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18 Aug 2019 at 01:33
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Bibliography on: Fecal Transplantation


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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: 2019-08-16

Mouries J, Brescia P, Silvestri A, et al (2019)

Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development.

Journal of hepatology pii:S0168-8278(19)30471-4 [Epub ahead of print].

BACKGROUND AND AIMS: Fatty liver disease, including nonalcoholic fatty liver (NAFLD) and steatohepatitis (NASH), has been associated with increased intestinal barrier permeability and translocation of bacteria or bacterial products into the blood circulation. In this study we aim to unravel the role of both intestinal barriers integrity and microbiota in NAFDL/NASH development.

METHODS: C57BL/6J mice were fed with High Fat Diet (HFD) or Methionine Choline Deficient Diet for one week or longer to recapitulate NASH disease aspects (steatosis, inflammation, insulin resistance). Genetic and pharmacological strategies have been used to modulate the intestinal barriers integrity.

RESULTS: We show that disruption of intestinal epithelial barrier and gut vascular barrier (GVB) are early events in NASH pathogenesis. Mice fed a HFD for only one week undergo a diet-induced dysbiosis that drives GVB damage and bacteria translocation into the liver. Fecal microbiota transplantation from HFD-fed mice into specific pathogen-free recipients induces GVB damage and epidydimal adipose tissue enlargement. GVB disruption depends on interference with the WNT/β-catenin signaling pathway, as shown by genetic intervention driving β-catenin activation only in endothelial cells, preventing GVB disruption and NASH development. The bile acid analogue and farnesoid X receptor agonist obeticholic acid drives β-catenin activation in endothelial cells. Accordingly, pharmacologic intervention with OCA protects against GVB disruption, both as preventive and therapeutic agent. Importantly, we found upregulation of the GVB leakage marker in the colon of NASH patients.

CONCLUSIONS: We have identified a new player in NASH development, the GVB, whose damage leads to bacteria or bacterial product translocation into the blood circulation. Treatment aimed at restoring β-catenin activation in endothelial cells, such as administration of OCA, protects against GVB damage and NASH development.

LAY SUMMARY: Fatty liver disease incidence is reaching epidemic in USA, with more than 30% of adults having NAFLD (nonalcoholic fatty liver disease). NAFLD can develop into NASH (steatohepatitis), a more severe stage, that can ultimately turn into cirrhosis and hepatocellularcarcinoma. There is a known link between increased intestinal permeability and the development of the disease, however there is no clear description of the initiation of NASH, i.e. if it is a cause or a consequence of NASH. Here, we demonstrate for the first time that high fat diet induces changes in the microbiota, that will in turn disrupt the intestinal barrier. Indeed, there exist two layers of barrier that are sequentially disrupted when microbiota changes following high fat diet consumption. This disruption allows bacteria from the intestine to reach the blood stream and disseminate to the liver fostering the development of a fatty liver. When using a genetically modified mouse model, or a drug (OCA) that protects against barrier disruption, there is no development of the disease. This clearly shows that barrier disruption is a prerequisite for the disease to develop. Finally, we also found indication of barrier disruption in human samples from NASH patients, supporting the idea of a general mechanism. Altogether, these data clearly decipher the very first steps of fatty liver disease onset, and lead the way for a treatment using OCA to block barrier disruption.

RevDate: 2019-08-15

Rosenbaum JT (2019)

Just another crappy commentary: the future of fecal microbiota transplantation.

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

RevDate: 2019-08-15

Khan I, Ullah N, Zha L, et al (2019)

Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome.

Pathogens (Basel, Switzerland), 8(3): pii:pathogens8030126.

Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn's disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.

RevDate: 2019-08-14

Yang J, H Yang (2019)

Non-antibiotic therapy for Clostridioides difficile infection: A review.

Critical reviews in clinical laboratory sciences [Epub ahead of print].

Clostridioides difficile infection (CDI) is a common infectious disease that is mainly caused by antibiotics. Antibiotic therapy is still the dominant treatment for CDI, although it is accompanied by side effects. Probiotics, fecal microbiota transplantation (FMT), engineered microorganisms, bacteriophages, diet, natural active substances, nanoparticles and compounds are examples of emerging non-antibiotic therapies that have received a great amount of attention. In this review, we collected data about different non-antibiotic therapies for CDI and provided a comprehensive analysis and detailed comparison of these therapies. The mechanism of action, therapeutic efficacy, and the strengths and weaknesses of these non-antibiotic therapies have been investigated to provide a basis for the reasonable alternative of non-antibiotic therapies for CDI. In summary, probiotics and FMT are currently the best choice for non-antibiotic therapy for CDI.

RevDate: 2019-08-14
CmpDate: 2019-08-14

Stallmach A, Reuken PA, N Teich (2018)

[Advances in the diagnosis and treatment of Clostridioides [Clostridium] difficile infections in inflammatory bowel disease].

Zeitschrift fur Gastroenterologie, 56(11):1369-1377.

Patients with chronic inflammatory bowel disease (IBD) have a significantly increased risk of clinically relevant clostridial infection (CDI). In turn, CDI can increase IBD activity. Therefore, rapid diagnosis and therapy is required. Many diagnostic and treatment studies on patients with CDI without inflammatory bowel disease are not congruent with IBD patients. This overview summarizes the everyday data of recent years and condenses these into four guiding principles. 1) patients with IBD present a risk population for a CDI. A CDI not only worsens the disease activity in the short term, but also causes increased morbidity and mortality in the long term. 2) If a CDI is suspected, glutamate-dehydrogenase (GDH) detection should be carried out quickly. If this is positive, and the disease activity is high, a therapy against C. difficile already may be initiated and-if necessary-terminated in cases of negative confirmation tests. 3) IBD patients with a proven CDI should be treated primarily with vancomycin. 4) In a relapsing CDI, fecal microbiome transfer is an effective therapeutic measure. However, activation of the IBD must be expected in about 15 % of cases. Consistent adherence to these guidelines may help treat a CDI in IBD patients.

RevDate: 2019-08-14
CmpDate: 2019-08-14

Milliken EJT (2019)

Fifty years of faecal microbiota transplant in Central Australia.

Gut, 68(8):1536.

RevDate: 2019-08-12

Gargiullo L, Del Chierico F, D'Argenio P, et al (2019)

Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.

Frontiers in microbiology, 10:1704.

The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.

RevDate: 2019-08-13
CmpDate: 2019-08-13

Tavoukjian V (2019)

Faecal microbiota transplantation for the decolonization of antibiotic-resistant bacteria in the gut: a systematic review and meta-analysis.

The Journal of hospital infection, 102(2):174-188.

Antibiotic resistance is a growing global problem associated with increased morbidity and mortality, and presents a significant financial and economic burden on healthcare. Faecal microbiota transplantation (FMT) has been proven effective for curing recurrent Clostridium difficile infections, however no systematic review to date has addressed its effectiveness for decolonization of antibiotic-resistant bacteria from the gut. The aim of this study was to establish whether faecal microbiota transplantation decolonizes antibiotic-resistant bacteria from the gut of colonized adults. A systematic review was performed by undertaking a comprehensive search on MEDLINE, Embase, CENTRAL, PubMed and CINAHL databases for evidence up until May 2018. Randomized and non-randomized studies evaluating the effects of FMT on gut colonization of antibiotic-resistant bacteria in adults were eligible. Studies were assessed using the Joanna Briggs Institution critical appraisal checklists. Quality of reporting was assessed using PROCESS and CARE checklists. Data was synthesized narratively, along with a meta-analysis of proportions for the primary outcome. Five studies with a total number of 52 participants were included. Evidence of low quality showed that decolonization was achieved in half of the cases one month after FMT with higher response noted in Pseudomonas aeruginosa, and lower response in Klebsiella pneumoniae with New Delhi metallo-beta-lactamase 1 (NDM-1) and extended-spectrum β-lactamase (ESBL) mechanisms of resistance. In successful cases, 70% of decolonization cases occurred within the first week after FMT. Few temporary adverse events were identified. Despite the limitations of the included studies, evidence from this review indicates a potential benefit of FMT as a decolonization intervention, which can only be confirmed by future well-designed RCTs.

RevDate: 2019-08-12
CmpDate: 2019-08-12

Saïdani N, Lagier JC, Cassir N, et al (2019)

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

International journal of antimicrobial agents, 53(4):355-361.

BACKGROUND: Colonisation 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. Faecal microbiota transplantation (FMT) has been proposed in order to reduce the duration of gut colonisation.

OBJECTIVES: This study 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 colonisation.

METHOD: A matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A-colonised patients addressed for initial clustering at the current institute. The study adjusted two controls per case based on sex, age, bacterial species, and carbapenemase type. The primary outcome was 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 spontaneous clearance at day 14 after CPE/A diagnosis. Faecal microbiota transplantation led patients to reduce the delay in decolonisation (median 3 days post FMT for treated patients vs. 50.5 days after the first documentation of digestive carriage for control patients) and discharge from hospital (median 19.5 days post FMT for treated patients vs. 41 for control patients).

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

RevDate: 2019-08-13
CmpDate: 2019-08-13

Dicks LMT, Mikkelsen LS, Brandsborg E, et al (2019)

Clostridium difficile, the Difficult "Kloster" Fuelled by Antibiotics.

Current microbiology, 76(6):774-782.

Clostridium difficile is normally present in low numbers in a healthy adult gastro-intestinal tract (GIT). Drastic changes in the microbial population, e.g., dysbiosis caused by extensive treatment with antibiotics, stimulates the growth of resistant strains and the onset of C. difficile infection (CDI). Symptoms of infection varies from mild diarrhea to colitis (associated with dehydration and bleeding), pseudomembranous colitis with yellow ulcerations in the mucosa of the colon, to fulminant colitis (perforation of the gut membrane), and multiple organ failure. Inflamed epithelial cells and damaged mucosal tissue predisposes the colon to other opportunistic pathogens such as Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp., and Salmonella spp. This may lead to small intestinal bacterial overgrowth (SIBO), sepsis, toxic megacolon, and even colorectal cancer. Many stains of C. difficile are resistant to metronidazole and vancomycin. Vaccination may be an answer to CDI, but requires more research. Success in treatment with probiotics depends on the strains used. Oral or rectal fecal transplants are partly effective, as spores in the small intestine may germinate and colonize the colon. The effect of antibiotics on C. difficile and commensal gut microbiota is summarized and changes in gut physiology are discussed. The need to search for non-antibiotic methods in the treatment of CDI and C. difficile-associated disease (CDAD) is emphasized.

RevDate: 2019-08-09

Riquelme E, Zhang Y, Zhang L, et al (2019)

Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.

Cell, 178(4):795-806.e12.

Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.

RevDate: 2019-08-09

Zhou GF, Jiang YH, Ma DF, et al (2019)

Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.

BioMed research international, 2019:9637479.

Background: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect.

Methods: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota.

Results: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF.

Conclusions: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

RevDate: 2019-08-09

El-Salhy M, Hatlebakk JG, T Hausken (2019)

Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.

Nutrients, 11(8): pii:nu11081824.

Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.

RevDate: 2019-08-09
CmpDate: 2019-08-09

Spychala MS, Venna VR, Jandzinski M, et al (2018)

Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.

Annals of neurology, 84(1):23-36.

OBJECTIVE: Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation.

METHODS: Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke. Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke. Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG). Mice were subjected to ischemic stroke (middle cerebral artery occlusion; MCAO) or sham surgery. During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S ribosomal RNA analysis of bacterial content.

RESULTS: We found that the microbiota is altered after experimental stroke in young mice and resembles the biome of uninjured aged mice. In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased ∼9-fold (p < 0.001) compared to young. This increased F:B ratio in aged mice is indicative of dysbiosis. Altering the microbiota in young by fecal gavage to resemble that of aged mice (∼6-fold increase in F:B ratio, p < 0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels. Conversely, altering the microbiota in aged to resemble that of young (∼9-fold decrease in F:B ratio, p < 0.001) increased survival and improved recovery following MCAO.

INTERPRETATION: Aged biome increased the levels of systemic proinflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age-related diseases. Ann Neurol 2018;83:23-36.

RevDate: 2019-08-08

Muscogiuri G, Cantone E, Cassarano S, et al (2019)

Gut microbiota: a new path to treat obesity.

International journal of obesity supplements, 9(1):10-19.

Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss.

RevDate: 2019-08-08

Zhu F, Guo R, Wang W, et al (2019)

Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.

Molecular psychiatry pii:10.1038/s41380-019-0475-4 [Epub ahead of print].

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.

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

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

Fifty shades of graft: How to improve the efficacy of faecal microbiota transplantation for decolonization of antibiotic-resistant bacteria.

International journal of antimicrobial agents, 53(5):553-556.

BACKGROUND: Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.

METHODS: Literature available to date concerning the use of FMT to eradicate ARB was reviewed, and the different factors that may have influenced the efficacy of decolonization were evaluated.

RESULTS: Four axes that could have played major roles in the efficacy of FMT were identified: bowel preparation before FMT; donor; dose; and thermal conditioning of faeces. The positive or negative impact of each on the outcome of FMT is discussed.

CONCLUSION: Although FMT is very efficient for the eradication of Clostridium difficile, the same 'recipe' cannot be used for the eradication of ARB. Working together with expert centres may help to improve the efficacy of FMT for this indication, and enable the reduction of in-hospital isolation precautions.

RevDate: 2019-08-07

Berbers RM, Franken IA, HL Leavis (2019)

Immunoglobulin A and microbiota in primary immunodeficiency diseases.

Current opinion in allergy and clinical immunology [Epub ahead of print].

PURPOSE OF REVIEW: With the emergence of the microbiota as a potential driver of host inflammation, the role of iIgA is becoming increasingly important. This review discusses the current evidence regarding the effects of clinical IgA deficiency on the microbiota, and the possible role of microbial dysbiosis in driving inflammation in PID patients.

RECENT FINDINGS: The gut microbiota has been investigated in selective IgA deficiency and common variable immunodeficiency, revealing an important role for IgA in maintaining gut microbiota homeostasis, with disparate effects of IgA on symbionts and pathobionts. Although IgA deficiency is associated with microbial translocation and systemic inflammation, this may be partially compensated by adequate IgG and IgM induction in IgA deficiency but not in common variable immunodeficiency. Therapeutic strategies aimed at correction of the microbiota mostly focus on fecal microbiota transplantation. Whether this may reduce systemic inflammation in PID is currently unknown.

SUMMARY: Clinical IgA deficiency is associated with microbial dysbiosis and systemic inflammation. The evidence for microbiota-targeted therapies in PID is scarce, but indicates that IgA-based therapies may be beneficial, and that fecal microbiota transplantation is well tolerated in patients with antibody deficiency.

RevDate: 2019-08-06

Santiago M, Eysenbach L, Allegretti J, et al (2019)

Microbiome predictors of dysbiosis and VRE decolonization in patients with recurrent C. difficile infections in a multi-center retrospective study.

AIMS microbiology, 5(1):1-18 pii:microbiol-05-01-001.

The gastrointestinal microbiome is intrinsically linked to the spread of antibiotic resistance. Antibiotic treatment puts patients at risk for colonization by opportunistic pathogens like vancomycin resistant Enterococcus and Clostridioides difficile by destroying the colonization resistance provided by the commensal microbiota. Once colonized, the host is at a much higher risk for infection by that pathogen. Furthermore, we know that microbiome community differences are associated with disease states, but we do not have a good understanding of how we can use these changes to classify different patient populations. To that end, we have performed a multicenter retrospective analysis on patients who received fecal microbiota transplants to treat recurrent Clostridioides difficile infection. We performed 16S rRNA gene sequencing on fecal samples collected as part of this study and used these data to develop a microbiome disruption index. Our microbiome disruption index is a simple index that is predictive across cohorts, indications, and batch effects. We are able to classify pre-fecal transplant vs post-fecal transplant samples in patients with recurrent C. difficile infection, and we are able to predict, using previously-published data from a cohort of patients receiving hematopoietic stem cell transplants, which patients would go on to develop bloodstream infections. Finally, we also identified patients in this cohort that were initially colonized with vancomycin resistant Enterococcus and that 92% (11/12) were decolonized after the transplant, but the microbiome disruption index was unable to predict such decolonization. We, however, were able to compare the relative abundance of different taxa between the two groups, and we found that increased abundance of Enterobacteriaceae predicts whether patients were colonized with vancomycin resistant Enterococcus. This work is an early step towards a better understanding of how microbiome predictors can be used to help improve patient care and patient outcomes.

RevDate: 2019-08-06

Sun J, Xu J, Ling Y, et al (2019)

Fecal microbiota transplantation alleviated Alzheimer's disease-like pathogenesis in APP/PS1 transgenic mice.

Translational psychiatry, 9(1):189 pii:10.1038/s41398-019-0525-3.

Alzheimer's disease (AD) is the most common dementia in the elderly. Treatment for AD is still a difficult task in clinic. AD is associated with abnormal gut microbiota. However, little is known about the role of fecal microbiota transplantation (FMT) in AD. Here, we evaluated the efficacy of FMT for the treatment of AD. We used an APPswe/PS1dE9 transgenic (Tg) mouse model. Cognitive deficits, brain deposits of amyloid-β (Aβ) and phosphorylation of tau, synaptic plasticity as well as neuroinflammation were assessed. Gut microbiota and its metabolites short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (NMR). Our results showed that FMT treatment could improve cognitive deficits and reduce the brain deposition of amyloid-β (Aβ) in APPswe/PS1dE9 transgenic (Tg) mice. These improvements were accompanied by decreased phosphorylation of tau protein and the levels of Aβ40 and Aβ42. We observed an increases in synaptic plasticity in the Tg mice, showing that postsynaptic density protein 95 (PSD-95) and synapsin I expression were increased after FMT. We also observed the decrease of COX-2 and CD11b levels in Tg mice after FMT. We also found that FMT treatment reversed the changes of gut microbiota and SCFAs. Thus, FMT may be a potential therapeutic strategy for AD.

RevDate: 2019-08-05

Dhakal S, Wang L, Antony L, et al (2019)

Amish (Rural) vs. non-Amish (Urban) Infant Fecal Microbiotas Are Highly Diverse and Their Transplantation Lead to Differences in Mucosal Immune Maturation in a Humanized Germfree Piglet Model.

Frontiers in immunology, 10:1509.

The gut microbiome plays an important role in the immune system development, maintenance of normal health status, and in disease progression. In this study, we comparatively examined the fecal microbiomes of Amish (rural) and non-Amish (urban) infants and investigated how they could affect the mucosal immune maturation in germ-free piglets that were inoculated with the two types of infant fecal microbiota (IFM). Differences in microbiome diversity and structure were noted between the two types of fecal microbiotas. The fecal microbiota of the non-Amish (urban) infants had a greater relative abundance of Actinobacteria and Bacteroidetes phyla, while that of the Amish (rural) counterparts was dominated by Firmicutes. Amish infants had greater species richness compared with the non-Amish infants' microbiota. The fecal microbiotas of the Amish and the non-Amish infants were successfully transplanted into germ-free piglets, and the diversity and structure of the microbiota in the transplanted piglets remained similar at phylum level but not at the genus level. Principal coordinates analysis (PCoA) based on Weighted-UniFrac distance revealed distinct microbiota structure in the intestines of the transplanted piglets. Shotgun metagenomic analysis also revealed clear differences in functional diversity of fecal microbiome between Amish and non-Amish donors as well as microbiota transplanted piglets. Specific functional features were enriched in either of the microbiota transplanted piglet groups directly corresponding to the predominance of certain bacterial populations in their gut environment. Some of the colonized bacterial genera were correlated with the frequency of important lymphoid and myeloid immune cells in the ileal submucosa and mesenteric lymph nodes (MLN), both important for mucosal immune maturation. Overall, this study demonstrated that transplantation of diverse IFM into germ-free piglets largely recapitulates the differences in gut microbiota structure between rural (Amish) and urban (non-Amish) infants. Thus, fecal microbiota transplantation to germ-free piglets could be a useful large animal model system for elucidating the impact of gut microbiota on the mucosal immune system development. Future studies can focus on determining the additional advantages of the pig model over the rodent model.

RevDate: 2019-08-07

Ma Y, Xu X, Li M, et al (2019)

Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.

Molecular medicine (Cambridge, Mass.), 25(1):35 pii:10.1186/s10020-019-0102-5.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.

METHODS: Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR).

RESULTS: The fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes.

CONCLUSIONS: SLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.

RevDate: 2019-08-01

Shin JH, CA Warren (2019)

Prevention and treatment of recurrent Clostridioides difficile infection.

Current opinion in infectious diseases [Epub ahead of print].

PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) is a significant burden on the health system, especially due to high recurrence rates. Since the beginning of the CDI epidemic in early 2000s, many strategies for combatting recurrence have been explored, with moderate success so far. This review will focus on the most recent developments in recurrent CDI prevention and treatment.

RECENT FINDINGS: There are two main mechanisms of CDI recurrence: alteration in microbiome and poor antibody response. Development of new antibiotics aims to minimize damage to the microbiome. Fecal transplant or other microbiome replacement therapies seek to replenish the missing elements in the microbiome. Fecal microbiota transplant is the most effective treatment for prevention of CDI recurrenceso far, but is difficult to standardize and regulate, leading to efforts to develop microbiome-derived therapeutics. A deficiency in developing antibodies to C. difficile toxins is another mechanism of recurrence. Active immunization using toxoid vaccines or passive immunization using mAbs address this aspect.

SUMMARY: There are promising new treatments for recurrent CDI in development. Fecal microbiota transplant remains the most effective therapy for multiply recurrent CDI. New antibiotics, microbiome-derived therapeutics, and immunologic therapies are in development.

RevDate: 2019-08-01

Yang Z, Bu C, Yuan W, et al (2019)

Fecal Microbiota Transplant via Endoscopic Delivering Through Small Intestine and Colon: No Difference for Crohn's Disease.

Digestive diseases and sciences pii:10.1007/s10620-019-05751-y [Epub ahead of print].

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disorder associated with intestinal dysbiosis. This study aimed to determine the efficacy and safety of different methods of fecal microbiota transplantation (FMT), a potential therapy for CD.

METHODS: Patients with CD were randomized to receive FMT by gastroscopy or colonoscopy; a second transplantation was performed 1 week later. Patients were assessed by clinical evaluation and serum testing (at weeks 1, 2, 4, 6, and 8) and endoscopy (8 weeks after transplantation). Fecal DNA was extracted and analyzed using the Illuminal sequencing platform.

RESULTS: Of the 27 patients included in the study, clinical remission was achieved in 18 (66.7%); no significant difference was seen between the two methods. 76.9% of gastroscopy group patients and 64.3% of colonoscopy group patients experienced mild adverse events during or shortly after treatment. Microbiota diversity analyses showed that, in comparison with the donors, patients had lower operational taxonomic units (OTU; 117 vs. 258, p < 0.05) and Shannon diversity index (2.05 vs. 3.46, p < 0.05). The CD patients showed a significant increase in OTU and Shannon diversity index 2 weeks after FMT. In comparison with the donors, CD patients had lower levels of Bacteroides, Eubacterium, faecalibacterium, and Roseburia, and higher levels of Clostridium, Cronobacter, Fusobacterium, and Streptococcus.

CONCLUSIONS: FMT was seen to be safe and effective in this cohort of patients with CD. No significant differences in clinical remission rate and adverse events were seen between the gastroscopy and colonoscopy groups. FMT was seen to increase the species richness in CD patients.

RevDate: 2019-08-04

Liu MT, Huang YJ, Zhang TY, et al (2019)

Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota.

World journal of gastroenterology, 25(27):3590-3606.

BACKGROUND: Obesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.

AIM: To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.

METHODS: We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.

RESULTS: We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 ± 1.02 vs 40.53 ± 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.

CONCLUSION: Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.

RevDate: 2019-08-06

Woodworth MH, Hayden MK, Young VB, et al (2019)

The Role of Fecal Microbiota Transplantation in Reducing Intestinal Colonization With Antibiotic-Resistant Organisms: The Current Landscape and Future Directions.

Open forum infectious diseases, 6(7):.

The intestinal tract is a recognized reservoir of antibiotic-resistant organisms (ARO), and a potential target for strategies to reduce ARO colonization. Microbiome therapies such as fecal microbiota transplantation (FMT) have been established as an effective treatment for recurrent Clostridioides difficile infection and may be an effective approach for reducing intestinal ARO colonization. In this article, we review the current published literature on the role of FMT for eradication of intestinal ARO colonization, review the potential benefit and limitations of the use of FMT in this setting, and outline a research agenda for the future study of FMT for intestinal ARO colonization.

RevDate: 2019-08-06

Wang X, Tsai T, Deng F, et al (2019)

Longitudinal investigation of the swine gut microbiome from birth to market reveals stage and growth performance associated bacteria.

Microbiome, 7(1):109 pii:10.1186/s40168-019-0721-7.

BACKGROUND: Despite recent advances in the understanding of the swine gut microbiome at different growth stages, a comprehensive longitudinal study of the lifetime (birth to market) dynamics of the swine gut microbiome is lacking.

RESULTS: To fill in this gap of knowledge, we repeatedly collected a total of 273 rectal swabs from 18 pigs during lactation (day (d) 0, 11, 20), nursery (d 27, 33, 41, 50, 61), growing (d 76, 90, 104, 116), and finishing (d 130, 146, 159, 174) stages. DNA was extracted and subjected to sequencing with an Illumina Miseq sequencer targeting the V4 region of the 16S rRNA gene. Sequences were analyzed with the Deblur algorithm in the QIIME2 package. A total of 19 phyla were detected in the lifetime pig gut microbiome with Firmicutes and Bacteroidetes being the most abundant. Alpha diversity including community richness (e.g., number of observed features) and diversity (e.g., Shannon index) showed an overall increasing trend. Distinct shifts in microbiome structure along different growth stages were observed. LEfSe analysis revealed 91 bacterial features that are stage-specific. To validate these discoveries, we performed fecal microbiota transplantation (FMT) by inoculating weanling pigs with mature fecal microbiota from a growing stage pig. Similar stage-specific patterns in microbiome diversity and structures were also observed in both the FMT pigs and their littermates. Although FMT remarkably increased growth performance, it did not change the overall swine gut microbiome. Only a few taxa including those associated with Streptococcus and Clostridiaceae were enriched in the FMT pigs. These data, together with several other lines of evidence, indicate potential roles these taxa play in promoting animal growth performance. Diet, especially crude fiber from corn, was a major factor shaping the swine gut microbiome. The priority effect, i.e., the order and timing of species arrival, was more evident in the solid feed stages.

CONCLUSIONS: The distinct stage-associated swine gut microbiome may be determined by the differences in diet and/or gut physiology at different growth stages. Our study provides insight into mechanisms governing gut microbiome succession and also underscores the importance of optimizing stage-specific probiotics aimed at improving animal health and production.

RevDate: 2019-08-07

Haber SL, Raney CRK, Larson TL, et al (2019)

Fecal microbiota transplantation for recurrent Clostridioides difficile infection.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 76(13):935-942.

PURPOSE: Randomized controlled trials investigating the efficacy and safety of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) are reviewed, and practical issues for pharmacists to consider are discussed.

SUMMARY: Eight randomized controlled trials evaluating the use of FMT for recurrent CDI were analyzed. The trials varied in the type of sample (fresh, frozen, lyophilized), route of administration (nasogastric tube, colonoscopy, enema, oral), and comparator agent (different type of FMT, vancomycin). Efficacy rates ranged from 43.8% to 96.2% with FMT, and safety data were relatively similar. With these favorable data, pharmacists are likely to be involved at multiple steps in the delivery of FMT to patients with recurrent CDI, including the procurement, documentation, and administration of various products and patient education.

CONCLUSION: FMT is an option for recurrent CDI that is supported by findings of randomized controlled trials, although a preferred method for the delivery remains to be defined. Pharmacists can play an important role in the successful management of patients with recurrent CDI who may benefit from FMT.

RevDate: 2019-07-30

Oksi J, Aalto A, Säilä P, et al (2019)

Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-019-03630-y [Epub ahead of print].

Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.

RevDate: 2019-08-02

Nowak A, Hedenstierna M, Ursing J, et al (2019)

Efficacy of Routine Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection: A Retrospective Cohort Study.

International journal of microbiology, 2019:7395127.

Background: Patients with recurrent Clostridium difficile infections (CDIs) constitute an increasing treatment problem. Fecal microbiota transplantation (FMT) has shown promising results of treating recurrent CDI, where treatment with antibiotics fails repeatedly. Our study describes retrospective cohort treated with FMT at two major hospitals in Stockholm.

Methods: Medical records of all patients with recurrent CDI treated with FMT during the period 2013-2017 were reviewed. We evaluated cure of CDI-related diarrhea without relapse 10 weeks after FMT.

Results: 47 patients were included. One treatment cured 25 patients (53%), and more than one treatment cured 32 patients (68%). Treatment outcome did not vary significantly with treatment with fresh donor feces or frozen fecal culture, days of use of antibiotics or days of hospitalization prior to CDI, and renal function or time from the first CDI to therapy. Treatment failure was associated with a significantly lower Karnofsky performance status score (70 points vs 90, p=0.02).

Conclusion: Fecal instillation, for the treatment of relapsing CDI, is a promising approach, with 68% success rate reported in this study. The success rate of FMT is high, regardless of multiple comorbidities, extended use of antibiotics, or long time hospitalization. Although generally FMT is performed with fresh donor feces, our data show that the usage of frozen fecal culture could be an effective treatment alternative in recurrent CDI.

RevDate: 2019-08-02

Metzler-Zebeli BU, Siegerstetter SC, Magowan E, et al (2019)

Fecal Microbiota Transplant From Highly Feed Efficient Donors Affects Cecal Physiology and Microbiota in Low- and High-Feed Efficient Chickens.

Frontiers in microbiology, 10:1576.

Fecal microbiota transplants (FMT) may be used to improve chicken's feed efficiency (FE) via modulation of the intestinal microbiota and microbe-host signaling. This study investigated the effect of the administration of FMT from highly feed efficient donors early in life on the jejunal and cecal microbiota, visceral organ size, intestinal morphology, permeability, and expression of genes for nutrient transporters, barrier function and innate immune response in chickens of diverging residual feed intake (RFI; a metric for FE). Chicks (n = 110) were inoculated with the FMT or control transplant (CT) on 1, 6, and 9 days posthatch (dph), from which 56 chickens were selected on 30 dph as the extremes in RFI, resulting in 15 low and 13 high RFI chickens receiving the FMT and 14 low and 14 high RFI chickens receiving the CT. RFI rank and FMT only caused tendencies for alterations in the jejunal microbiota and only one unclassified Lachnospiraceae genus in cecal digesta was indicative of high RFI. By contrast, the FMT caused clear differences in the short-chain fatty acid (SCFA) profile in the crop and cecal microbiota composition compared to the CT, which indicated alterations in amylolytic, pullulanolytic and hemicellulolytic bacteria such as Lactobacillus, Dorea, and Ruminococcus. Moreover, the FMT caused alterations in intestinal development as indicated by the longer duodenum and shallower crypts in the ceca. From the observed RFI-associated variation, energy-saving mechanisms and moderation of the mucosal immune response were indicated by higher jejunal permeability, shorter villi in the ileum, and enhanced cecal expression of the anti-inflammatory cytokine IL10 in low RFI chickens. Relationships obtained from supervised multigroup data integration support that certain bacteria, including Ruminococcocaceae-, Lactobacillus-, and unclassified Clostridiales-phylotypes, and SCFA in jejunal and cecal digesta modulated expression levels of cytokines, tight-junction protein OCLN and nutrient transporters for glucose and SCFA uptake. In conclusion, results suggest that the intestine only played a moderate role for the RFI-associated variation of the present low and high RFI phenotypes, whereas modulating the early microbial colonization resulted in long-lasting changes in bacterial taxonomic and metabolite composition as well as in host intestinal development.

RevDate: 2019-08-06

Dey P (2019)

Gut microbiota in phytopharmacology: A comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions.

Pharmacological research, 147:104367 pii:S1043-6618(19)30813-8 [Epub ahead of print].

The dynamic and delicate interactions amongst intestinal microbiota, metabolome and metabolism dictates human health and disease. In recent years, our understanding of gut microbial regulation of intestinal immunometabolic and redox homeostasis have evolved mainly out of in vivo studies associated with high-fat feeding induced metabolic diseases. Techniques utilizing fecal transplantation and germ-free mice have been instrumental in reproducibly demonstrating how the gut microbiota affects disease pathogenesis. However, the pillars of modern drug discovery i.e. evidence-based pharmacological studies critically lack focus on intestinal microflora. This is primarily due to targeted in vitro molecular-approaches at cellular-level that largely overlook the etiology of disease pathogenesis from the physiological perspective. Thus, this review aims to provide a comprehensive understanding of the key notions of intestinal microbiota and dysbiosis, and highlight the microbiota-phytochemical bidirectional interactions that affects bioavailability and bioactivity of parent phytochemicals and their metabolites. Potentially by focusing on the three major aspects of gut microbiota i.e. microbial abundance, diversity, and functions, I will discuss phytochemical-microbiota reciprocal interactions, biotransformation of phytochemicals and plant-derived drugs, and pre-clinical and clinical efficacies of herbal medicine on dysbiosis. Additionally, in relation to phytochemical pharmacology, I will briefly discuss the role of dietary-patterns associated with changes in microbial profiles and review pharmacological study models considering possible microbial effects. This review therefore, emphasize on the timely and critically needed evidence-based phytochemical studies focusing on gut microbiota and will provide newer insights for future pre-clinical and clinical phytopharmacological interventions.

RevDate: 2019-07-25

Lagier JC, Million M, D Raoult (2019)

Bouillabaisse or Fish soup: The Limitations of Meta-Analysis confronted to the Inconsistency of Fecal Microbiota Transplantation Studies.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:5538643 [Epub ahead of print].

RevDate: 2019-07-24

Turki AT, Bayraktar E, Basu O, et al (2019)

Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract.

Annals of hematology pii:10.1007/s00277-019-03754-3 [Epub ahead of print].

Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.

RevDate: 2019-08-07

Staley C, Kaiser T, Vaughn BP, et al (2019)

Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat Clostridium difficile Infection.

mBio, 10(4): pii:mBio.01586-19.

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

RevDate: 2019-07-25

Lu HF, Ren ZG, Li A, et al (2019)

Fecal Microbiome Data Distinguish Liver Recipients With Normal and Abnormal Liver Function From Healthy Controls.

Frontiers in microbiology, 10:1518.

Emerging evidence suggests that altered intestinal microbiota plays an important role in the pathogenesis of many liver diseases, mainly by promoting inflammation via the "intestinal microbiota-immunity-liver" axis. We aimed to investigate the fecal microbiome of liver recipients with abnormal/normal liver function using 16S rRNA gene sequencing. Fecal samples were collected from 90 liver recipients [42 with abnormal liver function (Group LT_A) and 48 with normal liver function (Group LT_N)] and 61 age- and gender-matched healthy controls (HCs). Fecal microbiomes were analyzed for comparative composition, diversity, and richness of microbial communities. Principal coordinates analysis successfully distinguished the fecal microbiomes of recipients in Group LT_A from healthy subjects, with the significant decrease of fecal microbiome diversity in recipients in Group LT_A. Other than a higher relative abundance of opportunistic pathogens such as Klebsiella and Escherichia/Shigella in all liver recipients, the main difference in gut microbiome composition between liver recipients and HC was the lower relative abundance of beneficial butyrate-producing bacteria in the recipients. Importantly, we established a fecal microbiome index (specific alterations in Staphylococcus and Prevotella) that could be used to distinguish Group LT_A from Group LT_N, with an area under the receiver operating characteristic curve value of 0.801 and sensitivity and specificity values of 0.771 and 0.786, respectively. These findings revealed unique gut microbial characteristics of liver recipients with abnormal and normal liver functions, and identified fecal microbial risk indicators of abnormal liver function in liver recipients.

RevDate: 2019-07-23

Qi X, Yun C, Sun L, et al (2019)

Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome.

Nature medicine pii:10.1038/s41591-019-0509-0 [Epub ahead of print].

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

RevDate: 2019-07-23

Bárcena C, Valdés-Mas R, Mayoral P, et al (2019)

Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice.

Nature medicine pii:10.1038/s41591-019-0504-5 [Epub ahead of print].

The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways1,2. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer3-6, but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.

RevDate: 2019-08-02

Dutta SK, Verma S, Jain V, et al (2019)

Parkinson's Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation.

Journal of neurogastroenterology and motility, 25(3):363-376.

The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread "prion like" via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.

RevDate: 2019-07-25

Kelly MS, Ward DV, Severyn CJ, et al (2019)

Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplant Recipients.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation pii:S1083-8791(19)30451-3 [Epub ahead of print].

INTRODUCTION: The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients.

METHODS: Within a prospective cohort study of children (<18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains.

RESULTS: Median age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n=5), Enterococcus faecium (n=2), Enterobacter cloacae (n=1), and Rothia mucilaginosa (n=1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median (range) of 17 (6-21) days. Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for beta-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains.

CONCLUSIONS: Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota prior to BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely to be necessary to effectively predict BSI in HSCT recipients.

RevDate: 2019-07-23

Gutin L, Piceno Y, Fadrosh D, et al (2019)

Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile.

United European gastroenterology journal, 7(6):807-814.

Background: Emerging trials suggest fecal microbiota transplantation (FMT) is a promising treatment for ulcerative colitis; however, there is a paucity of data in Crohn disease (CD).

Objective: The objectives of this article are to determine whether single-dose FMT improves clinical and endoscopic outcomes in CD patients and to identify meaningful changes in the microbiome in response to FMT.

Methods: We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT.

Results: Three of 10 patients responded to FMT. Two of 10 patients had significant adverse events requiring escalation of therapy. On microbiome analysis, bacterial communities of responders had increased relative abundance of bacteria commonly found in donor gut microbiota.

Conclusions: Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population.Clinicaltrials.gov number: NCT02460705.

RevDate: 2019-07-23

Lin DM, HC Lin (2019)

A theoretical model of temperate phages as mediators of gut microbiome dysbiosis.

F1000Research, 8:.

Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor's gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.

RevDate: 2019-07-18

Shin JH, Chaplin AS, Hays RA, et al (2019)

Outcomes of a Multidisciplinary Clinic in Evaluating Recurrent Clostridioides difficile Infection Patients for Fecal Microbiota Transplant: A Retrospective Cohort Analysis.

Journal of clinical medicine, 8(7): pii:jcm8071036.

Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infections (rCDIs). We assessed the benefits of a multidisciplinary C. difficile clinic for screening FMT eligibility in patients with rCDI. Patients seen at the University of Virginia Complicated C. difficile Clinic (CCDC) underwent comprehensive evaluation for possible FMT. Patients were eligible for FMT if there was history of greater than two episodes of rCDI. Patients were evaluated for the outcome after evaluation in the clinic. A total of 113 patients were evaluated: 77 were eligible for FMT, of which 25 patients did not undergo FMT. The rate of recurrence at three months and all-cause mortality were 4.5% and 7% for patients who received FMT and 16.7% and 12.5% for eligible patients who did not receive FMT. There were 36 patients who were not eligible for FMT, with two or fewer recurrences and a recurrence rate of 8.8% and all-cause mortality of 6%. One in three patients screened for FMT had a nutritional deficiency diagnosed, with zinc deficiency being most common (20%). Additional diagnoses, including inflammatory bowel disease, were made during the evaluation. FMT is a highly effective treatment for rCDI, most notably in patients with multiple recurrences. A systematic approach for evaluating patients with rCDI helps identify patients who benefit most from FMT and those who have other conditions.

RevDate: 2019-07-25

Catho G, BD Huttner (2019)

Strategies for the eradication of extended-spectrum beta-lactamase or carbapenemase-producing Enterobacteriaceae intestinal carriage.

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

Introduction: Among the multidrug resistant pathogens, extended-spectrum beta-lactamase (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE) are currently considered the main threat due to the scarcity of therapeutic options and their rapid spread around the globe. In addition to developing new antibiotics and stopping transmission, recent research has focused on 'decolonization' strategies to eradicate the carriage of ESBL-E/CPE before infection occurs. Areas covered: In this narrative review, we aim to describe the current evidence of decolonization strategies for ESBL-E or CPE intestinal carriage. We first define decolonization and highlight the issues related to the lack of standardized definitions, then we summarize the available data on the natural history of colonization. Finally, we review the strategies assessed over the past 10 years for ESBL and CPE decolonization: oral antibiotics, probiotics and more recently fecal microbiota transplantation. We conclude by presenting the risks and uncertainties associated with these strategies. Expert opinion: The evidence available today is too low to recommend decolonization strategies for ESBL-E or CPE in routine clinical practice. The potential increase of resistance and the impact of microbiome manipulation should not be underestimated. Some of these decolonization strategies may nevertheless be effective, at least in temporarily suppressing colonization, which could be useful for specific populations such as high-risk patients. Effectiveness and long-term effects must be properly assessed through well-designed randomized controlled trials.

RevDate: 2019-08-04

Lo GH (2019)

The Transplantation of Fecal Microbiota for Cirrhotic Patients.

RevDate: 2019-08-06

Chen X, Li HY, Hu XM, et al (2019)

Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure.

Chinese medical journal, 132(15):1843-1855.

OBJECTIVE: The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed.

DATA SOURCES: This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: "gut microbiota," "heart failure," "trimethylamine N-oxide (TMAO)," "short-chain fatty acid (SCFA)," "bile acid," "uremic toxin," "treatment," "diet," "probiotic," "prebiotic," "antibiotic," and "fecal microbiota transplantation."

RESULTS: Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure.

CONCLUSIONS: The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.

RevDate: 2019-08-06

Allegretti JR, Z Kassam (2019)

Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: The Next Steps in This Promising Story.

The American journal of gastroenterology, 114(8):1354-1355.

RevDate: 2019-07-29
CmpDate: 2019-07-29

Sun L, Li J, Lan LL, et al (2019)

The effect of fecal microbiota transplantation on Hepatic myelopathy: A case report.

Medicine, 98(28):e16430.

RATIONALE: Hepatic myelopathy (HM), also known as portal-systemic myelopathy, is a rare neurological complication that occurs in patients with chronic liver disease. There is no easy and feasible treatment, liver transplantation is the only accepted therapy that may be effective for patients at early stage at present. The pathogenesis of the disease is not clear yet, and the prognosis is poor. Here we describe a reversible HM after fecal microbiota transplantation.

PATIENT CONCERNS: In this report, a middle-aged female patient with hepatitis B cirrhosis, occurred HM after transjugular intrahepatic portosystemic shunt, a progressive spastic paraparesis in both legs were the main symptoms.

DIAGNOSIS: The patient was diagnosed with HM.

INTERVENTIONS: The patient received 3 times of fecal microbiota transplantations (FMT).

OUTCOMES: The patient's muscle strength of both legs were increased at various degrees, the patient's condition improved from HM2 to HM1.

LESSONS: FMT may be another effective way to treat HM. It is cheaper, more operable, and simpler than the approved treatment and worthy of further research.

RevDate: 2019-07-17

Borody TJ, A Clancy (2019)

Fecal microbiota transplantation for ulcerative colitis-where to from here?.

Translational gastroenterology and hepatology, 4:48 pii:tgh-04-2019.06.04.

RevDate: 2019-07-14

Selvig D, Piceno Y, Terdiman J, et al (2019)

Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.

Digestive diseases and sciences pii:10.1007/s10620-019-05715-2 [Epub ahead of print].

AIMS: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis.

METHODS: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4 weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing.

RESULTS: Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25 BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance.

CONCLUSIONS: A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.

RevDate: 2019-07-13

Allegretti JR, Kassam Z, Mullish BH, et al (2019)

Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(19)30739-6 [Epub ahead of print].

BACKGROUND & AIMS: Studies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.

METHODS: We performed a double-blind study of 22 obese patients (body mass index [BMI] ≥ 35kg/m2) without a diagnosis of diabetes, non-alcoholic steatohepatitis, or metabolic syndrome. Participants were randomly assigned (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single, lean donor (BMI, 17.5 kg/m2). Patients were followed through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8 and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were change in area under the curve for GLP1 at week 12.

RESULTS: We observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P<.05), compared with baseline; bile acid profiles began to more closely resemble those of the donor. We did not observe significant changes in mean BMI at week 12 in either group.

CONCLUSIONS: In a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabolically uncompromised patients. The FMT capsules were well tolerated and led to sustained changes in the intestinal microbiome and bile acid profiles that were similar to those of the lean donor.

RevDate: 2019-07-14

Campion D, Giovo I, Ponzo P, et al (2019)

Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis.

World journal of hepatology, 11(6):489-512.

Hepatic encephalopathy (HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis. Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.

RevDate: 2019-07-14

Ni J, Huang R, Zhou H, et al (2019)

Analysis of the Relationship Between the Degree of Dysbiosis in Gut Microbiota and Prognosis at Different Stages of Primary Hepatocellular Carcinoma.

Frontiers in microbiology, 10:1458.

Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (Ddys); and we investigated Ddys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The Ddys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the Ddys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.

RevDate: 2019-07-24

Liu T, Song X, Khan S, et al (2019)

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing.

International journal of cancer [Epub ahead of print].

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

RevDate: 2019-07-13

Pianko MJ, Devlin SM, Littmann ER, et al (2019)

Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition.

Blood advances, 3(13):2040-2044.

Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+ Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry-based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD- patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD- and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.

RevDate: 2019-07-17

Tian Y, Zhou Y, Huang S, et al (2019)

Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study.

BMC gastroenterology, 19(1):116 pii:10.1186/s12876-019-1010-4.

BACKGROUND: Fecal microbiota transplantation may contribute to disease remission in ulcerative colitis; however, the factors that determine the effects of treatment remain unknown. The aim of the present study was to prospectively investigate the clinical efficacy of fecal microbiota transplantation in patients with ulcerative colitis and identify the bacterial signatures associated with clinical remission.

METHODS: A total of 20 patients with ulcerative colitis were included in this prospective and uncontrolled study. All patients underwent gastroscopy five times, once every 3 weeks. Clinical indices were used to assess the efficacy of fecal microbiota transplantation, as well as the Mayo score, a score used to evaluate the extent of intestinal mucosal lesions in patients with ulcerative colitis. The changes in intestinal flora were detected by 16S ribosomal RNA-sequencing, and the relationship between ulcerative colitis and intestinal flora was analyzed.

RESULTS: After treatment, clinical index scores for diarrhea, abdominal pain, and blood stool decreased significantly (p < 0.05). Erythrocyte sedimentation rate and C-reactive protein levels had not changed significantly; however, the clinical index score for intestinal mucosal lesions and the Mayo score decreased significantly. In addition, 16S ribosomal RNA-sequencing revealed that the intestinal flora in patients diagnosed with ulcerative colitis was different from that of donors.

CONCLUSION: Fecal microbiota transplantation has a potential therapeutic value for the treatment of ulcerative colitis as it changes the abundance of bacterial flora and improves the scores for diarrhea, abdominal pain, and mucous membrane lesions in patients with this disease.

TRIAL REGISTRATION: The clinical trial was retrospectively registered with ClinicalTrials.gov (NCT03016780) on January 11th, 2017.

RevDate: 2019-07-03

Bradley KC, Finsterbusch K, Schnepf D, et al (2019)

Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection.

Cell reports, 28(1):245-256.e4.

Type I interferon (IFNα/β) pathways are fine-tuned to elicit antiviral protection while minimizing immunopathology; however, the initiating stimuli, target tissues, and underlying mechanisms are unclear. Using models of physiological and dysregulated IFNα/β receptor (IFNAR1) surface expression, we show here that IFNAR1-dependent signals set the steady-state IFN signature in both hematopoietic and stromal cells. Increased IFNAR1 levels promote a lung environment refractory to early influenza virus replication by elevating the baseline interferon signature. Commensal microbiota drive the IFN signature specifically in lung stroma, as shown by antibiotic treatment and fecal transplantation. Bone marrow chimera experiments identify lung stromal cells as crucially important for early antiviral immunity and stroma-immune cell interaction for late antiviral resistance. We propose that the microbiota-driven interferon signature in lung epithelia impedes early virus replication and that IFNAR1 surface levels fine-tune this signature. Our findings highlight the interplay between bacterial and viral exposure, with important implications for antibiotic use.

RevDate: 2019-07-03

Martel B, G Saint-Lorant (2019)

[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices].

Annales pharmaceutiques francaises pii:S0003-4509(19)30038-0 [Epub ahead of print].

OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation.

MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant.

RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another.

CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.

RevDate: 2019-07-02

Morjaria S, Schluter J, Taylor BP, et al (2019)

Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation.

Infection and immunity pii:IAI.00206-19 [Epub ahead of print].

Background: Dramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. In this study, we demonstrate these dynamic changes at high-resolution through daily stool sampling and assess the impact of individual antibiotics on those changes.Methods: We collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multi-parallel 16S rRNA gene sequencing, as well as density of bacteria in stool by qPCR. We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics.Results: The greatest shifts in microbiota composition occurred between stem cell infusion and reconstitution of healthy immune cells. Piperacillin-tazobactam caused the most severe declines among obligate anaerobes.Conclusions: Our approach of daily sampling, bacterial density determination and dynamic systems modeling allowed us to infer the independent effects of specific antibiotics on the microbiota of HCT patients.

RevDate: 2019-07-23
CmpDate: 2019-07-22

Huang H, Xu H, Luo Q, et al (2019)

Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report.

Medicine, 98(26):e16163.

RATIONALE: Fecal microbiota transplantation (FMT) is recognized as an emerging treatment through reconstruction of gut microbiota. Parkinson's disease is a neurodegenerative disorder, which is accompanied by constipation. Here we first reported a patient with Parkinson's disease and constipation that were obviously relieved after FMT.

PATIENT CONCERNS: A 71-year-old male patient presented with 7 years of resting tremor, bradykinesia (first inflicted the upper limbs and subsequently spread to lower limbs), and intractable constipation (defecation needing more than 30 minutes).

DIAGNOSES: Parkinson's disease for 7 years; constipation >3 years.

INTERVENTIONS: The patient had used madopar, pramipexole, and amantadine for anti-Parkinson and showed partially mitigation while laxative therapy for constipation failed. Finally FMT was performed.

OUTCOMES: The patient successfully defecated within 5 minutes and maintained daily unobstructed defecation until the end of follow-up. The patient's tremor in legs almost disappeared at 1 week after FMT but recurred in the right lower extremity at 2 months after FMT.

LESSONS: Gut microbiota reconstruction may have therapeutic effects for Parkinson's disease patients, especially those who have gastrointestinal symptoms and limited treatment choices.

RevDate: 2019-07-03

Leshem A, Horesh N, E Elinav (2019)

Fecal Microbial Transplantation and Its Potential Application in Cardiometabolic Syndrome.

Frontiers in immunology, 10:1341.

Newly revealed links between inflammation, obesity, and cardiometabolic syndrome have created opportunities to try previously unexplored therapeutic modalities in these common and life-risking disorders. One potential modulator of these complex disorders is the gut microbiome, which was described in recent years to be altered in patients suffering from features of cardiometabolic syndrome and to transmit cardiometabolic phenotypes upon transfer into germ-free mice. As a result, there is great interest in developing new modalities targeting the altered commensal bacteria as a means of treatment for cardiometabolic syndrome. Fecal microbiota transplantation (FMT) is one such modality in which a disease-associated microbiome is replaced by a healthy microbiome configuration. So far clinical use of FMT has been overwhelmingly successful in recurrent Clostridium difficile infection and is being extensively studied in other microbiome-associated pathologies such as cardiometabolic syndrome. This review will focus on the rationale, promises and challenges in FMT utilization in human disease. In particular, it will overview the role of the gut microbiota in cardiometabolic syndrome and the rationale, experience, and prospects of utilizing FMT treatment as a potential preventive and curative treatment of metabolic human disease.

RevDate: 2019-08-02

Otrompke J (2019)

Digestive Disease Week 2019.

P & T : a peer-reviewed journal for formulary management, 44(7):428-429.

We review selected sessions on the questionable benefits of fecal microbiota transplant; intrahepatic cholestasis of pregnancy; weight-loss drugs in combination with intragastric balloon endoscopy; and beta blockers in pancreatic cancer.

RevDate: 2019-07-25

Kelly CR, Fischer M, Grinspan A, et al (2019)

Patients Eligible for Trials of Microbe-Based Therapeutics Do Not Represent the Population With Recurrent Clostridioides difficile Infection.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(19)30725-6 [Epub ahead of print].

BACKGROUND & AIMS: Although there are many industry-funded trials of microbe-based therapeutics for Clostridioides (formerly Clostridium) difficile infection (CDI), not all patients are eligible for these trials, due to their strict enrollment criteria. Furthermore, given the widespread availability of fecal microbiota transplantation (FMT) and overwhelming evidence to support its efficacy, patients might refuse enrollment in trials with a placebo group. We analyzed willingness and eligibility of patients with recurrent CDI to participate in randomized controlled trials of microbe-based therapeutic agents.

METHODS: We performed a retrospective study of 199 patients referred to 4 tertiary referral centers for treatment of CDI from August 1, 2018 through January 31, 2019. We collected data on eligibility for FMT and enrollment in randomized controlled trials.

RESULTS: Of 130 patients deemed appropriate for FMT, 98 patients (75%) were ineligible for participation in a randomized controlled trial and 16 patients (17%) were eligible but refused to enroll. Immune compromise and inflammatory bowel diseases were the most common reasons for exclusion from trials.

CONCLUSIONS: Most patients with CDI who meet the guideline criteria for FMT are ineligible or unwilling to participate in randomized controlled trials of microbe-based therapeutics. Trial populations therefore do not represent the population of patients with CDI.

RevDate: 2019-08-03

Aron-Wisnewsky J, Clément K, M Nieuwdorp (2019)

Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?.

Current diabetes reports, 19(8):51 pii:10.1007/s11892-019-1180-z.

PURPOSE OF REVIEW: The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans.

RECENT FINDINGS: Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context. FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation.

RevDate: 2019-06-28

Wang G, Huang S, Wang Y, et al (2019)

Bridging intestinal immunity and gut microbiota by metabolites.

Cellular and molecular life sciences : CMLS pii:10.1007/s00018-019-03190-6 [Epub ahead of print].

The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota or by the metabolism of dietary components. Here, we review the interplay between the host immune system and the microbiota, how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several major innate and adaptive immune cells involved in modulating host immune homeostasis.

RevDate: 2019-06-30

Chong PP, Chin VK, Looi CY, et al (2019)

The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy.

Frontiers in microbiology, 10:1136.

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

RevDate: 2019-06-26

Jørgensen SMD, Hvas CL, Dahlerup JF, et al (2019)

Banking feces: a new frontier for public blood banks?.

Transfusion [Epub ahead of print].

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection and is potentially beneficial in other microbiota-related disorders. The provision of FMT in routine clinical practice requires an extensive infrastructure that is reliant on voluntary donors. Alongside an increasing demand for FMT, the logistic barriers of a large-scale donor-dependent operation and the difficulties among health authorities to regulate FMT limit the dissemination of sustainable FMT services. Blood centers are large organizations that handle a multitude of donor-dependent operations on a daily basis. Blood and feces share many of the same dependencies, and feces may present a new opportunity for the blood services to handle. In this paper, we describe how an FMT service may be established and embedded within the blood service infrastructure, and we explain the benefits of using blood donors as feces donors. We further explore the current indications of FMT, the challenges related to the lack of legislation, and the future perspectives for blood banks to meet a new and increasing demand.

RevDate: 2019-06-28

Xu Z, Liu T, Zhou Q, et al (2019)

Roles of Chinese Medicine and Gut Microbiota in Chronic Constipation.

Evidence-based complementary and alternative medicine : eCAM, 2019:9372563.

Chronic constipation is a common gastrointestinal dysfunction, but its aetiology and pathogenesis are still unclear. Interestingly, the compositions of the gut microbiota in constipation patients and healthy controls are different. Various studies reported the different gut microbiota alterations in constipation patients, but most studies indicated that constipation patients showed the decreased beneficial bacteria and the reduced species richness of gut bacteria. Besides, the alterations in the gut microbiota may lead to constipation and constipation-related symptoms and the regulation of gut microbiota has a positive effect on gut functional diseases such as constipation. Microbial treatment methods, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can be used to regulate gut microbiota. Increasing evidences have suggested that Chinese medicine (CM) has a good therapeutic effect on chronic constipation. Chinese medicine is well known for its multitarget and multimode effects on diseases as well as less side effects. In previous studies, after the treatment of constipation with CM, the gut microbiota was restored, indicating that the gut microbiota might be the target or important way for CM to exert its efficacy. In this review, we summarized the effects of microbial treatment and CM on the gut microbiota of constipation patients and discussed the relationship between CM and gut microbiota.

RevDate: 2019-06-28

Singh T, Bedi P, Bumrah K, et al (2019)

Updates in Treatment of Recurrent Clostridium difficile Infection.

Journal of clinical medicine research, 11(7):465-471.

Recurrent Clostridium difficile infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.

RevDate: 2019-06-24

Qi X, Zhang Y, Guo H, et al (2019)

Mechanism and intervention measures of iron side effects on the intestine.

Critical reviews in food science and nutrition [Epub ahead of print].

Excess oral iron in the intestinal tract usually produces reactive oxygen species via Fenton and Haber-Weiss reaction, so oxidative stress is triggered. Lipid peroxidation procedurally appears, ferroptosis, apoptosis and necrosis are often induced, subsequently, mitochondrial damage, endoplasmic reticulum dysfunction and even cell death occur. As a result, the intestinal epithelial cells are destroyed, leading to the incompleteness of intestinal mechanical barrier. Simultaneously, iron supplement can change the compositions and metabolic processes of intestinal microbes, and the intestinal inflammatory may be worsened. In principle, the easier dissociation of Fe2+ from oral iron supplements is, the more serious intestinal inflammation will occur. Fortunately, some interventions have been developed to alleviate these side effects. For instance, some antioxidants e.g. VE and ferulic acid have been used to prevent the formation of free radicals or to neutralize the formed free radicals. Furthermore, some new iron supplements with the ability of slow-releasing Fe2+, e.g. ferrous citrate liposome and EDTA iron sodium, have been successfully prepared. In order to recover the intestinal micro-ecological balance, probiotics and prebiotics, bacterial consortium transplantation, and fecal microbiota transplantation have been developed. This study is meaningful for us to develop safer oral iron supplements and to maintain intestinal micro-ecological health.

RevDate: 2019-06-27

Kellermayer R (2019)

Fecal microbiota transplantation: great potential with many challenges.

Translational gastroenterology and hepatology, 4:40 pii:tgh-04-2019.05.10.

In January of 2019, Samuel P. Costello and colleagues published a wonderfully executed, double blind placebo-controlled trial on fecal microbiota transplantation (FMT) versus autologous stool as placebo in mild to moderately active adult ulcerative colitis [UC: one type of inflammatory bowel disease (IBD)] patients. This review-commentary examines the current state of knowledge on human gut microbiome (live microbiota + their products and surrounding environment, i.e., fecal matter) and microbial therapeutics from a gastrointestinal (GI) clinician's standpoint. The varied forms of dysbiosis as the target of FMT, recipient donor and placebo considerations are also discussed in respect to randomized control trials in IBD [and the lack thereof in Crohn's disease (CD)] with this unconventional treatment modality.

RevDate: 2019-06-28

Burz SD, Abraham AL, Fonseca F, et al (2019)

A Guide for Ex Vivo Handling and Storage of Stool Samples Intended for Fecal Microbiota Transplantation.

Scientific reports, 9(1):8897 pii:10.1038/s41598-019-45173-4.

Owing to the growing recognition of the gut microbiota as a main partner of human health, we are expecting that the number of indications for fecal microbiota transplantation (FMT) will increase. Thus, there is an urgent need for standardization of the entire process of fecal transplant production. This study provides a complete standardized procedure to prepare and store live and ready-to-use transplants that meet the standard requirements of good practices to applied use in pharmaceutical industry. We show that, if time before transformation to transplants would exceed 24 hours, fresh samples should not be exposed to temperatures above 20 °C, and refrigeration at 4 °C can be a safe solution. Oxygen-free atmosphere was not necessary and simply removing air above collected samples was sufficient to preserve viability. Transplants prepared in maltodextrin-trehalose solutions, stored in a -80 °C standard freezer and then rapidly thawed at 37 °C, retained the best revivification potential as proven by 16S rRNA profiles, metabolomic fingerprints, and flow cytometry assays over a 3-month observation period. Maltodextrin-trehalose containing cryoprotectants were also efficient in preserving viability of lyophilized transplants, either in their crude or purified form, an option that can be attractive for fecal transplant biobanking and oral formulation.

RevDate: 2019-07-09
CmpDate: 2019-07-09

Frisbee AL, Saleh MM, Young MK, et al (2019)

IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection.

Nature communications, 10(1):2712 pii:10.1038/s41467-019-10733-9.

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.

RevDate: 2019-07-30

D'Haens GR, C Jobin (2019)

Fecal Microbial Transplantation for Diseases Beyond Recurrent Clostridium Difficile Infection.

Gastroenterology pii:S0016-5085(19)41017-2 [Epub ahead of print].

As microbiome research has moved from associative to mechanistic studies, the activities of specific microbes and their products have been investigated in the development of inflammatory bowel diseases, cancer, metabolic syndrome, and neuropsychiatric disorders. Findings from microbiome research have already been applied to the clinic, such as in fecal microbiota transplantation for treatment of recurrent Clostridium difficile infection. We review the evidence for associations between alterations in the intestinal microbiome and gastrointestinal diseases and findings from clinical trials of fecal microbiota transplantation. We discuss opportunities for treatment of other diseases with fecal microbiota transplantation, based on findings from small clinical and preclinical studies.

RevDate: 2019-07-31

Jagessar SAR, Long C, Cui B, et al (2019)

Improvement of Good's syndrome by fecal microbiota transplantation: the first case report.

The Journal of international medical research, 47(7):3408-3415.

RevDate: 2019-07-25

Foligné B, Plé C, Titécat M, et al (2019)

Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights.

Cells, 8(6): pii:cells8060577.

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn's disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn's disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.

RevDate: 2019-06-18

Reisinger EC, Ebbers M, M Löbermann (2019)

[Clostridium Difficile: Monoclonal Antibody Therapy and Vaccines].

Deutsche medizinische Wochenschrift (1946), 144(12):842-849.

Hospital-acquired Clostridium difficile infections have become much more frequent in recent years. Besides treatment with antibiotics and fecal microbiota transplant, new preventive strategies are available now. Bezlotoxumab is an antibody against toxin B and may reduce the risk of relapse by roughly 10 %. Several vaccine candidates against toxins A and B and surface-associated antigens were immunogenic and are tested in clinical trials to investigate the efficacy and safety.

RevDate: 2019-06-18

Kalinkovich A, G Livshits (2019)

A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies.

Seminars in arthritis and rheumatism pii:S0049-0172(19)30170-2 [Epub ahead of print].

BACKGROUND: Emerging evidence suggests that dysbiosis, imbalanced gut microbial community, might be a key player in the development of various diseases, including inflammatory arthropathies, such as rheumatoid arthritis, spondyloarthritis (mainly, ankylosing spondylitis and psoriatic arthritis), and osteoarthritis. Yet, the underlying mechanisms and corresponding interactions remain poorly understood.

METHODS: We conducted a critical and extensive literature review to explore the association between dysbiosis and the development of inflammatory arthropathies. We also reviewed the literature to assess the perspectives that ameliorate inflammatory arthropathies by manipulating the microbiota with probiotics, prebiotics or fecal microbiota transplantation.

RESULTS: Some bacterial species (e.g. Prevotella, Citrobacter rodentium, Collinsella aerofaciens, Segmented filamentous bacteria) participate in the creation of the pro-inflammatory immune status, presumably via epitope mimicry, modification of self-antigens, enhanced cell apoptosis mechanisms, and destruction of tight junction proteins and intestinal barrier integrity, all leading to the development and maintainance of inflammatory arthropathies. Whether dysbiosis is an epiphenomenon or is an active driver of these disorders remains unclear, yet, recent observations clearly suggest that dysbiosis precedes and triggers their development implying a causative relationship between dysbiosis and inflammatory arthropathies. The underlying mechanisms include dysbiosis-mediated changes in the functional activity of the intestinal immune cell subsets, such as innate lymphoid cells, mucosa-associated invariant T cells, invariant natural killer T cells, T-follicular helper and T-regulatory cells. In turn, disturbed functionality of the gut-associated immune system is shown to promote the overgrowth of many bacteria, thus establishing a detrimental vicious circle of actively maintaining arthritis.

CONCLUSIONS: Analysis of the data described in the review supports the notion that a close, dynamic and tightly regulated cross talk between dysbiosis and the gut-associated immune system governs the development of inflammatory arthropathies.

RevDate: 2019-08-06

Ahamed R, Philips CA, P Augustine (2019)

Fecal Microbiota Transplantation for Primary Sclerosing Cholangitis-A Beautiful but Incomplete Story.

The American journal of gastroenterology, 114(8):1353-1354.

RevDate: 2019-07-03

Khoruts A, LJ Brandt (2019)

Fecal Microbiota Transplant: A Rose by Any Other Name.

The American journal of gastroenterology, 114(7):1176.

RevDate: 2019-06-19

Wang B, Zhang L, Zhu SW, et al (2019)

Short chain fatty acids contribute to gut microbiota-induced promotion of colonic melatonin receptor expression.

Journal of biological regulators and homeostatic agents, 33(3):763-771.

RevDate: 2019-07-09

Smirnova DV, Zalomova LV, Zagainova AV, et al (2019)

Cryopreservation of the human gut microbiota: Current state and perspectives.

International journal of medical microbiology : IJMM, 309(5):259-269.

The human intestinal microbiota is a complex ecosystem that consists of thousands of bacterial species that are responsible for human health and disease. The intestinal microbiota is a natural resource for production of therapeutic and preventive medicals, such as probiotics and fecal transplants. Modern lifestyles have resulted in the extinction of evolutionally selected microbial populations upon exposure to environmental factors. Therefore, it is very important to preserve the human gut microbiota to have the opportunity for timely restoration with minimal safety risks. Cryopreservation techniques that are suitable for the preservation of viable, mixed microbial communities and a biobanking approach are currently under development in different countries. However, the number of studies in this area is very limited. The variety of morphological and physiological characteristics of microbes in the microbiota, the different cryopreservation goals, and the criteria for the evaluation of cryopreservation effectiveness are the main challenges in the creation of a universal and standardized cryopreservation protocol. In this review, we summarized the current progress of the main cryopreservation techniques for gut microbiota communities and the methods for the assessment of the effectiveness of these techniques in the context of practical application.

RevDate: 2019-06-15

Baron SA, Cassir N, Mékidèche T, et al (2019)

Successful treatment and digestive decolonization of a patient with osteitis caused by a Carbapenemase-producing Klebsiella pneumoniae isolate harboring both NDM-1 and OXA-48 enzymes.

Journal of global antimicrobial resistance pii:S2213-7165(19)30144-4 [Epub ahead of print].

OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae (CRKP) is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. Here we reported the case of a patient from Romania hospitalized in Bulgaria after an accident trauma that came in France for the treatment of an osteitis caused by a K. pneumoniae carrying both blaNDM-1 and blaOXA-48.

METHOD: The resistome of this extremely-drug-resistant bacterium was analyzed both with phenotypic (large antibiotic susceptibility testing) and genomic method (genome sequencing). The genetic environment of the two carbapenemases was studied.

RESULTS: K. pneumoniae ST307 carrying both a blaNDM-1 gene and a blaOXA-48 gene located on two different plasmids, an Inc L/M and an IncFII. Patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI 2 times/day), intravenous fosfomycin (4 g 3 times/day) and oral doxycycline (100 mg 2 times/day) for 3 months. Fecal microbiota transplantation was successfully conducted for a stool carriage.

CONCLUSION: The ST307 type is becoming endemic in hospital environment and is frequently associated with carbapenem resistance. Treatment of infection caused by multi-drug resistant bacteria are a clinical challenge and the use of old antibiotics associated with a screening and decolonization of the reservoirs can be an efficient therapeutic alternative.

RevDate: 2019-07-16

Wortelboer K, Nieuwdorp M, H Herrema (2019)

Fecal microbiota transplantation beyond Clostridioides difficile infections.

EBioMedicine, 44:716-729.

The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.

RevDate: 2019-06-14

Wang JW, Wang YK, Zhang F, et al (2019)

Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series.

The Kaohsiung journal of medical sciences [Epub ahead of print].

Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well-tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.

RevDate: 2019-06-13

Na SY, W Moon (2019)

Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.

Gut and liver pii:gnl19019 [Epub ahead of print].

New therapeutic strategies in inflammatory bowel disease (IBD) have shifted from symptom control towards treat-totarget algorithms in order to optimize treatment results. The treatment of IBD has evolved with the development of tumor necrosis factor-α inhibitors beyond the conventional therapies. In spite of their long-term effectiveness, many patients do not respond to or cannot sustain treatment with these drugs, which have various side effects. Therefore, the development of new drugs targeting specific pathways in the pathogenesis of IBD has become necessary. Some novel biologics and small molecule drugs have shown potential in IBD clinical trials, providing safe and effective results. In addition, clinicians are now trying to target the dysbiotic microbiome of patients with IBD using fecal microbiota transplantation. New tools such as stem cells have also been developed. The available therapeutic options for IBD are expanding rapidly. In the next few years, physicians will face an unprecedented number of options when choosing the best treatments for patients with IBD. This review provides an overview of recent advances in IBD treatment options.

RevDate: 2019-06-16

Ilan Y (2019)

Why targeting the microbiome is not so successful: can randomness overcome the adaptation that occurs following gut manipulation?.

Clinical and experimental gastroenterology, 12:209-217 pii:203823.

The microbiome is explored as a potential target for therapy of bowel and systemic diseases. Fecal microbiota transplantation (FMT) has demonstrated efficacy in Clostridium difficile infection. However, clinical results regarding other diseases are modest, despite the abundant research on the microbiome over the last decade. Both high rate variability of the microbiome and adaptation to gut manipulations may underlie the lack of ultimate effects of FMT, probiotics, prebiotics, synbiotics, and antibiotics, which are aimed at restoring a healthier microbiome. The present review discusses the inherent variability of the microbiome and multiple factors that affect its diversity, as possible causes of the adaptation of the gut microbiome to chronic manipulation. The potential use of randomness is proposed, as a means of overcoming the adaptation and of restoring some of the inherent variability, with the goal of improving the long-term efficacy of these therapies.

RevDate: 2019-06-13

Mazzawi T, Hausken T, Hov JR, et al (2019)

Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.

Scandinavian journal of gastroenterology [Epub ahead of print].

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.

RevDate: 2019-06-19
CmpDate: 2019-06-19

Costello SP, Conlon MA, JM Andrews (2019)

Fecal Microbiota Transplantation for Ulcerative Colitis-Reply.

JAMA, 321(22):2240-2241.

RevDate: 2019-06-19
CmpDate: 2019-06-19

Benech N, Kapel N, H Sokol (2019)

Fecal Microbiota Transplantation for Ulcerative Colitis.

JAMA, 321(22):2240.

RevDate: 2019-06-13

Smibert O, Satlin MJ, Nellore A, et al (2019)

Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles.

Current infectious disease reports, 21(7):26 pii:10.1007/s11908-019-0679-4.

PURPOSE OF REVIEW: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles.

RECENT FINDINGS: CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future. As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.

RevDate: 2019-06-12

Lam WC, Zhao C, Ma WJ, et al (2019)

The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis.

Gastroenterology research and practice, 2019:1287493.

Background and Purpose: Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation.

Methods: We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses.

Key Results: A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P < 0.001; I2 = 0%) and clinical response (OR, 2.75 [1.33, 5.67]; P = 0.006; I2 = 49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P = 0.37; I2 = 69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P = 0.44; I2 = 0%).

Conclusions and Inferences: Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.

RevDate: 2019-06-11

Lui RN, Wong SH, Lau LHS, et al (2019)

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

Hong Kong medical journal = Xianggang yi xue za zhi, 25(3):178-182.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong.

METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected.

RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported.

CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

RevDate: 2019-06-11

Borody TJ, Eslick GD, RL Clancy (2019)

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer.

Current opinion in pharmacology, 49:43-51 pii:S1471-4892(19)30022-0 [Epub ahead of print].

Fecal microbiota transplantation (FMT) represents the most effective means of therapeutically manipulating the gastrointestinal microbiome. Originally employed as a treatment of last-resort in patients with life-threatening Clostridioides difficile infection (CDI), FMT gained widespread acceptance during the CDI epidemic, where it achieved resolution rates approaching 100%. Following our newfound appreciation for the role of the gut microbiome in both health and disease and owing to FMT's unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. We review the role of FMT from its beginnings in CDI to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer.

RevDate: 2019-06-10

Herfarth H, Barnes EL, Long MD, et al (2019)

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment.

Inflammatory intestinal diseases, 4(1):1-6.

Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP.

Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene.

Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response.

Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.

RevDate: 2019-06-16

Martínez N, Hidalgo-Cantabrana C, Delgado S, et al (2019)

Filling the gap between collection, transport and storage of the human gut microbiota.

Scientific reports, 9(1):8327 pii:10.1038/s41598-019-44888-8.

Stool collection devices minimizing the exposure of gut bacteria to oxygen are critical for the standardization of further microbiota-based studies, analysis and developments. The aim of this work was to evidence that keeping anaerobiosis has a deep impact on the viability and diversity of the fecal microbiota that is recovered in the laboratory. Recovering certain microbial populations, such as obligate anaerobic bacteria, is particularly critical if the purpose of the study is to envisage personalized therapeutic purposes, such as autologous Fecal Microbiota Transplant. In this study the same fecal specimens were sampled in conventional stool containers and GutAlive, a disposable device that minimizes exposure of the gut microbiota to oxygen. Samples from five healthy donors were analysed and 150 differential colonies were recovered and identified by 16S rRNA gene sequencing. Globally, GutAlive maintained extremely oxygen sensitive (EOS) populations that were lost in conventional stool containers, and thus viability of species such as as Akkermansia muciniphila, Faecalibacterium prausnitzii and a novel member of the Clostridiales order was kept. These obligate anaerobes were not recovered using the conventional stool collection device. In conclusion, the use of GutAlive for stool collection and transport optimized the viability and recovery of EOS bacteria in the lab by diminishing oxygen toxicity.

RevDate: 2019-06-06

Gurram B, PK Sue (2019)

Fecal microbiota transplantation in children: current concepts.

Current opinion in pediatrics [Epub ahead of print].

PURPOSE OF REVIEW: Administration of fecal material into the gastrointestinal tract, termed fecal microbiota transplantation (FMT), is increasingly recognized as an effective treatment option for recurrent Clostridium difficile infection (RCDI). The impact of FMT on host microbial communities and subsequent disease states has also been explored in recent years for conditions as varied as inflammatory bowel disease especially ulcerative colitis, metabolic diseases, such as diabetes, graft-versus-host disease in hematopoietic stem cell transplant recipients, and autism and autism spectrum disorders. The purpose of this article is to review the evidence for FMT as a treatment option in various pediatric illnesses.

RECENT FINDINGS: The rate of C. difficile infection is rising among children, and is associated with significant morbidity and disease, with recurrence in up to 20% of pediatric patients. Several randomized controlled trials evaluating the utility of FMT in RCDI in comparison to vancomycin have been published and demonstrate high rates of efficacy between 70 and 100%. In addition, the safety of FMT in the treatment of RCDI has been well described in the adult population, with several pediatric case series demonstrating similar rates of tolerability and adverse events. FMT in ulcerative colitis appears promising, especially with multiple infusions administered via the lower gastrointestinal tract. However, there are several limitations, including the lack of uniformity of protocols used, source of FMT, route of administration and the lack of standardization of concomitant therapies. The data on usage of FMT for other indications are preliminary and limited.

SUMMARY: FMT is recognized as an effective treatment option for RCDI and is increasing sought by parents. Although limited, pediatric studies to date on the use of FMT for RCDI demonstrate similar efficacy rates as in the adult population. FMT has been proposed as a treatment option for an increasing number of pediatric conditions, and additional studies are needed to delineate the efficacy of FMT outside of RCDI, as well as its short and long-term impacts on human health.

RevDate: 2019-06-05

Lee CH, Chai J, Hammond K, et al (2019)

Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-019-03602-2 [Epub ahead of print].

Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered "much better" in 17 patients (73.9%); "somewhat better" in 3 patients (13.0%); and "about the same" in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48-96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported "much better" overall health following FMT.

RevDate: 2019-06-19
CmpDate: 2019-06-17

Stebegg M, Silva-Cayetano A, Innocentin S, et al (2019)

Heterochronic faecal transplantation boosts gut germinal centres in aged mice.

Nature communications, 10(1):2443 pii:10.1038/s41467-019-10430-7.

Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer's patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Yin GF, Li B, XM Fan (2019)

[Effects and mechanism of fecal transplantation on acute lung injury induced by lipopolysaccharide in rats].

Zhonghua yi xue za zhi, 99(20):1582-1587.

Objective: To investigate the effect of fecal microbiota transplantation (FMT) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its regulatory mechanism. Methods: Fifteen rats were divided into control group, LPS group and LPS+FMT group by random number table method. LPS group and LPS+FMT group were intraperitoneally injected with LPS to generate rat ALI model. After 24 h of modeling, feces (10 ml/kg) were given to the LPS+FMT group twice a day, and the control group and LPS group were given the same amount of normal saline. The intervention lasted for 2 days. After 24 h of the last fecal microbiota transplantation, arterial blood gas analysis was performed in each group. Then rats were sacrificed and enzyme-linked immunosorbent (ELISA) method was used to detect intercellular adhesion molecule 1 (ICAM-1) content in the serum and bronchoalveolar lavage fluid (BALF). The lung wet-dry weight ratio (W/D) was evaluated; HE staining and lung tissue pathology scoring, immunohistochemical detection of nuclear factor-kappa B (NF-κB) predominate nuclear expression and expression of ICAM-1 of alveolar epithelial cells were conducted; Western blot was used to detect the expression of proteins related to the intracellular phosphatidylinositol kinase (PI3K)/protein kinase (AKT) signaling pathway. Samples of rat feces were collected and DNA was extracted. Polymerase chain reaction (PCR) products of the V3 and V4 regions of the 16S ribosomal RNA gene (16SrDNA) were sequenced at high throughput, and bioinformatics analysis was conducted on the microbial community based on the operational classification unit. Results: The lung W/D and lung histopathological score of the LPS group were significantly higher than those of the control group, while the arterial partial oxygen pressure (PaO(2)) of the LPS group was significantly lower than that of the control group [(79.2±5.89 vs 95.2±2.77) mmHg, 1 mmHg=0.133 kPa](all P<0.05). The results of intestinal flora sequencing revealed that the diversity index of LPS group was significantly higher than that of the control group, while the lactobacillus of LPS group rats was significantly lower than that of the control group. The content of ICAM-1 in serum, BALF and its relative expression on the cell membrane in the LPS group was significantly higher than that in the control group [(8.64±0.87) vs (7.40±0.32) ng/L; (0.941±0.035) vs (0.739±0.079) ng/L; (0.250±0.010) vs (0.076±0.010)] (all P<0.05). Moreover, the relative expression levels of phosphorylated P65 (p-P65), p-PI3K and p-AKT nucleoprotein in the LPS group were significantly higher than those in the control group (4.89±0.27 vs 3.28±0.13, 0.265±0.030 vs 0.036±0.013 and 0.444±0.040 vs 0.109±0.016) (all P<0.05). The above injury effect was reduced after fecal fungus transplantation. The lung W/D and lung pathological score of LPS+FMT group were significantly lower than those of LPS group, and PaO(2) of LPS+FMT group was significantly higher than that of LPS group [(88.0±3.53) mmHg]. The results of intestinal flora sequencing revealed that the diversity index of LPS+FMT group was significantly lower than that of LPS group, and the lactobacillus genus of LPS+FMT group was significantly higher than that of LPS group. ICAM-1 in the blood serum ((7.44±0.46) ng/L), BALF (0.834±0.040) ng/L) and its relative expression on alveolar epithelial cell membrane (0.173±0.030), the relative expression of p-P65, p-PI3K and p-AKT protein of NF-κB in alveolar epithelial cells was down-regulated ((2.99±0.28, 0.090±0.013 and 0.206±0.018) in LPS+FMT group than those of LPS group, the differences were statistically significant (all P<0.05). Conclusion: Fecal transplantation can alleviate lipopolysaccharide-induced acute lung injury in rats, and its regulatory effect may be related to inhibiting the activation of PI3K/AKT/NF-κB signaling pathway and reducing the expression of inflammatory factor ICAM-1.


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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E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

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

Research Gate page for R J Robbins

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

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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