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Bibliography on: Fecal Transplantation

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 19 Apr 2019 at 01:37 Created: 

Fecal Transplantation

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

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

Citations The Papers (from PubMed®)

RevDate: 2019-04-18

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

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

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

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

RevDate: 2019-04-18
CmpDate: 2019-04-18

Tutková M, J Rudá-Kučerová (Summ)

Microbiome in connection with metabolic syndrome and the therapeutic potential of its influencing.

Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti, 67(2):71-80.

Several fields of medicine have been concerned with the role of the microbiome in maintaining the balance in the human body and its changes in the pathogenesis of diseases in recent years. The intestinal microbiome seems to play a key role in the regulation of metabolic pathways, inflammation and intestinal permeability. The aim of this review is to assess the importance of the intestinal microbiome in metabolic syndrome and the therapeutic or preventive potential of its manipulation. Key words: metabolic syndrome • microbiome • probiotics • prebiotics • fecal transplant.

RevDate: 2019-04-03
CmpDate: 2019-04-03

Cassard AM, D Ciocan (2018)

Microbiota, a key player in alcoholic liver disease.

Clinical and molecular hepatology, 24(2):100-107.

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Only 20% of heavy alcohol consumers develop alcoholic liver cirrhosis. The intestinal microbiota (IM) has been recently identified as a key player in the severity of liver injury in ALD. Common features of ALD include a decrease of gut epithelial tight junction protein expression, mucin production, and antimicrobial peptide levels. This disruption of the gut barrier, which is a prerequisite for ALD, leads to the passage of bacterial products into the blood stream (endotoxemia). Moreover, metabolites produced by bacteria, such as short chain fatty acids, volatile organic compounds (VOS), and bile acids (BA), are involved in ALD pathology. Probiotic treatment, IM transplantation, or the consumption of dietary fiber, such as pectin, which all alter the ratio of bacterial species, have been shown to improve liver injury in animal models of ALD and to be associated with an improvement in gut barrier function. Although the connections between the microbiota and the host in ALD are well established, the underlying mechanisms are still an active area of research. Targeting the microbiome through the use of prebiotic, probiotic, and postbiotic modalities could be an attractive new approach to manage ALD.

RevDate: 2019-04-16

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

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

Revista de gastroenterologia de Mexico pii:S0375-0906(19)30025-4 [Epub ahead of print].

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

RevDate: 2019-04-15

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

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

Zeitschrift fur Gastroenterologie [Epub ahead of print].

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

RevDate: 2019-04-15

Saha S, Tariq R, Tosh PK, et al (2019)

Fecal Microbiota Transplantation for Eradicating Carriage of Multidrug-Resistant Organisms: A Systematic Review.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases pii:S1198-743X(19)30158-2 [Epub ahead of print].

BACKGROUND: Multidrug resistant (MDR) microorganism development in the gut is frequently secondary to inappropriate antibiotic use. Fecal microbiota transplantation (FMT) restores normal gut microbiota in patients with C difficile infection; we hypothesized that it may help in decolonizing MDR organisms (MDROs) and in preventing recurrent MDR infections.

OBJECTIVES: To assess FMT efficacy (eradication rate) for decolonizing MDROs and preventing recurrent MDR infections.

DATA SOURCES: MEDLINE, EMBASE, and Web of Science (inception through February 11, 2019).

STUDY ELIGIBILITY CRITERIA: Clinical trials, retrospective studies, case reports, and case series.

PARTICIPANTS: Patients with MDR infections or MDRO colonization treated with FMT.

INTERVENTIONS: FMT.

METHODS: Systematic review.

RESULTS: Twenty-one studies (1 randomized clinical trial, 7 uncontrolled clinical trials, 2 retrospective cohort studies, 2 case series, 9 case reports) with 192 patients were included. Three studies assessed FMT efficacy in preventing MDR infections; 16 assessed its effect on MDRO colonization; 2 assessed both. Data from 151 patients were included in the final analyses. In studies with low to moderate risk of bias, the eradication rate was 37.5% to 87.5%. Efficacy was similar in studies looking at infection or colonization and did not differ by length of follow-up. No serious adverse events from FMT were reported. Seven patients died of other causes.

CONCLUSIONS: FMT could be used as a treatment for eradicating MDR colonization and, possibly, preventing recurrent MDR infections, once more supporting efficacy and safety data are available. Larger, well-designed randomized controlled trials are needed to further explore this therapy.

RevDate: 2019-04-12

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

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

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

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

RevDate: 2019-04-12
CmpDate: 2019-04-12

Stebel R, Svačinka R, Vojtilová L, et al (Wint)

Fecal bacteriotherapy in the treatment of Clostridium difficile infection.

Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne, 67(3):104-109.

AIM: Using a prospective analysis to assess the success of faecal bacteriotherapy (FBT) in antibiotic-associated colitis due to Clostridium difficile. To analyse whether any of the factors according to which the treated patients can be categorized has a statistically significant effect on the therapeutic outcome.

MATERIALS AND METHODS: During the 2-year study period (2015-2016), 71 patients received FBT. After treatment, the patients were followed up by means of clinic visits or by phone. If colitis did not recur within eight weeks of follow-up, the treatment was considered successful.

RESULTS: The overall success rate was 76%, with statistically insignificant decline in recurrences. Subgroup analysis did not show any statistically significant difference in the success rate between the routes of administration, i.e. through a naso-enteral feeding tube and rectal enema. Likewise, there were no statistically significant differences in the success rate between the types of prior antibiotic therapy or between using fresh and cryo-stored stool suspension. No unexpected adverse event or lethality occurred during the study period.

CONCLUSIONS: Faecal bacteriotherapy is a successful and safe therapeutic alternative for recurrent C. difficile infections.

RevDate: 2019-04-12
CmpDate: 2019-04-12

Berry D (2019)

Up-close-and-personal with the human microbiome.

Environmental microbiology reports, 11(1):17-19.

RevDate: 2019-04-11

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

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

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

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

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

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

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

TRIAL REGISTRATION: ClinicalTrials.gov NCT01790061, NCT02560727.

RevDate: 2019-04-10

Galperine TK, B Guery (2019)

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

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

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

RevDate: 2019-04-10

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

Safety and Efficacy of Fecal Microbiota Transplant in 9 Critically Ill Patients with Severe and Complicated Clostridium Difficile Infection with Impending Colectomy: A Case Series.

Journal of digestive diseases [Epub ahead of print].

BACKGROUND AND AIMS: There is significant data that support the efficacy and safety of Fecal Microbiota Transplant (FMT) in Recurrent Clostridium Difficile Infection (RCDI). The objective of our study was to determine the success rate of FMT in patients diagnosed with severe and complicated CDI with impending colectomy in the ICU setting.

METHODS: This was a 2 center study, which consisted of 9 patients who met criteria of severe and complicated CDI and had impending colectomy. All 9 patients failed conventional antibiotic therapy and were deemed too unstable to undergo colectomy. Hence, FMT was considered as the next step in management.

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

CONCLUSION: Our success with FMT in fulminant CDI shows that this therapeutic modality is a promising alternative and could be a potential bowel saving intervention. This article is protected by copyright. All rights reserved.

RevDate: 2019-04-10

Mrazek K, Bereswill S, MM Heimesaat (2019)

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

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

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

RevDate: 2019-04-10

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

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

Frontiers in immunology, 10:554.

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

RevDate: 2019-04-10

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

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

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

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

RevDate: 2019-04-10

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

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

Biochemical and biophysical research communications pii:S0006-291X(19)30603-5 [Epub ahead of print].

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

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

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

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

RevDate: 2019-04-10
CmpDate: 2019-04-10

Takahashi M, Ishikawa D, Sasaki T, et al (2019)

Faecal freezing preservation period influences colonization ability for faecal microbiota transplantation.

Journal of applied microbiology, 126(3):973-984.

AIMS: There has been growing interest in faecal microbiota transplantation (FMT) as treatment. Although, frozen donor faeces preserved at -20°C has been widely used for practical advantages, freezing at -20°C can affect bacterial viability. Adequacy evaluation of fresh and frozen faeces as the transplant is necessary for the methodological improvement of FMT.

METHODS AND RESULTS: The viable bacterial compositions of faecal specimens under fresh and freezing conditions were compared by a microbiome analysis using propidium monoazide (PMA microbiome). In addition, recovery abilities from bacterial reduction by antibiotics were compared between fresh and frozen FMT using a murine model. PMA microbiome results suggested that freezing and freeze-thawing did not significantly affect in vitro faecal bacterial viability. However, the recovery effect from antimicrobial cleansing in frozen FMT was reduced in a freezing time-dependent manner, especially prominent in Actinobacteria and Bacteroidetes phyla.

CONCLUSIONS: Short-term freezing preservation of faeces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1 month -20°C-preservation.

Long-term -20°C-preservation of transplanted faeces can result in instability of the clinical outcome in FMT therapy. The standardization of practical procedures of FMT therapy according to disease types is desirable.

RevDate: 2019-04-08

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

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

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

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

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

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

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

RevDate: 2019-04-08
CmpDate: 2019-04-08

Moelling K, Broecker F, C Willy (2018)

A Wake-Up Call: We Need Phage Therapy Now.

Viruses, 10(12): pii:v10120688.

The rise of multidrug-resistant bacteria has resulted in an increased interest in phage therapy, which historically preceded antibiotic treatment against bacterial infections. To date, there have been no reports of serious adverse events caused by phages. They have been successfully used to cure human diseases in Eastern Europe for many decades. More recently, clinical trials and case reports for a variety of indications have shown promising results. However, major hurdles to the introduction of phage therapy in the Western world are the regulatory and legal frameworks. Present regulations may take a decade or longer to be fulfilled. It is of urgent need to speed up the availability of phage therapy.

RevDate: 2019-04-04

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

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

Scandinavian journal of gastroenterology [Epub ahead of print].

BACKGROUND: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules.

METHODS: Seven patients with active UC, aged 27-50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months.

RESULTS: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p = .001) and 6 (p = .001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800 mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported.

CONCLUSION: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.

RevDate: 2019-04-04

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

Clostridium difficile infection: review.

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

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

RevDate: 2019-04-03

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

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

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

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

RevDate: 2019-04-02

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

Microbiota transplantation: Targeting cancer treatment.

Cancer letters, 452:144-151 pii:S0304-3835(19)30166-1 [Epub ahead of print].

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

RevDate: 2019-04-03
CmpDate: 2019-04-03

Draper LA, Ryan FJ, Smith MK, et al (2018)

Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation.

Microbiome, 6(1):220.

BACKGROUND: Faecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied.

RESULTS: We studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12 months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns.

CONCLUSIONS: The impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.

RevDate: 2019-04-03
CmpDate: 2019-04-03

Cheng CS, Wei HK, Wang P, et al (2019)

Early intervention with faecal microbiota transplantation: an effective means to improve growth performance and the intestinal development of suckling piglets.

Animal : an international journal of animal bioscience, 13(3):533-541.

Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-β and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.

RevDate: 2019-04-02

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

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

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

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

RevDate: 2019-04-01

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

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

Frontiers in physiology, 10:231.

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

RevDate: 2019-04-01

Caesar R (2019)

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

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

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

RevDate: 2019-03-29

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

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

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

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

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

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

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

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

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

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

PROSPERO registration number CRD42018075126.

RevDate: 2019-03-29

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

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

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

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

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

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

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

RevDate: 2019-03-28

Bajaj JS, RA Hays (2019)

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

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

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

RevDate: 2019-03-28

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

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

Microbiology and immunology [Epub ahead of print].

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

RevDate: 2019-03-28

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

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

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

RevDate: 2019-03-26

Kim KO, M Gluck (2019)

Fecal Microbiota Transplantation: An Update on Clinical Practice.

Clinical endoscopy pii:ce.2019.009 [Epub ahead of print].

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

RevDate: 2019-03-25

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

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

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

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

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

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

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

RevDate: 2019-03-25

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

Effect of fecal microbiota transplantation on experimental colitis in mice.

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

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

RevDate: 2019-03-25

Levy AN, JR Allegretti (2019)

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

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

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

RevDate: 2019-03-22

Fischer M (2019)

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

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

RevDate: 2019-03-22

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

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

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

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

RevDate: 2019-03-21
CmpDate: 2019-03-21

Hassoun A (2018)

Clostridium difficile associated disease.

BMJ (Clinical research ed.), 363:k4369.

RevDate: 2019-03-20

Alsahhar JS, RS Rahimi (2019)

Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy.

Current opinion in gastroenterology [Epub ahead of print].

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

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

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

RevDate: 2019-03-20

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

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

Frontiers in physiology, 10:171.

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

RevDate: 2019-03-19

Ohara T (2019)

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

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

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

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

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

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

RevDate: 2019-03-19

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

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

Frontiers in microbiology, 10:390.

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

RevDate: 2019-03-19
CmpDate: 2019-03-19

Tominaga K, Tsuchiya A, Yokoyama J, et al (2019)

How do you treat this diversion ileitis and pouchitis?.

Gut, 68(4):593-758.

RevDate: 2019-03-18

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

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

Journal of clinical gastroenterology [Epub ahead of print].

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

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

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

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

RevDate: 2019-03-18

Davido B, Batista R, Dinh A, et al (2019)

Fifty shades of graft: how to improve efficacy of Fecal Microbiota Transplantation (FMT) for decolonization of Antibiotic-Resistant Bacteria (ARB)?.

BACKGROUND: Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: about 25% after 30 days for Carbapenem-producing Enterobacteriaceae (CPE) or ESBL. Currently, fecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization, in order to reduce the risk of superinfection due to these ARB. We discuss the literature about FMT in this indication, and the improvement levers we have to promote its efficacy.

METHODS: We browsed the relevant literature available up to day concerning the use of FMT to eradicate ARB and evaluated the different factors that may have influenced the efficacy of decolonization.

RESULTS: We found 4 axes that could have led a major role in the efficacy of FMT: i) the bowel preparation before FMT ii) the donor, iii) the dose and iv) the thermal conditioning of feces. We discuss their positive or negative impact on the outcome of the FMT.

CONCLUSION: Although FMT is very efficient in the eradication of Clostridium difficile infection, the same recipe cannot be applied for the eradication of ARB. Working hand-in-hand with expert centers might help to improve its efficacy in such indication, and allow reducing in-hospital isolation precautions.

RevDate: 2019-03-16

Uchiyama K, Naito Y, T Takagi (2019)

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

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

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

RevDate: 2019-03-16

Ramesh MS, J Yee (2019)

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

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

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

RevDate: 2019-03-15

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

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

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

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

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

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

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

RevDate: 2019-03-15
CmpDate: 2019-03-15

Hwang IY, Lee HL, Huang JG, et al (2018)

Engineering microbes for targeted strikes against human pathogens.

Cellular and molecular life sciences : CMLS, 75(15):2719-2733.

Lack of pathogen specificity in antimicrobial therapy causes non-discriminant microbial cell killing that disrupts the microflora present. As a result, potentially helpful microbial cells are killed along with the pathogen, altering the biodiversity and dynamic interactions within the population. Moreover, the unwarranted exposure of antibiotics to microbes increases the likelihood of developing resistance and perpetuates the emergence of multidrug resistance. Synthetic biology offers an alternative solution where specificity can be conferred to reduce the non-specific, non-targeted activity of currently available antibiotics, and instead provides targeted therapy against specific pathogens and minimising collateral damage to the host's inherent microbiota. With a greater understanding of the microbiome and the available genetic engineering tools for microbial cells, it is possible to devise antimicrobial strategies for novel antimicrobial therapy that are able to precisely and selectively remove infectious pathogens. Herein, we review the strategies developed by unlocking some of the natural mechanisms used by the microbes and how these may be utilised in targeted antimicrobial therapy, with the promise of reducing the current global bane of multidrug antimicrobial resistance.

RevDate: 2019-03-14

Xu X, Fukui H, Ran Y, et al (2019)

Alteration of GLP-1/GPR43 expression and gastrointestinal motility in dysbiotic mice treated with vancomycin.

Scientific reports, 9(1):4381 pii:10.1038/s41598-019-40978-9.

Gut microbiota plays a pivotal role in various aspects of host physiology, including metabolism, gastrointestinal (GI) motility and hormonal secretion. In the present study, we investigated the effect of antibiotic-associated dysbiosis on metabolism and GI motility in relation to colonic expression of glucagon-like peptide-1 (GLP-1) and G protein coupled receptor (GPR)43. Specific pathogen-free (SPF) mice (ICR, 6 weeks old, female) were orally administered vancomycin (0.2 mg/ml) in drinking water for 7 days. In another experiment, germ-free (GF) mice (ICR, 6 weeks old, female) were subjected to oral fecal transplantation (FT) using a fecal bacterial suspension prepared from SPF mice that had received vancomycin treatment (FT-V) or one from untreated control SPF mice (FT-C). The gastrointestinal transit time (GITT) was measured by administration of carmine red (6% w/v) solution. The expression of GLP-1 and GPR43 was examined by immunohistochemistry and realtime RT-PCR, and the plasma GLP-1 level was measured by ELISA. In vancomycin-treated SPF mice, the diversity of the gut microbiota was significantly reduced and the abundance of Lactobacillus was markedly increased. Significant increases in body weight, cecum weight, plasma GLP-1 level and colonic GLP-1/GPR43 expression were also noted relative to the controls. These alterations were reproducible in GF mice with FT-V. Moreover, FT-V GF mice showed a significantly increased food intake and a significantly prolonged GITT in comparison with FT-C GF mice. Vancomycin-induced dysbiosis promotes body weight gain and prolongs GITT, accompanied by an increase of colonic GLP-1/GPR43 expression.

RevDate: 2019-03-14
CmpDate: 2019-03-14

Polívková S, Vojtilová L, Husa P, et al (2018)

[Guideline for fecal bacteriotherapy to treat recurrent Clostridium difficile colitis].

Klinicka mikrobiologie a infekcni lekarstvi, 24(2):57-64.

We present a case of a 17-year-old female with anti-NMDAR encephalitis probably associated with vaccination against yellow fever. Her symptoms occurred 27 days after vaccination against yellow fever. Anti-NMDAR encephalitis manifested as acute psychosis, memory loss and catatonia following fever with complex partial epileptic seizures. Interictal electroencephalogram showed slow-wave delta background activity with "delta brushes". The diagnosis was confirmed by NMDAR antibody positivity in serum and cerebrospinal fluid. Since ovarian teratoma, as the most common cause of anti-NMDAR encephalitis, did not develop within five years from its onset, the association with vaccination against yellow fever seems to be highly probable.

RevDate: 2019-03-14
CmpDate: 2019-03-14

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

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

Journal of Crohn's & colitis, 12(11):1359-1374.

Background and Aims: Faecal microbiota transplantation [FMT] has shown promise as a treatment for inflammatory bowel disease [IBD]. Using a piglet model, our previous study indicated that exogenous faecal microbiota can increase the expressions of tight junction proteins, mucin and antimicrobial peptide in the intestinal mucosa, suggesting a beneficial effect of FMT on gut barrier and gastrointestinal health. However, specific connections between FMT-induced microbial changes and modulation of the intestinal barrier 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 gene 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 a significant increase of the typical microbiota-derived tryptophan catabolite indole-3-acetic acid in the colonic lumen. In concordance with the metabolome data, metagenomics prediction analysis based on 16S rRNA gene sequencing also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with indole alkaloid biosynthesis, cytochrome P450 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 maintenance of the intestinal barrier.

RevDate: 2019-03-12

Roggenbrod S, Schuler C, Haller B, et al (2019)

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis].

Zeitschrift fur Gastroenterologie, 57(3):296-303.

INTRODUCTION: Fecal microbiota transplantation (FMT) represents a treatment option for recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating ulcerative colitis. This study examined the approval and willingness of affected patients who underwent FMT.

METHODS: A standardized questionnaire containing 27 polar and open questions was dispatched to a cohort of 262 patients suffering from UC. It included questions regarding the FMT process, donors, and possible concerns. Additionally, aspects of social background and disease activity were addressed.

RESULTS: The response rate was 31.3 % (n = 82). Forty-eight (58.5 %) patients were already aware of FMT. Forty-six (56.1 %) were willing to undergo FMT if given a respective indication. The effectiveness of the procedure (40.2 %), followed by failure of all other therapies (17.1 %), formed the principal motivation. The transmission of possible infectious agents (26.8 %), and the potential contamination of the stool graft leading to a deterioration of clinical symptoms, raised the most concerns. (20.7 %).The preferred delivery system of FMT was capsules (67.1 %), followed by colonoscopic application (47.6 %). The patients were in favour of a donor proposed by the physician (52,4 %). Willingness to undergo FMT did not differ significantly between genders (56.4 % women vs. 57.1 % men). Smokers (88.9 %), patients who did not watch television at all (77.8 %) and those with private health insurance, showed an increased willingness to undergo FMT.

CONCLUSION: For the majority of the UC patients surveyed, FMT represents a feasible treatment option. Approximately half of the respondents would consider FMT as an alternative treatment option, even inspite of a satisfactory disease response to current standard therapies. Unsurprisingly, there are concerns regarding the transmission of possible infectious agents and the hygienic implementation of FMT itself.

RevDate: 2019-03-12

Joseph J, Saha S, AJ Greenberg-Worisek (2019)

Fecal Microbiota Transplantation: An Ambiguous Translational Pathway for a Promising Treatment.

Clinical and translational science [Epub ahead of print].

RevDate: 2019-03-12

Wang J, Wang P, Li D, et al (2019)

Beneficial effects of ginger on prevention of obesity through modulation of gut microbiota in mice.

European journal of nutrition pii:10.1007/s00394-019-01938-1 [Epub ahead of print].

PURPOSE: Recent evidence has demonstrated that the gut microbiota plays a critical role in the treatment of obesity and other metabolic dysfunctions. Ginger (Zingiber officinale Roscoe), one of the most commonly used spices and dietary supplements, has been shown to exert beneficial effects against obesity and related disorders. However, to date, the mechanisms linking these effects to the gut microbiota remain unclear. This study aims to investigate the relationship between the gut microbiota and the metabolic adaptations resulting from ginger supplementation in mice.

METHODS: Four groups of mice were fed a normal chow diet (NCD) or a high-fat diet (HFD) with or without ginger supplementation for 16 weeks. Lipid profiles, proinflammatory cytokines, glucose tolerance, microbiota composition and short-chain fatty acid (SCFA) concentrations were analyzed at the end of the experiment. In addition, microbiota-depleted mice were transplanted with the fecal microbiota of mice fed a HFD or mice fed a HFD along with ginger supplementation. Glucose tolerance and microbiota composition were assessed after a 8-week fecal microbiota transplantation (FMT).

RESULTS: We observed marked decreases in body weight, liver steatosis, and low-grade inflammation as well as amelioration of insulin resistance in the HFD-fed mice treated with ginger. Furthermore, ginger supplementation modulated the gut microbiota composition and increased species belonging to the Bifidobacterium genus and SCFA-producing bacteria (Alloprevotella and Allobaculum), along with increases in fecal SCFA concentrations. The FMT experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral ginger-feeding experiment.

CONCLUSIONS: This study suggests that modulation of the gut microbiota as a result of ginger supplementation has a therapeutic effect on obesity in mice.

RevDate: 2019-03-12

Sartelli M, Di Bella S, McFarland LV, et al (2019)

2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients.

World journal of emergency surgery : WJES, 14:8 pii:228.

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

RevDate: 2019-03-10

Hirten RP, Grinspan A, Fu SC, et al (2019)

Microbial Engraftment and Efficacy of Fecal Microbiota Transplant for Clostridium Difficile in Patients With and Without Inflammatory Bowel Disease.

Inflammatory bowel diseases pii:5372769 [Epub ahead of print].

BACKGROUND: Recurrent and severe Clostridium difficile infections (CDI) are treated with fecal microbiota transplant (FMT). Uncertainty exists regarding FMT effectiveness for CDI with underlying inflammatory bowel disease (IBD) and regarding its effects on disease activity and effectiveness in transferring the donor microbiota to patients with and without IBD.

METHODS: Subjects with and without IBD who underwent FMT for recurrent or severe CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) frequency of IBD flare after FMT; (3) microbiota engraftment after FMT; (and 4) predictors of CDI recurrence.

RESULTS: One hundred thirty-four patients, 46 with IBD, were treated with FMT. Follow-up was available in 83 and 118 patients at 6 and 2 months, respectively. There was no difference in recurrence in patients with and without IBD at 6 months (38.7% vs 36.5%; P > 0.99) and 2 months (22.5% vs 17.9%; P = 0.63). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. Pre-FMT microbiota was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment, with no difference in engraftment based on CDI recurrence or IBD endoscopic severity at FMT.

CONCLUSIONS: Inflammatory bowel disease did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiota was not predictive of recurrence, and microbial engraftment was impacted in those requiring IBD treatment escalation, though not by CDI recurrence or IBD disease severity.

RevDate: 2019-03-09

Hibbard J, Jiang ZD, HL DuPont (2019)

Fecal Calprotectin and Fecal Indole Predicts Outcome of Fecal Microbiota Transplantation in Subjects with Recurrent Clostridium difficile Infection.

Anaerobe pii:S1075-9964(19)30045-9 [Epub ahead of print].

Fecal calprotectin and indole were studied in 134 subjects with recurrent CDI before and after FMT. Reduced fecal calprotectin (p=0.0353, 95% CI 0.1305-0.1439) and rising levels of indole (p<0.0001, 95% CI <0.0001-0.0003) predicted successful treatment. A ratio of recal calprotectin/indole may provide prognostic value for FMT (p=0.0004, 95% CI 0.22-0.87).

RevDate: 2019-03-08

Chen CC, Chen YN, Liou JM, et al (2019)

From germ theory to germ therapy.

The Kaohsiung journal of medical sciences, 35(2):73-82.

Germ theory of disease and Koch's postulates has been governing our understanding of the role of microbes in human health since 19th century. The discovery of Helicobacter pylori (H. pylori) and H. pylori associated diseases has typically represented the concept and framework of Koch's postulates. Eradication of H. pylori to prevent peptic ulcers recurrence and gastric cancer is the triumph of this microbiology paradigm. Advances of next generation sequencing provide great insight into the unculturable microbes and show trillions of microbes have evolved with human beings. Research into the microbiome-the microbial communities (microbiota) and the host environment that they inhabit-has changed our understanding about microbes in human health and disease. The gut microbiota, the largest reservoir of the microbiome in human, plays a critical role in our catabolic-metabolism and immunity. This review will show the changes of the view of microbes on human health. We will briefly discuss dysbiosis, the disruption of symbiotic relationship between the host and microbiota, and the associated diseases. This leads to an idea to manipulate the microbiota, either by restoring missing functions or by eliminating harmful functions, to prevent or treat a variety of diseases. Current evidences of two common germ therapies, fecal microbiota transplantation and probiotics, in treating diseases will be reviewed.

RevDate: 2019-03-08

Olmedo M, Reigadas E, Valerio M, et al (2019)

Is it reasonable to perform Fecal Microbiota Transplantation for recurrent Clostridium difficile Infection in patients with liver cirrhosis?.

RevDate: 2019-03-08

Biagi E, Zama D, Rampelli S, et al (2019)

Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders.

BMC medical genomics, 12(1):49 pii:10.1186/s12920-019-0494-7.

BACKGROUND: The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset.

METHODS: Thirty-six pediatric patients, from four transplantation centers, undergoing HSCT were enrolled in the study. Stools were collected at three time points: before HSCT, at time of engraftment and > 30 days following HSCT. Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation.

RESULTS: Children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This putative aGvHD-predisposing ecosystem state was characterized by (i) reduced diversity, (ii) lower Blautia content, (iii) increase in Fusobacterium abundance. At time of engraftment, the GM structure underwent a deep rearrangement in all patients but, regardless of the occurrence of aGvHD and its treatment, it reacquired a eubiotic configuration from day 30.

CONCLUSIONS: We found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. Our data may open the way to a GM-based stratification of the risk of developing aGvHD in children undergoing HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation.

RevDate: 2019-03-08
CmpDate: 2019-03-08

Ganesan K, Chung SK, Vanamala J, et al (2018)

Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes.

International journal of molecular sciences, 19(12): pii:ijms19123720.

The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced the risk of a variety of complications, such as diabetes and cardiovascular diseases. In the present review, we have highlighted the new insights on the complex relationships between diet-induced modulation of gut microbiota and metabolic disorders, including diabetes. Literature from various library databases and electronic searches (ScienceDirect, PubMed, and Google Scholar) were randomly collected. There exists a complex relationship between diet and gut microbiota, which alters the energy balance, health impacts, and autoimmunity, further causes inflammation and metabolic dysfunction, including diabetes. Faecalibacterium prausnitzii is a butyrate-producing bacterium, which plays a vital role in diabetes. Transplantation of F. prausnitzii has been used as an intervention strategy to treat dysbiosis of the gut's microbial community that is linked to the inflammation, which precedes autoimmune disease and diabetes. The review focuses on literature that highlights the benefits of the microbiota especially, the abundant of F. prausnitzii in protecting the gut microbiota pattern and its therapeutic potential against inflammation and diabetes.

RevDate: 2019-03-07

Chang CS, Ruan JW, CY Kao (2019)

An overview of microbiome based strategies on anti-obesity.

The Kaohsiung journal of medical sciences, 35(1):7-16.

With the significant global obesity epidemic and emerging strong scientific evidence that connected gut microbiota to obesity, intervening obesity by targeting gut microbiota has become a trendy strategy. Particularly the application of probiotics has become remarkably popular because of their expected association with gut microbiota modulation. Although there are many literatures on the effects of probiotics in obese animal models, most of them reported the effects of probiotic bacteria on metabolic indications with limited information on anti-obesity itself. Besides, some probiotics have been shown to reduce certain metabolic symptoms but they failed to achieve weight loss. This report reviewed the current literatures on the anti-obesity effects of next-generation probiotics in various animal obesity models and discussed the beneficial potential of fecal microbiota transplantation in treating obesity in humans. The purpose of this article is to help guide further research improve the probiotic bacteria experiments in more precise animal obesity models by standardizing the anti-obesogenesis, obesity control, and treatment assays and hopefully the evidence-based investigations on harnessing gut microbiota through next-generation probiotics or fecal microbiota transplantation will develop new interventions to promote and achieve anti-obesity.

RevDate: 2019-03-07

Cammarota G, Gallo A, Ianiro G, et al (2019)

Emerging drugs for the treatment of Clostridium difficile.

Expert opinion on emerging drugs [Epub ahead of print].

Introduction Clostridium difficile, or Clostridioides difficile, (C difficile) infection represents the most common cause of healthcare-associated infection. Over the last decades, the incidence and severity of C difficile infection is rapidly increasing, with a significant impact on morbidity and mortality, and burden on health care system. Orally administered vancomycin and fidaxomicin are the therapeutic options of choice for initial C difficile infection and fecal microbiota transplant for the recurrence infection. Furthermore, in recent years several new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed, including surotomycin, cadazolid, and ridinilazol, and novel toxoid vaccines are expected to be efficacious in the prevention of C difficile infection. Areas covered Literature review was performed to select publications about current guidelines and phase II/III trials on emerging drugs. These include novel antibiotics, monoclonal antibodies, vaccines, and fecal microbiota transplantation. Expert opinion We have today a wide spectrum of promising therapeutic possibilities against infection. Pivotal future clinical trials may be crucial in developing effective strategies to optimize outcomes, mainly in high-risk population.

RevDate: 2019-03-07
CmpDate: 2019-03-07

Bajaj JS, Kakiyama G, Savidge T, et al (2018)

Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant.

Hepatology (Baltimore, Md.), 68(4):1549-1558.

Patients with cirrhosis are often exposed to antibiotics that can lead to resistance and fungal overgrowth. The role of fecal microbial transplant (FMT) in restoring gut microbial function is unclear in cirrhosis. In a Food and Drug Administration-monitored phase 1 clinical safety trial, patients with decompensated cirrhosis on standard therapies (lactulose and rifaximin) were randomized to standard-of-care (SOC, no antibiotics/FMT) or 5 days of broad-spectrum antibiotics followed by FMT from a donor enriched in Lachnospiraceae and Ruminococcaceae. Microbial composition (diversity, family-level relative abundances), function (fecal bile acid [BA] deconjugation, 7α-dehydroxylation, short-chain fatty acids [SCFAs]), and correlations between Lachnospiraceae, Ruminococcaceae, and clinical variables were analyzed at baseline, postantibiotics, and 15 days post-FMT. FMT was well tolerated. Postantibiotics, there was a reduced microbial diversity and autochthonous taxa relative abundance. This was associated with an altered fecal SCFA and BA profile. Correlation linkage changes from beneficial at baseline to negative after antibiotics. All of these parameters became statistically similar post-FMT to baseline levels. No changes were seen in the SOC group.

CONCLUSION: In patients with advanced cirrhosis on lactulose and rifaximin, FMT restored antibiotic-associated disruption in microbial diversity and function. (Hepatology 2018; 00:000-000).

RevDate: 2019-03-06

Petito V, Fiore L, Lopetuso LR, et al (2019)

Commentary to "Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota Transplant in Children With Inflammatory Bowel Disease".

Inflammatory bowel diseases pii:5370426 [Epub ahead of print].

RevDate: 2019-03-06
CmpDate: 2019-03-06

Amedei A, F Boem (2018)

I've Gut A Feeling: Microbiota Impacting the Conceptual and Experimental Perspectives of Personalized Medicine.

International journal of molecular sciences, 19(12): pii:ijms19123756.

In recent years, the human microbiota has gained increasing relevance both in research and clinical fields. Increasing studies seem to suggest the centrality of the microbiota and its composition both in the development and maintenance of what we call "health" and in generating and/or favoring (those cases in which the microbiota's complex relational architecture is dysregulated) the onset of pathological conditions. The complex relationships between the microbiota and human beings, which invest core notions of biomedicine such as "health" and "individual," do concern not only problems of an empirical nature but seem to require the need to adopt new concepts and new perspectives in order to be properly analysed and utilized, especially for their therapeutic implementation. In this contribution we report and discuss some of the theoretical proposals and innovations (from the ecological component to the notion of polygenomic organism) aimed at producing this change of perspective. In conclusion, we summarily analyze what impact and what new challenges these new approaches might have on personalized/person centred/precision medicine.

RevDate: 2019-03-05

Lin P (2019)

Importance of the intestinal microbiota in ocular inflammatory diseases: a review.

Clinical & experimental ophthalmology [Epub ahead of print].

The purpose of this article is to review the literature on relationships between the intestinal microbiota and ocular inflammatory disease, specifically non-infectious uveitis and age-related macular degeneration. The findings show the importance of the intestinal microbiota in uveitis pathogenesis has been shown by multiple groups demonstrating that alterations in the microbiota induced by certain oral antibiotics results in reduced uveitis severity, and another group demonstrating that a commensal intestinal bacterial antigen activates retina-specific autoreactive T cells, potentially indicating a commensal trigger for uveitis. Additionally, commensal intestinal bacterial metabolite short chain fatty acids can be utilized to suppress autoimmune uveitis. Age-related macular degeneration is associated with intestinal dysbiosis, which is partially influenced by genetic risk alleles and AREDS supplementation. Strategies for therapeutically targeting the intestinal microbiota might involve several approaches, including the use of antibiotics, dietary changes, drugs that supplement beneficial bacterial metabolites or target causative bacterial strains, dietary strategies, or fecal microbial transplantation. In summary, the intestinal microbiota are at the cross-roads of genetic and environmental factors that can promote ocular conditions such as non-infectious uveitis and age-related macular degeneration, partially via its dynamic influence on mucosal and systemic immunity. The intestinal microbiome thus represents a salient potential target for therapeutic modulation to treat these potentially blinding conditions. This article is protected by copyright. All rights reserved.

RevDate: 2019-03-05

Kim P, Gadani A, Abdul-Baki H, et al (2019)

Fecal microbiota transplantation in recurrent Clostridium difficile infection: A retrospective single-center chart review.

JGH open : an open access journal of gastroenterology and hepatology, 3(1):4-9 pii:JGH312093.

Background and Aim: Fecal microbiota transplantation (FMT) has been proposed as a treatment option for patients with recurrent Clostridium difficile (C. difficile) infection but remains a novel option. We examined if FMT is an effective means of treating recurrent C. difficile infection.

Methods: A retrospective review of 35 patients who underwent FMT was completed. Demographics and other variables, including the use of proton pump inhibitor therapy and history of inflammatory bowel disease, were collected.

Results: Twenty-five patients (71.4%) belonged to a high-risk population (working in a hospital setting, rehabilitation center, or nursing facility) and a total of 74.3% of patients (n = 26 patients) had no history of proton pump inhibitor use. Twenty-five patients (71.4%) had used metronidazole prior to transplantation, 35 patients (100%) had used vancomycin, and 7 patients (20%) had used fidaxomicin for prior infection. Four patients (11.4%) had used all three antibiotics during prior treatment. Of the eight patients who had a history of inflammatory bowel disease, six (75%) experienced resolution of symptoms after transplantation. A total of 30 patients (85.7%) had resolution of their symptoms 6-8 weeks' posttransplant, while 5 patients (14.3%) continued to have symptoms.

Conclusions: Our retrospective chart review supports that patients benefit from FMT in the setting of recurrent C. difficile infection.

RevDate: 2019-03-05

Álvarez-Mercado AI, Navarro-Oliveros M, Robles-Sánchez C, et al (2019)

Microbial Population Changes and Their Relationship with Human Health and Disease.

Microorganisms, 7(3): pii:microorganisms7030068.

Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.

RevDate: 2019-03-04

Bakke D, Chatterjee I, Agrawal A, et al (2018)

Regulation of Microbiota by Vitamin D Receptor: A Nuclear Weapon in Metabolic Diseases.

Nuclear receptor research, 5:.

Metabolic syndrome is a multi-faceted disease. The microbiota, as a newly discovered organ, contributes to the pathogenesis and progression of metabolic syndrome. Recent studies have demonstrated that nuclear receptors play critical roles in metabolic diseases. In the current review, we discuss the general role of the microbiome in health and metabolic syndrome. We summarize the functions of the nuclear receptor vitamin D receptor (VDR) in metabolism. The focus of this review is the novel roles of vitamin D/VDR signaling in regulating inflammation and the microbiome, especially in obesity. Furthermore, we extend our discussion of potential gut-liver axis mediated by VDR signaling and microbiota in obesity. Finally, we discuss the potential clinical application of probiotics and fecal microbiota transplantation in prevention and treatment of metabolic syndrome. Insights into nuclear receptors in metabolism and metabolic diseases will allow us to develop new strategies for fighting metabolic diseases.

RevDate: 2019-03-04

Albarrak AA, Romana BS, Uraz S, et al (2019)

Clostridium difficile infection in Inflammatory Bowel Disease Patients.

Endocrine, metabolic & immune disorders drug targets pii:EMIDDT-EPUB-96975 [Epub ahead of print].

BACKGROUND: The rising incidence of Clostridium difficile infection (CDI) in the general population has been recognized by health care organizations worldwide. The emergence of hypervirulent strains has made CDI more challenging to understand and treat. Inflammatory bowel disease (IBD) patients are at higher risk of infection, including CDI.

OBJECTIVE: A diagnostic approach for recurrent CDI has yet to be validated, particularly for IBD patients. Enzyme immunoassay (EIA) for toxins A and B, as well as glutamate dehydrogenase EIA, are both rapid testing options for the identification of CDI. Without a high index of suspicion, it is challenging to initially differentiate CDI from an IBD flare based on clinical evaluation alone.

METHOD/RESULTS: Here, we provide and up-to-date review on CDI in IBD patients. When caring for an IBD patient with suspected CDI, it is appropriate to empirically treat the presumed infection while awaiting further test results. Treatment with vancomycin or fidaxomicin, but not oral metronidazole, has been advocated by an expert review from the clinical practice update committee of the American Gastroenterology Association. Recurrent CDI is more common in IBD patients compared to non-IBD patients (32% versus 24%), thus more aggressive treatment is recommended for IBD patients along with early consideration of fecal microbiota transplant.

CONCLUSION: Although the use of infliximab during CDI has been debated, clinical experience exists supporting its use in an IBD flare, even with active CDI when needed.

RevDate: 2019-03-01

Grace E, EB Chahine (2019)

Updates on Clostridioides (Clostridium) difficile Infection With Emphasis on Long-Term Care.

The Senior care pharmacist, 34(1):29-42.

OBJECTIVE: To provide a review of the classification, epidemiology, risk factors, diagnosis, treatment, and prevention of Clostridioides (Clostridium) difficile (C. difficile) infection (CDI) with an emphasis on longterm care.

DATA SOURCES: PubMed and Google Scholar were searched for relevant literature using a combination of the following terms: C. difficile, classification, epidemilogy, risk factors, diagnosis, treatment, prevention, and long-term care. Sources were limited to human data.

The main article reviewed was the 2017 CDI guidelines of the Infectious Diseases Society of American and the Society for Healthcare Epidemiology of America. Other articles were reviewed for relevance to CDI in long-term care settings.

DATA SYNTHESIS: CDI is associated with significant morbidity and mortality, particularly in older adults. The primary risk factors are advanced age and receipt of antibiotics. Diagnosis is suspected based on signs and symptoms and confirmed by laboratory tests. Vancomycin and fidaxomicin have replaced metronidazole as the drugs of choice for CDI. Fidaxomicin is associated with a lower risk of recurrence than vancomycin. Fecal microbiota transplantation is reserved for patients with multiple recurrences. Bezlotoxumab can be used in addition to standard therapy to prevent CDIs in patients at high risk for recurrence. Infection control strategies and antibiotic stewardship programs are known to reduce the rates of CDIs in institutional settings.

CONCLUSION: CDI is largely iatrogenic, and diagnosis is based on clinical presentation and laboratory tests. Treatment options include vancomycin, fidaxomicin, and fecal microbiota transplantation. Prevention centers around infection control and antibiotic stewardship. More research is needed in long-term care settings.

RevDate: 2019-03-01

Lam TJ, Y Ye (2019)

CRISPRs for Strain Tracking and Their Application to Microbiota Transplantation Data Analysis.

The CRISPR journal, 2(1):41-50.

CRISPR-Cas systems are adaptive immune systems naturally found in bacteria and archaea. Prokaryotes use these immune systems to defend against invaders, which include phages, plasmids, and other mobile genetic elements. Relying on the integration of spacers derived from invader sequences (protospacers) into CRISPR loci (forming spacers flanked by repeats), CRISPR-Cas systems are able to store the memory of past immunological encounters. While CRISPR-Cas systems have evolved in response to invading mobile genetic elements, invaders have also developed mechanisms to avoid detection. As a result of an arms race between CRISPR-Cas systems and their targets, CRISPR arrays typically undergo rapid turnover of spacers through the acquisition and loss events. Additionally, microbiomes of different individuals rarely share spacers. Here, we present a computational pipeline, CRISPRtrack, for strain tracking based on CRISPR spacer content, and we applied it to fecal transplantation microbiome data to study the retention of donor strains in recipients. Our results demonstrate the potential use of CRISPRs as a simple yet effective tool for donor-strain tracking in fecal transplantation and as a general purpose tool for quantifying microbiome similarity.

RevDate: 2019-03-01

Gundling F, Roggenbrod S, Schleifer S, et al (2019)

Patient perception and approval of faecal microbiota transplantation (FMT) as an alternative treatment option for obesity.

Obesity science & practice, 5(1):68-74 pii:OSP4302.

Introduction: Fecal microbiota transplantation (FMT) represents a treatment option for some diseases, e.g. recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating obesity. This pilot study established the approval and willingness of obese patients to undergo FMT.

Methods: We conducted a survey of adults with obesity using a questionnaire containing 21 both multiple choice and open questions was dispatched to a cohort of 101 persons with obesity. It included questions aiming at the process of FMT itself, donors as well as possible concerns. Additionally aspects of social background and disease activity were dealt with.

Results: The response rate amounted to 30.1% (n = 31). In our population, mean BMI was 40.5 kg/m2 while the vast majority already tried out treatment modalities to lose weight before. 25.8% of persons with obesity were aware of FMT. 62.1% were willing to undergo FMT if the donor was healthy and anonymous while only 6.9% clearly refused this option. Sixty preferred an anonymous donor or a person proposed by their doctor while colonoscopy was the preferred application by 76.7%. The absence of risks of the procedure (47.8%) formed the principal motivation while reduction of medication was considered as least important reason (in 26.1). Insufficient testing of the faeces concerning infections raised the most concerns (in 61.6%).

Conclusion: For the majority of the persons with obesity surveyed FMT represents a treatment option. Approximately two thirds of the questionees would consider FMT as an alternative treatment option, even in spite of a satisfactory disease response to current standard therapies. Unsurprisingly there are concerns in regard to the transmission of possible infectious agents as well as to the hygieneic implementation of FMT itself.

RevDate: 2019-02-28

Kay E, Hawramee S, Pollani S, et al (2019)

Nonpharmacologic options for treating irritable bowel syndrome.

JAAPA : official journal of the American Academy of Physician Assistants, 32(3):38-42.

Irritable bowel syndrome (IBS) is a chronic functional disorder with no organic cause. Risk factors are multifactorial and treatment typically consists of antimotility or stimulant laxatives and antidepressants. This article reviews several newer areas of interest: probiotics, fecal microbiota transplant, a low FODMAP diet, and cognitive behavioral therapy.

RevDate: 2019-02-28

Zhou ZL, Jia XB, Sun MF, et al (2019)

Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics pii:10.1007/s13311-019-00719-2 [Epub ahead of print].

Parkinson's disease (PD) is strongly associated with life style, especially dietary habits, which have gained attention as disease modifiers. Here, we report a fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting an involvement of BDNF in FMD-mediated neuroprotection. Furthermore, FMD decreased the number of glial cells as well as the release of TNF-α and IL-1β in PD mice, showing that FMD also inhibited neuro-inflammation. 16S and 18S rRNA sequencing of fecal microbiota showed that FMD treatment modulated the shifts in gut microbiota composition, including higher abundance of Firmicutes, Tenericutes, and Opisthokonta and lower abundance of Proteobacteria at the phylum level in PD mice. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed that FMD modulated the MPTP-induced lower propionic acid and isobutyric acid, and higher butyric acid and valeric acid and other metabolites. Transplantation of fecal microbiota, from normal mice with FMD treatment to antibiotic-pretreated PD mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD. These findings demonstrate that FMD can be a new means of preventing and treating PD through promoting a favorable gut microbiota composition and metabolites.

RevDate: 2019-02-28

Abu-Sbeih H, Ali FS, Y Wang (2019)

Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients.

Current gastroenterology reports, 21(4):8 pii:10.1007/s11894-019-0677-6.

Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.

RevDate: 2019-02-27

Ohkusa T, Koido S, Nishikawa Y, et al (2019)

Gut Microbiota and Chronic Constipation: A Review and Update.

Frontiers in medicine, 6:19.

Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: "IBS," "IBS-C," "irritable bowel syndrome," "irritable bowel syndrome with constipation," "functional constipation," "chronic constipation" in combination with "gut microbiota," "dysbiosis," "gut microflora" for microbiota in chronic constipation, and in combination with "probiotics," "prebiotics," "synbiotics," "antibiotics," and "fecal microbiota transplantation." Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.

RevDate: 2019-02-27

Li Y, Zou Z, Bian X, et al (2019)

Fecal microbiota transplantation research output from 2004 to 2017: a bibliometric analysis.

PeerJ, 7:e6411 pii:6411.

Background: Fecal microbiota transplantation (FMT) is an emerging therapy against Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although the therapy has gained prominence, there has been no bibliometric analysis of FMT.

Methods: Studies published from 2004 to 2017 were extracted from the Science Citation Index Expanded. Bibliometric analysis was used to evaluate the number or cooperation network of publications, countries, citations, references, journals, authors, institutions and keywords.

Results: A total of 796 items were included, showing an increasing trend annually. Publications mainly came from 10 countries, led by the US (n = 363). In the top 100 articles ranked by the number of citations (range 47-1,158), American Journal of Gastroenterology (2017 IF = 10.231) took the top spot. The co-citation network had 7 co-citation clusters headed by 'recurrent Clostridium difficile infection'. The top 7 keywords with the strongest citation bursts had three parts, 'microbiota', ' diarrhea ', and 'case series'. All keywords were divided into four domains, 'disease', 'nosogenesis', 'trial', and 'therapy'.

Conclusions: This study shows the research performance of FMT from 2004 to 2017 and helps investigators master the trend of FMT, which is also an ongoing hotspot of research.

RevDate: 2019-02-27
CmpDate: 2019-02-27

Kragsnaes MS, Kjeldsen J, Horn HC, et al (2018)

Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial.

BMJ open, 8(4):e019231.

INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.

METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study.

ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s).

TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

RevDate: 2019-02-26

Sougiannis AT, VanderVeen BN, Enos RT, et al (2019)

Impact of 5 Fluorouracil Chemotherapy on Gut Inflammation, Functional Parameters, and Gut Microbiota.

Brain, behavior, and immunity pii:S0889-1591(18)31227-3 [Epub ahead of print].

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

RevDate: 2019-02-26

Cheung SG, Goldenthal AR, Uhlemann AC, et al (2019)

Systematic Review of Gut Microbiota and Major Depression.

Frontiers in psychiatry, 10:34.

Background: Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. Methods: A PubMed literature search combined the terms "depression," "depressive disorder," "stool," "fecal," "gut," and "microbiome" to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Results: Six eligible studies were found in which 50 taxa exhibited differences (p < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria, and Protobacteria-were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum Firmicutes, in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family Lachnospiraceae differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (Anaerostipes, Blautia, Clostridium, Klebsiella, Lachnospiraceae incertae sedis, Parabacteroides, Parasutterella, Phascolarctobacterium, and Streptococcus), six were lower (Bifidobacterium, Dialister, Escherichia/Shigella, Faecalibacterium, and Ruminococcus), and six were divergent (Alistipes, Bacteroides, Megamonas, Oscillibacter, Prevotella, and Roseburia). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. Conclusions: No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.

RevDate: 2019-02-26

Mo R, Ren RR, Zhang XW, et al (2019)

[Fecal microbiota transplantation for the treatment of ulcerative colitis: a Meta-analysis].

Zhonghua nei ke za zhi, 58(3):202-208.

Objective: We aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of ulcerative colitis (UC) in this Meta-analysis. Methods: Literature related to FMT for the treatment of UC from PubMed, Embase, Cochrane databases, CNKI, VIP and Wanfang Data were searched and screened with update study in May 2018. Two independent investigators extracted information according to inclusion and exclusion criteria. The Meta-analysis was conducted by Stata 12.0 software. Results: A total of 4 randomized controlled trials (RCTs) and 19 non-randomized controlled trials (non-RCTs) including 536 participants met the inclusion criteria. Meta-analysis of RCTs showed that FMT significantly increased the clinical remission rate (OR=2.47, 95%CI 1.40-4.33, P=0.02) and clinical response rate (OR=1.86, 95%CI 1.15-3.02, P=0.01) in UC patients without increasing the incidence of severe adverse effects (OR=1.40, 95%CI 0.51-3.79, P=0.51). The results from 19 non-RCTs showed that clinical remission rate in UC patients with FMT treatment was 20%(95%CI 13%-28%) and the clinical response rate was 50%(95%CI 36%-65%). All adverse events were graded as mild and self-resolving. No FMT-related severe adverse effects were reported. Conclusions: Our analysis suggests that FMT is a safe and effective method for the treatment of UC. Considering several limitations of this Meta-analysis and previous clinical trials, further large-scale multicenter RCTs are still required to further verify the conclusion.

RevDate: 2019-02-25
CmpDate: 2019-02-25

Mushtaq A (2018)

New clinical recommendations for Clostridium difficile.

The Lancet. Infectious diseases, 18(4):384.

RevDate: 2019-02-23

Papanicolas LE, Choo JM, Wang Y, et al (2019)

Bacterial viability in faecal transplants: Which bacteria survive?.

EBioMedicine pii:S2352-3964(19)30095-7 [Epub ahead of print].

BACKGROUND: The therapeutic potential of faecal microbiota transplantation (FMT) is under investigation for a range of inflammatory conditions. While mechanisms of benefit are poorly understood, most models rely on the viability of transplanted microbes. We hypothesised that protocols commonly used in the preparation of faecal transplants will substantially reduce the number, diversity and functional potential of viable microbes.

METHODS: Stools from eight screened donors were processed under strict anaerobic conditions, in ambient air, and freeze-thawed. Propidium monoazide (PMA) sample treatment was combined with quantitative PCR, 16S rRNA gene amplicon sequencing and short-chain fatty acid (SCFA) analysis to define the viable microbiota composition and functional potential.

FINDINGS: Approximately 50% of bacterial content of stool processed immediately under strict anaerobic conditions was non-viable. Homogenisation in ambient air or freeze-thaw reduced viability to 19% and 23% respectively. Processing of samples in ambient air resulted in up to 12-fold reductions in the abundance of important commensal taxa, including the highly butyrogenic species Faecalibacterium prausnitzii, Subdoligranulum variable, and Eubacterium hallii. The adverse impact of atmospheric oxygen exposure on the capacity of the transplanted microbiota to support SCFA biosynthesis was demonstrated by significantly reduced butyrate and acetate production by faecal slurries processed in ambient air. In contrast, while reducing overall levels of viable bacteria, freeze-thaw did not significantly alter viable microbiota composition.

INTERPRETATION: The practice of preparing material for faecal transplantation in ambient air profoundly affects viable microbial content, disproportionately reducing the abundance of anaerobic commensals and the capacity for biosynthesis of important anti-inflammatory metabolites. FUND: This work was supported by the South Australian Health and Medical Research Institute. LP is supported by a scholarship from the Flinders Foundation. GR is supported by a Matthew Flinders Research Fellowship.

RevDate: 2019-02-22

Shin W, Wu A, Massidda MW, et al (2019)

A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With Human Intestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip.

Frontiers in bioengineering and biotechnology, 7:13.

The majority of human gut microbiome is comprised of obligate anaerobic bacteria that exert essential metabolic functions in the human colon. These anaerobic gut bacteria constantly crosstalk with the colonic epithelium in a mucosal anoxic-oxic interface (AOI). However, in vitro recreation of the metabolically mismatched colonic AOI has been technically challenging. Furthermore, stable co-culture of the obligate anaerobic commensal microbiome and epithelial cells in a mechanically dynamic condition is essential for demonstrating the host-gut microbiome crosstalk. Here, we developed an anoxic-oxic interface-on-a-chip (AOI Chip) by leveraging a modified human gut-on-a-chip to demonstrate a controlled oxygen gradient in the lumen-capillary transepithelial interface by flowing anoxic and oxic culture medium at various physiological milieus. Computational simulation and experimental results revealed that the presence of the epithelial cell layer and the flow-dependent conditioning in the lumen microchannel is necessary and sufficient to create the steady-state vertical oxygen gradient in the AOI Chip. We confirmed that the created AOI does not compromise the viability, barrier function, mucin production, and the expression and localization of tight junction proteins in the 3D intestinal epithelial layer. Two obligate anaerobic commensal gut microbiome, Bifidobacterium adolescentis and Eubacterium hallii, that exert metabolic cross-feeding in vivo, were independently co-cultured with epithelial cells in the AOI Chip for up to a week without compromising any cell viability. Our new protocol for creating an AOI in a microfluidic gut-on-a-chip may enable to demonstrate the key physiological interactions of obligate anaerobic gut microbiome with the host cells associated with intestinal metabolism, homeostasis, and immune regulation.

RevDate: 2019-02-22

Suk KT, DJ Kim (2019)

Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease.

Expert review of gastroenterology & hepatology, 13(3):193-204.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide with a prevalence of 20-33%. NAFLD may progress to fibrosis, compensated cirrhosis, advanced cirrhosis, or hepatocellular carcinoma. Despite the increasing prevalence of NAFLD, definitive medical treatment has not been established, with the exception of lifestyle modification with exercise. Because of the direct connection via portal vein between the intestines and the liver (gut-gut microbiota-liver axis), gut microbiota and associated dysbiosis have been known as regulators in the pathophysiology of NAFLD. Area covered: New therapeutic approaches for modulation of gut microbiota have been proposed and the effectiveness of new therapies including probiotics, prebiotics, synbiotics, bile acid regulation, absorbent, and fecal microbiota transplantation have been demonstrated in recent several studies. This review focuses on the available evidences for new therapies modulating gut microbiota in the management and the prevention of NAFLD. Expert commentary: Gut-gut microbiota-liver axis may play an important role in the etiology of many liver diseases, including NAFLD. It is logical to seek the manipulation of this axis, and further studies are required to understand the underlying precise mechanisms of microbiota-modulation on NAFLD.

RevDate: 2019-02-21
CmpDate: 2019-02-21

Coryell M, McAlpine M, Pinkham NV, et al (2018)

The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.

Nature communications, 9(1):5424 pii:10.1038/s41467-018-07803-9.

Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.

RevDate: 2019-02-20

Khan N, Mendonca L, Dhariwal A, et al (2019)

Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis.

Mucosal immunology pii:10.1038/s41385-019-0147-3 [Epub ahead of print].

Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT). Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota. Unexpectedly, treatment of mice with the pro-Mtb drugs INH and PYZ, but not RIF, prior to Mtb infection resulted in an increased bacterial burden, an effect that was reversible by fecal transplantation from untreated animals. Mechanistically, susceptibility of INH/PYZ-treated mice was associated with impaired metabolism of alveolar macrophages and defective bactericidal activity. Collectively, these data indicate that dysbiosis induced by ATT administered to millions of individuals worldwide may have adverse effects on the anti-Mtb response of alveolar macrophages.

RevDate: 2019-02-20

Cai T, Shi X, Yuan LZ, et al (2019)

Fecal microbiota transplantation in an elderly patient with mental depression.

International psychogeriatrics pii:S1041610219000115 [Epub ahead of print].

RevDate: 2019-02-19

Allegretti JR, Fischer M, Sagi SV, et al (2019)

Correction to: Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose.

The original version of the article unfortunately contained an error in article title. The corrected title is 'Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose'.

RevDate: 2019-02-19
CmpDate: 2019-02-18

Hochman J (2018)

Immunoassay helps limit overdiagnosis of Clostridium difficile infection.

The Journal of pediatrics, 199:283.

RevDate: 2019-02-14

Gogokhia L, Buhrke K, Bell R, et al (2019)

Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis.

Cell host & microbe, 25(2):285-299.e8.

Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-γ via the nucleotide-sensing receptor TLR9. The resultant immune responses were both phage and bacteria specific. Additionally, increasing bacteriophage levels exacerbated colitis via TLR9 and IFN-γ. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-γ positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-γ compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health.

RevDate: 2019-02-14

Li X, Song L, Zhu S, et al (2019)

Two Strains of Lactobacilli Effectively Decrease the Colonization of VRE in a Mouse Model.

Frontiers in cellular and infection microbiology, 9:6.

Vancomycin-resistant Enterococcus (VRE) infection is a serious challenge for clinical management and there is no effective treatment at present. Fecal microbiota transplantation (FMT) and probiotic intervention have been shown to be promising approaches for reducing the colonization of certain pathogenic bacteria in the gastrointestinal tract, however, no such studies have been done on VRE. In this study, we evaluated the effect of FMT and two Lactobacillus strains (Y74 and HT121) on the colonization of VRE in a VRE-infection mouse model. We found that both Lactobacilli strains reduced VRE colonization rapidly. Fecal microbiota and colon mRNA expression analyses further showed that mice in FMT and the two Lactobacilli treatment groups restored their intestinal microbiota diversity faster than those in the phosphate buffer saline (PBS) treated group. Administration of Lactobacilli restored Firmicutes more quickly to the normal level, compared to FMT or PBS treatment, but restored Bacteroides to their normal level less quickly than FMT did. Furthermore, these treatments also had an impact on the relative abundance of intestinal microbiota composition from phylum to species level. RNA-seq showed that FMT treatment induced the expression of more genes in the colon, compared to the Lactobacilli treatment. Defense-related genes such as defensin α, Apoa1, and RegIII were down-regulated in both FMT and the two Lactobacilli treatment groups. Taken together, our findings indicate that both FMT and Lactobacilli treatments were effective in decreasing the colonization of VRE in the gut.

RevDate: 2019-02-14

Heimesaat MM, Escher U, Grunau A, et al (2019)

Multidrug-Resistant Pseudomonas aeruginosa Accelerate Intestinal, Extra-Intestinal, and Systemic Inflammatory Responses in Human Microbiota-Associated Mice With Subacute Ileitis.

Frontiers in immunology, 10:49.

The globally rising incidences of multidrug-resistant (MDR) Pseudomonas aeruginosa (Psae) in humans and live-stock animals has prompted the World Health Organization to rate MDR Psae as serious threat for human health. Only little is known, however, regarding factors facilitating gastrointestinal Psae-acquisition by the vertebrate host and subsequently induced inflammatory sequelae. In the present study, we addressed whether subacute ileitis predisposed mice harboring a human gut microbiota for intestinal MDR Psae carriage and whether inflammatory responses might be induced following peroral challenge with the opportunistic pathogen. To accomplish this, secondary abiotic mice were associated with a human gut microbiota by fecal microbiota transplantation. Ten days later (i.e., on day 0), subacute ileitis was induced in human microbiota associated (hma) mice by peroral low-dose Toxoplasma gondii infection. On day 5 post-infection, mice were perorally challenged with 109 colony forming units of a clinical MDR Psae isolate by gavage and the fecal bacterial loads surveyed thereafter. Four days post-peroral challenge, only approximately one third of mice with a human gut microbiota and subacute ileitis harbored the opportunistic pathogen in the intestinal tract. Notably, the gut microbiota composition was virtually unaffected by the Psae-carriage status during subacute ileitis of hma mice. The Psae challenge resulted, however, in more pronounced intestinal epithelial apoptotic cell and T lymphocyte responses upon ileitis induction that were not restricted to the ileum, but also affected the large intestines. Higher Psae-induced abundances of T cells could additionally be observed in extra-intestinal compartments including liver, kidney, lung, and heart of hma mice with subacute ileitis. Furthermore, higher apoptotic cell numbers, but lower anti-inflammatory IL-10 concentrations were assessed in the liver of Psae as compared to mock treated mice with ileitis. Remarkably, Psae-challenge was accompanied by even more pronounced systemic secretion of pro-inflammatory cytokines such as TNF and IL-6 at day 9 post ileitis induction. In conclusion, whereas in one third of hma mice with subacute ileitis Psae could be isolated from the intestines upon peroral challenge, the opportunistic pathogen was responsible for inflammatory sequelae in intestinal, extra-intestinal, and even systemic compartments and thus worsened subacute ileitis outcome irrespective of the Psae-carrier status.

RevDate: 2019-02-10

Qi L, F Li (2019)

[Current Advances in the Fecal Microbiota Transplantation and Its Application in the Hematologic Diseases--Review].

Zhongguo shi yan xue ye xue za zhi, 27(1):306-310.

Intestinal microbiome closely relates with human health and disease, which plays a critical role in the immune response, homeostasis, drug metabolism and tumorigenesis. Imbalances in the composition and function of these intestinal microbes associate with diseases. Fecal microbiota transplantation (FMT) is an established successful treatment modality for recurrent Clostridium difficile infection (CDI). The safety profile and potential therapeutic advantages of FMT for diseases associated with dysbiosis and immune dysfunction have led to many publications, mainly case series. The literature on the use of FMT for hematologic diseases is very limited, however, immune thrombocytopenic purpura(ITP), CDI and aGVHD after HSCT were reported to be improved by FMT. The aim of this review is to briefly summarize the research current state, procedures and clinical application of FMT.

RevDate: 2019-02-08

Battipaglia G, Malard F, Rubio MT, et al (2019)

Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematological malignancies carrying multidrug-resistance bacteria.

Haematologica pii:haematol.2018.198549 [Epub ahead of print].

Fecal microbiota transplantation is an effective treatment in recurrent Clostridium difficile infection. Promising results to eradicate multidrug-resistant bacteria have also been reported with this procedure, but there are safety concerns in immunocompromised patients. We report results in 10 adult patients colonized with multidrug-resistant bacteria, undergoing fecal microbiota transplantation before (n=4) or after (n=6) allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Stools were obtained from healthy related or unrelated donors. Fecal material was delivered either by enema or via nasogastric tube. Patients were colonized or had infections from either carbapenemase-producing bacteria (n=8) or vancomycin-resistant enterococci (n=2). The median age at fecal microbiota transplantation was 48 (range 16-64) years. Three patients needed a second transplant from the same donor, due to initial failure of the procedure. With a median follow-up of 13 (range 4-40) months, decolonization was achieved in seven out of ten patients. In all patients, fecal microbiota transplantation was safe: one patient presented with constipation during the first 5 days after FMT and 2 patients had grade I diarrhea. One case of gut grade III acute graft-versus-host disease occurred after fecal microbiota transplantation. In patients carrying or infected by multidrug-resistant bacteria, fecal microbiota transplantation is an effective and safe decolonization strategy, even in those with hematologic malignancies undergoing hematopoietic stem cell transplantation.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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