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Metabolic syndrome is a cluster of the most dangerous cardiovascular (CV) risk factors including visceral obesity, insulin resistance, hyperglycemia, alterations in lipid metabolism and arterial hypertension (AH). In particular, AH plays a key role in the complications associated with metabolic syndrome. High salt intake is a well-known risk factor for AH and CV diseases. Vasoconstriction, impaired vasodilation, extracellular volume expansion, inflammation, and an increased sympathetic nervous system (SNS) activity are the mechanisms involved in the pathogenesis of AH, induced by Western diet. Gut dysbiosis in AH is associated with reduction of short chain fatty acid-producing bacteria: acetate, butyrate and propionate, which activate different pathways, causing vasoconstriction, impaired vasodilation, salt and water retention and a consequent high blood pressure. Moreover, increased trimethylamine N-oxide and lipopolysaccharides trigger chronic inflammation, which contributes to endothelial dysfunction and target organs damage. Additionally, a high salt-intake diet impacts negatively on gut microbiota composition. A bidirectional neuronal pathway determines the "brain–gut" axis, which, in turn, influences blood pressure levels. Then, we discuss the possible adjuvant novel treatments related to gut microbiota modulation for AH control. [ABSTRACT FROM AUTHOR]

Background: The gut-brain axis is a bidirectional signaling pathway between the gastrointestinal tract and the brain; it is being studied because of its potential influence in mediating mood, anxiety, and other neuropsychiatric symptoms. Previous research examining the effects of gut microbiota on neuropsychiatric disorders suggests that gut repopulation treatments such as probiotics, microbe therapy, and fecal microbiota transplantation show promising results in treating symptoms of anxiety and depression. This study explores the use of an alternative gut repopulation treatment to fecal microbiota transplantation, known as Microbial Ecosystem Therapeutic (MET)-2, as an intervention against symptoms of depression. MET-2 is a daily, orally administered capsule containing 40 bacterial strains purified from a single healthy donor., Objective: The primary aim of this study is to assess changes in mood in people with major depression that occur pre-, post-, and during the administration of MET-2. The secondary aims are to assess changes in anxiety symptoms, blood biomarker concentrations, and the level of repopulation of healthy gut bacteria as a response to treatment., Methods: In this study, we will recruit 60 adults aged between 18 and 45 years old with major depression and randomly assign them to treatment or placebo groups. Patients in the treatment group will receive MET-2 once a day for 6 weeks, whereas patients in the placebo group will receive a matching placebo for 6 weeks. Participants will complete biweekly visits during the treatment period and a follow-up visit at 2 weeks post treatment. As a primary outcome measure, participants' mood will be assessed using the Montgomery-Asberg Depression Rating Scale. Secondary outcome measures include changes in mood, anxiety, early stress, gastrointestinal symptoms, and tolerability of MET-2 treatment using a series of clinical scales and changes in blood markers, particularly immunoglobulins (Igs; IgA, IgG, and IgM) and inflammatory markers (C-reactive protein, tumor necrosis factor-α, transforming growth factor-β, interleukin-6, and interleukin-10). Changes in the relative abundance, diversity, and level of engraftment in fecal samples will be assessed using 16S rRNA sequencing. All data will be integrated to identify biomarkers that could indicate disease state or predict improvement in depressive symptoms in response to MET-2 treatment., Results: Given the association between the gut microbiome and depression, we hypothesized that participants receiving MET-2 would experience greater improvement in depressive symptoms than those receiving placebo owing to the recolonization of the gut microbiome with healthy bacteria modulating the gut-brain axis connection., Conclusions: This study is the first of its kind to evaluate the safety and efficacy of a microbial therapy such as MET-2 in comparison with placebo for major depressive disorder. We hope that this study will also reveal the potential capabilities of microbial therapies to treat other psychiatric illnesses and mood disorders., Trial Registration: ClinicalTrials.gov NCT04602715; https://clinicaltrials.gov/ct2/show/NCT04602715., International Registered Report Identifier (irrid): DERR1-10.2196/31439., (©Arthi Chinna Meyyappan, Cassandra Sgarbossa, Gustavo Vazquez, David J Bond, Daniel J Müller, Roumen Milev. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.09.2021.)

In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We transplanted gnotobiotic mice with feces from humans to assess the transferability of BAT activity through the microbiota. Individuals with NAFLD (n = 29) have lower BAT activity than those without, and BAT activity is inversely related to hepatic fat content. BAT activity is not related to the characteristics of the fecal microbiota and is not transmissible through fecal transplantation to mice. Thus, low BAT activity is associated with higher hepatic fat accumulation in human adults, but this does not appear to have been mediated through the gut microbiota., Competing Interests: B.A.A. holds the Lau Family scholarship for science and engineering and was funded by the Ontario graduate scholarship. D.P.B. holds the GlaxoSmithKline (GSK) Chair in Diabetes of Université de Sherbrooke, which was created in part through a donation of $1 million by GSK to Université de Sherbrooke. D.P.B. has received honoraria and consulting fees from Boehringer Ingelheim. S.A.S. holds a CIHR Vanier Canada Graduate Scholarship. E.M.D. holds a CIHR Vanier Canada Graduate Scholarship. F.F.A. holds a CIHR postdoctoral fellowship and Diabetes Canada incentive funding. A.C.H. holds research funding from the CIHR and the Natural Sciences and Engineering Research Council of Canada. A.C.C. holds the Canada Research Chair in Molecular Imaging of Diabetes and research funding from the CIHR, Fonds de recherche Québec – Santé, and has participated in advisory boards for Amgen, UniQure, Merck, Janssen, Novo Nordisk, Novartis, HLS Therapeutics Inc., TVM Life Science Management, AstraZeneca, and Eli Lilly and participated in one conference sponsored by AstraZeneca. M.G.S. is funded by the CIHR, Genome Canada, and the W. Garfield Weston Foundation and holds a Tier 1 Canada Research Chair in Interdisciplinary Microbiome Research. J.D.S. receives funding from the CIHR (FDN-154295) and holds a Canada Research Chair in Metabolic Inflammation. Z.P. has received honoraria for advice and speaking from Abbott, Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, and Sanofi, and has received research funds from Amgen, Astra Zeneca/Bristol Myers Squibb, Lexicon, Merck, Novo Nordisk, Sanofi, and the CIHR. G.R.S. receives funding from the CIHR (201709FDN-CEBA-116200), Diabetes Canada Investigator Award (DI-5-17-5302-GS), a Tier 1 Canada Research Chair, and the J. Bruce Duncan Endowed Chair in Metabolic Diseases. He also receives research funding from Espervita Therapeutics, Esperion Therapeutics, Novo Nordisk, and Poxel Pharma and honoraria and consulting fees from Astra Zeneca, Eli Lilly, Esperion Therapeutics, Poxel, and Merck. K.M.M. holds research funding from the CIHR, Heart and Stroke Foundation of Canada, McMaster Children’s Hospital Foundation, and McMaster University. She has received research funds from Astra Zeneca and is an advisory board member for Novo Nordisk and Akcea Therapeutics, Canada., (© 2021 The Author(s).)

Background & Aims: Clostridium difficile infection (CDI) can relapse in patients with significant comorbidities. A subset of these patients becomes dependent on oral vancomycin therapy for prolonged periods with only temporary clinical improvement. These patients incur significant morbidity from recurrent diarrhea and financial costs from chronic antibiotic therapy. Methods: We sought to investigate whether self- or family-administered fecal transplantation by low volume enema could be used to definitively treat refractory CDI. Results: We report a case series (n = 7) where 100% clinical success was achieved in treating these individuals with up to 14 months of follow-up. Conclusions: Fecal transplantation by low volume enema is an effective and safe option for patients with chronic relapsing CDI, refractory to other therapies. Making this approach available in health care settings has the potential to dramatically increase the number of patients who could benefit from this therapy. [Copyright &y& Elsevier]

The microbiome lies at the forefront of scientific research, as researchers work to uncover its mysterious influence on human development and disease. This paper reviews how the microbiome is studied, how researchers can improve its study, and what clinical applications microbiome research might yield. For this review, we analyzed studies concerning the role of the microbiome in disease and early development, the common methodologies by which the microbiome is researched in the lab, and modern clinical treatments for dysbiosis and their possible future applications. We found that the gut microbiome is essential for proper development of various physiological systems and that gut dysbiosis is a clear factor in the etiology of various diseases. Furthermore, we found that germ-free animal models and microbiome manipulation techniques are inadequate, reducing the efficacy of microbiome research. Nonetheless, research continues to show the significance of microbiome manipulation in the clinical treatment of disease, having shown great promise in the prevention and treatment of dysbiosis. Though the clinical applications of microbiome manipulation are currently limited, the significance of dysbiosis in the etiology of a wide array of diseases indicates the significance of this research and highlights the need for more effective research methods concerning the microbiome. [ABSTRACT FROM AUTHOR]

Keywords: parkinson's disease; gut microbiota; enteric nervous system; gut-brain axis; microbiota-targeted therapies; fecal transplant Parkinson's disease, gut microbiota, enteric nervous system, gut-brain axis, microbiota-targeted therapies, fecal transplant. [Extracted from the article]

Parkinson's disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. This shift in understanding has opened the door to potential new biomarkers from multiple sites in the body. This review focuses on emerging candidates for PD biomarkers in the context of current diagnostic approaches and multiple organ systems that contribute to disease.

As the importance of the gut microbiota in health and disease is a subject of growing interest, fecal microbiota transplantation (FMT) was suggested as an attractive therapeutic strategy to restore homeostasis of the gut microbiota, thereby treating diseases that were associated with alteration of the gut microbiota. FMT involves the administration of fresh, frozen, or dried fecal microorganisms from the gut of a healthy donor into the intestinal tract of a patient. This rediscovery of the potential benefits of an ancient practice was accompanied by a rapid progression of our understanding of the roles and mechanisms of gut microbes in the pathogenesis of disease. With a growing number of diseases being associated with dysbiosis or the alteration of gut microbiota, FMT was suggested as an attractive therapeutic strategy to "reset the gut" and initiate clinical resolutions or remissions. The number of FMT clinical trials is increasing worldwide, but no trials are registered in the Gulf region; this suggested the need for raising awareness of the latest studies on FMT. This review presented the emergent preclinical and clinical data to give an overview of the potential clinical applications, the benefits, and inconveniences that were worth considering for eventual future testing of fecal transplants in Qatar and the Middle East. This study highlighted the diversity of methods tested and commented on the variables that can affect the assessment of the effectiveness of FMT in specific diseases. The risks associated with FMT and the threat of antimicrobial resistance for this therapeutic approach were reviewed. From gastrointestinal diseases to neurodevelopmental disorders, understanding the roles of the gut microbiota in health and disease should be at the heart of developing novel, standardized, yet personalized, methods for this ancient therapeutic approach., (© 2021 Al-Ali, Ahmed, Shafiq, McVeigh, Chaari, Zakaria, Bendriss, licensee HBKU Press.)

The microbiome lies at the forefront of scientific research, as researchers work to uncover its mysterious influence on human development and disease. This paper reviews how the microbiome is studied, how researchers can improve its study, and what clinical applications microbiome research might yield. For this review, we analyzed studies concerning the role of the microbiome in disease and early development, the common methodologies by which the microbiome is researched in the lab, and modern clinical treatments for dysbiosis and their possible future applications. We found that the gut microbiome is essential for proper development of various physiological systems and that gut dysbiosis is a clear factor in the etiology of various diseases. Furthermore, we found that germ-free animal models and microbiome manipulation techniques are inadequate, reducing the efficacy of microbiome research. Nonetheless, research continues to show the significance of microbiome manipulation in the clinical treatment of disease, having shown great promise in the prevention and treatment of dysbiosis. Though the clinical applications of microbiome manipulation are currently limited, the significance of dysbiosis in the etiology of a wide array of diseases indicates the significance of this research and highlights the need for more effective research methods concerning the microbiome.

The gut microbiome is an exciting new area of research in chronic liver disease. It has shown promise in expanding our understanding of these complicated disease processes and has opened up new treatment modalities. The aim of this review is to increase understanding of the microbiome and explain the collection and analysis process in the context of liver disease. It also looks at our current understanding of the role of the microbiome in the wide spectrum of chronic liver diseases and how it is being used in current therapies and treatments., Competing Interests: Disclosure None for B. Reuter, JSB’s institution received research grants from Salix Pharmaceuticals and he has served on advisory boards for Norgine and Merz Pharmaceuticals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rarely, in fulminant Clostridium difficile infection (CDI), the rectal stump is persistently infected following total abdominal colectomy. We report cure of a septic patient with proctitis by fecal microbiota transplant via rectal swabs (mini-FMT). This novel procedure offers a management option for recurrent CDI following total abdominal colectomy. [ABSTRACT FROM AUTHOR]

Antibiotic use within the first 8 weeks after fecal microbiota transplantation (FMT) may disrupt microbial engraftment and limit FMT effectiveness. We aimed to assess the burden of antibiotic use within 8 weeks of FMT and its impact on FMT efficacy. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the fecal microbial transplantation (FMT) to treat life-threatening sepsis. Topics discussed include antimicrobial and steroidal therapy disrupting the microbiome and causing alterations in epithelial permeability and the role of normal microbiota in maintaining epithelial structure and function.

• The gut microbiome plays an important role in host immune response. • Alterations in lung bacterial content may influence COPD and asthma. • Gut microbiota has shown to alter effects of cancer therapy in murine models. • NSCLC patients responding to checkpoint inhibitors had higher microbiome diversity. • Best approaches to modulate the gut microbiome are under investigation. The gut microbiome is a collection of diverse bacteria that normally reside within the gastrointestinal tract. In recent years, the relationship between the gut microbiome, and fluctuations in it, and overall health has been an intense area of interest in medical research. In addition to having a barrier role in the gastrointestinal tract, there appears to be an immune function of gut microbiota, with a correlation between dysbiosis of gut microbiota and certain inflammatory and malignant disease states of the gastrointestinal system. We have also seen evidence that the gut microbiome can impact response to immunotherapy in melanoma patients. Evidence has also emerged to show that the lung has a microbiome of its own. In this review we will explore the relationship between the gut and lung microbiomes, known as the gut-lung axis, and the potential effects of this axis on anticancer therapy in lung cancer, including checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. Although RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immunodeficient mice, which, we hypothesized, reflected select microbes protecting against RV. Accordingly, such RV resistance was transferred by co-housing and fecal transplant. RV-protecting microbiota were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. This approach revealed that segmented filamentous bacteria (SFB) were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of previously defined RV-impeding factors, including interferon, IL-17, and IL-22. Colonization of the ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Incubation of RV with SFB-containing feces reduced infectivity in vitro , suggesting direct neutralization of RV. Thus, independent of immune cells, SFB confer protection against certain enteric viral infections and associated diarrheal disease. • Some mouse colonies developed spontaneous resistance to rotavirus (RV) infection • Fecal microbial transplantation transfers RV resistance • Protection against RV was mediated by segmented filamentous bacteria (SFB) • SFB impeded RV by increasing epithelial cell turnover A bacterium can protect against rotavirus infection in mice independent of the immune system. [ABSTRACT FROM AUTHOR]

Background Fecal microbiota transplantation (FMT) treats Clostridioides difficile infection (CDI). Little is known regarding the changes in antimicrobial resistance (AMR) genes and potential pathogen burden that occur in pediatric recipients of FMT. The aim of this study was to investigate changes in AMR genes, potential pathogens, species, and functional pathways with FMT in children. Methods Nine children with recurrent CDI underwent FMT. Stool was collected from donor and recipient pre-FMT and longitudinally post-FMT for up to 24 weeks. Shotgun metagenomic sequencing was performed. Reads were analyzed using PathoScope 2.0. Results All children had resolution of CDI. AMR genes decreased post-FMT (P <.001), with a sustained decrease in multidrug resistance genes (P <.001). Tetracycline resistance genes increased post-FMT (P <.001). Very low levels of potential pathogens were identified in donors and recipients, with an overall decrease post-FMT (P <.001). Prevotella sp. 109 expanded in all recipients post-FMT, and no recipients had any clinical infection. Alpha diversity was lower in recipients vs donors pre-FMT (P <.001), with an increase post-FMT (P ≤.002) that was sustained. Beta diversity differed significantly in pre- vs post-FMT recipient samples (P <.001). Bacterial species Faecalibacterium prausnitzii and Bacteroides ovatus showed higher abundance in donors than recipients (P =.008 and P =.040, respectively), with expansion post-FMT. Biosynthetic pathways predominated in the donor and increased in the recipient post-FMT. Conclusions FMT for CDI in children decreases AMR genes and potential pathogens and changes microbiota composition and function. However, acquisition of certain AMR genes post-FMT combined with low levels of potential pathogens found in donors suggests that further study is warranted regarding screening donors using metagenomics sequencing before FMT. [ABSTRACT FROM AUTHOR]

Highlights from the article: Corrigendum: The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy. Copyright © 2019 Chong, Chin, Looi, Wong, Madhavan and Yong. Copyright of Frontiers in Microbiology is the property of Frontiers Media S.A. and its content.

Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background & Aims: In short-bowel syndrome (SBS), inadequate intestinal adaptation is responsible for the majority of complications, including sepsis, liver failure, and death. In this study, we sought to further delineate the adaptive response to identify potential therapeutic targets., Methods: We performed a 75% small-bowel resection (SBR) or sham operation on C57Bl/6J wild-type (WT), lipocalin-2 (LCN2) -/- , and interleukin 22 (IL22) -/- mice. Exogenous IL22 was administered to SBR WT mice. Cecal fecal matter from SBR WT and SBR LCN2 -/- mice were transplanted into germ-free mice. Intestinal permeability, inflammation, proliferation, and the microbiome were evaluated 1 week after surgery. CD4 + IL22 + laminal propria lymphocytes were sorted by flow cytometry. Naïve T cells were polarized to T-helper cells with or without LCN2., Results: A 75% SBR in a mouse re-creates the increased intestinal permeability, enterocyte proliferation, and intestinal dysbiosis seen in SBS. LCN2 expression increases after 75% SBR, and this increase can be abrogated with broad-spectrum antibiotic treatment. LCN2 -/- mice have less intestinal inflammation, increased IL22 expression, and greater adaptation as evidenced by less intestinal permeability, increased carbohydrate enzyme expression, less weight loss, and less dysbiosis after 75% SBR than WT mice. The proinflammatory and anti-adaptive effects of LCN2 can be transferred to germ-free mice via a fecal transplant. Administration of exogenous IL22 improves adaptation and restores the normal microbiome after 75% SBR in WT mice., Conclusions: LCN2 promotes inflammation and slows intestinal adaptation through changes in the microbiome and IL22 inhibition in a mouse SBS model. Strategies to reduce LCN2 may offer novel therapeutic approaches to enhance adaptation in SBS., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent decades, there has been a very rapid increase in the prevalence of diabetes globally, with serious health and economic implications. Although today there are several therapeutic treatments for this disease, these do not address the causes of the disease and have serious side effects, so it is necessary to seek new treatments to replace or complement the existing ones. Among these complementary treatments, a strong link between the intestinal microbiota and diabetes has been demonstrated, which has focused attention on the use of biotherapy to regulate the function of the intestinal microbiota and, thus, treat diabetes. In this way, the main objective of this work is to provide a review of the latest scientific evidence on diabetes, gathering information about new trends in its management, and especially, the influence of the intestinal microbiota and microbiome on this pathology. It is possible to conclude that the relationship between the intestinal microbiota and diabetes is carried out through alterations in energy metabolism, the immune system, changes in intestinal permeability, and a state of low-intensity systemic inflammation. Although, currently, most of the experimental work, using probiotics for diabetes management, has been done on experimental animals, the results obtained are promising. Thus, the modification of the microbiota through biotherapy has shown to improve the symptoms and severity of diabetes through various mechanisms related to these alterations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It is well-recognized that the gut microbiota (GM) is crucial for gut function, metabolism, and energy cycles. The GM also has effects on neurological outcomes via many mechanisms, such as metabolite production and the gut-brain axis. Emerging evidence has gradually indicated that GM dysbiosis plays a role in several neurological diseases, such as Parkinson's disease (PD), Alzheimer's disease, depression, and multiple sclerosis. Several studies have observed that PD patients generally suffer from gastrointestinal disorders and GM dysbiosis prior to displaying motor symptoms, but the specific link between the GM and PD is not clearly understood. In this review, we aim to summarize what is known regarding the correlation between the GM and PD pathologies, including direct, and indirect evidence., (Copyright © 2019 Yang, Zhao, Ali Shah, Wu, Lai, Zhang, Li, Guan, Zhao, Li, Gao, Zhou and Yang.)

Non-alcoholic fatty-liver disease (NAFLD) is now considered one of the leading causes of liver disease worldwide and is associated with metabolic syndrome and obesity. There are several factors contributing to the disease state. Recent research suggests that the intestinal microbiota (IM) and bacterial products may play a role through several mechanisms which include increased energy uptake, intestinal permeability and chronic inflammation. In addition to diet and exercise, treatment options targeting the IM are being investigated and include the use of pre-, pro- and synbiotics as well as the possibility of fecal microbial transfers. This literature review explores the relationship between NAFLD and the IM as well as highlight new IM treatment options that may become available in the near future.

Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10-15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fecal microbiota transplantation (FMT) has become a common rescue therapy for recurrent Clostridium difficile infection, and encapsulated delivery (cFMT) of healthy donor microbiota shows similar clinical efficacy as more traditional routes of administration. In this study, we characterized long-term patterns of bacterial engraftment in a cohort of 18 patients, who received capsules from one of three donors, up to 409 days post-FMT. Bacterial communities were characterized using Illumina sequencing of the V5-V6 hypervariable regions of the 16S rRNA gene, and engraftment was determined by using the Bayesian algorithm SourceTracker. All patients recovered clinically and were free of C. difficile infection following cFMT. The majority of patients (61%) showed high levels of engraftment after the first week following FMT, which were sustained throughout the year. A small subset, 22%, experienced a decline in donor engraftment after approximately 1 month, and a few patients (17%), two of whom were taking metformin, showed delayed and low levels of donor engraftment. Members of the genera Bacteroides , Parabacteroides , and Faecalibacterium were significantly and positively correlated with donor similarity (ρ = 0.237 to 0.373, P  ≤ 0.017). Furthermore, throughout the year, patient fecal communities showed significant separation based on the donor fecal microbiota that they received ( P  < 0.001). Results of this study, which characterize long-term engraftment following cFMT, suggest that numerical donor similarity is not strictly related to clinical outcome and identify a persistent donor-specific effect on patient fecal microbial communities. Furthermore, results suggest that members of the Bacteroidetes may be important targets to improve engraftment via cFMT. IMPORTANCE Recurrent Clostridium difficile infection (rCDI) is the most common cause of hospital- and community-acquired diarrheal infection associated with antibiotic use. Fecal microbiota transplantation (FMT), a treatment that involves administration of fecal bacteria from a healthy donor to a recipient patient, is a highly effective rescue therapy for rCDI that is increasingly being incorporated into standard clinical practice. Encapsulated, freeze-dried preparations of fecal microbiota, administered orally, offer the simplest and most convenient route of FMT delivery for patients (cFMT). In this study, we evaluated the extent of bacterial engraftment following cFMT and the duration of donor bacterial persistence. All patients studied recovered clinically but showed differing patterns in long-term microbial community similarity to the donor that were associated with members of the bacterial group Bacteroidetes , previously shown to be prominent contributors to rCDI resistance. Results highlight long-lasting, donor-specific effects on recipient patient microbiota and reveal potential bacterial targets to improve cFMT engraftment., (Copyright © 2019 Staley et al.)

Background: Emerging trials suggest fecal microbiota transplantation (FMT) is a promising treatment for ulcerative colitis; however, there is a paucity of data in Crohn disease (CD)., Objective: The objectives of this article are to determine whether single-dose FMT improves clinical and endoscopic outcomes in CD patients and to identify meaningful changes in the microbiome in response to FMT., Methods: We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT., Results: Three of 10 patients responded to FMT. Two of 10 patients had significant adverse events requiring escalation of therapy. On microbiome analysis, bacterial communities of responders had increased relative abundance of bacteria commonly found in donor gut microbiota., Conclusions: Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population. Clinicaltrials.gov number: NCT02460705.

Irritable bowel syndrome (IBS) is a functional disorder which affects a large proportion of the population globally. The precise etiology of IBS is still unknown, although consensus understanding proposes IBS to be of multifactorial origin with yet undefined subtypes. Genetic and epigenetic factors, stress-related nervous and endocrine systems, immune dysregulation and the brain-gut axis seem to be contributing factors that predispose individuals to IBS. In addition to food hypersensitivity, toxins and adverse life events, chronic infections and dysbiotic gut microbiota have been suggested to trigger IBS symptoms in tandem with the predisposing factors. This review will summarize the pathophysiology of IBS and the role of gut microbiota in relation to IBS. Current methodologies for microbiome studies in IBS such as genome sequencing, metagenomics, culturomics and animal models will be discussed. The myriad of therapy options such as immunoglobulins (immune-based therapy), probiotics and prebiotics, dietary modifications including FODMAP restriction diet and gluten-free diet, as well as fecal transplantation will be reviewed. Finally this review will highlight future directions in IBS therapy research, including identification of new molecular targets, application of 3-D gut model, gut-on-a-chip and personalized therapy.

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.

Two immunocompromised patients with relapsing gastrointestinal infection with relatively resistant Salmonella infantis were cured with prolonged ertapenem followed by encapsulated fecal transplant. [ABSTRACT FROM AUTHOR]

Background & Aims Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (CDI). However, transferring undefined living bacteria entails uncontrollable risks for infectious and metabolic or malignant diseases, particularly in immunocompromised patients. We investigated whether sterile fecal filtrates (containing bacterial debris, proteins, antimicrobial compounds, metabolic products, and oligonucleotides/DNA), rather than intact microorganisms, are effective in patients with CDI. Methods We performed a clinical case series to investigate the effects of fecal filtrate transfer (FFT) in 5 patients with symptomatic chronic-relapsing CDI at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (Kiel, Germany). Patients were followed up for at least 6 months and for up to 33 months. Stool was collected from 5 donors selected by the patients, and fully characterized according to FMT standards. Stool was sterile-filtered to remove small particles and bacteria; the filtrate was transferred to patients in a single administration via nasojejunal tube. Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared. Results In all 5 patients, FFT restored normal stool habits and eliminated symptoms of CDI for a minimum period of 6 months. Proteome analyses of selected FFT filtrates showed no obvious protein candidates associated with therapeutic efficacy. 16S ribosomal RNA gene sequencing detected diverse bacterial DNA signatures in the filtrates. Analysis of virus-like particles from a filtrate found to reduce symptoms of CDI showed a complex signature of bacteriophages. Bacterial phylogeny and virome profile analyses of fecal samples from recipients indicated longitudinal changes in microbial and viral community structures after FFT. Conclusions A preliminary investigation of 5 patients with CDI shows that transfer of sterile filtrates from donor stool (FFT), rather than fecal microbiota, can be sufficient to restore normal stool habits and eliminate symptoms. This finding indicates that bacterial components, metabolites, or bacteriophages mediate many of the effects of FMT, and that FFT might be an alternative approach, particularly for immunocompromised patients. [ABSTRACT FROM AUTHOR]

Intestinal microbiota are involved in the pathogenesis of Crohn’s disease, ulcerative colitis, and pouchitis. We review the mechanisms by which these gut bacteria, fungi, and viruses mediate mucosal homeostasis via their composite genes (metagenome) and metabolic products (metabolome). We explain how alterations to their profiles and functions under conditions of dysbiosis contribute to inflammation and effector immune responses that mediate inflammatory bowel diseases (IBD) in humans and enterocolitis in mice. It could be possible to engineer the intestinal environment by modifying the microbiota community structure or function to treat patients with IBD—either with individual agents, via dietary management, or as adjuncts to immunosuppressive drugs. We summarize the latest information on therapeutic use of fecal microbial transplantation and propose improved strategies to selectively normalize the dysbiotic microbiome in personalized approaches to treatment. [ABSTRACT FROM AUTHOR]

Colonization by toxin-producing bacteria in the gut plays a major role in bowel problems in autistic patients. Prebiotics can inhibit the growth of these pathogenic microbes by nourishing beneficial bacteria, while probiotics--live microorganisms--can balance the gut bacteria; thus, both together can maintain healthy bacteria in the gut. The present study was conducted to find the effect of probiotics and prebiotics in balancing the gut flora in a rodent model of autism linked with a clindamycin-induced altered gut. The effects of probiotics and prebiotics on oxidative stress markers in the brain were also evaluated. Eight groups of hamsters were assigned, with Group I serving as the control; Group II, as the autistic model, was treated with 250 mg propionic acid/kg BW/day for 3 days; Group III was treated with clindamycin 30 mg/kg BW for 3 days; Groups IV and V were treated with bee pollen and propolis (supposed prebiotics) at a dose of 250 mg/kg BW/day for 28 days; Group VI and Group VII were treated with Lactobacillus paracaseii and Protexin® (supposed probiotics) for 28 days; and finally, Group VIII was anorectally transplanted with stool from normal animals for 5 days. Remarkable changes were measured in oxidative stress markers, primarily glutathione and vitamin C, in the brains of hamsters in the propionic acid- and clindamycin-treated group. All probiotic/prebiotic treatments showed ameliorative effects; however, lactobacillus had the strongest effect. We conclude that pro-and prebiotic supplements may be effective to revive healthy digestive system function in autistic patients. The disappointing results of the fecal transplants suggest that further study is needed to develop an appropriate technique.

Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States with significant risk of both morbidity and mortality. While antimicrobial therapy forms the basis of treatment, there are several clinical scenarios in which antimicrobial therapy alone is insufficient. Evidence continues to show the safety and efficacy fecal microbiota transplantation (FMT) in recurrent and severe CDI. This review will outline FMT efficacy, safety, and indications and present practical advice for clinicians interested in best practices around delivery of FMT., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that resveratrol can improve glucose homeostasis in obesity via changes in the gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest that either live gut microbiota or bacterial-derived metabolites from resveratrol ingestion are responsible for producing the observed benefits in recipients. Herein, we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. The effects of FMTs from resveratrol-fed mice are also associated with decreased inflammation in the colon of obese recipient mice. Furthermore, we show that sterile fecal filtrates from resveratrol-fed mice are sufficient to improve glucose homeostasis in obese mice, demonstrating that nonliving bacterial, metabolites, or other components within the feces of resveratrol-fed mice are sufficient to reduce intestinal inflammation. These postbiotics may be an integral mechanism by which resveratrol improves hyperglycemia in obesity. Resveratrol-FMTs also reduced the systolic blood pressure of hypertensive mice within 2 wk of the first transplant, indicating that the beneficial effects of resveratrol-FMTs may also assist with improving cardiovascular conditions associated with the metabolic syndrome.