiota transplantation therapy for chronic intractable constipation using 16s rRNA amplicon sequencing.

PloS one, 14(3):e0214085 pii:PONE-D-18-34661.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapeutic approach for the treatment of functional gastrointestinal disease by restoring gut microbiota; however, there is a lack of sufficient understanding regarding which microbial populations successfully colonize the recipient gut. This study characterized microbial composition and diversity in patients diagnosed with chronic constipation at 1 month and 1 year after FMT.

METHODS: We explored the microbial diversity of pre- and posttransplant stool specimens from patients using 16S rRNA gene sequencing, followed by functional analysis.

RESULTS: The results identified 22 species of microorganisms colonized in the recipients from the donors at 1 month after FMT. One-year follow-up of the patient identified the colonization of 18 species of microorganisms, resulting in identification of species in significant abundance, including Bacteroides fragilis and Hungatella hathewayi in the recipient at 1 month after FMT and Dialister succinatiphilus, Coprococcus catus, and Sutterella stercoricanis at 1 year after FMT. The majority of the colonized species belong to the phylum Firmicutes and carry genes related to polysaccharide metabolism and that enhance the energy-harvesting efficiency of the host.

CONCLUSION: These results suggest that FMT is effective for the treatment of chronic constipation through the restoration and colonization of donor microbiota in the recipient gut up to 1 year after FMT.

RevDate: 2019-03-29

Liu Z, Wang N, Ma Y, et al (2019)

Hydroxytyrosol Improves Obesity and Insulin Resistance by Modulating Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Frontiers in microbiology, 10:390.

Obesity is a common chronic metabolic disease that is harmful to human health and predisposes the affected individuals to a cluster of pathologies. Insulin resistance (IR) is one of the most frequent complications of obesity. Hydroxytyrosol (HT) may reduce obesity and IR in high-fat diet (HFD)-fed mice; however, the mechanism underlying is still unknown. Systemic low-grade inflammation and intestinal dysfunction are thought to be associated with obesity and IR. In this study, we found that HFD feeding for 8 weeks altered the intestinal microbiota, injured intestinal barrier function, increased endotoxin release into the blood, enhanced the expression of inflammatory factors (TNF-α, IL-1β, IL-6) and lipid accumulation in liver, caused obesity, and aggravated IR via the JNK/IRS (Ser 307) pathway in HFD mice. We also found that HT gavage could reverse those effects and the beneficial effects of HT were transferable through fecal microbiota transplantation. Our data indicate that HT can improve obesity and IR by altering the composition of the intestinal microbiota and improving integrity of the intestinal wall. We propose that HT replenishment may be used as a dietary intervention strategy to prevent obesity and IR.

RevDate: 2019-03-18

Allegretti JR, Kassam Z, Fischer M, et al (2019)

Risk Factors for Gastrointestinal Symptoms Following Successful Eradication of Clostridium difficile by Fecal Microbiota Transplantation (FMT).

Journal of clinical gastroenterology [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapy for recurrent Clostridioides difficile infection (CDI). Many patients report altered bowel habits including constipation, bloating, gas and loose stool post-FMT despite resolution of CDI, and the etiology remains unclear.

METHODS: This was a prospective cohort study of adult patients with recurrent CDI who underwent FMT (1) via colonoscopy with patient-selected donor stool, (2) via colonoscopy from a universal stool bank donor, or (3) via capsules from a universal stool bank. Reassessment occurred 8 weeks post-FMT. Those cured were assessed for gastrointestinal symptoms (bloating, loose stools, constipation). Multivariate logistic regression was performed to assess predictors of post-FMT gastrointestinal symptoms.

RESULTS: A total of 150 subjects underwent FMT for recurrent CDI, of which 68.7% (103) were female, mean age was 61.5 years±18.1 and 31 patients (20.7%) had preexisting irritable bowel syndrome. Thirty-six had FMT via colonoscopy with a patient-selected donor, 67 via colonoscopy with stool bank donors, and 47 via FMT capsules from stool bank donors. Among those cured, 41 (31.2%) had gastrointestinal symptoms post-FMT. The factors associated with symptoms included younger age (57.2 vs. 64.1 y, P=0.03), a baseline history of irritable bowel syndrome (36.6% vs. 13.3%, P=0.002) and preexisting inflammatory bowel disease (31.7% vs. 10%, P=0.002). Small bowel exposure to donor stool was not related to symptoms (63.4% vs. 62.2%, P=0.89).

CONCLUSIONS: Altered bowel habits are a consequence of CDI and are common after FMT. This study suggests that donor type and FMT delivery modality are not related to the presence of irregular gastrointestinal symptoms after FMT.

RevDate: 2019-03-31

Uchiyama K, Naito Y, T Takagi (2019)

Intestinal microbiome as a novel therapeutic target for local and systemic inflammation.

Pharmacology & therapeutics pii:S0163-7258(19)30045-2 [Epub ahead of print].

Recently, the pathogenesis of systemic inflammatory disease such as inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic inflammatory arthritis, asthma, and non-alcoholic fatty liver disease has been reported to be related to the dysbiosis of gut microbiota. The contribution of special bacteria for the development of those diseases has been elucidated by disease animal models such as germ-free mice. Besides, the contribution by several bacteria for the pathogenesis of those diseases has been suggested by detailed analysis of the 16 small ribosomal subunit RNA (16S rRNA) from stool samples of the patients. Gut microbiota-targeted treatment for systemic inflammatory diseases such as fecal microbiota transplant (FMT), and probiotics has been now reported. Though there are several issues to be understood, these treatments have been highlighted as an innovative approach to intractable systemic inflammatory disease. In the present review, recent reports regarding the relation between gut microbiota and systemic inflammatory diseases are discussed with treatments to target gut microbiota.

RevDate: 2019-03-16

Ramesh MS, J Yee (2019)

Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.

Advances in chronic kidney disease, 26(1):30-34.

Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.

RevDate: 2019-03-15

Sood A, Mahajan R, Singh A, et al (2019)

Role of Fecal Microbiota Transplantation for Maintenance of Remission in Patients with Ulcerative Colitis: A Pilot Study.

Journal of Crohn's & colitis pii:5381070 [Epub ahead of print].

OBJECTIVES: To study the role of fecal microbiota transplantation (FMT) in maintenance of remission in ulcerative colitis (UC).

METHODS: In this pilot study, patients with UC in clinical remission after multi-session FMT were randomly allocated to either maintenance FMT or placebo colonoscopic infusion every 8 weeks, for 48 weeks. The standard of care (SOC) therapy was continued in all patients. The primary end point was maintenance of steroid-free clinical remission (Mayo score ≤2, all sub scores ≤ 1) at week 48. Secondary end points were achievement of endoscopic remission (endoscopic Mayo score 0) and histological remission (Nancy grade 0, 1) at week 48.

RESULTS: Sixty one patients in clinical remission were randomized to receive either FMT n=31) or placebo (n=30). The primary outcome was achieved in 27/31 (87.1%) patients allocated FMT versus 20/30 (66.7%) patients assigned placebo (p=0.111). Secondary end points of endoscopic remission [FMT: 18/31 (58.1%) versus placebo: 8/30 (26.7%), p=0.026] and histological remission [FMT: 14/31 (45.2%) versus placebo: 5/30 (16.7%), p=0. 033] were achieved in significantly higher number of patients with FMT. Three patients receiving FMT (9.7%) and 8 patients on placebo (26.7%) relapsed. There were no serious adverse events necessitating discontinuation in patients on FMT, 1 patient who relapsed on placebo required colectomy.

CONCLUSIONS: Maintenance FMT in patients who are in clinical remission may help sustain clinical, endoscopic and histological remission in patients with UC. Keywords: Inflammatory Bowel Disease; Clinical remission; Endoscopic remission; Histological remission.


ESP Quick Facts

ESP Origins

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

ESP Support

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

ESP Rationale

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

ESP Goal

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

ESP Usage

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

ESP Content

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

ESP Help

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

ESP Plans

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

Electronic Scholarly Publishing
21454 NE 143rd Street
Woodinville, WA 98077

E-mail: RJR8222 @

Papers in Classical Genetics

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

Digital Books

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


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


Biographical information about many key scientists.

Selected Bibliographies

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

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