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21 Feb 2019 at 01:38
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Bibliography on: Fecal Transplantation


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RJR: Recommended Bibliography 21 Feb 2019 at 01:38 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: 2019-02-20

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

Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis.

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

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

RevDate: 2019-02-20

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

Fecal microbiota transplantation in an elderly patient with mental depression.

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

RevDate: 2019-02-19

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

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

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

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

Hochman J (2018)

Immunoassay helps limit overdiagnosis of Clostridium difficile infection.

The Journal of pediatrics, 199:283.

RevDate: 2019-02-14

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

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

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

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

RevDate: 2019-02-14

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

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

Frontiers in cellular and infection microbiology, 9:6.

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

RevDate: 2019-02-14

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

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

Frontiers in immunology, 10:49.

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

RevDate: 2019-02-10

Qi L, F Li (2019)

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

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

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

RevDate: 2019-02-08

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

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

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

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

RevDate: 2019-02-07

Bekker V, Zwittink RD, Knetsch CW, et al (2019)

Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment During Hematopoietic Stem Cell Transplantation.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation pii:S1083-8791(19)30095-3 [Epub ahead of print].

Bloodstream infections and Graft-versus-Host disease (GvHD) are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota which acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, since studies have shown conflicting results, the use of these treatments remain subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these to the dynamics of SGD. In this prospective, observational, single-center study, fecal samples were longitudinally collected from nineteen children eligible for allogenic HSCT (TGD n=12, SGD n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from three family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, while it showed high inter- and intra-individual variation and low Bacteroides abundance during TGD. In some children, TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving a stem cell transplant did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.

RevDate: 2019-02-07

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

Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial.

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

BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT.

METHODS: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed.

RESULTS: Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02).

CONCLUSIONS: To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.

RevDate: 2019-02-06

Cruz R, Monrroy H, Flandez J, et al (2018)

[Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center].

Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia, 35(5):566-573.

Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.

RevDate: 2019-02-10

Cuevas-Sierra A, Ramos-Lopez O, Riezu-Boj JI, et al (2019)

Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications.

Advances in nutrition (Bethesda, Md.), 10(suppl_1):S17-S30.

Diverse evidence suggests that the gut microbiota is involved in the development of obesity and associated comorbidities. It has been reported that the composition of the gut microbiota differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. However, the mechanisms by which the gut microbiota participates in energy homeostasis are unclear. Gut microbiota can be modulated positively or negatively by different lifestyle and dietary factors. Interestingly, complex interactions between genetic background, gut microbiota, and diet have also been reported concerning the risk of developing obesity and metabolic syndrome features. Moreover, microbial metabolites can induce epigenetic modifications (i.e., changes in DNA methylation and micro-RNA expression), with potential implications for health status and susceptibility to obesity. Also, microbial products, such as short-chain fatty acids or membrane proteins, may affect host metabolism by regulating appetite, lipogenesis, gluconeogenesis, inflammation, and other functions. Metabolomic approaches are being used to identify new postbiotics with biological activity in the host, allowing discovery of new targets and tools for incorporation into personalized therapies. This review summarizes the current understanding of the relations between the human gut microbiota and the onset and development of obesity. These scientific insights are paving the way to understanding the complex relation between obesity and microbiota. Among novel approaches, prebiotics, probiotics, postbiotics, and fecal microbiome transplantation could be useful to restore gut dysbiosis.

RevDate: 2019-02-07

Wilson BC, Vatanen T, Cutfield WS, et al (2019)

The Super-Donor Phenomenon in Fecal Microbiota Transplantation.

Frontiers in cellular and infection microbiology, 9:2.

Fecal microbiota transplantation (FMT) has become a highly effective bacteriotherapy for recurrent Clostridium difficile infection. Meanwhile the efficacy of FMT for treating chronic diseases associated with microbial dysbiosis has so far been modest with a much higher variability in patient response. Notably, a number of studies suggest that FMT success is dependent on the microbial diversity and composition of the stool donor, leading to the proposition of the existence of FMT super-donors. The identification and subsequent characterization of super-donor gut microbiomes will inevitably advance our understanding of the microbial component of chronic diseases and allow for more targeted bacteriotherapy approaches in the future. Here, we review the evidence for super-donors in FMT and explore the concept of keystone species as predictors of FMT success. Possible effects of host-genetics and diet on FMT engraftment and maintenance are also considered. Finally, we discuss the potential long-term applicability of FMT for chronic disease and highlight how super-donors could provide the basis for dysbiosis-matched FMTs.

RevDate: 2019-02-07

Harsch IA, PC Konturek (2019)

Adhesion Ileus after Fecal Microbiota Transplantation in Long-Standing Radiation Colitis.

Case reports in gastrointestinal medicine, 2019:2543808.

Fecal microbiota transplantation (FMT) is a novel strategy for the therapy of dysbiosis-associated disorders via modulation of the gut microbiota. Intestinal dysbiosis is associated not only with digestive disorders, but also with a variety of extra-digestive disorders. A worldwide increasing number of FMT can be expected in the future as well as an increase in adverse events. We describe the case of a patient with chronic radiation colitis that developed adhesion ileus 2 days after FMT. Since these problems never occured before and the short time interval favours a causality, we speculate about FMT-induced alterations in gut motility causing a "trapping" of the small intestine in an adhesion and other mechanisms beyond "pure" coincidence.

RevDate: 2019-02-02

Evrensel A, Önen Ünsalver B, ME Ceylan (2019)

Therapeutic Potential of the Microbiome in the Treatment of Neuropsychiatric Disorders.

Medical sciences (Basel, Switzerland), 7(2): pii:medsci7020021.

The search for rational treatment of neuropsychiatric disorders began with the discovery of chlorpromazine in 1951 and continues to evolve. Day by day, new details of the intestinal microbiota⁻brain axis are coming to light. As the role of microbiota in the etiopathogenesis of neuropsychiatric disorders is more clearly understood, microbiota-based (or as we propose, "fecomodulation") treatment options are increasingly discussed in the context of treatment. Although their history dates back to ancient times, the importance of psychobiotics and fecal microbiota transplantation (FMT) has only recently been recognized. Despite there being few preclinical and clinical studies, the evidence gathered to this point suggests that consideration of the microbiome in the treatment of neuropsychiatric disorders represents an area of significant therapeutic potential. It is increasingly hoped that such treatment options will be more reliable in terms of their side effects, cost, and ease of implementation. However, there remains much to be researched. Questions will be answered through germ-free animal experiments and randomized controlled trials. In this article, the therapeutic potential of microbiota-based options in the treatment of neuropsychiatric disorders is discussed in light of recent research.

RevDate: 2019-02-07

Yang C, Fang X, Zhan G, et al (2019)

Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain.

Translational psychiatry, 9(1):57 pii:10.1038/s41398-019-0379-8.

Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia, which is a core symptom of depression. Accumulating studies suggest that gut microbiota may play a role in depression via gut-microbiota-brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.

RevDate: 2019-02-01

Sun SS, Wang K, Ma K, et al (2019)

An insoluble polysaccharide from the sclerotium of Poria cocos improves hyperglycemia, hyperlipidemia and hepatic steatosis in ob/ob mice via modulation of gut microbiota.

Chinese journal of natural medicines, 17(1):3-14.

Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 106 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.

RevDate: 2019-01-31

Marchukov D, B Misselwitz (2019)

[Insights into the Pathogenesis of Inflammatory Bowel Diseases: Genetics and Microbiota].

Therapeutische Umschau. Revue therapeutique, 75(5):273-279.

Insights into the Pathogenesis of Inflammatory Bowel Diseases: Genetics and Microbiota Abstract. An inadequate immune response against bacteria of the gastrointestinal tract is the basic mechanism mediating the pathophysiology of inflammatory bowel diseases (IBD). The risk of IBD is partially heritable and approximately 12 % of patients have a family history of IBD. Large genome-wide association studies (GWAS) were able to identify 240 genetic regions associated with IBD. Many of the implicated genes have a function in the immune system, are associated with primary immunodeficiencies or the defense against mycobacteria. Together these 240 genetic regions form an excellent framework for further investigations into the pathogenesis and therapy of IBD. However, GWAS so far were able to unravel only a fraction of the genetic IBD risk. New strategies like genome wide sequencing are currently used to identify additional (rare) genetic variants. In rare cases, IBD is also inherited as a monogenetic disease. Moreover, there likely is significant interaction between genes and environmental factors which can only be unraveled if both, genes and the environment are simultaneously considered. Interestingly, the information provided by genetic risk factors for IBD is unable to predict the clinical course of IBD. New GWAS therefore focus on IBD prognosis and first insights have already been made. The gastrointestinal tract harbors a huge number of microorganisms (microbiota). It remains an enormous challenge for the immune system to contain this bacterial load while enabling the host to benefit from the many essential contributions of the microbiota. In IBD, the microbiota is altered to a dysfunctional (dysbiotic) state showing reduced diversity and a higher amount of potential pathogenic Proteobacteriae, such as Escherichia coli. In IBD, the microbiota is also more dynamic in its composition over time compared to health. Further, IBD dysbiosis is more pronounced in Crohn's disease than in ulcerative colitis. In animal experiments, dysbiosis could be transferred by fecal microbiota transplantation from one mouse to another, triggering inflammation in the recipient. In contrast, a healthy microbiota can downregulate the immune response of the host, for instance by bacterial short chain fatty acids (SCFA) synthesis. In addition, some bacteria with close physical contact to the intestinal wall also have specific immunosuppressive properties. So far, the highly complex network of microbiota, genetics, immune system and environment is only partially understood. The microbiota is a potential therapeutic target which up to now can only be non-specifically influenced by antibiotics, probiotics, prebiotics or fecal microbiota transplantation. A better understanding of the microbiota will likely yield in the discovery of new therapeutic options in the future.

RevDate: 2019-02-01

Jianguo L, Xueyang J, Cui W, et al (2019)

Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress.

Translational psychiatry, 9(1):40 pii:10.1038/s41398-019-0391-z.

The gut microbiota has been increasingly correlated with depressive disorder. It was recently shown that the transplantation of the gut microbiota from depressed patients to animals can produce depressive-like behaviors, suggesting that the gut microbiota plays a causal role in the development of depression. In addition, metabolic disorder, which is strongly associated with depression, is exacerbated by changes in the composition of the gut microbiota and is alleviated by treatment with antidepressants. However, the key players and pathways that link the gut microbiota to the pathogenesis of depression remain largely unknown. To evaluate the relationships between depression and metabolic disorders in feces and plasma, we monitored changes in fecal and plasma metabolomes during the development of depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS). In these animals, the fecal metabolome was altered first and subjected to changes in the plasma metabolome. Changes in the abundance of fecal metabolites were associated with depressive-like behaviors and with altered levels of neurotransmitters in the hippocampus. Furthermore, the analysis of the fecal metabolome and the fecal microbiota in CUMS rats demonstrated consistent changes in the levels of several amino acids, including L-threonine, isoleucine, alanine, serine, tyrosine, and oxidized proline. Finally, we observed significant correlations between these amino acids and the altered fecal microbiota. The results of this study suggest that changes in amino acid metabolism by the gut microbiota contribute to changes in circulating amino acids and are associated with the behavior indices of depression.

RevDate: 2019-02-01

Le Roy T, Debédat J, Marquet F, et al (2018)

Comparative Evaluation of Microbiota Engraftment Following Fecal Microbiota Transfer in Mice Models: Age, Kinetic and Microbial Status Matter.

Frontiers in microbiology, 9:3289.

The intestinal microbiota and its functions are intricately interwoven with host physiology. Colonizing rodents with donor microbiota provides insights into host-microbiota interactions characterization and the understanding of disease physiopathology. However, a better assessment of inoculation methods and recipient mouse models is needed. Here, we compare the engraftment at short and long term of genetically obese mice microbiota in germ-free (GF) mice and juvenile and adult specific pathogen free (SPF) mice. We also tested the effects of initial microbiota depletion before microbiota transfer. In the present work, donor microbiota engraftment was better in juvenile SPF mice than in adult SPF mice. In juvenile mice, initial microbiota depletion using laxatives or antibiotics improved donor microbiota engraftment 9 weeks but not 3 weeks after microbiota transfer. Microbiota-depleted juvenile mice performed better than GF mice 3 weeks after the microbiota transfer. However, 9 weeks after transfer, colonized GF mice microbiota had the lowest Unifrac distance to the donor microbiota. Colonized GF mice were also characterized by a chronic alteration in intestinal absorptive function. With these collective results, we show that the use of juvenile mice subjected to initial microbiota depletion constitutes a valid alternative to GF mice in microbiota transfer studies.

RevDate: 2019-01-28

Dinleyici M, Y Vandenplas (2019)

Clostridium difficile Colitis Prevention and Treatment.

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

Clostridium difficile (C. diff) is the most common causative agent of antibiotic-associated diarrhea and colitis. This spore-forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, the use of probiotics, especially Saccharomyces boulardii, and more recently of fecal microbiota transplantation have become valid forms of prevention and/or therapy and are here critically examined.

RevDate: 2019-01-30

Basso PJ, Câmara NOS, H Sales-Campos (2018)

Microbial-Based Therapies in the Treatment of Inflammatory Bowel Disease - An Overview of Human Studies.

Frontiers in pharmacology, 9:1571.

Inflammatory bowel disease (IBD) is a group of multifactorial and inflammatory infirmities comprised of two main entities: Ulcerative colitis (UC) and Crohn's disease (CD). Classic strategies to treat IBD are focused on decreasing inflammation besides inducing and extending disease remission. However, these approaches have several limitations such as low responsiveness, excessive immunosuppression, and refractoriness. Despite the multifactorial causality of IBD, immune disturbances and intestinal dysbiosis have been suggested as the central players in disease pathogenesis. Hence, therapies aiming at modulating intestinal microbial composition may represent a promising strategy in IBD control. Fecal microbiota transplantation (FMT) and probiotics have been explored as promising candidates to reestablish microbial balance in several immune-mediated diseases such as IBD. These microbial-based therapies have demonstrated the ability to reduce both the dysbiotic environment and production of inflammatory mediators, thus inducing remission, especially in UC. Despite these promising results, there is still no consensus on the relevance of such treatments in IBD as a potential clinical strategy. Thus, this review aims to critically review and describe the use of FMT and probiotics to treat patients with IBD.

RevDate: 2019-01-25

Fukuda T, Naganuma M, T Kanai (2019)

Current new challenges in the management of ulcerative colitis.

Intestinal research, 17(1):36-44.

Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulated to be multifactorial in nature, including genetic predisposition, epithelial barrier defects, dysregulation of immune responses, and environmental factors, the specific pathogenesis of UC is still incompletely understood. In the treatment of UC so far, a method of suppressing immunity and treating it has been mainstream. Immunosuppressant drugs, including thiopurines (azathioprine or 6-mercaptopurine), anti-tumor necrosis factor-α (anti-TNF-α) antibody (infliximab and adalimumab), and calcineurin inhibitor, can be used in treat patients with corticosteroid-dependent and/or corticosteroid-refractory moderateto- severe UC. Recently, in addition to such a conventional therapeutic agent, golimumab, which is the first transgenic human monoclonal anti-TNF-α antibody to be fabricated, anti α-4/β-7 integrin antibody, and Janus kinase inhibitor have been reported to novel immunosuppressant therapy. Furthermore, other treatments with unique mechanisms different from immunosuppression, have also been suggested, including fecal microbiota transplantation and Indigo naturalis, which is a Chinese herbal medicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options for these new treatments is reviewed.

RevDate: 2019-01-25

Cho YS (2019)

Multi-session fecal microbiota transplantation using colonoscopy has favorable outcomes for the treatment of steroid-dependent ulcerative colitis.

Intestinal research, 17(1):6-8.

RevDate: 2019-02-03

Hui W, Li T, Liu W, et al (2019)

Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis.

PloS one, 14(1):e0210016 pii:PONE-D-18-19847.

OBJECTIVES: Although systematic evaluation has confirmed the efficacy of fresh fecal microbiota transplantation (FMT) for treatment of recurrent and/or refractory and/or relapse C. difficile infection (RCDI), it lacks the support of well-designed randomized controlled trials (RCTs), and the latest guidelines do not optimize the management of FMT. In this paper, we focus on an in-depth study of fresh FMT and fecal infusion times to guide clinical practice.

METHODS: We reviewed studies in PubMed, Medline, Embase, the Cochrane library and Cochrane Central written in English. The retrieval period was from the establishment of the databases to September 20th, 2018. The retrieval objects were published RCTs of RCDI treated by fresh FMT. The intervention group was fresh FMT group, while the control group included antibiotic therapy or placebo or frozen FMT or capsule. The primary and secondary outcomes were the clinical remission of diarrhea without relapse after 8-17 weeks and the occurrence of severe adverse events, respectively. Subgroup analysis analyzed the effect of single and multiple fecal infusions. Two authors independently completed the information extraction and assessed risk of bias and overall quality of the evidence.

RESULTS: 8 randomized controlled trials met the inclusion criteria, involving 537 patients (273 in the fresh FMT group and 264 in the control group). The recurrence rate of clinical diarrhea in the fresh FMT group was 11.0% (30/273), which was significantly lower than the control group (24.6%, 65/264; P < 0.05); the pooled relative risk (RR) was 0.38 (95%CI:0.16-0.87; I2 = 67%; P = 0.02) in the fresh FMT group, and the clinical heterogeneity was significant and random effects model was used; However, there was no significant difference neither for the effect of antibiotic treatment/frozen feces transplanted by enema (RR = 1.07; 95%CI: 0.64-1.80; I2 = 0%; P = 0.79) or capsule/frozen feces transplanted by colonoscopy (RR = 0.42; 95%CI: 0.05-3.94; I2 = 43%; P = 0.45) compared with fresh FMT. The subgroup analysis showed that FMT by multiple infusions could effectively and significantly (RR = 0.24; 95%CI:0.10-0.58; I2 = 0%; P = 0.001) improve the clinical diarrhea remission rate. Most mild to moderate adverse events caused by FMT were self-limited and could be quickly alleviated; no severe adverse events happened because of FMT.

CONCLUSIONS: Overall, the use of fresh feces for bacterial transplantation was the best efficiency for RCDI compared to antibiotic therapy or placebo. The fecal transmission method by enema was not ideal, but capsules or frozen feces transported by colonoscopy could be an alternative treatment compared to fresh FMT. For patients with severe RCDI, multiple fecal transplants can effectively improve their diarrhea remission rate. The focus of future research should be on how to standardize the production of capsules or frozen feces to better guide the clinical management of RCDI patients by FMT.

RevDate: 2019-01-22

De Sire R, Talocco C, Petito V, et al (2018)

[Microbiota and inflammatory bowel disease: an update.].

Recenti progressi in medicina, 109(12):570-573.

Over the last few years, the gut microbiota has been the focus of countless studies conducted both on mouse models and human population, aimed at analyzing its functions and interactions with the host, including nutrition, metabolic homeostasis, protection from infections and development of systemic and mucosal immunity both in inflammatory bowel disease (IBD) as well as other intestinal and extra-intestinal diseases. In IBD microbiota is impaired in overall composition and biodiversity, stability as well as functions. Microbial signature of IBD can be considered also a decrease in F. prausnitzii, increase of Proteonbacteria as well as the described increase of Candida albicans, Basidiomycota/Ascomycota ratio over Saccharomyces cerevisiae and of the Caudovirales over Microviridae. The indirect (through antibiotics, probiotics) and direct (through fecal microbiota transplantation) modulation of gut microbiota has relevant clinical implication in IBD management. In the near future role and clinical implication of gut microbiota characterization in the therapeutic personalized approach to IBD patients will eventually become clear.

RevDate: 2019-01-27

Contijoch EJ, Britton GJ, Yang C, et al (2019)

Gut microbiota density influences host physiology and is shaped by host and microbial factors.

eLife, 8: pii:40553.

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.

Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

RevDate: 2019-01-21

Bajaj JS, Fagan A, Gavis EA, et al (2019)

Long-term Outcomes after Fecal Microbiota Transplant in Cirrhosis.

Gastroenterology pii:S0016-5085(19)30093-9 [Epub ahead of print].

RevDate: 2019-01-21

Ihekweazu FD, Fofanova TY, Queliza K, et al (2019)

Bacteroides ovatus ATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model.

Gut microbes [Epub ahead of print].

BACKGROUND AND AIMS: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD.

METHODS: We induced experimental colitis in 8- 12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes.

RESULTS: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus.

CONCLUSIONS: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.

RevDate: 2019-01-23

Xiao J, Peng Z, Liao Y, et al (2018)

Organ transplantation and gut microbiota: current reviews and future challenges.

American journal of translational research, 10(11):3330-3344.

Organ transplantation is often the only effective treatment for patients with end-stage diseases, such as heart, liver, kidney and small bowel failure and is carried out frequently worldwide. Still the post-transplantation complications remain health- and life-threatening outcome that needed to be resolved. With the rapid development of molecular technologies in recent years, more and more researchers realize that the gut microbiota may play a critical role in human diseases. The intestinal microbiome has been proved to provide a lot of functions to the host, such as digesting food, modulating metabolism, promoting angiogenesis and regulating the immune system. Several studies have investigated the alteration of intestinal microbiota in post-transplantation patients and observed significant changes in the intestinal microbiome compared to the pre-transplant condition. Due to the abovementioned features that the gut microbiota may be used in the prognosis of clinical outcome of organ transplantation. In addition, the FMT (fecal microbiota transplantation), probiotics and prebiotics as the newest therapy methods, effectiveness of which has been verified in some diseases, such as Clostridium difficile infection, inflammatory bowel disease and other chronic disorders, might be used as the prognosis tool in organ transplantation as well. The purpose of this present review is to elucidate the relationship between gut microbiota and organ transplantation as well as the potential use of new therapies like fecal microbiota transplantation, probiotic and prebiotic administration after the transplantation, and provide some ideas for future researches in field of organ transplantation.

RevDate: 2019-01-20

Knox NC, Forbes JD, Van Domselaar G, et al (2019)

The Gut Microbiome as a Target for IBD Treatment: Are We There Yet?.

Current treatment options in gastroenterology pii:10.1007/s11938-019-00221-w [Epub ahead of print].

PURPOSE OF REVIEW: This review aims to highlight recent research on the gut microbiome in IBD and the application of microbiome-modulating therapies for the treatment of IBD including the use of the microbiome as an indicator for disease severity and treatment response.

RECENT FINDINGS: Despite the high number of gut microbiome studies and emerging evidence supporting the gut microbiome's involvement in disease pathogenesis, no single microorganism has been identified as a pathogenic agent in IBD. Retrospective studies and meta-analyses on antibiotic use in ulcerative colitis and Crohn's disease and long-term outcomes are conflicting. Similarly, the use of probiotics for the treatment of IBD remains inconclusive; however, some encouraging results are emerging as microbial concoctions are optimized to include beneficial bacterial strains. Fecal microbial transplantation (FMT) is currently emerging as one of the more promising microbiome-modulating IBD therapies. FMT studies in ulcerative colitis have shown improved remission rates compared to placebo; however, relatively small study sample sizes and varied treatment methods, limit definitive conclusions. With clear evidence of an IBD gut dysbiosis, novel therapies to treat and prevent disease relapse will undoubtedly require a microbiome-modulating approach. The complexity and variability of IBD disease pathogenesis (disease phenotype, gut microbiome, host genetic susceptibility, and environmental factors) will likely require a personalized and multidimensional treatment approach where microbiome-modulating therapy is coupled with other therapies to target other IBD disease components.

RevDate: 2019-02-07

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: 2019-02-03

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: 2019-01-17

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: 2019-01-18

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: 2019-02-07

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: 2019-02-08

Kelly CR, AN Ananthakrishnan (2019)

Manipulating the Microbiome With Fecal Transplantation to Treat Ulcerative Colitis.

JAMA, 321(2):151-152.

RevDate: 2019-01-18

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: 2019-01-18

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: 2019-02-11

Felizardo RJF, Watanabe IKM, Dardi P, et al (2019)

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

Pharmacological research, 141:366-377 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. These 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: 2019-01-16

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: 2019-02-12

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, 47(2):1072-1079.

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: 2019-02-11

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: 2019-01-13

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

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: 2019-01-10

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: 2019-01-10

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: 2019-01-24
CmpDate: 2019-01-24

Sugita K, Yanuma N, Ohno H, et al (2019)

Oral faecal microbiota transplantation for the treatment of Clostridium difficile-associated diarrhoea in a dog: a case report.

BMC veterinary research, 15(1):11 pii:10.1186/s12917-018-1754-z.

BACKGROUND: Successful clinical outcomes of faecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection have been reported in humans and a marmoset. However, it has been unclear whether oral FMT was effective for the treatment of C. difficile-associated diarrhoea in dogs.

CASE PRESENTATION: An 8-month-old, intact male French bulldog was presented with a 4-month history of intermittent large bowel diarrhoea. Physical and clinical examinations did not identify any specific causes for diarrhoea. Real-time PCR analysis and immunochromatography detected C. difficile antigen and toxin A&B genes and proteins in a faecal sample. Based on these findings, diarrhoea in the dog was considered to be induced by C. difficile-associated colitis. The dog was treated with oral FMT, in which a faecal solution obtained from a healthy beagle was orally administered to the subject. Stool consistency and frequency and faecal blood and mucus became normal 2-3 days after oral FMT, and real-time PCR analysis and immunochromatography was negative for C. difficile antigen and toxin A&B genes and proteins. No adverse events were observed.

CONCLUSION: The present case report demonstrated that oral FMT was an effective treatment for C. difficile-associated diarrhoea in a dog. The findings in this report provide a rationale to evaluate clinical efficacy of oral FMT for other gastrointestinal diseases in dogs.

RevDate: 2019-01-09

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: 2019-01-09

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: 2019-01-08

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: 2019-01-28
CmpDate: 2019-01-28

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: 2019-01-28

Tang TWH, Chen HC, Chen CY, et al (2019)

Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair.

Circulation, 139(5):647-659.

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 MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA 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 high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.

RESULTS: Antibiotic-treated 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 SCFAs, 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 after 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 antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward 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: 2019-01-20

Brandsma E, Kloosterhuis NJ, Koster M, et al (2019)

A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis.

Circulation research, 124(1):94-100.

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 proinflammatory microbiota from Caspase1-/- (Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice.

METHOD AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a cohousing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were cohoused for 8 or 13 weeks and fed chow or high-fat cholesterol-rich diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA (ribosomal DNA) 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 high-fat cholesterol-fed Ldlr-/-(Casp1-/-) mice compared with Ldlr-/-(Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated proinflammatory cytokine levels in plasma in high-fat cholesterol-fed Ldlr-/-(Casp1-/-) compared with Ldlr-/-(Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-(Casp1-/-) mice was enhanced compared with Ldlr-/-(Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid-producing taxonomies Akkermansia, Christensenellaceae, Clostridium, and Odoribacter in Ldlr-/-(Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory short-chain fatty acids propionate, acetate and butyrate in the cecum were significantly reduced in 13-week high-fat cholesterol-fed Ldlr-/-(Casp1-/-) compared with Ldlr-/-(Ldlr-/-) mice.

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

RevDate: 2019-01-15

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(6):360-371.

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: 2019-02-09

Singh S, Feuerstein JD, Binion DG, et al (2019)

AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis.

Gastroenterology, 156(3):769-808.e29.

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 (eg, sulfasalazine, diazo-bonded 5-aminosalicylates [ASA], mesalamines, and corticosteroids, including budesonide) 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 American Gastroenterological Association prioritized clinical guidelines on this topic. To inform clinical guidelines, this technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework for interventional studies. Focused questions included the following: (1) comparative effectiveness and tolerability of different oral 5-ASA therapies (sulfalsalazine vs diazo-bonded 5-ASAs vs mesalamine; low- (<2 g) vs standard (2-3 g/d) vs high-dose (>3 g/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: 2019-01-11

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: 2019-01-15

Limketkai BN, Hendler S, Ting PS, et al (2019)

Fecal Microbiota Transplantation for the Critically Ill Patient.

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 34(1):73-79.

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: 2019-01-15
CmpDate: 2019-01-04

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: 2019-01-31

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: 2019-01-17

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: 2019-01-16

Davidovics ZH, Michail S, Nicholson MR, et al (2019)

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, 68(1):130-143.

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: 2018-12-17

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: 2018-12-17

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.

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: 2019-02-06

Huang C, Yang X, Zeng B, et al (2019)

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

Journal of proteomics, 194:132-147.

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: 2018-12-30

Kaako A, Al-Amer M, Y Abdeen (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, 55:112-116 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 highlights 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: 2019-02-05

Burrello C, Garavaglia F, Cribiù FM, et al (2018)

Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells.

Nature communications, 9(1):5184 pii:10.1038/s41467-018-07359-8.

Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies.

RevDate: 2019-01-23
CmpDate: 2019-01-23

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.

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: 2019-01-11

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: 2019-02-03

Hu XF, Zhang WY, Wen Q, et al (2019)

Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition.

Pharmacological research, 139:412-421.

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: 2019-01-02

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 prevent CDI successfully include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Because CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, a number of patient- and facility-level strategies 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 policymakers.

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: 2019-01-16
CmpDate: 2019-01-16

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: 2019-01-08

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: 2019-02-04

Mathias F, Curti C, Montana M, et al (2019)

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, 38(2):209-231.

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: 2018-12-07

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.

RevDate: 2018-12-10

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.

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: 2019-01-08

Wang Y, Wiesnoski DH, Helmink BA, et al (2019)

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

Nature medicine, 25(1):188.

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: 2019-02-08

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, 37(6):559-562.

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: 2019-01-15

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: 2019-02-05
CmpDate: 2019-02-01

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):.

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: 2018-12-31

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 1,000 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 preclinical 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.

RevDate: 2018-12-07

Ohara T, T Suzutani (2018)

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

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

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.


RJR Experience and Expertise


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.


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.


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.


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.


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.


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.


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.


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

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Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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