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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 20 Jan 2019 at 01:36 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: 2019-01-19

Milosevic I, Vujovic A, Barac A, et al (2019)

Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature.

International journal of molecular sciences, 20(2): pii:ijms20020395.

The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called "the new virtual metabolic organ", makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of "ancient" microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.

RevDate: 2019-01-18

Markowski MC, Boorjian SA, Burton JP, et al (2019)

The Microbiome and Genitourinary Cancer: A Collaborative Review.

European urology pii:S0302-2838(18)31051-0 [Epub ahead of print].

CONTEXT: The recent discovery of the existence of a human genitourinary microbiome has led to the investigation of its role in mediating the pathogenesis of genitourinary malignancies, including bladder, kidney, and prostate cancers. Furthermore, although it is largely recognized that members of the gastrointestinal microbiota are actively involved in drug metabolism, new studies demonstrate additional roles and the potential necessity of the gastrointestinal microbiota in dictating cancer treatment response.

OBJECTIVE: To summarize the current evidence of a mechanistic role for the genitourinary and gastrointestinal microbiome in genitourinary cancer initiation and treatment response.

EVIDENCE ACQUISITION: We conducted a literature search up to October 2018. Search terms included microbiome, microbiota, urinary microbiome, bladder cancer, urothelial carcinoma, renal cell carcinoma, kidney cancer, testicular cancer, and prostate cancer.

EVIDENCE SYNTHESIS: There is preliminary evidence to implicate the members of the genitourinary microbiota as causative factors or cofactors in genitourinary malignancy. Likewise, the current evidence for gastrointestinal microbes in dictating cancer treatment response is mainly correlative; however, we provide examples where therapeutic agents used for the treatment of genitourinary cancers are affected by the human-associated microbiota, or vice versa. Clinical trials, such as fecal microbiota transplant to increase the efficacy of immunotherapy, are currently underway.

CONCLUSIONS: The role of the microbiome in genitourinary cancer is an emerging field that merits further studies. Translating microbiome research into clinical action will require incorporation of microbiome surveillance into ongoing and future clinical trials as well as expansion of studies to include metagenomic sequencing and metabolomics.

PATIENT SUMMARY: This review covers recent evidence that microbial populations that reside in the genitourinary tract-and were previously not known to exist-may influence the development of genitourinary malignancies including bladder, kidney, and prostate cancers. Furthermore, microbial populations that exist at sites outside of the genitourinary tract, such as those that reside in our gut, may influence cancer development and/or treatment response.

RevDate: 2019-01-18
CmpDate: 2019-01-18

Wu TR, Lin CS, Chang CJ, et al (2019)

Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis.

Gut, 68(2):248-262.

OBJECTIVE: The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota.

DESIGN: High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis.

RESULTS: Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii, a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1's anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance.

CONCLUSIONS: HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.

RevDate: 2019-01-18
CmpDate: 2019-01-18

Knudsen JK, Bundgaard-Nielsen C, Hagstrøm S, et al (2017)

[The human gut microbiota].

Ugeskrift for laeger, 179(49):.

Characterization of the human gut microbiota has caused a paradigm shift in modern biomedical research. Maintenance of gut microbiota depends on mutual microbe-host interactions, which when disturbed can lead to dysbiosis. Dysbiosis has been associated with a variety of autoimmune and metabolic diseases. Studies attempt to define bacterial compositional changes, immunity responses or molecular patterns associated with specific diseases. The immense research in the human microbiota may lead to novel therapeutic strategies by development of commensal microbe products in management of diseases.

RevDate: 2019-01-17

Goethel A, Turpin W, Rouquier S, et al (2019)

Nod2 influences microbial resilience and susceptibility to colitis following antibiotic exposure.

Mucosal immunology pii:10.1038/s41385-018-0128-y [Epub ahead of print].

Inflammatory bowel disease (IBD) etiology involves genetic susceptibility, environmental triggers, and the gut microbiome. Antibiotic exposure is associated with IBD, both in early life and adulthood. Here, we investigated whether Nod2-deficiency influenced response of the gut microbiota to antibiotics and subsequent colitis susceptibility. Wild-type and Nod2-/- littermate mice were treated with amoxicillin as adults or neonates, and fecal samples were collected for 16S rRNA sequencing. Five weeks after antibiotic exposure, dextran sulfate sodium (DSS) colitis was induced. Antibiotic treatment altered the microbiota of adult WT and Nod2-/- mice, but recovery was delayed in Nod2-/- mice. Neonatal antibiotic treatment significantly changed the microbiota at weaning in WT and Nod2-/- littermates; however, Nod2-/- mice maintained reduced microbial diversity 14 days after cessation of antibiotics. Although treatment of adult mice did not influence susceptibility to colitis, neonatally treated Nod2-/- mice developed a more severe colitis. Moreover, the colitis phenotype was transferable through fecal transplantation into germ-free Nod2-/- recipients, and was associated with changes in intestinal T cells and the cytokine milieu following inflammation. These data demonstrate that neonatal antibiotic exposure has long-lasting influence on the microbiota and mucosal immunity, and may explain how NOD2 contributes to the risk of intestinal inflammation.

RevDate: 2019-01-16

Torres Soto M, Hammond S, Elshaboury RH, et al (2019)

Recurrent Relatively Resistant Salmonella infantis Infection in 2 Immunocompromised Hosts Cleared With Prolonged Antibiotics and Fecal Microbiota Transplantation.

Open forum infectious diseases, 6(1):ofy334 pii:ofy334.

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

RevDate: 2019-01-15

Costello SP, Hughes PA, Waters O, et al (2019)

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.

JAMA, 321(2):156-164.

Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.

Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.

A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.

Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.

Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.

Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.

Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.

Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.

RevDate: 2019-01-15

Tran V, Phan J, Nulsen B, et al (2018)

Severe Ileocolonic Crohn's Disease Flare Associated with Fecal Microbiota Transplantation Requiring Diverting Ileostomy.

ACG case reports journal, 5:e97 pii:crj.2018.97.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) is an effective therapy with a high success rate in preventing recurrent CDI. However, patients with IBD have decreased response to FMT for recurrent CDI, with several reports also suggesting potential IBD flare post-FMT. We present a case of mild ileocolonic Crohn's disease in a patient treated with FMT for recurrent CDI who subsequently developed severe steroid-refractory flare requiring surgical intervention 1 week post-FMT. Greater understanding of risk factors associated with post-FMT IBD flare is indicated.

RevDate: 2019-01-15

Zhang K, Beckett P, Abouanaser S, et al (2019)

Prolonged oral vancomycin for secondary prophylaxis of relapsing Clostridium difficile infection.

BMC infectious diseases, 19(1):51 pii:10.1186/s12879-019-3676-1.

BACKGROUND: Clostridium difficile infection (CDI) is an important cause of diarrhea and continues to be a major burden within healthcare institutions and in the community. For a small subset of patients with frequently relapsing CDI who do not have access to fecal microbiota transplantation (FMT), or fail FMT, there are no clear treatment recommendations. We review our experience with prolonged oral vancomycin for secondary prophylaxis of relapsing CDI.

METHODS: We performed a retrospective chart review of cases from the C. difficile consultation service at our institution since 2013. The service had three primary physicians providing consultations and performing over 1000 FMTs over the five-year period. Patients with relapsing CDI who were not candidates for FMT, refused, or relapsed after FMT were treated with vancomycin, followed by long-term oral vancomycin at a dose of 125 mg once daily.

RESULTS: Twenty patients received at least 8 weeks of once-daily oral vancomycin for prophylaxis of relapsing CDI. Patients had a median age of 80 years, and experienced a median of four episodes of CDI prior to long-term vancomycin. Most were female and 75% had received FMT. Only a single case of C. difficile relapse occurred while on long-term vancomycin during 200 patient-months of follow-up. Amongst those who stopped long-term vancomycin, 31% relapsed within 6 weeks. No adverse events were observed.

CONCLUSIONS: For elderly patients with frequently relapsing C. difficile, prolonged vancomycin once daily at a dose of 125 mg orally was effective in preventing further relapse. Vancomycin secondary prophylaxis may be considered in patients who have failed FMT, or in cases where FMT is not available.

RevDate: 2019-01-14

Ferreira Felizardo RJ, Mizuno Watanabe IK, Dardi P, et al (2019)

The interplay among gut microbiota, hypertension and kidney diseases: the role of short-chain fatty acids.

Pharmacological research pii:S1043-6618(18)31684-0 [Epub ahead of print].

The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been associated with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely associated diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced number of short-chain fatty acids (SCFAs) producing bacteria is associated with modifications in gut environment, involving reduction of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the reduction of SCFAs plasma levels. Those modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria composition and fecal metabolite profile, inducing a positive feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota composition can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial composition uncovering to improve human health maintenance and, especially, for the development of new alternative therapies.

RevDate: 2019-01-14

Philips CA, Augustine P, N Phadke (2018)

Healthy Donor Fecal Microbiota Transplantation for Recurrent Bacterial Cholangitis in Primary Sclerosing Cholangitis - A Single Case Report.

Journal of clinical and translational hepatology, 6(4):438-441.

Recurrent acute bacterial cholangitis is a unique indication for liver transplantation in primary sclerosing cholangitis. We present the first report on utility of healthy donor fecal transplantation for management of recurrent acute bacterial cholangitis in a primary sclerosing cholangitis patient. We demonstrate the striking liver biochemistry, bile acid and bacterial community changes following intestinal microbiota transplantation associated with amelioration of recurrent cholangitis.

RevDate: 2019-01-14
CmpDate: 2019-01-14

Pan F, Zhang L, Li M, et al (2018)

Predominant gut Lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice.

Microbiome, 6(1):54.

BACKGROUND: Calorie restriction (CR), which has a potent anti-inflammaging effect, has been demonstrated to induce dramatic changes in the gut microbiota. Whether the modulated gut microbiota contributes to the attenuation of inflammation during CR is unknown, as are the members of the microbial community that may be key mediators of this process.

RESULTS: Here, we report that a unique Lactobacillus-predominated microbial community was rapidly attained in mice within 2 weeks of CR, which decreased the levels of circulating microbial antigens and systemic inflammatory markers such as tumour necrosis factor alpha (TNF-α). Lactobacillus murinus CR147, an isolate in the most abundant operational taxonomic unit (OTU) enriched by CR, downregulated interleukin-8 production in TNF-α-stimulated Caco-2 cells and significantly increased the lifespan and the brood size of the nematode Caenorhabditis elegans. In gnotobiotic mice colonized with the gut microbiota from old mice, this strain decreased their intestinal permeability and serum endotoxin load, consequently attenuating the inflammation induced by the old microbiota.

CONCLUSIONS: Our study demonstrated that a strain of Lactobacillus murinus was promoted in CR mice and causatively contributed to the attenuation of ageing-associated inflammation.

RevDate: 2019-01-11

Moutinho BD, Baima JP, Rigo FF, et al (2019)

Fecal microbiota transplantation in refractory ulcerative colitis - a case report.

The Journal of international medical research [Epub ahead of print].

Studies comparing gut microbiota profiles of inflammatory bowel disease (IBD) patients have shown several changes in microbiota composition, with marked reduction of local biodiversity relative to that of healthy controls. Modulation of the bacterial community is a promising strategy to reduce the proportion of harmful microorganisms and increase the proportion of beneficial bacteria; this is expected to prevent or treat IBD. The exact mechanism of fecal microbiota transplantation (FMT) remains unknown; however, replacing the host microbiota can reestablish gut microbial composition and function in IBD patients. The present report describes an ulcerative colitis patient who underwent FMT. A 17-year-old male with moderate to severe clinical activity, which was refractory to mesalazine, azathioprine, and infliximab, underwent FMT as alternative therapy. The patient exhibited clinical improvement after the procedure; however, the symptoms returned. A second FMT was performed 8 months after the first procedure, but the patient did not improve. In conclusion, despite the FMT failure observed in this patient, the procedure is a promising therapeutic option for IBD patients, and more in-depth studies of this method are needed.

RevDate: 2019-01-11

Allegretti JR, Kao D, Phelps E, et al (2019)

Risk of Clostridium difficile Infection with Systemic Antimicrobial Therapy Following Successful Fecal Microbiota Transplant: Should We Recommend Anti-Clostridium difficile Antibiotic Prophylaxis?.

Digestive diseases and sciences pii:10.1007/s10620-018-5450-4 [Epub ahead of print].

INTRODUCTION: The risk of a new Clostridium difficile infection (CDI) after FMT is unknown if non-CDI antibiotics are required. It is uncertain if anti-CDI prophylaxis or probiotics would reduce risk. We therefore aimed to compare the risk of CDI with and without antibiotic exposure and the benefit of concomitant anti-CDI antibiotic or probiotic prophylaxis.

METHODS: This is a multicenter retrospective study carried out at three large FMT referral centers of patients who underwent FMT for recurrent CDI. Patients were assessed for antibiotic use, as well as concomitant use of prophylactic anti-CDI antibiotics or probiotics. Time to CDI recurrence after FMT was evaluated using the Kaplan-Meier method.

RESULTS: A total of 404 patients were included: 63% were females, with a mean age of 61.3 ± 18.8 years. Mean length of post-FMT follow-up was 18.1 ± 11.9 months (range 2.2-45.2). Among the entire cohort 8.1% (n = 33) experienced a CDI recurrence. Overall, 111 patients (27.4%) used a non-CDI antibiotic, of which 16.2% (n = 18) experienced a CDI recurrence. Patients who used non-CDI antibiotics were more likely to develop CDI (HR 8.44, 95% CI 4.21-16.93, p < 0.001). The risk of CDI recurrence was not different between patients who received anti-CDI antibiotic prophylaxis to those who did not (HR = 1.88, 95% CI 0.72-4.86, p = 0.2); however, probiotic prophylaxis was associated with a greater risk of CDI recurrence (HR = 2.65, 95% CI 1.02-6.86, p = 0.045).

CONCLUSION: Non-CDI antibiotic use was not uncommon after successful FMT and significantly increased the risk of a new episode of CDI. In this study, we found that the prophylactic use of anti-CDI antibiotics or probiotics was not protective.

RevDate: 2019-01-11

Jiang X, Hall AB, Arthur TD, et al (2019)

Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut.

Science (New York, N.Y.), 363(6423):181-187.

Phase variation, the reversible alternation between genetic states, enables infection by pathogens and colonization by commensals. However, the diversity of phase variation remains underexplored. We developed the PhaseFinder algorithm to quantify DNA inversion-mediated phase variation. A systematic search of 54,875 bacterial genomes identified 4686 intergenic invertible DNA regions (invertons), revealing an enrichment in host-associated bacteria. Invertons containing promoters often regulate extracellular products, underscoring the importance of surface diversity for gut colonization. We found invertons containing promoters regulating antibiotic resistance genes that shift to the ON orientation after antibiotic treatment in human metagenomic data and in vitro, thereby mitigating the cost of antibiotic resistance. We observed that the orientations of some invertons diverge after fecal microbiota transplant, potentially as a result of individual-specific selective forces.

RevDate: 2019-01-11
CmpDate: 2019-01-11

Zhao L, Huang Y, Lu L, et al (2018)

Saturated long-chain fatty acid-producing bacteria contribute to enhanced colonic motility in rats.

Microbiome, 6(1):107.

BACKGROUND: The gut microbiota is closely associated with gastrointestinal (GI) motility disorder, but the mechanism(s) by which bacteria interact with and affect host GI motility remains unclear. In this study, through using metabolomic and metagenomic analyses, an animal model of neonatal maternal separation (NMS) characterized by accelerated colonic motility and gut dysbiosis was used to investigate the mechanism underlying microbiota-driven motility dysfunction.

RESULTS: An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency. Increase of SLCFAs was positively correlated with elevated abundances of Prevotella, Lactobacillus, and Alistipes. Functional annotation found that the level of bacterial LCFA biosynthesis was highly enriched in NMS group. Essential synthetic genes Fabs were largely identified from the genera Prevotella, Lactobacillus, and Alistipes. Pseudo germ-free (GF) rats receiving fecal microbiota from NMS donors exhibited increased defecation frequency and upregulated bacterial production of intracolonic SLCFAs. Modulation of gut dysbiosis by neomycin effectively attenuated GI motility and reduced bacterial SLCFA generation in the colon lumen of NMS rats.

CONCLUSIONS: These findings reveal a previously unknown relationship between gut bacteria, intracolonic SLCFAs, and host GI motility, suggesting the importance of SLCFA-producing bacteria in GI motility disorders. Further exploration of this relationship could lead to a precise medication targeting the gut microbiota for treating GI motility disorders.

RevDate: 2019-01-11
CmpDate: 2019-01-11

Wullaert A, Lamkanfi M, KD McCoy (2018)

Defining the Impact of Host Genotypes on Microbiota Composition Requires Meticulous Control of Experimental Variables.

Immunity, 48(4):605-607.

RevDate: 2019-01-10

Tabbaa OM, Aboelsoud MM, MC Mattar (2018)

Long-Term Safety and Efficacy of Fecal Microbiota Transplantation in the Treatment of Clostridium difficile Infection in Patients With and Without Inflammatory Bowel Disease: A Tertiary Care Center's Experience.

Gastroenterology research, 11(6):397-403.

Background: Clostridium difficile infection (CDI) carries a large burden on the national public health with its high morbidity and mortality rates. Patients with inflammatory bowel disease (IBD) are generally at higher risk of infection, recurrence and complications. Therefore, the need for more reliable and safe therapy is necessary. Our study aims to evaluate long-term fecal microbiota transplant (FMT) outcomes in the general population compared to patients with IBD.

Methods: A single center long-term follow-up study was conducted to evaluate the outcomes of FMT in patients with and without IBD. Prior to FMT data including demographics, prior treatment of CDI and severity of symptoms were gathered via chart review. Post FMT, all patients were surveyed after 2 days, 30 days and > 1 year to assess clinical and laboratory response. Our study outcomes included primary cure rate (negative CDI testing > 1 year after single FMT), and secondary cure rate (negative CDI testing > 1 year after repeat FMT or after an additional course of antibiotic with or without repeat FMT).

Results: Seventy-eight patients with recurrent or refractory CDI and subsequent FMT treatment were included. Mean age was 57 years, and 69% were females and twenty-one (27%) had IBD. Primary cure rate was achieved in 77% of the cases while secondary cure rate reached 100% at the end of the study. IBD patients were younger with an average age of 47 years, and had more complains of abdominal pain (71%), and required escalation of therapy in 50% of patients.

Conclusions: FMT was effective in the eradication of CDI in patients with and without IBD, but with no significant symptoms improvement in patients with IBD. Future randomized control studies are needed to examine the long-term progression of IBD and quality of life in patients treated with FMT compared to standard therapy of antibiotics for recurrent CDI.

RevDate: 2019-01-09
CmpDate: 2019-01-09

Rode AA, Chehri M, Petersen AM, et al (2017)

[Faecal microbiota transplantation for the treatment of bowel disease].

Ugeskrift for laeger, 179(31):.

Faecal microbiota transplantation (FMT) is the transferral of faeces from a healthy donor to a patient with a disease linked to disturbances in the gut microbiota. The treatment has been implemented at several hospitals in Denmark, and banks with frozen donor stool material have been established. The effect of FMT for recurrent Clostridium difficile infection is well-documented. FMT cannot be recommended for routine clinical use for inflammatory bowel disease and irritable bowel syndrome because of lack of data from clinical trials.

RevDate: 2019-01-09

de Clercq NC, Frissen MN, Davids M, et al (2019)

Weight Gain after Fecal Microbiota Transplantation in a Patient with Recurrent Underweight following Clinical Recovery from Anorexia Nervosa.

RevDate: 2019-01-08

Porras D, Nistal E, Martínez-Flórez S, et al (2018)

Intestinal Microbiota Modulation in Obesity-Related Non-alcoholic Fatty Liver Disease.

Frontiers in physiology, 9:1813.

Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.

RevDate: 2019-01-08

Yang H, Xiang Y, Robinson K, et al (2018)

Gut Microbiota Is a Major Contributor to Adiposity in Pigs.

Frontiers in microbiology, 9:3045.

Different breeds of pigs vary greatly in their propensity for adiposity. Gut microbiota is known to play an important role in modulating host physiology including fat metabolism. However, the relative contribution of gut microbiota to lipogenic characteristics of pigs remains elusive. In this study, we transplanted fecal microbiota of adult Jinhua and Landrace pigs, two breeds of pigs with distinct lipogenic phenotypes, to antibiotic-treated mice. Our results indicated that, 4 weeks after fecal transplantation, the mice receiving Jinhua pigs' "obese" microbiota (JM) exhibited a different intestinal bacterial community structure from those receiving Landrace pigs' "lean" microbiota (LM). Notably, an elevated ratio of Firmicutes to Bacteroidetes and a significant diminishment of Akkermansia were observed in JM mice relative to LM mice. Importantly, mouse recipients resembled their respective porcine donors in many of the lipogenic characteristics. Similar to Jinhua pig donors, JM mice had elevated lipid and triglyceride levels and the lipoprotein lipase activity in the liver. Enhanced expression of multiple key lipogenic genes and reduced angiopoietin-like 4 (Angptl4) mRNA expression were also observed in JM mice, relative to those in LM mice. These results collectively suggested that gut microbiota of Jinhua pigs is more capable of enhancing lipogenesis than that of Landrace pigs. Transferability of the lipogenic phenotype across species further indicated that gut microbiota plays a major role in contributing to adiposity in pigs. Manipulation of intestinal microbiota will, therefore, have a profound impact on altering host metabolism and adipogenesis, with an important implication in the treatment of human overweight and obesity.

RevDate: 2019-01-07

Zhang XY, Wang YZ, Li XL, et al (2018)

Safety of fecal microbiota transplantation in Chinese children: A single-center retrospective study.

World journal of clinical cases, 6(16):1121-1127.

BACKGROUND: Fecal microbiota transplantation (FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient's digestive tract, which is recommended as a therapeutic method for recurrent Clostridium difficile infection (CDI). Many clinical trials focusing on different diseases are in progress. To date, scarce research and long-term follow-up have been conducted on FMT in children or on the proper guidelines. Our center first performed FMT to treat a 13-month-old boy with severe CDI in 2013. Until February 2018, our center had performed 114 pediatric FMT procedures in 49 subjects.

AIM: To investigate the safety of FMT in children.

METHODS: A retrospective study was conducted on 49 patients who underwent 114 FMT treatments at our hospital. All FMT processes followed uniform standards. Adverse events (AEs) related to FMT were divided into short-term (48 h post-FMT) and long-term (3 mo). All potential influencing factors for AEs, such as gender, age, time of FMT infusion, route of administration, disease type, immune function state, and donor relative genetic background, were analyzed as independent factors. The significant independent factors and risk ratio with 95% confidence interval (CI) were assessed by multivariate logistic regression analysis.

RESULTS: Forty-nine patients (mean age 68.1 mo, range 4 to 193 mo) were recruited. Their average follow-up time after the first FMT was 23.1 mo. The incidence of short-term AEs was 26.32% (30/114). The most common short-term AEs were abdominal pain, diarrhea, fever, and vomiting, which were all self-limited and symptom-free within 48 h. Two severe AEs occurred, and one patient died in the fourth week after FMT. All-cause mortality was 2.04%. As independent factors, age (P = 0.006) and immune state (P = 0.002) had significant effects. Age greater than 72 mo seemed to be correlated with more AEs than age 13 to 36 mo (P = 0.04). In multivariate logistic regression analysis, immune state was an independent risk factor for AE occurrence (P = 0.035), and the risk ratio in immunodeficient patients was 3.105 (95%CI: 1.080-8.923).

CONCLUSION: Although FMT was proven to be tolerated in children, we need to be more cautious with immunodeficient patients. The effect on children's long-term health is unpredictable.

RevDate: 2019-01-07

Guirong YE, Minjie Z, Lixin YU, et al (2018)

[Gut microbiota in renal transplant recipients, patients with chronic kidney disease and healthy subjects].

Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 38(12):1401-1408.

OBJECTIVE: Recent studies have shown that gut microbiota is associated with immunomodulation in transplant recipients, but the composition and function of gut microbiota in renal transplant recipients have not been understood.

METHODS: We analyzed the composition and function of gut microbiota in the fecal samples from 16 renal transplant (RT) recipients by deep sequencing of the 16S rRNA V3 variable region. The gut microbiota of RT recipients was compared to that of 84 patients with chronic kidney disease (CKD) and 53 healthy subjects.

RESULTS: The overall microbial structure of RT recipients was similar to that of CKD. The abundance of Firmicutes, Lachnospiraceae, Ruminococcaceae and Faecalibacterium was decreased and that of Bacteroidetes, Proteobacteria, Clostridiales, and Enterobacteriaceae was increased significantly in RT recipients and CKD patients compared with the healthy control subjects. Functional comparison revealed significantly enhanced carbohydrate metabolism and decreased metabolism of cofactors, vitamins, cell motility and genetic information processing in RT recipients and CKD patients. RT recipients and CKD patients also showed slight differences in that the abundance of Proteobacteria and Enterobacteriaceae and the pathways involving transport system members and carbohydrate metabolism were much greater in the former. We found that several beneficial genera in the Lachnospiraceae and Veillonellaceae were negatively correlated with such clinical markers as serum creatinine and blood urea nitrogen.

CONCLUSIONS: Our results suggested that alterations in the composition and function of gut microbiota are significantly correlated with the clinical conditions of in RT recipients, and future prospective studies of these correlations may provide evidence for predicting the clinical outcomes of RT recipients.

RevDate: 2019-01-06

Bermejo Boixareu C, Ramos Martínez A, P Tutor-Ureta (2019)

Ninety-eight years old female treated with fecal microbiota transplantation after recurrent Clostridium difficile infection.

RevDate: 2019-01-05

Hvas CL, Jørgensen SMD, Jørgensen SP, et al (2019)

Fecal Microbiota Transplantation is Superior to Fidaxomicin for Treatment of Recurrent Clostridium difficile Infection.

Gastroenterology pii:S0016-5085(18)35434-9 [Epub ahead of print].

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center, randomized trial to compare the effects of FMT with those of fidaxomicin and vancomycin.

METHODS: We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark, from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube after 4-10 days of vancomycin (125 mg 4 times daily; FMTv; n = 24), 10 days of fidaxomicin (200 mg twice daily; n = 24), or 10 days of vancomycin (125 mg 4 times daily; n = 16). Patients who had recurrence of CDI following this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a PCR test for Clostridium difficile (CD) toxin 8 weeks following the allocated treatment. Secondary endpoints included clinical resolution at week 8.

RESULTS: All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients with FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%) (P for FMTv vs fidaxomicin = .009; P for FMTv vs vancomycin = .001; P for fidaxomicin vs vancomycin = .31). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%) (P = .0002; P < .0001; P = .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv.

CONCLUSIONS: In a randomized trial of patients with rCDI, we found the combination of vancomycin and FMT to be superior to fidaxomicin or vancomycin, based on endpoints of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov no: NCT02743234. EudraCT j.no: 2015-003004-24.

RevDate: 2019-01-04

Dai M, Zhang T, Li Q, et al (2019)

The bowel preparation for magnetic resonance enterography in patients with Crohn's disease: study protocol for a randomized controlled trial.

Trials, 20(1):1 pii:10.1186/s13063-018-3101-x.

BACKGROUND: Adequate bowel preparation is required for magnetic resonance enterography (MRE), which can be achieved by administering contrast solution after mid-gut tubing or taking contrast solution orally. We present the design of randomized controlled trial (RCT) to compare the efficacy and compliance of bowel preparation between mid-gut tubing and oral administering for MRE in patients with Crohn's disease (CD).

METHODS/DESIGN: This is an open-label, multicenter RCT. Ninety-six patients with CD in need of MRE examination and mid-gut tubing (prepared for fecal microbiota transplantation and/or enteral nutrition), aged ≥ 14 years, will be included. Patients will be randomized 1:1 into either bowel preparation by oral administering (oral group) or bowel preparation through mid-gut transendoscopic enteral tubing (TET) (tubing group). The primary outcome measures are: (1) degree of discomfort before/during/after bowel preparation for MRE using a visual 5-grade scale (1 = few, 5 = very severe); and (2) grade of bowel distention evaluated by a 5-grade scale (1 = 0-20% segmental distention, 2 = 20-40% distention, 3 = 40-60% distention, 4 = 60-80% distention, 5 = 80-100% distention). The secondary outcome measure is the accuracy of lesion detection through MRE confirmed by colonoscopy which is evaluated by a 5-point scale.

DISCUSSION: The outcome of this study is expected to provide a novel effective clinical protocol of bowel preparation for MRE in patients with CD. We hope to highlight the concept of physician-patient satisfaction based on different methods of bowel preparation for MRE.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03541733 . Registered on 30 May 2018.

RevDate: 2019-01-01

Ramai D, Zakhia K, Ofosu A, et al (2019)

Fecal microbiota transplantation: donor relation, fresh or frozen, delivery methods, cost-effectiveness.

Annals of gastroenterology, 32(1):30-38.

Fecal microbiota transplantation (FMT) has evolved into a robust and efficient means for treating recurrent Clostridium difficile infection (CDI). Our narrative review looks at the donor selection, preparation, delivery techniques and cost-effectiveness of FMT. We searched electronic databases, including PubMed, MEDLINE, Google Scholar, and Cochrane Databases, for studies that compared the biological effects of donor selection, fresh or frozen fecal preparation, and various delivery techniques. We also evaluated the cost-effectiveness and manually searched references to identify additional relevant studies. Overall, there is a paucity of studies that directly compare outcomes associated with related and non-related stool donors. However, inferences from prior studies indicate that the success of FMT does not depend on the donor-patient relationship. Over time, the use of unrelated donors has increased because of the formation of stool banks and the need to save processing time and capital. However, longitudinal studies are needed to clarify the optimal freezing time before microbial function declines. Several FMT techniques have been developed, such as colonoscopy, enema, nasogastric or nasojejunal tubes, and capsules. The comparable and high efficacy of FMT capsules, combined with their convenience, safety and aesthetically tolerable mode of delivery, makes it an attractive option for many patients. Cost-effective models comparing these various approaches support the use of FMT via colonoscopy as being the best strategy for the treatment of recurrent CDI.

RevDate: 2019-01-01

Greenberg SA, Youngster I, Cohen NA, et al (2018)

Five years of fecal microbiota transplantation - an update of the Israeli experience.

World journal of gastroenterology, 24(47):5403-5414.

AIM: To evaluate and describe the efficacy of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in a national Israeli cohort.

METHODS: All patients who received FMT for recurrent (recurrence within 8 wk of the previous treatment) or refractory CDI from 2013 through 2017 in all the five medical centers in Israel currently performing FMT were included. Stool donors were screened according to the Israeli Ministry of Health guidelines. Clinical and laboratory data of patients were collected from patients' medical files, and they included indications for FMT, risk factors for CDI and disease severity. Primary outcome was FMT success (at least 2 mo free of CDI-related diarrhea post-FMT). Secondary outcomes included initial response to FMT (cessation of diarrhea within 7 d) and recurrence at 6 mo.

RESULTS: There were 111 FMTs for CDI, with a median age of 70 years [interquartile range (IQR): 53-82], and 42% (47) males. Fifty patients (45%) were treated via the lower gastrointestinal (LGI, represented only by colonoscopy) route, 37 (33%) via capsules, and 24 (22%) via the upper gastrointestinal (UGI) route. The overall success rate was 87.4% (97 patients), with no significant difference between routes of administration (P = 0.338). In the univariant analysis, FMT success correlated with milder disease (P = 0.01), ambulatory setting (P < 0.05) and lower Charlson comorbidity score (P < 0.05). In the multivariant analysis, only severe CDI [odd ratio (OR) = 0.14, P < 0.05] and inpatient FMT (OR = 0.19, P < 0.05) were each independently inversely related to FMT success. There were 35 (32%) patients younger than 60 years of age, and 14 (40%) of them had a background of inflammatory bowel disease.

CONCLUSION: FMT is a safe and effective treatment for CDI, with capsules emerging as a successful and well-tolerated route. Severe CDI is less likely to respond to FMT.

RevDate: 2018-12-29

Liptak R, Gromova B, Maronek M, et al (2019)

Reverse phenotype transfer via fecal microbial transplantation in inflammatory bowel disease.

Medical hypotheses, 122:41-44.

Inflammatory bowel disease (IBD) is characterized by a disbalance in the composition of intestinal microbiota. It is not clear whether such dysbiosis is a cause or a consequence of a disease state. Fecal microbiota transplantation (FMT) from a healthy donor to a patient or diseased animal is a valuable tool for targeted modification of microbiome leading to therapeutic response. Positive effect has been shown in therapy of a number of gastrointestinal as well as non-gastrointestinal diseases. In addition, FMT has been successfully used to transfer the diseased phenotype form a donor with the disease to a healthy recipient. However, targeted modification of the microbiome before the onset of colitis has not been shown previously. Based on our preliminary results, we propose the hypothesis of so called reverse phenotype transfer in IBD. This term describes the phenomenon, in which the transplantation of gut microbiota from a donor more sensitive to IBD to a healthy recipient leads to resistance of the recipient to IBD and vice versa. Mice that received FMT from donors with severe colitis have shown improved colitis score compared with mice that received FMT from donors more resistant to development of colitis. Such reverse phenotype transfer has broad implications, especially in terms of preventive medicine. However, detailed mechanisms need to be elucidated to conclude the validity of the phenomenon.

RevDate: 2018-12-28
CmpDate: 2018-12-28

Hota SS, Tomlinson G, SM Poutanen (2017)

Reply to Galperine et al and Jansen.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 64(9):1293-1295.

RevDate: 2018-12-27

Tang TW, Chen HC, Chen CY, et al (2018)

Loss of Gut Microbiota Alters Immune System Composition and Cripples Post-Infarction Cardiac Repair.

Circulation [Epub ahead of print].

BACKGROUND: The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.

METHODS: To investigate the effects of gut microbiota on cardiac repair after myocardial infarction (MI), C57BL/6J mice were treated with antibiotics 7 days prior to MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S ribosomal DNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by HPLC. Fecal reconstitution, transplantation of monocytes, dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.

RESULTS: Antibiotic-treated mice (ABX mice) displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells, and SCFA, more specifically acetate, butyrate and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved following fecal reconstitution, transplantation of monocytes or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community, such as a reduction in Lactobacillus. Supplementing ABX mice with a Lactobacillus probiotic prior to MI restored myeloid cell proportions, yielded cardioprotective effects and shifted the balance of SCFAs towards propionate.

CONCLUSIONS: Gut microbiota-derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI, and indeed human health and disease as a whole.

RevDate: 2018-12-26

Vigvári S, Vincze Á, Solt J, et al (2018)

Experiences with fecal microbiota transplantation in Clostridium difficile infections via upper gastrointestinal tract.

Acta microbiologica et immunologica Hungarica [Epub ahead of print].

Dramatic changes in the epidemiology of Clostridium difficile infections have been reported from the western world in the past decade. The proportion of severe cases is significantly elevating and clinicians now have to contend with the problem of additional and more frequent episodes of recurrences including an upward trend in the mortality rate. This situation led us to investigate the possibility of the fecal microbiota transplantation (FMT). An amount of 100 ml of fecal microbiota solution was instilled into a nasojejunal (NJ) tube in 16 cases and into a nasogastric (NG) tube in 44 cases. In all of the cases, where the solution was instilled via nasojejunal tubes, the symptoms resolved within 24 h. We did not note any recurrences in this group. When the material was flushed in through nasogastric tubes, the symptoms resolved in 39 (88.64%) cases within 24 h. In this group, we have experienced a recurrent episode of C. difficile infection in five (11.36%) cases. Three of them were cured with a second transplantation. We have found that in our practice the upper gastrointestinal tract methods had the primary cure rate of 91.67%, whereas the secondary cure rate is 96.67%. When we compared the NJ and NG methods, we have found that the differences in the outcomes are not significant statistically (p = 0.3113 using Fisher's exact probability test). In conclusion, FMT proved to be very effective, particularly in recurrent infections and in cases where conventional treatment had failed.

RevDate: 2018-12-24

Brandsma E, Kloosterhuis NJ, Koster MH, et al (2018)

A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis.

Circulation research [Epub ahead of print].

RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation and atherosclerosis has not been explored previously.

OBJECTIVE: Here, we investigated whether a pro-inflammatory microbiota from Caspase1-/- (Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice.

METHODS AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a co-housing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were co-housed for 8 or 13 weeks and fed chow or a high-fat cholesterol-rich (HFC) diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA sequences confirmed the introduction of the Casp1-/- and Ldlr-/- microbiota into Ldlr-/- mice (referred to as Ldlr-/-(Casp1-/-) or Ldlr-/-(Ldlr-/-) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week HFC-fed Ldlr-/-(Casp1-/-) mice compared to Ldlr-/-(Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated pro-inflammatory cytokine levels in plasma in HFC-fed Ldlr-/-(Casp1-/-) compared to Ldlr-/-(Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-(Casp1-/-) mice was enhanced compared to Ldlr-/-(Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid (SCFA)-producing taxonomies Akkermansia, Christensenellaceae, Clostridium and Odoribacter in Ldlr-/-(Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory SCFAs proprionate, acetate and butyrate in the cecum were significantly reduced in 13-week HFC-fed Ldlr-/-(Casp1-/-) compared to Ldlr-/-(Ldlr-/-) mice.

CONCLUSIONS: Introduction of the pro-inflammatory Casp1-/- microbiota into Ldlr-/- mice enhances systemic inflammation and accelerates atherogenesis.

RevDate: 2018-12-24

Xu Z, Liu Z, Dong X, et al (2018)

Fecal Microbiota Transplantation from Healthy Donors Reduced Alcohol-induced Anxiety and Depression in an Animal Model of Chronic Alcohol Exposure.

The Chinese journal of physiology, 61: pii:CJP.2018.BAH633 [Epub ahead of print].

RevDate: 2018-12-22

Nobili V, Mosca A, Alterio T, et al (2018)

Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).

Advances in experimental medicine and biology [Epub ahead of print].

Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to "decipher" operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and, hence, to address the function of the intestinal microbiome within the gut microbiota-liver axis.Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of obesity and NAFLD in adults and children. Several randomized clinical trials (RCTs) have been already published on fecal microbiota transplantation (FMT), T2D, NASH, and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions, probiotics, symbiotics, and FMT.

RevDate: 2018-12-21

Singh S, Feuerstein JD, Binion DG, et al (2018)

American Gastroenterological Association Technical Review on the Management of Mild to Moderate Ulcerative Colitis.

Gastroenterology pii:S0016-5085(18)35406-4 [Epub ahead of print].

Most patients with ulcerative colitis (UC) have mild to moderate disease activity, with low risk of colectomy, and are managed by primary care physicians or gastroenterologists. Optimal management of these patients decreases the risk of relapse and proximal disease extension, and may prevent disease progression, complications and need for immunosuppressive therapy. With several medications (sulfasalazine, diazo-bonded 5-aminosalicylates [ASA], mesalamines, corticosteroids including budesonide, etc.) and complex dosing formulations, regimens and routes, to treat a disease with variable anatomic extent, there is considerable practice variability in the management of patients with mild-moderate UC. Hence, the AGA prioritized clinical guidelines on this topic. To inform clinical guidelines, this technical review was developed in accordance with the GRADE framework for interventional studies. Focused questions included: (1) comparative effectiveness and tolerability of different oral 5-ASA therapies (sulfalsalazine vs. diazo-bonded 5-ASAs vs. mesalamine; low- (<2g) vs. standard (2-3g/d) vs. high-dose (>3g/d) mesalamine); (2) comparison of different dosing regimens (once-daily vs. multiple times per day dosing) and routes (oral vs. rectal vs. both oral and rectal); (3) role of oral budesonide in patients mild-moderate UC; (4) comparative effectiveness and tolerability of rectal 5-ASA and corticosteroid formulations in patients with distal colitis; and (5) role of alternative therapies like probiotics, curcumin and fecal microbiota transplantation in the management of mild-moderate UC.

RevDate: 2018-12-19

Mizuno S, T Kanai (2017)

Fecal microbiota transplantation.

Nihon rinsho. Japanese journal of clinical medicine, 75(3):492-497.

Various strains of microorganisms inhabit the human intestinal tract, and disturbance of intestinal flora, dysbiosis, is thought to be pathogenesis of various diseases. Inducing symbiosis of intestinal flora has therapeutic potential for gastrointestinal diseases, but there are limited therapeutic options including probiotics.'Previous reports suggested that fecal microbiota transplantation (FMT) was a very useful choice in treatment for recurrent Clostridium difficile infection. FMT for ulcerative colitis (UC) patients is proposed as a potential treatment for resolving dysbiosis. There is some debate as to whether FMT for UC patients is effective or not. It remains a challenge for future research to make more sophisticated and convenient methods of FMT.

RevDate: 2018-12-19

Lin C, Wan J, Su Y, et al (2018)

Effects of Early Intervention with Maternal Fecal Microbiota and Antibiotics on the Gut Microbiota and Metabolite Profiles of Piglets.

Metabolites, 8(4): pii:metabo8040089.

We investigated the effects of early intervention with maternal fecal microbiota and antibiotics on gut microbiota and the metabolites. Five litters of healthy neonatal piglets (Duroc × Landrace × Yorkshire, nine piglets in each litter) were used. Piglets in each litter were orally treated with saline (CO), amoxicillin treatment (AM), or maternal fecal microbiota transplantation (MFMT) on days 1⁻6, with three piglets in each treatment. Results were compared to the CO group. MFMT decreased the relative abundances of Clostridium sensu stricto and Parabacteroides in the colon on day 7, whereas the abundance of Blautia increased, and the abundance of Corynebacterium in the stomach reduced on day 21. AM reduced the abundance of Arcanobacterium in the stomach on day 7 and reduced the abundances of Streptococcus and Lachnoclostridium in the ileum and colon on day 21, respectively. The metabolite profile indicated that MFMT markedly influenced carbohydrate metabolism and amino acid (AA) metabolism on day 7. On day 21, carbohydrate metabolism and AA metabolism were affected by AM. The results suggest that MFMT and AM discriminatively modulate gastrointestinal microflora and alter the colonic metabolic profiles of piglets and show different effects in the long-term. MFMT showed a location-specific influence on the gastrointestinal microbiota.

RevDate: 2018-12-18

Limketkai BN, Hendler S, Ting PS, et al (2018)

Fecal Microbiota Transplantation for the Critically Ill Patient.

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition [Epub ahead of print].

The gut microbiome has been implicated in a diversity of diseases, such as irritable bowel syndrome, inflammatory bowel disease, hepatic steatosis, metabolic syndrome, obesity, and anxiety. Current research also suggests the presence of a bidirectional relationship between the composition of the gut microbiome and critical illness. In the critical care setting, multiple factors (eg, use of antibiotics, aberrant nutrition, bloodstream infections, bowel ischemia, and abnormal bowel motility) strongly contribute to intestinal dysbiosis. Conversely, early studies have associated intestinal dysbiosis with worse clinical outcomes in the intensive care unit (ICU), such as infection, organ failure, and mortality. The possibility of intestinal dysbiosis influencing these clinical outcomes has prompted the question of whether microbiome manipulation strategies, such as fecal microbiota transplantation (FMT), may have a role in the management of critical illness. After a literature search of FMT used in the ICU for indications other than Clostridium difficile infections, we found 4 case reports that describe the use of FMT in 5 critically ill patients with systemic inflammatory responses and no clear source of infection. This review discusses the relationship between the gut microbiome and critical illness, early data on the use of FMT in critical care, and safety considerations of FMT in the critically ill and immunocompromised populations.

RevDate: 2018-12-18

Cai TT, Ye XL, Yong HJ, et al (2018)

Fecal microbiota transplantation relieve painful diabetic neuropathy: A case report.

Medicine, 97(50):e13543.

RATIONALE: Fecal microbiota transplantation (FMT) has been used in a wide variety of diseases. In this article, we reported a 46-year-old female with diabetic neuropathy (DN) achieved remission by the treatment of FMT.

PATIENT CONCERNS: The patient with an 8-year history of diabetes and hypertension was admitted to hospital due to sensitive pain of her right thigh and poor blood glucose control. The traditional hypoglycemic and analgesic treatment were useless to her symptoms.

DIAGNOSIS: Diabetic-induced neuropathy was considered.

INTERVENTIONS: This patient received twice FMTs for 3 months.

OUTCOMES: After twice FMTs, the clinical response of patient was pleasant. The glycemic control was improved, with a remarkable relief of the symptoms of painful DN in particular. No obvious adverse effects were observed during the FMTs and follow-up observation-testing.

LESSONS: We proposed that FMT could be a promising treatment in patients with diabetes or diabetes-related complications like DN. FMT also appeared to be definitely safer and more tolerable than the pharmacologic treatment in patients with DN.

RevDate: 2018-12-14

McClave SA, RG Martindale (2018)

Why do current strategies for optimal nutritional therapy neglect the microbiome?.

Nutrition (Burbank, Los Angeles County, Calif.), 60:100-105 pii:S0899-9007(18)30511-2 [Epub ahead of print].

Strategies for providing optimal nutritional therapy have evolved over time, with the emphasis on specific directives (such as route, use of immunonutrition, high protein, organ-specific formulas, etc.), achieving variable degrees of success for improving outcomes in the intensive care unit. As the largest immune organ in the body comprising the largest interface between the host and the external environment, the gut can have an amplifying effect on a pattern of dysbiosis, immune dysregulation, and multiple organ failure seen in the critically ill patient. Conversely, maintenance of gut integrity can serve to restore a pattern of homeostasis, appropriate immune responses, symbiosis, and clinical recovery. Simply providing refined polymeric formulas as enteral nutrition may not take full advantage of the potential for optimal outcome that could be derived by giving therapy designed to directly stimulate gut defenses and support the intestinal microbiota. This article describes a series of strategies (such as use of intact whole food formulas, soluble fiber, fecal microbial transplantation, serum bovine immunoglobulin, or agents to promote commensal behavior) that should modulate the gut microbiome and shift the critically ill patient toward a pattern of health and recovery.

RevDate: 2018-12-13

Hu J, Ma L, Nie Y, et al (2018)

A Microbiota-Derived Bacteriocin Targets the Host to Confer Diarrhea Resistance in Early-Weaned Piglets.

Cell host & microbe, 24(6):817-832.e8.

Alternatives to antibiotics for preventing diarrhea in early-weaned farm animals are sorely needed. CM piglets (a native Chinese breed) are more resistant to early-weaning stress-induced diarrhea than the commercial crossbred LY piglets. Transferring fecal microbiota, but not saline, from healthy CM into LY piglets by oral administration prior to early weaning conferred diarrhea resistance. By comparing the relative abundance of intestinal microbiota in saline and microbiota transferred LY piglets, we identified and validated Lactobacillus gasseri LA39 and Lactobacillus frumenti as two bacterial species that mediate diarrhea resistance. Diarrhea resistance depended on the bacterial secretory circular peptide gassericin A, a bacteriocin. The binding of gassericin A to Keratin 19 (KRT19) on the plasma membrane of intestinal epithelial cells was essential for enhancement of fluid absorption and decreased secretion. These findings suggest the use of L. gasseri LA39 and L. frumenti as antibiotic alternatives for preventing diarrhea in mammals.

RevDate: 2018-12-12

Davidovics ZH, Michail S, Nicholson MR, et al (2018)

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Journal of pediatric gastroenterology and nutrition [Epub ahead of print].

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

RevDate: 2018-12-12

Leustean AM, Ciocoiu M, Sava A, et al (2018)

Implications of the Intestinal Microbiota in Diagnosing the Progression of Diabetes and the Presence of Cardiovascular Complications.

Journal of diabetes research, 2018:5205126.

The prevalence of diabetes is steadily rising, and once it occurs, it can cause multiple complications with a negative impact on the whole organism. Complications of diabetes may be macrovascular: such as stroke and ischemic heart disease as well as peripheral vascular and microvascular diseases-retinopathy, nephropathy, and neuropathy. Key factors that cause cardiovascular disease in people with diabetes include hyperglycemia, dyslipidemia, obesity, insulin resistance, inflammation, hypertension, autonomic dysfunction, and decreased vascular response capacity. Microbes can be considered a complex endocrine system capable of ensuring the proper functioning of the body but are also responsible for the development of numerous pathologies (diabetes, coronary syndromes, peripheral arterial disease, neoplasia, Alzheimer's disease, and hepatic steatosis). Changes in the intestinal microbiota may influence the host's sensitivity to insulin, body weight, and lipid and carbohydrate metabolism. Dysbiosis causes activation of proinflammatory mechanisms, metabolic toxicity, and insulin resistance. Trimethylamine N-oxide (TMAO) is a microbial organic compound generated by the large intestine, and its concentration increases in the blood after ingestion of foods rich in L-carnitine and choline, such as red meat, eggs, and fish. The interest for TMAO in cardiometabolic research has recently emerged, given the preclinical evidence that reveals a link between TMAO, diabetes, and cardiovascular complications. Intestinal microbiota can be modulated by changing one's lifestyle but also by antibiotic, probiotic, prebiotic, and fecal transplantation. The purpose of this article is to highlight issues related to the involvement of microbiota and trimethylamine N-oxide in the pathogenesis of diabetes mellitus and cardiovascular disease. Better appreciation of the interactions between food intake and intestinal floral-mediated metabolism can provide clinical insights into the definition of individuals with diabetic risk and cardiometabolic disease as well as potential therapeutic targets for reducing the risk of progression of the disease.

RevDate: 2018-12-11

Kalla R, Pitt M, A Sharma (2018)

The Role of Autologous Fecal Microbiota Transplantation in Diversion Colitis: A Case Report.

Inflammatory bowel diseases pii:5078833 [Epub ahead of print].

RevDate: 2018-12-11

Quera R, Ibáñez P, Simian D, et al (2018)

[Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection. Report of eight cases].

Revista medica de Chile, 146(8):823-830.

BACKGROUND: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested.

AIM: To describe the efficacy and safety of FMT for the treatment of recurrent CDI.

PATIENTS AND METHODS: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction.

RESULTS: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary.

CONCLUSIONS: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.

RevDate: 2018-12-11

Lindheim L, Manti M, Fornes R, et al (2018)

Reproductive and Behavior Dysfunction Induced by Maternal Androgen Exposure and Obesity Is Likely Not Gut Microbiome-Mediated.

Journal of the Endocrine Society, 2(12):1363-1380 pii:js_201800266.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder of unclear etiology in women and is characterized by androgen excess, insulin resistance, and mood disorders. The gut microbiome is known to influence conditions closely related with PCOS, and several recent studies have observed changes in the stool microbiome of women with PCOS. The mechanism by which the gut microbiome interacts with PCOS is still unknown. We used a mouse model to investigate if diet-induced maternal obesity and maternal DHT exposure, mimicking the lean and obese PCOS women, cause lasting changes in the gut microbiome of offspring. Fecal microbiome profiles were assessed using Illumina paired-end sequencing of 16S rRNA gene V4 amplicons. We found sex-specific effects of maternal and offspring diet, and maternal DHT exposure on fecal bacterial richness and taxonomic composition. Female offspring exposed to maternal obesity and DHT displayed reproductive dysfunction and anxietylike behavior. Fecal microbiota transplantation from DHT and diet-induced obesity exposed female offspring to wild-type mice did not transfer reproductive dysfunction and did not cause the expected increase in anxietylike behavior in recipients. Maternal obesity and androgen exposure affect the gut microbiome of offspring, but the disrupted estrous cycles and anxietylike behavior are likely not microbiome-mediated.

RevDate: 2018-12-11

Paramsothy S, Nielsen S, Kamm MA, et al (2018)

Specific Bacteria and Metabolites Associated with Response to Fecal Microbiota Transplantation in Patients with Ulcerative Colitis.

Gastroenterology pii:S0016-5085(18)35387-3 [Epub ahead of print].

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized, controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy.

METHODS: We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multi-donor FMT or placebo enemas, 5 days/week for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT, after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 colonoscopic large bowel biopsies from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT if applicable. We analyzed the 105 fecal samples from the 14 individual donors (n=55), which were combined into 21 multi-donor batches (n=50). Bacteria in colonic and fecal samples were analyzed by both 16S rRNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics and 60 fecal samples were analyzed for metabolome features.

RESULTS: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared to patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans, compared to patients who did not achieve remission after FMT, and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus in donor stool associated with no response to FMT.

CONCLUSIONS: In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov no: NCT01896635.

RevDate: 2018-12-11
CmpDate: 2018-12-11

Peng J, Xiao X, Hu M, et al (2018)

Interaction between gut microbiome and cardiovascular disease.

Life sciences, 214:153-157.

Traditional cardiovascular risk factors do not underlie all incidence of cardiovascular disease. In recent years, accumulating evidence has demonstrated that gut microbiota and its metabolites also play a pivotal role in the onset and development of cardiovascular disease, including atherosclerosis, hypertension, heart failure, atrial fibrillation and myocardial fibrosis. Trillions of bacteria indwell the gastrointestinal tract and metabolize nutrients into trimethylamine-N-oxide, short-chain fatty acids and so on. Targeting these microorganisms and relevant metabolic pathways has beneficial effects in cardiovascular disease. This review will summarize the role of gut microbiota and its metabolites, mainly trimethylamine-N-oxide, in the pathogenesis of cardiovascular diseases, and discuss the possible mechanisms that drive cardiovascular diseases and highlight potential therapies in this field.

RevDate: 2018-12-11
CmpDate: 2018-12-11

Xu KY, Xia GH, Lu JQ, et al (2017)

Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients.

Scientific reports, 7(1):1445.

Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such as Roseburia, Coprococcus, and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.

RevDate: 2018-12-06

Huang C, Yang X, Zeng B, et al (2018)

Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression.

Journal of proteomics pii:S1874-3919(18)30421-4 [Epub ahead of print].

Major depressive disorders impact approximately 17% of the population worldwide, whose high morbidity and considerable adversity have resulted in enormous social and economic burden. In addition, clinically depressed patients often show reduced volume of olfactory bulb (OB) and decreased olfactory sensitivity. Although mounting evidence conveyed that the gut microbiota may implicate the pathophysiology of major depressive disorder (MDD) via the microbe-gut-brain axis, knowledge about its distinctive molecular mechanism is rudimentary. Herein, iTRAQ coupled with LC-MS/MS was applied to compare the OB proteome between "pathological microbiota" and "healthy microbiota" germ-free mice. A set of 367 proteins were differentially identified in the OB, including 119 up-regulated and 248 down-regulated proteins compared with the levels in controls. A combined analysis with significantly changed OB proteins from CUMS depression model supported the role of CREB signaling, whose dysregulation is likely to disrupt the axonogenesis of OB under microbiota condition. With that, the down-regulated CACNA1E and its downstream proteins (CALM/ CaMKII/ CREB/ BDNF) in CREB pathway were validated by Western blot. Meanwhile, the canonical pathways involved Nuclear Receptor Signaling highlighted the fecal microbiota transplantation (FMT) model, which would be a new breakthrough for depressive research. These findings enrich the previous research achievements about the gut microbiota in psychiatric disorders, providing a creative insight into the intricate mechanisms of OB dysfunction in depression. SIGNIFICANCE: Emerging evidence has shown that gut microbiota can greatly influence brain functions and even behaviors. As one of the post-developmental neurogenesis areas for the adult brain, the OB is becoming increasingly important in the study of the pathogenesis of depression. Using an iTRAQ-based proteomics, we identified 367 altered proteins in the OB of fecal microbiota transplanted mouse, which provide a novel insight for further research of the "microbiota-gut-brain axis". In addition, combined analyses with the CUMS depression model and the validation of key proteins by Western blot may assist in the investigation of OB dysfunction in mental sickness.

RevDate: 2018-12-06

Al-Amer M, Abdeen Y, A Kaako (2018)

Bezlotoxumab Use as Adjunctive Therapy with the Third Fecal Microbiota Transplant in Refractory Recurrent Clostridium Difficile Colitis; A Case Report and Concise Literature Review.

Anaerobe pii:S1075-9964(18)30205-1 [Epub ahead of print].

Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and healthcare expenditure. The use of Fecal Microbiota Transplantation (FMT) is one of the current standard therapies for recurrent C. difficile infection (CDIr). One emerging promising approach is the use of monoclonal antibodies that bind to and neutralize C. difficile toxins such as Bezlotoxumab. We present the first case report on combining the third FMT with bezlotoxumab after the failure of standard-of-care antibiotics and two trials of FMT alone, with subsequent success in preventing the recurrence of refractory CDI for 12 weeks following treatment. This case highlight the need for further studies and guidelines to recommend the best combination among different treatment options and modalities.

RevDate: 2018-12-06

Allegretti JR, Fischer M, Sagi SV, et al (2018)

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

Digestive diseases and sciences pii:10.1007/s10620-018-5396-6 [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy.

METHODS: We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT.

RESULTS: 51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity.

DISCUSSION: To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.

RevDate: 2018-12-06

Zhu Y, He C, Li X, et al (2018)

Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice.

Journal of gastroenterology pii:10.1007/s00535-018-1529-0 [Epub ahead of print].

BACKGROUND: The gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown.

METHODS: We collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing.

RESULTS: The structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such as Blautia was decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance of Escherichia-Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease.

CONCLUSIONS: This study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.

RevDate: 2018-12-06

Bin P, Tang Z, Liu S, et al (2018)

Intestinal microbiota mediates Enterotoxigenic Escherichia coli-induced diarrhea in piglets.

BMC veterinary research, 14(1):385 pii:10.1186/s12917-018-1704-9.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in humans, cows, and pigs. The gut microbiota underlies pathology of several infectious diseases yet the role of the gut microbiota in the pathogenesis of ETEC-induced diarrhea is unknown.

RESULTS: By using an ETEC induced diarrheal model in piglet, we profiled the jejunal and fecal microbiota using metagenomics and 16S rRNA sequencing. A jejunal microbiota transplantation experiment was conducted to determine the role of the gut microbiota in ETEC-induced diarrhea. ETEC-induced diarrhea influenced the structure and function of gut microbiota. Diarrheal piglets had lower Bacteroidetes: Firmicutes ratio and microbiota diversity in the jejunum and feces, and lower percentage of Prevotella in the feces, but higher Lactococcus in the jejunum and higher Escherichia-Shigella in the feces. The transplantation of the jejunal microbiota from diarrheal piglets to uninfected piglets leaded to diarrhea after transplantation. Microbiota transplantation experiments also supported the notion that dysbiosis of gut microbiota is involved in the immune responses in ETEC-induced diarrhea.

CONCLUSION: We conclude that ETEC infection influences the gut microbiota and the dysbiosis of gut microbiota after ETEC infection mediates the immune responses in ETEC infection.

RevDate: 2018-12-06

Huang E, Kang S, Park H, et al (2018)

Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition.

Biomedicines, 6(4): pii:biomedicines6040113.

Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut⁻brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.

RevDate: 2018-12-03

Hu XF, Zhang WY, Wen Q, et al (2018)

Fecal Microbiota Transplantation Alleviates Myocardial Damage in Myocarditis by Restoring the Microbiota Composition.

Pharmacological research pii:S1043-6618(18)30355-4 [Epub ahead of print].

Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4+IFN-γ+ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.

RevDate: 2018-12-03

Leedahl DD, Personett HA, Nagpal A, et al (2018)

Prevention of Clostridium difficile Infection in Critically Ill Adults.

Pharmacotherapy [Epub ahead of print].

The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to successfully prevent CDI include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Since CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, there are a number of patient- and facility-level strategies that can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policy makers. This article is protected by copyright. All rights reserved.

RevDate: 2018-12-03

Gong S, Yan Z, Liu Z, et al (2018)

Intestinal microbiota mediates the susceptibility to polymicrobial sepsis-induced liver injury by granisetron generation in mice.

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

Sepsis-induced liver injury is recognized as a key problem in intensive care units (ICUs). The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was employed to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res, survived to 7 days after CLP) and sepsis-sensitive (Sen, moribund before or approximately 24 h after CLP) mice. Mice gavaged with feces from Sen mice displayed more severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP-induced death and liver injury. Moreover, proinflammatory cytokines expression by macrophages after LPS challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5-HT3A receptor in cells suppressed NF-кB transactivation and p-p38 accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma ALT/AST levels in septic patients. Conclusion: Our study revealed that gut microbiota plays a key role in the sensitization of sepsis-induced liver injury and identified granisetron as a novel hepatoprotective compound during sepsis development. This article is protected by copyright. All rights reserved.

RevDate: 2018-12-03

Niederwerder MC (2018)

Fecal microbiota transplantation as a tool to treat and reduce susceptibility to disease in animals.

Veterinary immunology and immunopathology, 206:65-72.

Fecal microbiota transplantation (FMT) is the process by which fecal microbiota are donated from a healthy individual and subsequently transplanted into a diseased or young individual. The mechanism by which FMT is effective is believed to be due to enhanced beneficial microbes, increased microbiome diversity, and restored normal flora. Beneficial gut microorganisms not only play a role in maintaining an intestinal barrier and metabolizing nutrients, but importantly, these microbes help regulate local and systemic immune function. Although FMT has been described for several centuries, only recently has it been utilized as a mainstream therapy in humans and significantly considered for applications in other species. In humans and animals, gastrointestinal diseases are by far the most widely accepted FMT-treatable conditions; however, recent research has shown exceptional promise for FMT being used to treat or prevent other conditions, including those outside of the gastrointestinal tract. Overall, FMT is likely an underutilized, widely-available, and inexpensive tool for improving the health and response to disease in animals. In this review, the effects of FMT on veterinary diseases and potential applications for FMT in animals are discussed.

RevDate: 2018-12-03

Davido B, Batista R, Fessi H, et al (2018)

Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.

Medecine et maladies infectieuses pii:S0399-077X(18)30002-7 [Epub ahead of print].

OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization.

PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT.

RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized.

CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.

RevDate: 2018-12-05

Carrera-Quintanar L, Ortuño-Sahagún D, Franco-Arroyo NN, et al (2018)

The Human Microbiota and Obesity: A Literature Systematic Review of In Vivo Models and Technical Approaches.

International journal of molecular sciences, 19(12): pii:ijms19123827.

Obesity is a noncommunicable disease that affects a considerable part of humanity. Recently, it has been recognized that gut microbiota constitutes a fundamental factor in the triggering and development of a large number of pathologies, among which obesity is one of the most related to the processes of dysbiosis. In this review, different animal model approaches, methodologies, and genome scale metabolic databases were revisited to study the gut microbiota and its relationship with metabolic disease. As a data source, PubMed for English-language published material from 1 January 2013, to 22 August 2018, were screened. Some previous studies were included if they were considered classics or highly relevant. Studies that included innovative technical approaches or different in vivo or in vitro models for the study of the relationship between gut microbiota and obesity were selected after a 16-different-keyword exhaustive search. A clear panorama of the current available options for the study of microbiota's influence on obesity, both for animal model election and technical approaches, is presented to the researcher. All the knowledge generated from the study of the microbiota opens the possibility of considering fecal transplantation as a relevant therapeutic alternative for obesity and other metabolic disease treatment.

RevDate: 2018-11-30

Mathias F, Curti C, Montana M, et al (2018)

Management of adult Clostridium difficile digestive contaminations: a literature review.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-018-3419-z [Epub ahead of print].

Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole.

RevDate: 2018-11-29

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

Fecal Freezing Preservation Period Influences Colonization Ability for Fecal Microbiota Transplantation.

Journal of applied microbiology [Epub ahead of print].

AIMS: There has been growing interest in fecal microbiota transplantation (FMT) as treatment. Although, frozen donor feces 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 feces as the transplant is necessary for the methodological improvement of FMT.

METHODS AND RESULTS: The viable bacterial compositions of fecal 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 didn't significantly affect in vitro fecal 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 feces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1 month -20°C-preservation.

SIGNIFICANCE AND IMPACT: Long-term -20°C-preservation of transplanted feces 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. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-28

Shi YC, YS Yang (2018)

Fecal microbiota transplantation: Current status and challenges in China.

JGH open : an open access journal of gastroenterology and hepatology, 2(4):114-116 pii:JGH312071.

RevDate: 2018-11-27

Imdad A, Nicholson MR, Tanner-Smith EE, et al (2018)

Fecal transplantation for treatment of inflammatory bowel disease.

The Cochrane database of systematic reviews, 11:CD012774 [Epub ahead of print].

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD.

OBJECTIVES: The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD.

SEARCH METHODS: We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index.

SELECTION CRITERIA: Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention.

DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria.

MAIN RESULTS: Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence).

AUTHORS' CONCLUSIONS: Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.

RevDate: 2018-11-27

Wang Y, Wiesnoski DH, Helmink BA, et al (2018)

Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.

RevDate: 2018-11-26

Mehta R, Kabrawala M, Nandwani S, et al (2018)

Preliminary experience with single fecal microbiota transplant for treatment of recurrent overt hepatic encephalopathy-A case series.

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology pii:10.1007/s12664-018-0906-1 [Epub ahead of print].

Experimental studies demonstrated that fecal microbiota transplant (FMT) may reverse intestinal microbial dysbiosis. In this retrospective case series, we share our experience of treating recurrent overt hepatic encephalopathy (HE) with single FMT treatment. A total of 10 patients, age ranged from 25 to 65 years, were treated with single FMT through colonoscopy using fecal material received from rigorously screened patient-identified donors. There was sustained clinical response with single FMT treatment in 6 patients at post-treatment week 20. Arterial ammonia concentration decreased considerably (96 [87.25-117.75] vs. 74 [70-82]; p = 0.024) at post-treatment week 20. Moreover, there was statistically significant decrease in Child-Turcotte-Pugh (CTP) score (9.5 [9-10.75] vs. 8 [7-8]; p = 0.005) and model for end-stage liver disease (MELD) score (18 [16.25-19] vs. 15 [14-16]; p = 0.008). Four patients experienced six adverse-events. Overt HE and re-hospitalization were observed in 3 and 2 patients, respectively. One patient (who also experienced overt HE) died within 2 months of the index procedure.

RevDate: 2018-11-26

Dai Z, Zhang J, Wu Q, et al (2018)

The role of microbiota in the development of colorectal cancer.

International journal of cancer [Epub ahead of print].

Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.

RevDate: 2018-11-25

Saïdani N, Lagier JC, Cassir N, et al (2018)

Fecal microbiota transplantation shortens the colonization period and allows the re-entry of patients carrying carbapenamase-producing bacteria into medical care facilities.

International journal of antimicrobial agents pii:S0924-8579(18)30339-X [Epub ahead of print].

BACKGROUND: Colonization with carbapenemase producing Enterobacteriaceae or Acinetobacter (CPE/A) is associated with complex medical care requiring implementation of specific isolation policies and limitation of patient discharge to other medical facilities. Fecal Microbiota Transplantation (FMT) has been proposed in order to reduce the duration of gut colonization.

OBJECTIVES: We investigated whether a dedicated protocol of FMT could reduce the negativation time of CPE/A intestinal carriage in patients whose medical care has been delayed due to such colonization.

METHOD: We performed a matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A colonized patient addressed for initial clustering at our institute. We adjusted two controls per case based on sex, age, bacterial species and carbapenemase type. The primary outcome was the delay in negativation of rectal-swab cultures.

RESULTS: At day 14 post-FMT, 8/10 (80%) treated patients were cleared for intestinal CPE/A carriage. In the control group, 2/20 (10%) had a spontaneous clearance at day 14 after CPE/A diagnostic. FMT led patients to reduce the delay of decolonization (median 3 days post-FMT for treated patients versus 50.5 days after the first documentation of digestive carriage for control patients) and discharge from the hospital (median 19.5 days post-FMT for treated patients versus 41 for control patients).

CONCLUSION: FMT is a safe and time saving procedure to discharge CPE/A-colonized patients from the hospital. A standardized protocol including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal should improve the effectiveness of the protocol.

RevDate: 2018-11-24

Tillmann S, Abildgaard A, Winther G, et al (2018)

Altered fecal microbiota composition in the Flinders sensitive line rat model of depression.

Psychopharmacology pii:10.1007/s00213-018-5094-2 [Epub ahead of print].

RATIONALE: The gut microbiota is increasingly recognized as a potential mediator of psychiatric diseases. Depressed patients have been shown to have a different microbiota composition compared with healthy controls, and several lines of research now aim to restore this dysbiosis. To develop novel treatments, preclinical models may provide novel mechanistic insights.

OBJECTIVE AND METHODS: We characterized the gut microbiota of male adult Flinders sensitive line (FSL) rats, an animal model of depression, and their controls, Flinders resistant line (FRL) rats using 16S rRNA amplicon sequencing. Moreover, we performed fecal microbiota transplantation (using saline or pooled FRL/FSL feces) to study if the potential strain-specific differences could be transferred from one strain to the other, and if these differences were reflected in their depressive-like behavior in the forced swim test.

RESULTS: FSL rats tended to have lower bacterial richness and altered relative abundances of several bacterial phyla, families, and species, including higher Proteobacteria and lower Elusimicrobia and Saccharibacteria. There was a clear separation between FRL and FSL rat strains, but no effect of treatment, i.e., the bacterial composition of FSL rats receiving FRL feces was still more similar to FSL and not FRL rats. Similarly, the transplantation did not reverse behavioral differences in the forced swim test, although FSL feces significantly increased immobility compared with saline.

CONCLUSIONS: Our study showed that the gut microbiota composition of the depressive-like rats markedly differed from their controls, which may be of value for future microbiota-targeted work in this and similar animal models.

RevDate: 2018-11-22

Bulow C, Langdon A, Hink T, et al (2018)

Impact of Amoxicillin-Clavulanate followed by Autologous Fecal Microbiota Transplantation on Fecal Microbiome Structure and Metabolic Potential.

mSphere, 3(6): pii:3/6/e00588-18.

Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity after exposure to amoxicillin-clavulanic acid (Amox-Clav). Ten healthy participants were enrolled. All received 5 days of Amox-Clav. Half were randomized to autoFMT, derived from stool collected pre-antimicrobial exposure, by enema, and half to saline enema. Participants submitted stool samples pre- and post-Amox-Clav and enema and during a 90-day follow-up period. Shotgun metagenomic sequencing revealed taxonomic composition, resistance gene content, and metabolic capacity. Amox-Clav significantly altered gut taxonomic composition in all participants (n = 10, P < 0.01); however, only three participants exhibited major changes at the phylum level following exposure. In the cohort as a whole, beta-lactamase genes were enriched following Amox-Clav (P < 0.05), and predicted metabolic capacity was significantly altered (P < 0.01). Species composition, metabolic capacity, and beta-lactamase abundance returned to pre-antimicrobial exposure state 7 days after either autoFMT or saline enema (P > 0.05, compared to enrollment). Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption, potentially creating open niches for pathogen colonization. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome. AutoFMT was well tolerated and may have contributed to phylogenetic recovery. (This study has been registered at ClinicalTrials.gov under identifier NCT02046525.)IMPORTANCE The spread of multidrug resistance among pathogenic organisms threatens the efficacy of antimicrobial treatment options. The human gut serves as a reservoir for many drug-resistant organisms and their resistance genes, and perturbation of the gut microbiome by antimicrobial exposure can open metabolic niches to resistant pathogens. Once established in the gut, antimicrobial-resistant bacteria can persist even after antimicrobial exposure ceases. Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of amoxicillin-clavulanic acid (Amox-Clav) exposure and autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity. Importantly, we found that metabolic capacity was perturbed even in cases where gross phylogeny remained unchanged and that autoFMT was safe and well tolerated.

RevDate: 2018-11-21

Riddle MS, BA Connor (2018)

Fecal microbiota transplantation: what is the role in travelers' diarrhea?.

Journal of travel medicine pii:5194706 [Epub ahead of print].

RevDate: 2018-11-20

Chen D, Wu J, Jin D, et al (2018)

Fecal microbiota transplantation in cancer management: Current status and perspectives.

International journal of cancer [Epub ahead of print].

The human gut is home to a large and diverse microbial community, comprising about 1000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity, and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent pre-clinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer-treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-22

Ohara T, T Suzutani (2018)

Efficacy of fecal microbiota transplantation in a patient with chronic intractable constipation.

Clinical case reports, 6(11):2029-2032 pii:CCR31798.

We have presented the first case report of FMT therapy for a patient with chronic intractable constipation. This therapy resulted in good, medium-term outcomes. Follow-up analysis of the intestinal flora suggested that transplanted microbes from the donor, particularly Bifidobacterium and Clostridium cluster IX, may have been incorporated into the recipient.

RevDate: 2018-11-20

Weis M (2018)

Impact of the gut microbiome in cardiovascular and autoimmune diseases.

Clinical science (London, England : 1979), 132(22):2387-2389 pii:CS20180410.

The gut microbiome functions like an endocrine organ, generating enzymes and bioactive metabolites, which affect host physiology. In addition metabolism-independent processes like impaired intestinal barrier function may result in bacterial translocation and an increased inflammation. Specific microbe-associated molecular patterns (MAMPs) have been detected that induce immune activation via cognate pattern-recognition receptors on host immune cells, with subsequent consequences on inflammatory-induced endothelial dysfunction. Alterations in intestinal microbial and metabolic composition play an important role in human health and disease, including cardiovascular and autoimmune diseases. Changes in the composition of gut microbiota (dysbiosis) are linked to chronic inflammation, thrombosis, atherogenesis, chronic heart, and kidney disease, as well as to autoimmune diseases like systemic lupus erythematodes. Although non-selective approaches that broadly alter microbial community structure, such as prebiotics, probiotics, and fecal microbial transplantation, may have some promise, targeting defined microbial pathways and adjacent host immune responses may be the ultimate scientific goal.

RevDate: 2018-11-21

Li X, Gao X, Hu H, et al (2018)

Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection.

Frontiers in microbiology, 9:2622.

Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the alpha diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples (beta diversity) was apart from that of healthy controls and donors. No significant differences in alpha diversity, beta diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.

RevDate: 2018-11-19

Sood A, Mahajan R, Juyal G, et al (2018)

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis.

Intestinal research pii:ir.2018.00089 [Epub ahead of print].

Background/Aims: Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC.

Methods: This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT.

Results: Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation.

Conclusions: A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal.

RevDate: 2018-11-29

Kaito S, Toya T, Yoshifuji K, et al (2018)

Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease.

Blood advances, 2(22):3097-3101.

RevDate: 2018-11-22

Zhou W, Chow KH, Fleming E, et al (2018)

Selective colonization ability of human fecal microbes in different mouse gut environments.

The ISME journal pii:10.1038/s41396-018-0312-9 [Epub ahead of print].

Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.

RevDate: 2018-11-14

Mazzawi T, Lied GA, Sangnes DA, et al (2018)

The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation.

PloS one, 13(11):e0194904 pii:PONE-D-17-36974.

BACKGROUND: Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS.

MATERIAL AND METHODS: The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression.

RESULTS: Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients' microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects.

CONCLUSIONS: FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03333291.

RevDate: 2018-11-25

Kaliannan K, Robertson RC, Murphy K, et al (2018)

Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.

Microbiome, 6(1):205 pii:10.1186/s40168-018-0587-0.

BACKGROUND: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.

RESULTS: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.

CONCLUSIONS: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.

RevDate: 2018-11-28

Wang Y, Wiesnoski DH, Helmink BA, et al (2018)

Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

Nature medicine pii:10.1038/s41591-018-0238-9 [Epub ahead of print].

We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.

RevDate: 2018-11-11

Fang X (2018)

Microbial treatment: the potential application for Parkinson's disease.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology pii:10.1007/s10072-018-3641-6 [Epub ahead of print].

Alterations in the composition of the intestinal flora are associated with the pathophysiology of Parkinson's disease (PD). More importantly, the possible cause-effect links between gut flora and PD pathogenesis have been identified using PD animal models. Recent studies have found that probiotics improve the symptoms associated with constipation in PD patients. In addition, fecal microbiota transplantation (FMT) was recently shown to provide a protective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Effective microbial therapy for PD includes probiotics and FMT. Therefore, microbial therapy may be a useful and novel approach for treatment of PD. In this review, I discuss the use of microbial treatment in PD.

RevDate: 2018-11-11

Prado C, Michels M, Ávila P, et al (2018)

The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis.

Journal of pediatric surgery pii:S0022-3468(18)30668-7 [Epub ahead of print].

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious disease that affects premature neonates, causing high mortality. In the search for new options of treatment it was investigated whether fecal microbiota transplantation (FMT) decreased the inflammatory response during NEC development in experimental model.

METHODS: Wistar rats were used and divided as follows: naïve, control (NEC induction), FMT-before (transplantation of microbiota before insult) and FMT-after (microbiota transplantation after insult). The microbiota transplantation was performed by administering a feces solution obtained from an adult donor rat. The induction of enterocolitis involves feeding by artificial formula, hypothermia, hypoxia and endotoxin administration. MPO activity, TNF-α, IL-1β and IL-6 levels, oxidative and nitrosative damage and the grade of intestinal mucosa lesion were analyzed.

RESULTS: The control group had a significant increase of inflammatory and oxidative parameters when compared to naive animals. Both FMT-before and after decreased all inflammatory and oxidative damage parameters when compared to control group. This was also true to the intestinal mucosa damage.

CONCLUSION: FMT administered just before or after NEC induction improved gut and systemic inflammation, and gut oxidative damage and intestinal injury.

RevDate: 2018-11-20

Ma C, Sun Z, Zeng B, et al (2018)

Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis.

Microbiome, 6(1):200 pii:10.1186/s40168-018-0578-1.

BACKGROUND: Mastitis, which affects nearly all lactating mammals including human, is generally thought to be caused by local infection of the mammary glands. For treatment, antibiotics are commonly prescribed, which however are of concern in both treatment efficacy and neonate safety. Here, using bovine mastitis which is the most costly disease in the dairy industry as a model, we showed that intestinal microbiota alone can lead to mastitis.

RESULTS: Fecal microbiota transplantation (FMT) from mastitis, but not healthy cows, to germ-free (GF) mice resulted in mastitis symptoms in mammary gland and inflammations in serum, spleen, and colon. Probiotic intake in parallel with FMT from diseased cows led to relieved mastitis symptoms in mice, by shifting the murine intestinal microbiota to a state that is functionally distinct from either healthy or diseased microbiota yet structurally similar to the latter. Despite conservation in mastitis symptoms, diseased cows and mice shared few mastitis-associated bacterial organismal or functional markers, suggesting striking divergence in mastitis-associated intestinal microbiota among lactating mammals. Moreover, an "amplification effect" of disease-health distinction in both microbiota structure and function was apparent during the cow-to-mouse FMT.

CONCLUSIONS: Hence, dysbiosis of intestinal microbiota may be one cause of mastitis, and probiotics that restore intestinal microbiota function are an effective and safe strategy to treat mastitis.

RevDate: 2018-11-08

DeFilipp Z, Hohmann E, Jenq RR, et al (2018)

Fecal microbiota transplantation: restoring the injured microbiome after allogeneic hematopoietic cell transplantation.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation pii:S1083-8791(18)30693-1 [Epub ahead of print].

Disruption of the intestinal microbiome early after allogeneic hematopoietic cell transplantation (allo-HCT) has been linked to adverse outcomes in transplant recipients. To date, it remains unknown as to whether microbiome-directed interventions will be able to impact important clinical endpoints. Fecal microbiota transplantation (FMT) is a compelling intervention to restore healthy diversity to the intestinal microenvironment after allo-HCT, but currently has no established role in transplant recipients. In this review, we examine the utilization of FMT as treatment for Clostridium difficile infections and acute graft-versus-host disease, as well as a restorative intervention early after allo-HCT. Ongoing and planned studies will help determine the ultimate role of FMT in recipients of allo-HCT.

RevDate: 2018-11-14

Niccum BA, Stein DJ, Behm BW, et al (2018)

Zinc Deficiency and the Recurrence of Clostridium difficile Infection after Fecal Microbiota Transplant: A Retrospective Cohort Study.

Journal of nutrition and metabolism, 2018:9682975.

Background: Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT.

Methods: We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013-9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency.

Results: Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162-59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015-0.704, p=0.021).

Conclusion: Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.

RevDate: 2018-11-08

Morand A, Cornu F, Dufour JC, et al (2018)

Human bacterial repertoire of the urinary tract: a potential paradigm shift.

Journal of clinical microbiology pii:JCM.00675-18 [Epub ahead of print].

The aim of this article is to review the human repertoire of bacteria already described by culture and metagenomic techniques in urine, and published in the literature. Our study led us to compare this repertoire with other human repertoires available.We followed automatic and manual bibliographical methods and found 562 bacterial species reported in the literature as part of the human urinary microbiota. Of the 562 species, 322 were described only by culture, 101 by both culture and metagenomics, and 139 only by metagenomic. Three hundred and fifty-two species (62.6%) have been associated with at least one case report of human infection, of which 225 (40.0%) have been described as causative agents of urinary tract infection. The urinary tract bacterial repertoire contains 21.4% of the known prokaryotic diversity associated with human beings (464 in common) and share 23.6% species with the human gut microbiota (350 in common, 62.3% of the urine species). Urinary repertoire shares a significant difference in aero-intolerant species compared with gut microbiota (100/562; 17.8% and 505/1484; 34.0% respectively; p<0.001; OR=9.0 [7.0-11.4]). Studies using high-throughput sequencing show a higher proportion of aero-intolerant bacteria in urine (74/240, 30.8%).Most pathogenic bacteria are part of the commensal human urinary tract bacteria and their pathogenicity may occur following any imbalance of this microbiota. The restoration of urinary tract health can occur following a fecal transplantation. The potential gut origin of the human bacterial microbiota has to be explored.

RevDate: 2018-11-07

Ooijevaar RE, Terveer EM, Verspaget HW, et al (2018)

Clinical Application and Potential of Fecal Microbiota Transplantation.

Annual review of medicine [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy. In addition, FMT has been beneficial in treating several other conditions, such as the eradication of multidrug-resistant organisms and graft-versus-host disease. We expect that FMT will soon be implemented as a treatment strategy for several new indications, although further studies are needed. Expected final online publication date for the Annual Review of Medicine Volume 70 is January 27, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RevDate: 2018-11-07

Song JH, YS Kim (2018)

Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention.

Gut and liver pii:gnl18071 [Epub ahead of print].

The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.

RevDate: 2018-11-21

Jiang ZD, Jenq RR, Ajami NJ, et al (2018)

Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

PloS one, 13(11):e0205064 pii:PONE-D-18-09615.

BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI).

AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema.

METHODS: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied.

RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema.

CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.

RevDate: 2018-11-02

Gopalsamy SN, Woodworth MH, Wang T, et al (2018)

The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms.

The American journal of the medical sciences, 356(5):433-440.

Antibiotic resistance (AR) has been described by the World Health Organization as an increasingly serious threat to global public health. Many mechanisms of AR have become widespread due to global selective pressures such as widespread antibiotic use. The intestinal tract is an important reservoir for many multidrug-resistant organisms (MDROs), and next-generation sequencing has expanded understanding of the resistome, defined as the comprehensive sum of genetic determinants of AR. Intestinal decolonization has been explored as a strategy to eradicate MDROs with selective digestive tract decontamination and probiotics being notable examples with mixed results. This review focuses on fecal microbiota transplantation and the early evidence supporting its efficacy in decolonizing MDROs and potential mechanisms of action to reduce AR genes. Current evidence suggests that fecal microbiota transplantation may have promise in restoring healthy microbial diversity and reducing AR, and clinical trials are underway to better characterize its safety and efficacy.

RevDate: 2018-11-02

Stripling J, M Rodriguez (2018)

Current Evidence in Delivery and Therapeutic Uses of Fecal Microbiota Transplantation in Human Diseases-Clostridium difficile Disease and Beyond.

The American journal of the medical sciences, 356(5):424-432.

The use of fecal microbiota transplantation (FMT) was first described in China in the 4th century by Ge Hong when "yellow soup," a fecal slurry, was administered for the treatment of severe food poisoning and diarrhea, a practice that continued for centuries. Bedouin groups also consumed stools of their camels as a remedy for dysentery. FMT was also applied in veterinary medicine in Europe in the 16th century. Additional therapeutic use of human excretions was described in Europe in the 18th and 19th century and in World War II, when gut bacteria were administered to German soldiers suffering from dysentery in the North African campaign. More scientifically, Eismann, in 1958, utilized fecal transplantation via enema in 4 patients for the treatment of severe pseudomembranous colitis with success. Following this report a number of isolated cases were published describing the use of FMT by different delivery routes for the treatment of a variety of illnesses.

RevDate: 2018-11-20

Khoruts A (2018)

Targeting the microbiome: from probiotics to fecal microbiota transplantation.

Genome medicine, 10(1):80 pii:10.1186/s13073-018-0592-8.

The modern techniques of microbiome science can be applied to the development and evaluation of all microbiota-directed products, including probiotics and fecal microbiota transplantation.

RevDate: 2018-11-14

Sun W, Guo Y, Zhang S, et al (2018)

Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis.

BioMed research international, 2018:8308671.

Aim: We tested the hypothesis that fecal microbiota transplantation (FMT) could regulate the biotransformation of bile acids, such as deoxycholic acid (DCA) and cholic acid (CA), which in turn regulate the biosynthesis of serotonin in the gut and relieve gastrointestinal dysmotility in high-fat diet- (HFD-) induced obesity in rats.

Methods: Male Sprague-Dawley rats were randomly divided into the control diet group, HFD group, and HFD-fed with receiving FMT. HFD was fed for 12 weeks. At the end of two-week HFD, FMT was carried out for two weeks. The gastrointestinal transit, serotonin concentration, the expression of tryptophan hydroxylase 1 (TPH1) and serotonin reuptake transporter (SERT), and the levels of bile acids in intestinal contents were examined.

Results: Compared with the control group, the gastrointestinal transit and small intestinal serotonin concentration of HFD-fed rats were increased. In HFD-fed rats, TPH1 protein expression was increased significantly, while SERT protein expression was decreased, but not significant. The levels of CA and DCA in intestinal contents were also significantly increased in HFD-fed rats compared with the control group. After HFD-fed rats receiving FMT treatment, the gastrointestinal transit, small intestinal serotonin concentration, and TPH1 expression were decreased, while SERT expression was not affected. Moreover, the levels of CA and DCA in intestinal contents were also decreased.

Conclusions: FMT could alleviate small intestinal transit in the HFD-fed rats by regulating the serotonin biosynthesis. In this process, CA and DCA may be related to the regulation of synthesis of serotonin.

RevDate: 2018-10-27

Brunse A, Martin L, Rasmussen TS, et al (2018)

Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs.

The ISME journal pii:10.1038/s41396-018-0301-z [Epub ahead of print].

This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.

RevDate: 2018-10-25

Kiouptsi K, Ruf W, C Reinhardt (2018)

Microbiota-Derived Trimethylamine.

Circulation research, 123(10):1112-1114.

RevDate: 2018-11-14

Skye SM, Zhu W, Romano KA, et al (2018)

Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.

Circulation research, 123(10):1164-1176.

RATIONALE: Gut microbes influence cardiovascular disease and thrombosis risks through the production of trimethylamine N-oxide (TMAO). Microbiota-dependent generation of trimethylamine (TMA)-the precursor to TMAO-is rate limiting in the metaorganismal TMAO pathway in most humans and is catalyzed by several distinct microbial choline TMA-lyases, including the proteins encoded by the cutC/D (choline utilization C/D) genes in multiple human commensals.

OBJECTIVE: Direct demonstration that the gut microbial cutC gene is sufficient to transmit enhanced platelet reactivity and thrombosis potential in a host via TMA/TMAO generation has not yet been reported.

METHODS AND RESULTS: Herein, we use gnotobiotic mice and a series of microbial colonization studies to show that microbial cutC-dependent TMA/TMAO production is sufficient to transmit heightened platelet reactivity and thrombosis potential in a host. Specifically, we examine in vivo thrombosis potential employing germ-free mice colonized with either high TMA-producing stable human fecal polymcrobial communities or a defined CutC-deficient background microbial community coupled with a CutC-expressing human commensal±genetic disruption of its cutC gene (ie, Clostridium sporogenes Δ cutC).

CONCLUSIONS: Collectively, these studies point to the microbial choline TMA-lyase pathway as a rational molecular target for the treatment of atherothrombotic heart disease.

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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.

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