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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 25 Sep 2018 at 01:34 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: 2018-09-24

Shogbesan O, Poudel DR, Victor S, et al (2018)

A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients.

Canadian journal of gastroenterology & hepatology, 2018:1394379.

Background: Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown.

Methods: We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated.

Results: Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations.

Conclusion: We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.

RevDate: 2018-09-24
CmpDate: 2018-09-24

Kang Y, Y Cai (2018)

Future prospect of faecal microbiota transplantation as a potential therapy in asthma.

Allergologia et immunopathologia, 46(3):307-309.

There is convincing evidence from both human and animal studies suggesting that the gut microbiota plays an important role in regulating immune responses associated with the development of asthma. Certain intestinal microbial strains have been demonstrated to suppress or impair immune responsiveness in asthma experimental models, suggesting that specific species among gut commensal microbiota may play either a morbific or phylactic role in the progression of asthma. Evidence to date suggests that the intestinal microbiota represent fertile targets for prevention or management of asthma. The faecal microbiota transplantation (FMT) is a rather straightforward therapy that manipulates the human gastrointestinal (GI) microbiota, by which a healthy donor microbiota is transferred into an existing but disturbed microbial ecosystem. The FMT may therefore represent a therapeutic approach for asthma treatment in the foreseeable future. At present, FMT therapy for asthma is very limited and should be actively studied. Considerable efforts are needed to increase our knowledge in the field of FMT therapy for asthma. In this review, we aimed to provide several insights into the development of FMT therapy for asthma.

RevDate: 2018-09-21
CmpDate: 2018-09-21

Dunwoody R, Steel A, Landy J, et al (2018)

Clostridium difficile and cystic fibrosis: management strategies and the role of faecal transplantation.

Paediatric respiratory reviews, 26:16-18.

Clostridium difficile is a bacterial infection that colonises the gut in susceptible hosts. It is associated with exposure to healthcare settings and antibiotic use. It could be assumed that cystic fibrosis (CF) patients are a high-risk group for C.difficile. However, despite high carriage rates, CF patients have low rates of active disease. There are guidelines for the treatment of C.difficile, however little is published specific to treating C.difficile in CF. This article provides an overview of the current management strategies for C.difficile in CF, including a description of the first faecal transplantation in this patient population.

RevDate: 2018-09-21
CmpDate: 2018-09-21

Van Laethem Y (2016)


Revue medicale de Bruxelles, 37(3):133-134.

RevDate: 2018-09-20

Fortier LC (2018)

Bacteriophages Contribute to Shaping Clostridioides (Clostridium) difficile Species.

Frontiers in microbiology, 9:2033.

Bacteriophages (phages) are bacterial viruses that parasitize bacteria. They are highly prevalent in nature, with an estimated 1031 viral particles in the whole biosphere, and they outnumber bacteria by at least 10-fold. Hence, phages represent important drivers of bacterial evolution, although our knowledge of the role played by phages in the mammalian gut is still embryonic. Several pathogens owe their virulence to the integrated phages (prophages) they harbor, which encode diverse virulence factors such as toxins. Clostridioides (Clostridium) difficile is an important opportunistic pathogen and several phages infecting this species have been described over the last decade. However, their exact contribution to the biology and virulence of this pathogen remains elusive. Current data have shown that C. difficile phages can alter virulence-associated phenotypes, in particular toxin production, by interfering with bacterial regulatory circuits through crosstalk with phage proteins for example. One phage has also been found to encode a complete binary toxin locus. Multiple regulatory genes have also been identified in phage genomes, suggesting that their impact on the host can be complex and often subtle. In this minireview, the current state of knowledge, major findings, and pending questions regarding C. difficile phages will be presented. In addition, with the apparent role played by phages in the success of fecal microbiota transplantation and the perspective of phage therapy for treatment of recurrent C. difficile infection, it has become even more crucial to understand what C. difficile phages do in the gut, how they impact their host, and how they influence the epidemiology and evolution of this clinically important pathogen.

RevDate: 2018-09-20

Lu M, Z Wang (2018)

Microbiota and Aging.

Advances in experimental medicine and biology, 1086:141-156.

The human gut microbiota is a huge ecosystem that provides lots of functions for host development, immune system, and metabolism. Gut microbiota is linked to lots of diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), irritable bowel syndrome, and cardiovascular disease (CVD). Few studies, however, have noted the relationship between aging and microbiota; the connection between aging and microbiota remains largely to be researched. In this review, recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in antiaging medicine.

RevDate: 2018-09-20
CmpDate: 2018-09-20

Diamond C, T McNeilly (2017)

Faecal Microbiota Transplantation for Clostridium Difficile - a local perspective.

The Ulster medical journal, 86(2):108-110.

Clostridium Difficile represents one of the major challenges of the antimicrobial era with associated significant morbidity. Treatment options are limited to a number of specific antibiotics with significant failure rates. Faecal Microbiota Transplantation has been recognised as a possible treatment option when standard therapy fails. We report a local case of Clostridium Difficile Infection ultimately requiring Faecal Microbiota Transplantation with good success. While no formal service providing the treatment is available within Northern Ireland it is a feasible treatment option for Clostridium Difficile Infection.

RevDate: 2018-09-20
CmpDate: 2018-09-20

Nishimura N, Tanabe H, Komori E, et al (2018)

Transplantation of High Hydrogen-Producing Microbiota Leads to Generation of Large Amounts of Colonic Hydrogen in Recipient Rats Fed High Amylose Maize Starch.

Nutrients, 10(2): pii:nu10020144.

The hydrogen molecule (H₂), which has low redox potential, is produced by colonic fermentation. We examined whether increased hydrogen (H₂) concentration in the portal vein in rats fed high amylose maize starch (HAS) helped alleviate oxidative stress, and whether the transplantation of rat colonic microbiota with high H₂ production can shift low H₂-generating rats (LG) to high H₂-generating rats (HG). Rats were fed a 20% HAS diet for 10 days and 13 days in experiments 1 and 2, respectively. After 10 days (experiment 1), rats underwent a hepatic ischemia-reperfusion (IR) operation. Rats were then categorized into quintiles of portal H₂ concentration. Plasma alanine aminotransferase activity and hepatic oxidized glutathione concentration were significantly lower as portal H₂ concentration increased. In experiment 2, microbiota derived from HG (the transplantation group) or saline (the control group) were orally inoculated into LG on days 3 and 4. On day 13, portal H₂ concentration in the transplantation group was significantly higher compared with the control group, and positively correlated with genera Bifidobacterium, Allobaculum, and Parabacteroides, and negatively correlated with genera Bacteroides, Ruminococcus, and Escherichia. In conclusion, the transplantation of microbiota derived from HG leads to stable, high H₂ production in LG, with the resultant high production of H₂ contributing to the alleviation of oxidative stress.

RevDate: 2018-09-19

Staley C, Kaiser T, Vaughn BP, et al (2018)

Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.

Microbiome, 6(1):166 pii:10.1186/s40168-018-0549-6.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery.

RESULTS: In total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P < 0.05) observed among patient's pre-FMT samples was restored following cap-FMT. At 1 week post-FMT, community composition varied by clinical outcome (ANOSIM P < 0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7 days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8-20 days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20-30% of the communities were similar to a composite healthy microbiota consisting of all donor samples.

CONCLUSIONS: Regression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7 days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor.

RevDate: 2018-09-18

Tariq R, Weatherly RM, Kammer PP, et al (2017)

Experience and Outcomes at a Specialized Clostridium difficile Clinical Practice.

Mayo Clinic proceedings. Innovations, quality & outcomes, 1(1):49-56 pii:S2542-4548(17)30012-7.

Objective: To report our experience with and outcomes among patients referred to a specialized Clostridium difficile clinical practice.

Patients and Methods: We retrospectively identified consecutive patients referred for Clostridium difficile infection (CDI) management from January 1, 2013, through May 30, 2015. Data were collected for demographic characteristics, CDI history, final diagnoses, and management.

Results: Overall, 211 patients (median age, 65 years; 66.4% women) were included. The most common indications for referral were recurrent CDI in 199 patients (94.3%), first CDI episode in 5 patients (2.4%), and chronic diarrhea in 7 patients (3.3%). After evaluation, the diagnoses were recurrent CDI in 127 patients (60.2%), resolved CDI in 36 patients (17.1%), first-episode CDI in 5 patients (2.4%), and non-CDI in 43 patients (20.4%). The most common non-CDI diagnoses were postinfection irritable bowel syndrome (PI-IBS) in 32 patients (15.2% overall), inflammatory bowel disease (n=3), small intestinal bacterial overgrowth (n=2), microscopic colitis (n=1), and asymptomatic C difficile colonization (n=2). Two patients had diabetic gastroparesis and food intolerances, and 1 had chronic constipation with overflow diarrhea. Of 127 patients with recurrent CDI, 30 (23.6%) received antibiotics; of these 30, 12 had antibiotic treatment failure and received fecal microbiota transplantation (FMT) for recurrent CDI. Among 97 patients (76.4%) who underwent FMT, 85 (87.6%) were cured after the first FMT, 5 were cured after the second FMT, and 7 were treated with antibiotics for FMT failure, with resolution of symptoms.

Conclusion: A substantial proportion of patients referred for CDI subsequently received alternative diagnoses; PI-IBS was the most common. Patients being referred for recurrent CDI should be evaluated carefully for alternative diagnoses.

RevDate: 2018-09-19
CmpDate: 2018-09-19

Akrami K, DA Sweeney (2018)

The microbiome of the critically ill patient.

Current opinion in critical care, 24(1):49-54.

PURPOSE OF REVIEW: Advances in the understanding of the human microbiome outside of the ICU have led investigators to consider the role of the microbiome in critical illness. The picture that is being elucidated is one of dysbiosis occurring at multiple sites in the critically ill patient. This review describes the changes that occur in the various microbiomes of a critically ill patient, the implications of these changes and shows how advances in the understanding of dysbiosis may lead to microbiome-targeted therapies.

RECENT FINDINGS: Critically ill patients undergo dysbiosis at several organ sites including the skin, gastrointestinal system and the lungs with loss of microbial diversity and a propensity for potentially pathogenic organisms to dominate a particular microbiome. These microbiome changes appear to be predictive of clinical outcome. While the use of fecal microbial transplantation has been demonstrated to be an effective treatment for recurrent Clostridium difficile infection, the use of fecal microbial transplantation and other microbiome modifying therapies may have a role in managing critical illness in the ICU.

SUMMARY: A growing understanding of the microbiome in the critically ill may modify current dogma regarding the pathogenesis of sepsis and other life-threatening conditions seen in the ICU, thereby fundamentally changing antibiotic stewardship and the management of the critically ill patient.

RevDate: 2018-09-18

Drastich P, Bajer L, M Kverka (2018)

Possibilities of therapeutic manipulation of the gut microbiota.

Vnitrni lekarstvi, 64(6):665-671.

Human gut microbiota, complex ecosystem of microbes associated with human gut, is essential for the development of the host's immune system and many other physiological functions. Recently, numerous diseases and syndromes were associated with disruption of this ecosystem thus stressing its importance in maintaining the host's health. Growing evidence suggests that by manipulating the gut microbiota, some of these diseases could be treated or even prevented. These manipulations include changes in diet, use of probiotics, prebiotics, antibiotics and fecal microbiota transplantation (FMT). The successes in FMT treatment of recurrent infection of Clostridium difficile led recently to a great interest in extending this treatment modality to other diseases with proven disruption of gut microbiota, such as ulcerative colitis or metabolic syndrome. Key words: Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota - prebiotics - probiotics.

RevDate: 2018-09-18
CmpDate: 2018-09-18

Ooijevaar RE, van Beurden YH, Terveer EM, et al (2018)

Update of treatment algorithms for Clostridium difficile infection.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 24(5):452-462.

BACKGROUND: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI.

AIM: To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies and gut microbiota modulating therapies.

SOURCES: A literature review was performed for clinical trials published in PubMed, Embase or Cochrane Library between January 2013 and November 2017.

CONTENT: We analysed 28 clinical trials and identified 14 novel agents. Completed phase 2 studies were found for cadazolid, LFF571, ridinilazole and nontoxigenic C. difficile strains. Four phase 3 active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n = 2) and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with faecal microbiota transplantation were analysed, describing faecal microbiota transplantation by upper or lower gastrointestinal route (n = 5) or by capsules (n = 2).

IMPLICATIONS: Metronidazole is mentioned in the ESCMID guideline as first-line therapy, but we propose that oral vancomycin will become the first choice when antibiotic treatment for CDI is necessary. Fidaxomicin is a good alternative, especially in patients at risk of relapse. Vancomycin combined with faecal microbiota transplantation remains the primary therapy for multiple recurrent CDI. We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy.

RevDate: 2018-09-18
CmpDate: 2018-09-18

Chilton CH, Pickering DS, J Freeman (2018)

Microbiologic factors affecting Clostridium difficile recurrence.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 24(5):476-482.

BACKGROUND: Recurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy.

AIMS: To discuss the importance of microbiologic factors in the development of rCDI.

SOURCES: Literature was drawn from a search of PubMed from 2000 onwards with the search term 'recurrent Clostridium difficile infection' and further references cited within these articles.

CONTENT: Meta-analyses and systematic reviews have shown that CDI and rCDI risk factors are similar. Development of rCDI is attendant on many factors, including immune status or function, comorbidities and concomitant treatments. Studies suggest that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole) are in development for CDI treatment, while microbiota therapeutics (faecal microbiota transplantation, nontoxigenic C. difficile, stool substitutes) are increasingly being explored. rCDI can only occur when viable C. difficile spores are present, either within the gut lumen after infection or when reacquired from the environment. C. difficile spore germination can be influenced by gut environmental factors resulting from dysbiosis, and spore outgrowth may be affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin, oritavancin).

IMPLICATIONS: rCDI is a significant challenge for healthcare professionals, requiring a multifaceted approach; optimized infection control to minimize reinfection; C. difficile-targeted antibiotics to minimize dysbiosis; and gut microflora restoration to promote colonization resistance. These elements should be informed by our understanding of the microbiologic factors involved in both C. difficile itself and the gut microbiome.

RevDate: 2018-09-17

Reigadas E, Olmedo M, Valerio M, et al (2018)

Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results.

Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia pii:reigadas14sep2018 [Epub ahead of print].

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI). Despite its excellent efficacy, it is still not a routine procedure in most European centers. FMT has not been widely used in Spain to date. We describe our experience with FMT, including a novel approach based on oral fecal capsules.

METHODS: We analyzed a prospectively recorded case series of patients with R-CDI treated with FMT at a single center (June 2014-July 2017). Primary outcome was defined as resolution of CDI without recurrence in a two-month period. FMT was administered via colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously screened.

RESULTS: FMT was performed in 13 patients with R-CDI. Median age was 75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5 via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse events, except for bacteremia in one patient. During follow-up, R- CDI was observed in one patient at one month after FMT. The primary resolution rate was 83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100% resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%.

CONCLUSIONS: In our cohort, FMT proved to be safe and effective, even in high risk patients. Oral administration in capsules also proved to be safe, well-tolerated, and highly effective for R-CDI. In our experience, the FMT capsule formulation seems feasible in the routine of a hospital. This administration method will allow FMT to be more widely used.

RevDate: 2018-09-17

Daniels LM, WD Kufel (2018)

Clinical review of Clostridium difficile infection: an update on treatment and prevention.

Expert opinion on pharmacotherapy [Epub ahead of print].

INTRODUCTION: Clostridium difficile infection (CDI) has become a significant healthcare-associated infection and is strongly associated with antibiotic use. Practice guidelines have recently been revised incorporating updated recommendations for diagnosis, treatment, and prevention. Areas Covered: This review discusses updated aspects of CDI management. New and emerging pharmacologic options for treatment and prevention are reviewed. Expert opinion: Metronidazole is associated with lower rates of treatment success compared to vancomycin and should no longer be used as primary therapy for the first episode of CDI or recurrent disease. Vancomycin or fidaxomicin are now recommended for first line therapy for most cases of CDI. Fecal microbiota transplant is effective and safe for the treatment of recurrent CDI. Evidence supports the use of fidaxomicin and bezlotoxumab for prevention of recurrent CDI; however, the costs associated with these therapies may limit their use. Validated risk prediction tools are needed to identify patients most likely to benefit from these treatments. Future advancements in microbiota targeting treatments will emerge as promising alternatives to standard CDI treatments. Antibiotic stewardship and infection control measures will remain essential components for CDI management.

RevDate: 2018-09-17
CmpDate: 2018-09-17

Arab JP, Martin-Mateos RM, VH Shah (2018)

Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg.

Hepatology international, 12(Suppl 1):24-33.

The term gut-liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a "chicken and egg" situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.

RevDate: 2018-09-15

Schmulson M, M Bashashati (2018)

Fecal microbiota transfer for bowel disorders: efficacy or hype?.

Current opinion in pharmacology, 43:72-80 pii:S1471-4892(18)30074-2 [Epub ahead of print].

PURPOSE OF REVIEW: Dysbiosis has been related to the pathophysiology of disorders of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and functional constipation (FC). Accordingly, modulation of gut microbiota has been proposed as a potential treatment for these disorders. Gut microbiota modulation can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics and fecal transplantation (FMT) or bacteriotherapy. The latter is currently used for recurrent or severe Clostridium difficile colitis and has been the focus of recent research in IBS and FC.

RECENT FINDINGS: Several case series reported promising results for FMT in patients with IBS and FC, which prompted the conduction of randomized controlled trials (RCT) in these DGBI.

SUMMARY: Both case series and RCTs are herein discussed. To the best of our knowledge, as of yet, 5 RCTs have been published on IBS and one in FC with slow colonic transit. In IBS, the majority of studies have used the IBS severity scoring system (IBS-SSS) as an outcome measure; however, the selection criteria were different among the trials as well as the route and form of administration of the FMT. Therefore, the results are inconsistent and no conclusion can be drawn. Some studies suggest that the presence of post-infection (PI)-IBS and the baseline microbiota status in the donors could be predictor factors of successful FMT in IBS. In constipation with slow colonic transit, the FMT seems to be more effective, although the data is based on only one RCT. We believe that larger RCTs, controlled with true placebos and considering baseline intestinal microbiota of the study subjects as well as donors' microbiota are still needed before recommending FMT in IBS and/or FC. History of previous GI infection (e.g. PI-IBS) and IBS subtypes should also be taken into account.

RevDate: 2018-09-14

Diorio C, Robinson PD, Ammann RA, et al (2018)

Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology [Epub ahead of print].

Purpose The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. Methods An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. Results The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. Conclusion We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.

RevDate: 2018-09-14

Sunkara T, Rawla P, Ofosu A, et al (2018)

Fecal microbiota transplant - a new frontier in inflammatory bowel disease.

Journal of inflammation research, 11:321-328 pii:jir-11-321.

Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects the gastrointestinal tract and results from an aberrant immune response toward luminal antigens in genetically susceptible people. Most of the current therapies for IBD focus on the management of the inflammation by using corticosteroids, immune modulators, and more recently, monoclonal antibodies (biological therapy). Although these therapies provide benefit in most cases, there are still a significant number of patients who do not respond or become refractory over time, suggesting the need for alternative therapeutic options. In the last decade, it has been recognized that "dysbiosis," an imbalanced gut microbiota, is a key element in IBD suggesting microbiome-based therapies as an attractive approach. Recently, fecal microbiota transplant (FMT) has been successfully used for the treatment of Clostridium difficile infection, and it is now under investigation for the treatment of IBD. Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD.

RevDate: 2018-09-14
CmpDate: 2018-09-14

Frossard JL, D Moradpour (2016)


Revue medicale suisse, 12(528):1403.

RevDate: 2018-09-14
CmpDate: 2018-09-14

Biedermann L (2017)

Vancomycin in Very-Early Onset Inflammatory Bowel Disease-Dysbiosis: Fight Fire with Fire?.

Digestion, 95(4):327-328.

RevDate: 2018-09-14
CmpDate: 2018-09-14

Hecker MT, Ho E, CJ Donskey (2017)

Fear of Failure: Engaging Patients in Antimicrobial Stewardship after Fecal Transplantation for Recurrent Clostridium difficile Infection.

Infection control and hospital epidemiology, 38(1):127-129.

RevDate: 2018-09-13

Ossorio PN, Y Zhou (2018)

Regulating stool for microbiota transplantation.

Gut microbes [Epub ahead of print].

In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.

RevDate: 2018-09-13

Wang Z, Lou H, Wang Y, et al (2018)

GePMI: A statistical model for personal intestinal microbiome identification.

NPJ biofilms and microbiomes, 4:20 pii:65.

Human gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.

RevDate: 2018-09-13
CmpDate: 2018-09-13

Digby-Bell J, Williams A, Irving P, et al (2018)

Successful faecal microbiota transplant for recurrent Clostridium difficile infection delivered by colonoscopy through a diverted ileostomy in a patient with severe perianal Crohn's disease.

BMJ case reports, 2018: pii:bcr-2017-222958.

We present the first reported case of successful treatment of recurrent Clostridium difficile infection with faecal microbiota transplantation delivered antegrade with a colonoscope through a diverting ileostomy.

RevDate: 2018-09-13
CmpDate: 2018-09-13

Quraishi MN, Critchlow T, Bhala N, et al (2017)

Faecal transplantation for IBD management-pitfalls and promises.

British medical bulletin, 124(1):181-190.

Background: Faecal microbiota transplantation (FMT) as a potential treatment for inflammatory bowel disease (IBD) is an area of active current research, having been stimulated by the remarkable efficacy of FMT in treatment of Clostridium difficile-associated colitis.

Sources of data: This review is based on data from numerous case series on FMT in IBD since 1989 and results of four RCTs in ulcerative colitis (UC); three fully published.

Areas of agreement: Early signals of short to medium-term efficacy of FMT for UC are promising.

Areas of controversy: Methodology, underlying mechanisms and questions regarding safety of FMT remain controversial.

Growing points: Many trials of FMT in adults and children are currently recruiting.

Future trials of FMT will likely revisit Crohn's disease and patients undergoing pouch surgery. Advances in microbial culture complementing genetic sequencing and investigations into the virome and mycobiome in IBD will be of great future interest.

RevDate: 2018-09-12
CmpDate: 2018-09-12

Evans TJ, Hilton R, S Douthwaite (2018)

Treating chronic hepatitis E: when is enough enough?.

BMJ case reports, 2018: pii:bcr-2017-223592.

We present a 38-year-old white British man who was taking long-term immunosuppressive medication following kidney transplantation. On routine review, he was noted to have an isolated and asymptomatic rise in alanine aminotransferase. After thorough investigation, he was found to have positive IgM and IgG serology to hepatitis E virus-and given the duration of his transaminitis, he was determined to have chronic hepatitis E infection. Treatment options were complicated by the presence of his kidney transplant, by chronic anaemia and by his wish for concomitant fertility treatment. Ribavirin therapy was instituted with a dramatic and immediate drop in serum viral load, although stool viraemia persisted. No clear protocols guide duration of treatment in chronic hepatitis E infection, but protracted faecal virus shedding predicts viral recrudescence, and treatment should continue at least until the stool is clear of virus.

RevDate: 2018-09-11

Zuo T, Wong SH, Cheung CP, et al (2018)

Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection.

Nature communications, 9(1):3663 pii:10.1038/s41467-018-06103-6.

Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT ("responders") display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas "nonresponders" and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.

RevDate: 2018-09-11
CmpDate: 2018-09-11

Sadowsky MJ, A Khoruts (2016)

Faecal microbiota transplantation is promising but not a panacea.

Nature microbiology, 1:16015 pii:nmicrobiol201615.

RevDate: 2018-09-10

Wei YL, Chen YQ, Gong H, et al (2018)

Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR.

Frontiers in microbiology, 9:1921.

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.

RevDate: 2018-09-10
CmpDate: 2018-09-10

Spindelboeck W, Schulz E, Uhl B, et al (2017)

Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft-versus-host-disease.

Haematologica, 102(5):e210-e213.

RevDate: 2018-09-08

Luo Y, Zeng B, Zeng L, et al (2018)

Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus.

Translational psychiatry, 8(1):187 pii:10.1038/s41398-018-0240-5.

Gut microbiota has an important role in the immune system, metabolism, and digestion, and has a significant effect on the nervous system. Recent studies have revealed that abnormal gut microbiota induces abnormal behaviors, which may be associated with the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we investigated the behavioral changes in germ-free (GF) mice by behavioral tests, quantified the basal serum cortisol levels, and examined glucocorticoid receptor pathway genes in hippocampus using microarray analysis followed by real-time PCR validation, to explore the molecular mechanisms by which the gut microbiota influences the host's behaviors and brain function. Moreover, we quantified the basal serum cortisol levels and validated the differential genes in an Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal "depression microbiota" transplantation mouse model by real-time PCR. We found that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E. coli LPS-treated mice showed antidepressant-like behavior, but did not show antianxiety-like behavior. However, "depression microbiota" recipient mice exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in "depression microbiota" recipient mice. Furthermore, basal serum cortisol levels were decreased in E. coli LPS-treated mice but not in GF mice and "depression microbiota" recipient mice. These results indicated that the gut microbiota may lead to behavioral abnormalities in mice through the downstream pathway of the glucocorticoid receptor. Herein, we proposed a new insight into the molecular mechanisms by which gut microbiota influence depressive-like behavior.

RevDate: 2018-09-07
CmpDate: 2018-09-07

Yoon MY, Min KB, Lee KM, et al (2016)

A single gene of a commensal microbe affects host susceptibility to enteric infection.

Nature communications, 7:11606 pii:ncomms11606.

Indigenous microbes inside the host intestine maintain a complex self-regulating community. The mechanisms by which gut microbes interact with intestinal pathogens remain largely unknown. Here we identify a commensal Escherichia coli strain whose expansion predisposes mice to infection by Vibrio cholerae, a human pathogen. We refer to this strain as 'atypical' E. coli (atEc) because of its inability to ferment lactose. The atEc strain is resistant to reactive oxygen species (ROS) and proliferates extensively in antibiotic-treated adult mice. V. cholerae infection is more severe in neonatal mice transplanted with atEc compared with those transplanted with a typical E. coli strain. Intestinal ROS levels are decreased in atEc-transplanted mice, favouring proliferation of ROS-sensitive V. cholerae. An atEc mutant defective in ROS degradation fails to facilitate V. cholerae infection when transplanted, suggesting that host infection susceptibility can be regulated by a single gene product of one particular commensal species.

RevDate: 2018-09-06
CmpDate: 2018-09-06

Verspohl E (2016)

[In process].

Medizinische Monatsschrift fur Pharmazeuten, 39(12):539-542.

RevDate: 2018-09-05

Monaghan T, Mullish BH, Patterson J, et al (2018)

Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway.

Gut microbes [Epub ahead of print].

The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.

RevDate: 2018-09-05

Wang JW, Kuo CH, Kuo FC, et al (2018)

Fecal microbiota transplantation: Review and update.

Journal of the Formosan Medical Association = Taiwan yi zhi pii:S0929-6646(18)30555-2 [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.

RevDate: 2018-09-04

Han R, Ma J, H Li (2018)

Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota.

Frontiers of medicine pii:10.1007/s11684-018-0645-9 [Epub ahead of print].

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical "Two-hit" theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a "metabolic organ" that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.

RevDate: 2018-09-03

Ruiz L, López P, Suárez A, et al (2018)

The role of gut microbiota in lupus: what we know in 2018?.

Expert review of clinical immunology [Epub ahead of print].

INTRODUCTION: The role of the human intestinal microbiota in the maintenance of a healthy physiological condition, as well as its relation to the development of disease, remains to be clarified. Current evidence suggests that intestinal microbes could be involved in the initiation and amplification of autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus (SLE). Despite recent progress in understanding how these microbes influence the pathophysiology of lupus, studies are still limited. Areas covered: In this review, we have tried to summarize the most relevant findings that have contributed to our understanding of the links between the human intestinal microbiota and the development of lupus. We also describe the potential role of individual microbial players in the physiology of lupus, and how they can shape relevant immune responses. Expert commentary: Culture-independent techniques based on massive sequencing represent a powerful tool to unravel the biological activity of gut microbes. Current data demonstrates that, depending on the pattern of intestinal microorganisms or the presence of specific bacteria, different responses related to lupus physiology can be triggered. Fecal Microbiota Transplantation, live biotherapeutics or dietary interventions targeting the microbiota will likely become a treatment for SLE.

RevDate: 2018-09-03

Delaune V, Orci LA, Lacotte S, et al (2018)

Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response.

Expert opinion on biological therapy [Epub ahead of print].

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies. Areas covered: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to hepatocellular carcinoma and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response. Expert Opinion: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global "resetting" using FMT. However, the composition of a "harmful" gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed.

RevDate: 2018-08-30

Wang S, Huang M, You X, et al (2018)

Gut microbiota mediates the anti-obesity effect of calorie restriction in mice.

Scientific reports, 8(1):13037 pii:10.1038/s41598-018-31353-1.

Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.

RevDate: 2018-08-30

Enck P (2018)

Primum non nocere: is faecal microbiota transplantation doing harm to patients with IBS?.

Gut pii:gutjnl-2018-317277 [Epub ahead of print].

RevDate: 2018-08-29

Barfuss S, Knackstedt ED, Jensen K, et al (2018)

Cardiac allograft vasculopathy following fecal microbiota transplantation for recurrent C. difficile infection.

We report the case of a 3-year-old male who developed recurrent Clostridium difficile infection after receiving an orthotopic heart transplant. Despite multiple courses of antibiotics, C. difficile infection was persistent and he underwent a fecal microbiota transplant. The patient responded with resolution of his diarrhea. However, within 2 months he developed severe mixed rejection with high circulating donor specific antibodies and significant coronary vasculopathy. Organ dysfunction led to the need for re-transplantation. The patient's post-operative course has since been complicated by pneumatosis intestinalis and recurrent C. difficile infection. This article is protected by copyright. All rights reserved.

RevDate: 2018-08-29

Kho ZY, SK Lal (2018)

The Human Gut Microbiome - A Potential Controller of Wellness and Disease.

Frontiers in microbiology, 9:1835.

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

RevDate: 2018-08-28

Zhang X, Zhao S, Song X, et al (2018)

Inhibition effect of glycyrrhiza polysaccharide (GCP) on tumor growth through regulation of the gut microbiota composition.

Journal of pharmacological sciences pii:S1347-8613(18)30059-8 [Epub ahead of print].

Glycyrrhiza Uralensis Polysaccharide (GCP), as a macromolecular polysaccharide extracted from the Traditional Chinese Medicine (TCM) - Licorice has been proved to inhibit tumor growth in vitro and in vivo; however, the specific anti-tumor mechanism of GCP needs to be further investigated. In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship between the anti-tumor effects of GCP and gut microbiota. Following depletion of gut microbiota, GCP cannot inhibit tumor growth. Fecal transplantation experiments found that transplanting the feces of GCP-treated mice, to a certain extent, could inhibit tumor growth and metastasis. These results indicate that Glycyrrhiza Polysaccharides exert anti-tumor effects by affecting gut microbiota composition.

RevDate: 2018-08-27

Tampaki EC, Tampakis A, Posabella A, et al (2018)

Current clostridium difficile treatments: Lessons that need to be learned from the clinical trials.

Human vaccines & immunotherapeutics [Epub ahead of print].

Clostridium difficile infection (CDI) is the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. Judging from the clinical trials on drugs used in CDIs, no approved treatment for recurrences exists, possibly indicating that a combination of treatment approaches are mandatory especially in severe infections, with current studies not being fully representative. Among the new strategies researched intensively fidaxomicin is presented, which demonstrates reduced CDI recurrences. Moreover, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally monoclonal antibodies against C. difficile toxins which offer protection against recurrences. Careful interpretation of the results based on lessons learned from previous trials conducted seems crucial. Questions are raised regarding how the results of future studies regarding new strategies researched will be managed and interpreted especially with regard to recurrence management as relevant data must be monitored for at least 30 days after end of treatment.

RevDate: 2018-08-27

Pouch SM, RJ Friedman-Moraco (2018)

Prevention and Treatment of Clostridium difficile-Associated Diarrhea in Solid Organ Transplant Recipients.

Infectious disease clinics of North America, 32(3):733-748.

Clostridium difficile infection is a significant cause of morbidity and mortality in solid organ transplant recipients. Risk factors in this population include frequent hospitalizations, receipt of immunosuppressive agents, and intestinal dysbiosis triggered by several factors, including exposure to broad-spectrum antimicrobials. The incidence and potential for significant adverse outcomes among solid organ transplant recipients with C difficile infection highlight the evolving need for strategic C difficile infection risk factor modification and novel approaches to disease management in this patient population. This review focuses on current concepts related to the prevention and treatment of C difficile infection in solid organ transplant recipients.

RevDate: 2018-08-24

Dias C, Pipa S, Duarte-Ribeiro F, et al (2018)

Fecal microbiota transplantation as a potential way to eradicate multiresistant microorganisms.

IDCases, 13:e00432 pii:e00432.

Multiresistant microorganism infection often can produce a life-threatening situation. We report two cases in which fecal microbiota transplantation used for the treatment of recurrent Clostridium difficile infection were effective in eradicating colonization by carbapenemase-producing Enterobacteriaceae. The presented cases illustrate the potential benefit of fecal microbiota transplantation in resolution of asymptomatic carrier states of multiresistant microorganisms, suggesting the need for further investigations with a view to their applicability in this area.

RevDate: 2018-08-23

Khan MY, Dirweesh A, Khurshid T, et al (2018)

Comparing fecal microbiota transplantation to standard-of-care treatment for recurrent Clostridium difficile infection: a systematic review and meta-analysis.

European journal of gastroenterology & hepatology [Epub ahead of print].

BACKGROUND: The use of fecal microbiota transplantation (FMT) as a treatment option for recurrent Clostridium difficile infection (rCDI) is well established. Various studies have used different forms and administration routes for FMT. We performed a systemic review and meta-analysis to update the clinical knowledge about different FMT modalities for curing rCDI compared with medical treatment (MT).

PATIENTS AND METHODS: We searched PubMed and Medline from inception through 10 May 2018 for randomized control trials (RCTs) comparing FMT (fresh or frozen) versus MT. We used Cochrane Collaboration's Risk of Bias tool to assess bias in the RCTs. We estimated odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random effects model. P values of less than 0.05 were considered significant.

RESULTS: We included seven RCTs comprising a total of 543 patients with recurrent CDI. There was a nonsignificant trend toward resolution of diarrhea following a single fresh FMT infusion compared with frozen FMT and MT (OR=2.45, 95% CI=0.78-7.71, P=0.12, I=69%). Subgroup analysis of fresh FMT vs. frozen FMT showed no difference between the two groups (OR=2.13, 95% CI=0.22-20.41, P=0.51, I=61%). Frozen FMT infusion through upper route versus lower route showed no difference (OR=0.62, 95% CI=0.15-2.54, P=0.51, I=0%). There was a nonsignificant trend favoring multiple treatments with FMT versus multiple courses of MT (OR=3.68, 95% CI=0.74-18.22, P=0.11, I=0%).

CONCLUSION: FMT is a promising treatment modality for rCDI compared with MT alone. Different forms and routes of FMT administration seem to be equally efficacious. In future, more well-designed RCTs directed at homogenous FMT preparation and delivery methods are required to validate these findings.

RevDate: 2018-08-20

Ishikawa D, Sasaki T, Takahashi M, et al (2018)

The Microbial Composition of Bacteroidetes Species in Ulcerative Colitis Is Effectively Improved by Combination Therapy With Fecal Microbiota Transplantation and Antibiotics.

Inflammatory bowel diseases pii:5074053 [Epub ahead of print].

Background: We previously reported that fresh fecal microbiota transplantation (FMT) after triple-antibiotic therapy (amoxicillin, fosfomycin, and metronidazole [AFM]; A-FMT) synergistically contributed to the recovery of phylum Bacteroidetes composition associated with the endoscopic severity and treatment efficacy of ulcerative colitis (UC). Here, we performed further microbial analyses using a higher-resolution method to identify the key bacterial species in UC and determine whether viable Bacteroidetes species from donor feces were successfully colonized by A-FMT.

Methods: The taxonomic composition of Bacteroidetes in 25 healthy donors and 27 UC patients at baseline was compared at the species level using a heat-shock protein (hsp) 60-based microbiome method. Microbiota alterations before and after treatment of UC patients were also analyzed in 24 cases (n = 17 A-FMT; n = 3 mono-AFM; n = 4 mono-FMT).

Results: We found species-level dysbiosis within the phylum Bacteroidetes in UC samples, which was associated with reduced species diversity, resulting from hyperproliferation and hypoproliferation of particular species. Moreover, in responders treated with A-FMT, diversity was significantly recovered at 4 weeks after a fresh round of FMT, after which high degrees of similarity in Bacteroidetes species composition among recipients and donors were observed.

Conclusions: A-FMT alleviated intestinal dysbiosis, which is caused by the loss of Bacteroidetes species diversity in patients with UC. Eradication of dysbiotic indigenous Bacteroidetes species by AFM pretreatment might promote the colonization of viable Bacteroidetes cells, thereby improving the intestinal microbiota dysbiosis induced by UC. Our findings serve as a basis for further investigations into the mechanisms of FMT.

RevDate: 2018-08-20

Williamson IA, Arnold JW, Samsa LA, et al (2018)

A High-Throughput Organoid Microinjection Platform to Study Gastrointestinal Microbiota and Luminal Physiology.

Cellular and molecular gastroenterology and hepatology, 6(3):301-319 pii:S2352-345X(18)30080-8.

Background & Aims: The human gut microbiota is becoming increasingly recognized as a key factor in homeostasis and disease. The lack of physiologically relevant in vitro models to investigate host-microbe interactions is considered a substantial bottleneck for microbiota research. Organoids represent an attractive model system because they are derived from primary tissues and embody key properties of the native gut lumen; however, access to the organoid lumen for experimental perturbation is challenging. Here, we report the development and validation of a high-throughput organoid microinjection system for cargo delivery to the organoid lumen and high-content sampling.

Methods: A microinjection platform was engineered using off-the-shelf and 3-dimensional printed components. Microinjection needles were modified for vertical trajectories and reproducible injection volumes. Computer vision (CVis) and microfabricated CellRaft Arrays (Cell Microsystems, Research Triangle Park, NC) were used to increase throughput and enable high-content sampling of mock bacterial communities. Modeling preformed using the COMSOL Multiphysics platform predicted a hypoxic luminal environment that was functionally validated by transplantation of fecal-derived microbial communities and monocultures of a nonsporulating anaerobe.

Results: CVis identified and logged locations of organoids suitable for injection. Reproducible loads of 0.2 nL could be microinjected into the organoid lumen at approximately 90 organoids/h. CVis analyzed and confirmed retention of injected cargos in approximately 500 organoids over 18 hours and showed the requirement to normalize for organoid growth for accurate assessment of barrier function. CVis analyzed growth dynamics of a mock community of green fluorescent protein- or Discosoma sp. red fluorescent protein-expressing bacteria, which grew within the organoid lumen even in the presence of antibiotics to control media contamination. Complex microbiota communities from fecal samples survived and grew in the colonoid lumen without appreciable changes in complexity.

Conclusions: High-throughput microinjection into organoids represents a next-generation in vitro approach to investigate gastrointestinal luminal physiology and the gastrointestinal microbiota.

RevDate: 2018-08-17

Farowski F, Els G, Tsakmaklis A, et al (2018)

Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales.

Gut microbes [Epub ahead of print].

OBJECTIVES: After allogeneic hematopoietic stem cell transplantation (allo-HCT), urinary levels of 3-indoxyl sulfate (3-IS) correlate with the relative abundance of bacteria from the class Clostridia (RAC), and antibiotic treatment is considered the major determinant of this outcome. A high RAC has been associated with favorable outcome after allo-HCT and protection from Clostridium difficile infection (CDI). We assessed correlations between alpha diversity, RAC and urinary 3-IS levels in a non-allo-HCT clinical cohort of antibiotic treated patients to further explore 3-IS as a biomarker of reduced diversity and predisposition to CDI.

METHODS: Fecal and urinary specimens were analyzed from 40 non-allo-HCT hospitalized patients before and 9 ± 2 days after initiation of intravenous antibiotic treatment. Fecal microbiota were analyzed by 16s RNA sequencing and urinary 3-IS was analyzed by liquid chromatography-tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of 3-IS.

RESULTS: At a RAC cutoff of <30%, the binary logarithm of 3-IS (medium 3-IS: ≤2.5; high 3-IS: >2.5) was predictive with an accuracy of 82% (negative predictive value: 87%, positive predictive value 67%). Accuracy was improved by combing antibiotic history with 3-IS levels (accuracy 89%, npv 88%, ppv 92%).

CONCLUSION: In conjunction with patient antibiotic history, 3-IS is a candidate marker to predict RAC.

RevDate: 2018-08-17
CmpDate: 2018-08-17

Terveer EM, van Beurden YH, van Dorp S, et al (2016)

Is the Lower Gastrointestinal Route Really Preferred Over the Upper Gastrointestinal Route for Fecal Microbiota Transfer?.

Journal of clinical gastroenterology, 50(10):895.

RevDate: 2018-08-16
CmpDate: 2018-08-16

Schroeder BO, Birchenough GMH, Ståhlman M, et al (2018)

Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration.

Cell host & microbe, 23(1):27-40.e7.

Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.

RevDate: 2018-08-15

Biehl LM, Cruz Aguilar R, Farowski F, et al (2018)

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection.

Infection pii:10.1007/s15010-018-1190-9 [Epub ahead of print].

PURPOSE: We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.

METHODS: FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.

RESULTS: The patient remained without symptoms after FMT.

CONCLUSIONS: Underlying mechanisms of action need to be addressed in depth by future research.

RevDate: 2018-08-12

Colombel JF, Shin A, PR Gibson (2018)

Functional gastrointestinal symptoms in patients with inflammatory bowel disease: A clinical challenge.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(18)30810-3 [Epub ahead of print].

DESCRIPTION: The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD).

METHODS: The evidence and best practices summarized in this manuscript are based on relevant scientific publications, systematic reviews, and expert opinion where applicable. BEST PRACTICE ADVICE 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging). BEST PRACTICE ADVICE 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management. BEST PRACTICE ADVICE 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation. BEST PRACTICE ADVICE 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns. BEST PRACTICE ADVICE 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy. BEST PRACTICE ADVICE 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms. BEST PRACTICE ADVICE 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation. BEST PRACTICE ADVICE 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. BEST PRACTICE ADVICE 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided. BEST PRACTICE ADVICE 10: Probiotics may be considered for treatment of functional symptoms in IBD. BEST PRACTICE ADVICE 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder. BEST PRACTICE ADVICE 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD. BEST PRACTICE ADVICE 13: Physical exercise should be encourage in IBD patients with functional GI symptoms. BEST PRACTICE ADVICE 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD.

RevDate: 2018-08-10

Filip M, Tzaneva V, DL Dumitrascu (2018)

Fecal transplantation: digestive and extradigestive clinical applications.

Clujul medical (1957), 91(3):259-265.

Background and aim: Fecal transplantation or fecal material transplantation (FMT) became a hot topic in gastroenterology in recent years. Therefore it is important to disseminate the up-to-date information on FMT. The aim of the paper is to review the knowledge on FMT and its clinical applications.

Methods: An extensive review of the literature was carried out. Titles from Pubmed were searched and analyzed. A narrative review has been written with emphasis on indications of FMT in different conditions.

Results: The guidelines recommend FMT in relapsing infection with Clostridium difficile. Several attempts to use FMT in other conditions have been analyzed. Attempts were recorded in other bowel disorders like IBD, IBS, chronic constipation and even colorectal cancer. The attempt to change the microbiota by FMT in diabetes and obesity represent challenges for the future.

Conclusions: Fecal transplantation represents an important therapeutic method, intensively investigated these years. Beside the indication for persistent and recurrent Clostridium difficile infection, several attempts were undertaken in other intestinal diseases and in metabolic conditions. The efficiency of these applications has to be demonstrated.

RevDate: 2018-08-10
CmpDate: 2018-08-10

Walker MM, Potter M, NJ Talley (2018)

Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.

The lancet. Gastroenterology & hepatology, 3(4):271-280.

Under normal physiological conditions, eosinophils are present throughout the gastrointestinal tract distal to the squamous oesophagus. Increases in their numbers signify primary and secondary eosinophilic conditions. The rare primary eosinophilic diseases eosinophilic gastroenteritis and eosinophilic colitis affect fewer than ten in 100 000 people, and are characterised by numerous mucosal eosinophils, distributed in sheets and sometimes extending from the mucosa into the submucosa. Pathogenesis of these diseases is poorly understood, but food allergies and intestinal dysbiosis have been implicated. Presentation ranges from vague abdominal symptoms and systemic complaints to, rarely, an acute abdomen with intestinal obstruction. Diagnosis is made from mucosal biopsy samples taken at endoscopy or from surgically resected specimens that demonstrate substantially increased numbers of eosinophils. Eosinophilia secondary to other conditions, such as pathogenic infections, must be excluded. Subtle eosinophilia has also been identified in the duodenum in functional dyspepsia and in the colon in spirochaetosis. Treatment of eosinophilic gastroenteritis and eosinophilic colitis is based on evidence from case reports and small case series, and first-line therapy includes empirical food-elimination diets and single courses of steroids, whereas relapsing or refractory disease might respond to steroid-sparing immunosuppressive agents and biological agents. The progression of disease in eosinophilic gastroenteritis and eosinophilic colitis is variable: a considerable number of patients have just one episode without relapse, whereas others have relapsing-remitting or chronic disease. Primary and secondary eosinophilia in the gastrointestinal tract is increasingly recognised as a clinical conundrum waiting to be solved.

RevDate: 2018-08-09

Micic D, Hirsch A, Setia N, et al (2018)

Enteric infections complicating ulcerative colitis.

Intestinal research, 16(3):489-493.

Enteric infections have previously been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD), however, little evidence exists in the etiologic role of specific enteric infections in the development of IBD. When encountered in the setting of IBD, enteric infections pose a clinical challenge in management given the competing treatment strategies for infectious conditions and autoimmune disorders. Here we present the case of a young male with enteric infections complicating a new diagnosis of IBD. Our patient's initial clinical presentation included diagnoses of Klebsiella oxytoca isolation and Clostridium difficile infection. Directed therapies to include withdrawal of antibiotics and fecal microbiota transplantation were performed without resolution of clinical symptoms. Given persistence of symptoms and active colitis, the patient was diagnosed with ulcerative colitis (UC), requiring treatments directed at severe UC to include cyclosporine therapy. The finding of multiple enteric infections in a newly presenting patient with IBD is an unexpected finding that has treatment implications.

RevDate: 2018-08-09

Yu LC, Wei SC, YH Ni (2018)

Impact of microbiota in colorectal carcinogenesis: lessons from experimental models.

Intestinal research, 16(3):346-357.

A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.

RevDate: 2018-08-08

Gagliardi A, Totino V, Cacciotti F, et al (2018)

Rebuilding the Gut Microbiota Ecosystem.

International journal of environmental research and public health, 15(8): pii:ijerph15081679.

A microbial ecosystem in which bacteria no longer live in a mutualistic association is called dysbiotic. Gut microbiota dysbiosis is a condition related with the pathogenesis of intestinal illnesses (irritable bowel syndrome, celiac disease, and inflammatory bowel disease) and extra-intestinal illnesses (obesity, metabolic disorder, cardiovascular syndrome, allergy, and asthma). Dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. These strategies include the administration of probiotics, prebiotics, and synbiotics; phage therapy; fecal transplantation; bacterial consortium transplantation; and a still poorly investigated approach based on predatory bacteria. This review discusses the various aspects of these strategies to counteract intestinal dysbiosis.

RevDate: 2018-08-08
CmpDate: 2018-08-08

Allamneni C, Nelson G, F Weber (2018)

A Rare Cause of Recurrent Abdominal Pain and Diarrhea.

Gastroenterology, 155(2):e11-e12.

RevDate: 2018-08-07

Cheng YW, Phelps E, Ganapini V, et al (2018)

Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Epub ahead of print].

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment, however use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C. difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. 94 SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprised of self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying IBD had worsening disease activity, while 14% of CMV seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3% Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT. This article is protected by copyright. All rights reserved.

RevDate: 2018-08-07

Niederwerder MC, Constance LA, Rowland RRR, et al (2018)

Fecal Microbiota Transplantation Is Associated With Reduced Morbidity and Mortality in Porcine Circovirus Associated Disease.

Frontiers in microbiology, 9:1631.

Porcine circovirus associated disease (PCVAD) is a term used to describe the multi-factorial disease syndromes caused by porcine circovirus type 2 (PCV-2), which can be reproduced in an experimental setting through the co-infection of pigs with PCV-2 and porcine reproductive and respiratory syndrome virus (PRRSV). The resulting PCVAD-affected pigs represent a subpopulation within the co-infected group. In co-infection studies, the presence of increased microbiome diversity is linked to a reduction in clinical signs. In this study, fecal microbiota transplantation (FMT) was investigated as a means to prevent PCVAD in pigs co-infected with PRRSV and PCV-2d. The sources of the FMT material were high-parity sows with a documented history of high health status and robust litter characteristics. The analysis of the donated FMT material showed the absence of common pathogens along with the presence of diverse microbial phyla and families. One group of pigs (n = 10) was administered the FMT while a control group (n = 10) was administered a sterile mock-transplant. Over the 42-day post-infection period, the FMT group showed fewer PCVAD-affected pigs, as evidenced by a significant reduction in morbidity and mortality in transplanted pigs, along with increased antibody levels. Overall, this study provides evidence that FMT decreases the severity of clinical signs following co-infection with PRRSV and PCV-2 by reducing the prevalence of PCVAD.

RevDate: 2018-08-07

Montassier E, Al-Ghalith GA, Hillmann B, et al (2018)

CLOUD: a non-parametric detection test for microbiome outliers.

Microbiome, 6(1):137 pii:10.1186/s40168-018-0514-4.

BACKGROUND: Dysbiosis of the human gut microbiome is defined as a maladaptive or clinically relevant deviation of the community profile from the healthy or normal state. Dysbiosis has been implicated in an extensive set of metabolic, auto-immune, and infectious diseases, and yet there is substantial inter-individual variation in microbiome composition even within body sites of healthy humans. An individual's microbiome varies over time in a high-dimensional space to form their personal microbiome cloud. This cloud may or may not be similar to that of other people, both in terms of the average microbiome profile (conformity) and the diameter of the cloud (stability). However, there is currently no robust non-parametric test that determines whether a patient's microbiome cloud is an outlier with respect to a reference group of healthy individuals with widely varying microbiome profiles.

METHODS: Here, we propose a test for outliers' detection in the human gut microbiome that accounts for the wide range of microbiome phenotypes observed in a typical set of healthy individuals and for intra-individual temporal variation. Our robust nonparametric outlier detection test, the CLOUD test, performs two assessments of a patient's microbiome health: conformity, the extent to which the patient's microbiome cloud is ecologically similar to a subset of healthy subjects; and stability, which compares the cloud diameter of a patient to those of healthy subjects. The CLOUD test is based on locally linear embedded ecological distances, allowing it to account for widely varying microbiome compositions among reference individuals. It also leverages temporal variability within patients and reference individuals to increase the robustness of the test.

RESULTS: We describe the CLOUD test, and we apply it to one novel and two previously published cohorts of patients receiving fecal microbiota transplantation for recurrent Clostridium difficile colitis, as well as to two known healthy cohorts, demonstrating high concordance of the CLOUD conformity and stability indices with clinical outcomes.

CONCLUSIONS: Although the CLOUD test is not, on its own, a test for clinical dysbiosis, it nonetheless provides a framework for outlier testing that could be incorporated into evaluation of suspected dysbiosis, which may play a role in diagnosis and prognosis of numerous pediatric and adult diseases.

RevDate: 2018-08-06
CmpDate: 2018-08-06

Liu C, Frank DN, Horch M, et al (2017)

Associations between acute gastrointestinal GvHD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors.

Bone marrow transplantation, 52(12):1643-1650.

Growing evidence suggests that host-microbiota interactions influence GvHD risk following allogeneic hematopoietic stem cell transplant. However, little is known about the influence of the transplant recipient's pre-conditioning microbiota nor the influence of the transplant donor's microbiota. Our study examines associations between acute gastrointestinal GvHD (agGvHD) and 16S rRNA fecal bacterial profiles in a prospective cohort of N=57 recipients before preparative conditioning, as well as N=22 of their paired HLA-matched sibling donors. On average, recipients had lower fecal bacterial diversity (P=0.0002) and different phylogenetic membership (UniFrac P=0.001) than the healthy transplant donors. Recipients with lower phylogenetic diversity had higher overall mortality rates (hazard ratio=0.37, P=0.008), but no statistically significant difference in agGvHD risk. In contrast, high bacterial donor diversity was associated with decreased agGvHD risk (odds ratio=0.12, P=0.038). Further investigation is warranted as to whether selection of hematopoietic stem cell transplant donors with high gut microbiota diversity and/or other specific compositional attributes may reduce agGvHD incidence, and by what mechanisms.

RevDate: 2018-08-06
CmpDate: 2018-08-06

Torres-Fuentes C, Schellekens H, Dinan TG, et al (2017)

The microbiota-gut-brain axis in obesity.

The lancet. Gastroenterology & hepatology, 2(10):747-756.

Changes in microbial diversity and composition are increasingly associated with several disease states including obesity and behavioural disorders. Obesity-associated microbiota alter host energy harvesting, insulin resistance, inflammation, and fat deposition. Additionally, intestinal microbiota can regulate metabolism, adiposity, homoeostasis, and energy balance as well as central appetite and food reward signalling, which together have crucial roles in obesity. Moreover, some strains of bacteria and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms. Therefore, the gut microbiota is becoming a target for new anti-obesity therapies. Further investigations are needed to elucidate the intricate gut-microbiota-host relationship and the potential of gut-microbiota-targeted strategies, such as dietary interventions and faecal microbiota transplantation, as promising metabolic therapies that help patients to maintain a healthy weight throughout life.

RevDate: 2018-08-05

Singh S (2018)

Evolution of Clinical Trials in Inflammatory Bowel Diseases.

Current gastroenterology reports, 20(9):41 pii:10.1007/s11894-018-0648-3.

PURPOSE OF REVIEW: Since the first clinical trial of cortisone in ulcerative colitis in 1955, remarkable progress has been made in the design and conduct of clinical trials in inflammatory bowel diseases (IBD). In this review article, we will discuss evolution of clinical trials in IBD over the last 3-5 years.

RECENT FINDINGS: Recognizing limitations intrinsic to clinical disease activity indices in IBD, regulatory authorities have recommended evaluating co-primary endpoints of patient-reported outcomes and endoscopic disease activity in clinical trials. Biomarker-enriched trial enrolment and central endoscopy reading have emerged as critical events in trial recruitment and outcome assessment and have driven placebo response rates down. While trials of novel biologic therapies and advanced small molecules continue at an accelerated pace, pragmatic comparative efficacy trials of treatment strategy aimed at optimizing current therapies (such as early combined immunosuppression [REACT], tight disease control [CALM], therapeutic drug monitoring [TAXIT, TAILORIX]) have directly informed clinical practice. With emphasis on value-based care and population health management, multi-pronged remote monitoring, self-management, and telemedicine approaches in the era of smartphones have re-emerged with promise. Non-conventional therapies such as fecal microbiota transplantation, though still experimental, have provided insight into disease pathogenesis and offered hope for microbial manipulation strategies for treating these complex diseases. Clinical trials have rapidly evolved over the last 5 years not only focusing on novel therapies but also optimizing existing treatment approaches and population health management. Over the next decade, these trials will continue to advance the field, and be readily translatable into clinical practice.

RevDate: 2018-08-05

Ye Z, Zhang N, Wu C, et al (2018)

A metagenomic study of the gut microbiome in Behcet's disease.

Microbiome, 6(1):135 pii:10.1186/s40168-018-0520-6.

BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease.

METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD.

RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ.

CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.

RevDate: 2018-08-04

Chehri M, Christensen AH, Halkjær SI, et al (2018)

Case series of successful treatment with fecal microbiota transplant (FMT) oral capsules mixed from multiple donors even in patients previously treated with FMT enemas for recurrent Clostridium difficile infection.

Medicine, 97(31):e11706.

RATIONALE: Studies have shown that fecal microbiota transplantation (FMT) is a safe and highly efficient treatment for recurrent Clostridium difficile infection (rCDI). However, it is still unknown if one versus multiple donors or enemas versus capsule FMT are most efficient.

PATIENT CONCERNS: 10 patients with at least 3 previous episodes of CDI were offered treatment with FMT capsules. 9 patients decided to participate.

DIAGNOSES: In this study, we treated 9 patients (25-86 years) with rCDI.

INTERVENTIONS: From October to November 2016, a total of 9 patients with recurrent CDI were treated with oral fecal microbiota capsules, with mixed donor feces from 4 donors with high microbiota diversity. All patients received treatment with vancomycin prior to the capsule regime.

OUTCOME: Patients had previous recurrences ranging from 2 to 10 recurrences. All 9 patients were successfully treated without recurrence after 180 days follow-up, even 2 patients previously treated with FMT enemas.

LESSONS: FMT capsules based on multiple donors are highly efficient in patients with rCDI.

RevDate: 2018-08-03
CmpDate: 2018-08-03

Fenollar F, D Raoult (2016)

Does Bacterial Vaginosis Result From Fecal Transplantation?.

The Journal of infectious diseases, 214(11):1784.

RevDate: 2018-07-31

Fluitman KS, De Clercq NC, Keijser BJF, et al (2017)

The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids.

Expert review of endocrinology & metabolism, 12(3):215-226.

INTRODUCTION: Malnutrition refers to both over- and undernutrition and results from a disruption in energy balance. It affects one in three people worldwide and is associated with increased morbidity and mortality. The intestinal microbiota represents a newly identified factor that might contribute to the development of malnutrition, as it harbors traits that complement the human metabolic and endocrine capabilities, thereby influencing energy balance. Areas covered: In the current review, we aim to give a comprehensive overview on the microbiota, its development and its possible influence on energy balance, with emphasis the role of short-chain fatty acids. We also consider microbial characteristics associated with obesity and undernutrition and evaluate microbial manipulating strategies. The PubMed database was searched using the terms: 'gastrointestinal microbiota', 'volatile fatty acids', 'malnutrition', 'undernutrition', 'obesity', 'insulin resistance', 'prebiotics', 'probiotics', 'antibiotics' and 'fecal microbiota transplantation'. Expert commentary: Microbiota make important contributions to the regulation of energy balance, whereas microbial disturbances might predispose to malnutrition. If we manage to manipulate the microbiota to our benefit, it could lead to preventive or therapeutic strategies targeting malnutrition.

RevDate: 2018-08-01
CmpDate: 2018-08-01

van der Lelie D, Taghavi S, Henry C, et al (2017)

The microbiome as a source of new enterprises and job creation: Considering clinical faecal and synthetic microbiome transplants and therapeutic regulation.

Microbial biotechnology, 10(1):4-5.

RevDate: 2018-07-30
CmpDate: 2018-07-30

Chassaing B, AT Gewirtz (2018)

Mice harboring pathobiont-free microbiota do not develop intestinal inflammation that normally results from an innate immune deficiency.

PloS one, 13(4):e0195310 pii:PONE-D-17-32530.

BACKGROUND: Inability to maintain a stable and beneficial microbiota is associated with chronic gut inflammation, which classically manifests as colitis but may more commonly exist as low-grade inflammation that promotes metabolic syndrome. Alterations in microbiota, and associated inflammation, can originate from dysfunction in host proteins that manage the microbiota, such as the flagellin receptor TLR5. That the complete absence of a microbiota (i.e. germfree conditions) eliminates all evidence of inflammation in TLR5-deficient mice demonstrates that this model of gut inflammation is microbiota-dependent. We hypothesize that such microbiota dependency reflects an inability to manage pathobionts, such as Adherent-Invasive E. coli (AIEC). Herein, we examined the extent to which microbiota mismanagement and associated inflammation in TLR5-deficient mice would manifest in a limited and pathobiont-free microbiota. For this purpose, WT and TLR5-deficient mice were generated and maintained with the 8-member consortium of bacteria referred to as "Altered Schaedler Flora" (ASF). Such ASF animals were subsequently inoculated with AIEC reference strain LF82. Feces were assayed for bacterial loads, fecal lipopolysaccharide and flagellin loads, fecal inflammatory marker lipocalin-2 and microbiota composition.

RESULTS: Relative to similarly maintained WT mice, mice lacking TLR5 (T5KO) did not display low-grade intestinal inflammation nor metabolic syndrome under ASF conditions. Concomitantly, the ASF microbial community was similar between WT and T5KO mice, while inoculation with AIEC strain LF82 resulted in alteration of the ASF community in T5KO mice compared to WT control animals. AIEC LF82 inoculation in ASF T5KO mice resulted in microbiota components having elevated levels of bioactive lipopolysaccharide and flagellin, a modest level of low-grade inflammation and increased adiposity.

CONCLUSIONS: In a limited-complexity pathobiont-free microbiota, loss of the flagellin receptor TLR5 does not impact microbiota composition nor its ability to promote inflammation. Addition of AIEC to this ecosystem perturbs microbiota composition, increases levels of lipopolysaccharide and flagellin, but only modestly promotes gut inflammation and adiposity, suggesting that the phenotypes previously associated with loss of this innate immune receptor require disruption of complex microbiota.

RevDate: 2018-07-28

Vaughn BP, Rank KM, A Khoruts (2018)

Fecal Microbiota Transplantation: Current Status in Treatment of GI and Liver Disease.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(18)30751-1 [Epub ahead of print].

Fecal microbiota transplantation was originally introduced as a method to repair intestinal microbiota following failure of multiple treatments of recurrent Clostridium difficile infection with antibiotics. However, it is hypothesized that intestinal dysbiosis may contribute to pathogenesis of many diseases, especially those involving the gastrointestinal tract. Therefore, fecal microbiota transplantation is increasingly being explored as a potential treatment that aims to optimize microbiota composition and functionality. Here we review the current state of fecal microbiota transplantation development and applications in conditions of greatest interest to a gastroenterologist.

RevDate: 2018-07-28

Su HJ, Chiu YT, Chiu CT, et al (2018)

Inflammatory bowel disease and its treatment in 2018: Global and Taiwanese status updates.

Journal of the Formosan Medical Association = Taiwan yi zhi pii:S0929-6646(18)30202-X [Epub ahead of print].

The global incidence and prevalence of inflammatory bowel disease (IBD) has increased over the last 2-4 decades, likely because of the adoption of a more "western" lifestyle as well as improved detection and awareness, and Taiwan is no exception. To characterize the increasing burden of IBD, we conducted a comprehensive review of IBD in the existing literature. The following parameters were reviewed: background knowledge and current standard care for IBD, including natural history, epidemiology, pathogenesis, diagnosis, monitoring, and treatment. In addition, new imaging modalities and treatment options such as combined positron emission tomography and magnetic resonance enterography, new biologic agents, small-molecule therapy, biosimilar therapeutics, mesenchymal stem cell transplantation, and fecal microbiota transplantation, all of which have been introduced for IBD management, were reviewed. We also used the hospital-based as well as population-based Taiwan National Health Insurance Research Database to assess Taiwan-specific trends for comparison with global trends.

RevDate: 2018-07-27

Chaitman J, Jergens AE, Gaschen F, et al (2016)

Commentary on key aspects of fecal microbiota transplantation in small animal practice.

Veterinary medicine (Auckland, N.Z.), 7:71-74 pii:vmrr-7-071.

The gastrointestinal tract of dogs, cats, and other mammals including humans harbors millions of beneficial microorganisms that regulate and maintain health. Fecal microbiota transplantation (FMT) is a procedure involving the administration of a fecal infusion from a healthy individual (donor) to a patient with disease to help improve health. Despite the effectiveness of FMT to treat intestinal disorders in humans, in particular recurrent Clostridium difficile infection, there is a paucity of scientific data regarding the application of FMT in veterinary patients. Here, we outline key aspects of FMT in small animal practice.

RevDate: 2018-07-26

Jiang M, Leung NH, Ip M, et al (2018)

Cost-effectiveness analysis of ribotype-guided fecal microbiota transplantation in Chinese patients with severe Clostridium difficile infection.

PloS one, 13(7):e0201539 pii:PONE-D-18-12178.

BACKGROUND: Clostridium difficile infection (CDI) caused by ribotype 002 strain is associated with poor outcomes in Chinese patients. Fecal microbiota transplantation (FMT) is an effective but costly treatment for CDI. We aimed to examine potential cost-effectiveness of ribotype-guided FMT in Chinese patients with severe CDI.

METHODS: A decision-analytic model was designed to simulate outcomes of ribotype 002-guided FMT versus vancomycin treatment in Chinese patients with severe CDI in the hospital setting. Outcome measures included mortality rate; direct medical cost; and quality-adjusted life year (QALY) loss for CDI. Sensitivity analysis was performed to examine robustness of base-case results.

RESULTS: Comparing to vancomycin treatment, ribotype-guided FMT group reduced mortality (11.6% versus 17.1%), cost (USD8,807 versus USD9,790), and saved 0.472 QALYs in base-case analysis. One-way sensitivity analysis found the ribotype-guided FMT group to remain cost-effective when patient acceptance rate of FMT was >0.6% and ribotype 002 prevalence was >0.07%. In probabilistic sensitivity analysis, ribotype-guided FMT gained higher QALYs at 100% of simulations with mean QALY gain of 0.405 QALYs (95%CI: 0.400-0.410; p<0.001). The ribotype-guided group was less costly in 97.9% of time, and mean cost-saving was USA679 (95%CI: 670-688; p<0.001).

CONCLUSIONS: In the present model, ribotype-guided FMT appears to be a potential option to save QALYs and cost when comparing with vancomycin. The cost-effectiveness of ribotype-guided FMT is subject to the patient acceptance to FMT and prevalence of ribotype 002.

RevDate: 2018-07-26

Mogilnicka I, M Ufnal (2018)

Gut Mycobiota and Fungal Metabolites in Human Homeostasis.

Current drug targets pii:CDT-EPUB-91929 [Epub ahead of print].

BACKGROUND: Accumulating evidence suggests that microbiota plays an important role in host's homeostasis. Thus far researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.

METHODS: We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.

RESULTS: Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.

CONCLUSION: The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

RevDate: 2018-07-25

Preda CM, Meianu C, Sandra I, et al (2016)

Fecal Microbiota Transplantation in Recurrent NAP1/B1/027 Clostridium Difficile Infection (CDI) Resistant to Vancomycin and Metronidazole in a Patient with Ulcerative Colitis (UC): A Case Report.

Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi, 120(3):563-567.

Most of the studies showed that IBD patients inflammatory bowel diseases (IBD) with CDI have more of the whole range of short- and long-term worst outcomes than those without CDI. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. However, current literature is suggesting increasingly that for patients with infections that fail to resolve with traditional antibiotic regimens, FMAT's average cure rate of >90%. We report a case of a 40-year-old man, diagnosed with ulcerative colitis (UC) in 2012 who presented in our clinic for 20 watery stools per day with mucus and blood, hypogastric pain, pyrexia and chills. Rectosigmoidoscopy and histopathological examination diagnosed a ctive lesions of ulcerative colitis with Clostridium difficile toxins A/B enzyme immunoassays (EIA) testing initially negative. The patient was non-responder at day 10 of intravenous (iv) corticotherapy and received induction therapy with Infliximab 5 mg/kg. EIA testing for Clostridium difficile was repeated at day 12 of hospitalization with positive results for toxins A/B, and associated oral therapy with Vancomycin and Metronidazole was initiated without clinical response in day 7, reasons for what intravenously therapy with Tigecycline was started with good response. Patient was discharged after 10 days of Tigecycline, but came back twice for two relapses of Clostridium difficile colitis treated successfully with Tigecycline, reasons for what fecal transplantation was performed in Matei Bals Institute, which induced remission of both CDI and UC.

RevDate: 2018-07-22

Leclercq S, Stärkel P, Delzenne NM, et al (2018)

The gut microbiota: A new target in the management of alcohol dependence?.

Alcohol (Fayetteville, N.Y.) pii:S0741-8329(18)30046-6 [Epub ahead of print].

The gastrointestinal tract is the natural habitat for a huge community of microorganisms, comprising bacteria, viruses, fungi and yeast. This microbial ecosystem codevelops with the host throughout life and is subject to a complex interplay that depends on multiple factors including host genetics, nutrition, life-style, stress, diseases and antibiotics use. The gut microbiota, that refers to intestinal bacteria, has profound influence on the host immune system, metabolism and nervous system. Indeed, intestinal bacteria supply the host with essential nutrients such as vitamins, metabolize bile acids and undigested compounds, defend against pathogen invasion, participate to the development of the intestinal architecture and the intestinal immune system and play an important role in the maintenance of the gut barrier function. More recently, the gut microbiota has been shown to influence brain functions, such as myelin synthesis, the blood-brain barrier permeability and neuroinflammatory responses but also mood and behavior. The cross-talk between microbes and the host implicates a vast array of signaling pathways that involve many different classes of molecules like metabolites produced by the bacteria from dietary or endogenous sources of carbohydrates and proteins (i.e. short-chain fatty acids (SCFAs), indole), neurotransmitters and inflammatory cytokines. This review will focus on the involvement of the gut microbiota in the pathophysiological aspects of alcohol dependence related to the gut barrier function, liver damage and psychological disturbances. We will also discuss the possibility to create new and realistic humanized animal models of alcohol dependence by the use of fecal transplantation.

RevDate: 2018-07-20

McDonald JAK, Mullish BH, Pechlivanis A, et al (2018)

Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota.

Gastroenterology pii:S0016-5085(18)34771-1 [Epub ahead of print].

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but there are concerns about its long-term safety. Understanding the mechanisms of the effects of FMT could help us design safer, targeted therapies. We aimed to identify microbial metabolites that are important for C difficile growth.

METHODS: We used a CDI chemostat model as a tool to study the effects of FMT in vitro. The following analyses were performed: C difficile plate counts, 16S rRNA gene sequencing, 1H-NMR spectroscopy, and UPLC mass spectrometry bile acid profiling. FMT mixtures were prepared using fresh fecal samples provided by donors enrolled in an FMT program in the United Kingdom. Results from chemostat experiments were validated using human stool samples, C difficile batch cultures, and C57BL/6 mice with CDI. Human stool samples were collected from 16 patients with recurrent CDI and healthy donors (n=5) participating in an FMT trial in Canada.

RESULTS: In the CDI chemostat model, clindamycin decreased valerate and deoxycholic acid concentrations and increased C difficile total viable counts (TVC) and valerate precursors, taurocholic acid, and succinate concentrations. After we stopped adding clindamycin, levels of bile acids and succinate recovered, whereas levels of valerate and valerate precursors did not. In the CDI chemostat model, FMT increased valerate concentrations and decreased C difficile TVC (94% reduction), spore counts (86% reduction), and valerate precursor concentrations-concentrations of bile acids were unchanged. In stool samples from patients with CDI, valerate was depleted before FMT, but restored after FMT. C difficile batch cultures confirmed that valerate decreased vegetative growth, and that taurocholic acid is required for germination but had no effect on vegetative growth. C difficile TVC were decreased by 95% in mice with CDI given glycerol trivalerate compared to phosphate-buffered saline.

CONCLUSIONS: We identified valerate as a metabolite that is depleted with clindamycin and only recovered with FMT. Valerate is a target for a rationally designed recurrent CDI therapy.

RevDate: 2018-07-16

Lin SC, Alonso CD, AC Moss (2018)

Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants: an institutional experience and review of the literature.

Clostridium difficile, an anaerobic gram-positive, spore-forming bacillus, has become the most common cause of nosocomial infectious diarrhea, and is associated with increased mortality in all populations. Patients who have received solid organ transplants (SOT) are at increased risk of Clostridium difficile infection (CDI) and CDI recurrence (rCDI). This may be related to chronic immunosuppression, frequent antibiotic exposure, and increased or prolonged hospitalizations. Increased morbidity and mortality from CDI is well described in SOT patients. Conventional treatments for index and recurrent CDI include vancomycin and fidaxomicin. Fecal microbiota transplantation has emerged as an effective and safe alternative for treating rCDI in the general population. Reports of its safety in certain immunocompromised populations, such as those with inflammatory bowel disease, appear reassuring, but outcomes among SOT patients are less well known. Here, we summarize the experiences published to date on the treatment of rCDI with FMT in SOT patient, and also describe our detailed FMT protocol and experience in treating a series of SOT patients with rCDI. In addition to reporting the safety and efficacy of our FMT experience, we also discuss the diagnostic challenges and considerations in this population of solid organ transplant recipients. This article is protected by copyright. All rights reserved.

RevDate: 2018-07-16

Nusbaum DJ, Sun F, Ren J, et al (2018)

Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.

FEMS microbiology ecology pii:5053801 [Epub ahead of print].

Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis, and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.

RevDate: 2018-07-16

Geng S, Cheng S, Li Y, et al (2018)

Fecal Microbiota Transplantation Reduces Susceptibility to Epithelial Injury and Modulates Tryptophan Metabolism of Microbial Community in a Piglet Model.

Journal of Crohn's & colitis pii:5053909 [Epub ahead of print].

Background and Aims: Fecal microbiota transplantation [FMT] has shown promise as a treatment for inflammatory bowel disease [IBD]. Using a piglet model, our previous study indicated that exogenous fecal microbiota can enhance gastrointestinal health through enhancing intestinal barrier. However, specific connections between FMT-induced microbial changes and modulation of intestinal barrier still remain to be fully illustrated. Here, we aimed to determine the potential role of metabolic function of gut microbiota in the beneficial effects of FMT.

Methods: The influence of FMT on the maintenance of intestinal homeostasis was assessed by early-life gut microbiota intervention on newborn piglets and subsequent lipopolysaccharide [LPS] challenge. Analysis of the gut microbiome and metabolome was carried out by 16S rRNA sequencing and multiple mass spectrometry platforms.

Results: FMT modulated the diversity and composition of colonic microbiota and reduced the susceptibility to LPS-induced destruction of epithelial integrity and severe inflammatory response. Metabolomic analysis revealed functional changes of the gut metabolome along with significant increase of typical microbiota-derived tryptophan catabolite indole-3-acetic acid in the colonic lumen. Further, metagenomics prediction analysis based on 16S rRNA sequencing also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with tryptophan metabolism and intestinal homeostasis, which coincided with up-regulation of cytokine interleukin-22 and enhanced activation of aryl hydrocarbon receptor in the recipient colon.

Conclusions: Our data reveal a regulatory effect of FMT on tryptophan metabolism of gut microbiota in the recipient colon, which may play a potential role in the maintenance of intestinal barrier.

RevDate: 2018-07-16

Cheminet G, Kapel N, Bleibtreu A, et al (2018)

Faecal microbiota transplantation with frozen capsules for relapsing Clostridium difficile infections: the first experience from 15 consecutive patients in France.

RevDate: 2018-07-19

Inserra A, Rogers GB, Licinio J, et al (2018)

The Microbiota-Inflammasome Hypothesis of Major Depression.

BioEssays : news and reviews in molecular, cellular and developmental biology [Epub ahead of print].

We propose the "microbiota-inflammasome" hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long-lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro-inflammatory pathways mediated by the Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review we describe MDD/chronic stress-induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive-like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co-morbid conditions. A number of testable predictions surface from this microbiota-gut-inflammasome-brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.

RevDate: 2018-07-15

Heimesaat MM, Escher U, Grunau A, et al (2018)

Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice - A Subacute Ileitis Model to Unravel Pathogen-Host Interactions.

European journal of microbiology & immunology, 8(2):53-61.

Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the "ménage à trois" of pathogens, human gut microbiota, and immunity.

RevDate: 2018-07-15

Escher U, Giladi E, Dunay IR, et al (2018)

Anti-inflammatory Effects of the Octapeptide NAP in Human Microbiota-Associated Mice Suffering from Subacute Ileitis.

European journal of microbiology & immunology, 8(2):34-40.

The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.

RevDate: 2018-07-13

Bai T, Zhang L, Wang H, et al (2018)

Fecal Microbiota Transplantation Is Effective in Relieving Visceral Hypersensitivity in a Postinfectious Model.

BioMed research international, 2018:3860743.

Aim: To investigate the effect of fecal microbiota transplantation on visceral hypersensitivity compared with Bifidobacterium longum.

Methods: Mice visceral hypersensitivity was induced by Trichinella spiralis. After 8 weeks, they were divided into three groups (controls, Bifidobacterium longum, and fecal microbiota transplantation) and were daily treated by gavage with 0.2 ml PBS, Bifidobacterium longum HB55020, or fecal microbiota for 7 days. Visceral hypersensitivity was tested with abdominal withdrawal reflex. Permeability of colon epithelium was assessed with Ussing chamber.

Results: After administration of Bifidobacterium longum, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). After administration of fecal microbiota, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). Fecal microbiota transplantation was as effective as Bifidobacterium in relieving visceral hypersensitivity. Administration of Bifidobacterium longum or fecal microbiota transplantation improved colon epithelium permeability. Expression of occluding-1 was increased.

Conclusion: Manipulation of microbiota is effective in relieving visceral hypersensitivity. Fecal microbiota transplantation is as effective as Bifidobacterium longum administration.

RevDate: 2018-07-13

Moayyedi P (2018)

Update on Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Disease.

Gastroenterology & hepatology, 14(5):319-322.

RevDate: 2018-07-07

Imangaliyev S, Prodan A, Nieuwdorp M, et al (2018)

Domain Intelligible Models.

Methods (San Diego, Calif.) pii:S1046-2023(17)30423-1 [Epub ahead of print].

Mining biological information from rich "-omics" datasets is facilitated by organizing features into groups that are related to a biological phenomenon or clinical outcome. For example, microorganisms can be grouped based on a phylogenetic tree that depicts their similarities regarding genetic or physical characteristics. Here, we describe algorithms that incorporate auxiliary information in terms of groups of predictors and the relationships between them into the metagenome learning task to build intelligible models. In particular, our cost function guides the feature selection process using auxiliary information by requiring related groups of predictors to provide similar contributions to the final response. We apply the developed algorithms to a recently published dataset analyzing the effects of fecal microbiota transplantation (FMT) in order to identify factors that are associated with improved peripheral insulin sensitivity, leading to accurate predictions of the response to the FMT.

RevDate: 2018-07-19

Wang J, Wang P, Tian H, et al (2018)

Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice.

Innate immunity, 24(5):297-306.

Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials. Importantly, our study shows that down-regulation of aryl hydrocarbon receptor (AhR), interleukin-22 (IL-22), and phosphorylated Stat3 (p-Stat3) is associated with decreased antimicrobials, which might mediate the antibiotic-associated intestinal mucosa injury. Last, exogenous activation of the AhR/IL-22/Stat3 signaling pathway with the AhR agonist 6-formylindolo(3,2-b)carbazole (Ficz) rescued antimicrobial molecule levels markedly after antibiotic treatment to levels similar to those following reconstitution of intestinal microbiota by FMT. Together, our results demonstrate that the AhR/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota and suggest this pathway as a promising target in the treatment of antibiotic-associated gut barrier damage.

RevDate: 2018-07-23
CmpDate: 2018-07-23

Klag T, J Wehkamp (2018)

[Crohn's Disease - New Therapies].

Deutsche medizinische Wochenschrift (1946), 113(13):953-959.

New promising treatment options for chronic inflammatory bowel diseases, confirm the expanded pathophysiological understanding in terms of the interactions of the gastrointestinal microbiome with the adaptive and innate immune response and barrier protection. Therefore, these interrelations are focus of research and therapeutic strategies. The following review will give insights into the pathomechanisms, current treatment options and future developments.

RevDate: 2018-07-06

Hu J, Chen L, Tang Y, et al (2018)

Standardized Preparation for Fecal Microbiota Transplantation in Pigs.

Frontiers in microbiology, 9:1328.

The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.

RevDate: 2018-07-03

Chai J, CH Lee (2018)

Management of Primary and Recurrent Clostridium difficile Infection: An Update.

Antibiotics (Basel, Switzerland), 7(3): pii:antibiotics7030054.

BACKGROUND: Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections (HAI) in the United States and Canada, and incidence rates have increased worldwide in recent decades. Currently, antibiotics are the mainstay treatments for both primary and recurrent CDI, but their efficacy is limited, prompting further therapies to be developed. Aim: This review summarizes current and emerging therapies in CDI management including antibiotics, fecal microbiota transplantation, monoclonal antibodies, spore-based therapies, and vaccinations.

RevDate: 2018-06-28

van der Beek CM, Canfora EE, Kip AM, et al (2018)

The Prebiotic Inulin Improves Substrate Metabolism and Promotes Short-Chain Fatty Acid Production in Overweight to Obese Men.

Metabolism: clinical and experimental pii:S0026-0495(18)30151-3 [Epub ahead of print].

BACKGROUND AND AIMS: Human gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology.

METHODS: In a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-13C-inulin (INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal samples were collected, and hunger and satiety scores were assessed.

RESULTS: Fat oxidation increased in the early postprandial phase (0-3 h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P<0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P<0.05). In addition, we found continuous increases in plasma 13C-SCFA enrichments (P<0.05 from t=120 onwards) and breath 13CO2 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and hunger and satiety scores.

CONCLUSIONS: Ingestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with the fermentable inulin may favor human substrate metabolism.

CLINICAL TRIAL REGISTRY: The trial was registered at under number NCT02009670.

RevDate: 2018-06-29

Baktash A, Terveer EM, Zwittink RD, et al (2018)

Mechanistic Insights in the Success of Fecal Microbiota Transplants for the Treatment of Clostridium difficile Infections.

Frontiers in microbiology, 9:1242.

Fecal microbiota transplantation has proven to be an effective treatment for infections with the gram-positive enteropathogen Clostridium difficile. Despite its effectiveness, the exact mechanisms that underlie its success are largely unclear. In this review, we highlight the pleiotropic effectors that are transferred during fecal microbiota transfer and relate this to the C. difficile lifecycle. In doing so, we show that it is likely that multiple factors contribute to the elimination of symptoms of C. difficile infections after fecal microbiota transplantation.

RevDate: 2018-06-29

Bellocchi C, ER Volkmann (2018)

Update on the Gastrointestinal Microbiome in Systemic Sclerosis.

Current rheumatology reports, 20(8):49 pii:10.1007/s11926-018-0758-9.

PURPOSE OF REVIEW: Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. The purpose of this review is to summarize recent studies reporting gastrointestinal microbiota aberrations associated with the systemic sclerosis disease state.

RECENT FINDINGS: The studies described herein have identified common changes in gut microbial composition. Specifically, patients with SSc have decreased abundance of beneficial commensal genera (e.g., Faecalibacterium, Clostridium, and Bacteroides) and increased abundance of pathobiont genera (e.g., Fusobacterium, Prevotella, Erwinia). In addition, some studies have linked specific genera with the severity of gastrointestinal symptoms in systemic sclerosis. More research is needed to further characterize the gastrointestinal microbiota in systemic sclerosis and understand how microbiota perturbations can affect inflammation, fibrosis, and clinical outcomes. Interventional studies aimed at addressing/correcting these perturbations, either through dietary modification, pro/pre-biotic supplementation, or fecal transplantation, may lead to improved outcomes for patients with systemic sclerosis.

RevDate: 2018-07-11

Zhao M, Xiong X, Ren K, et al (2018)

Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.

EMBO molecular medicine pii:emmm.201708736 [Epub ahead of print].

Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis. Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis. On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis. Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.


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
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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 )