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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 15 Sep 2019 at 01:37 Created: 

Fecal Transplantation

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

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

Citations The Papers (from PubMed®)

RevDate: 2019-09-14

McCormack UM, Curião T, Metzler-Zebeli BU, et al (2019)

Seeking to improve feed efficiency in pigs through microbial modulation via fecal microbiota transplantation in sows and dietary supplementation of offspring with inulin.

Applied and environmental microbiology pii:AEM.01255-19 [Epub ahead of print].

As previous studies have demonstrated a link between the porcine intestinal microbiome and feed efficiency (FE), microbiota manipulation may offer a means of improving FE in pigs. A fecal microbiota transplantation procedure (FMTp), using fecal extracts from highly feed efficient pigs, was performed in pregnant sows (n=11), with a control group (n=11) receiving no FMTp. At weaning, offspring were allocated, within sow treatment, to 1) control (n=67; no dietary supplement) or 2) inulin (n=65; 6-week dietary inulin supplementation) treatments. The sow FMTp, alone or in combination with offspring inulin supplementation, reduced offspring body weight by 8.1-10.6 Kg at ∼140 days of age, but there was no effect on feed intake. It resulted in better FE, higher bacterial diversity and higher relative abundances of potentially beneficial bacterial taxa (Fibrobacter, Prevotella) in offspring. Due to FMTp and/or inulin supplementation, relative abundance of potential pathogens (Chlamydia, Treponema) in the ileum, and cecal concentrations of butyric acid were significantly lower. Maternal FMTp led to a greater number of jejunal goblet cells in offspring. Inulin supplementation alone did not affect growth or FE, but up-regulated duodenal genes linked to glucose and volatile fatty acid homeostasis and increased mean platelet volume, but reduced ileal propionic acid, granulocyte counts, and serum urea. Overall, FMTp in pregnant sows, with/without offspring dietary inulin supplementation, beneficially modulated offspring intestinal microbiota (albeit mostly low relative abundance taxa) and associated physiological parameters. Although FE was improved, the detrimental effect on growth limits the application of this FMTp/inulin strategy in commercial pig production.IMPORTANCE As previous research suggests a link between microbiota and FE, modulation of the intestinal microbiome may be effective in improving FE in pigs. The FMTp in gestating sows, alone/in combination with offspring post-weaning dietary inulin supplementation, achieved improvements in FE, and resulted in higher relative abundance of intestinal bacteria associated with fiber degradation, and lower relative abundance of potential pathogens. However, there was a detrimental effect on growth, although this may not be wholly attributable to microbiota transplantation, as antibiotic and other interventions were also part of the FMT regime. Therefore, further work with additional control groups is needed to disentangle the effects of each component of the FMTp in order to develop a regime with practical applications in pig production. Additional research based on findings from this study may also identify specific dietary supplements for promotion/maintenance of the microbiota transferred via maternal FMTp, thereby optimizing pig growth and FE.

RevDate: 2019-09-13

Zhao W, Hu Y, Li C, et al (2019)

Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse.

BioFactors (Oxford, England) [Epub ahead of print].

Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC ε may be the underlying mechanism.

RevDate: 2019-09-13

Wu X, Dai M, Buch H, et al (2019)

The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study.

Therapeutic advances in gastroenterology, 12:1756284819869144 pii:10.1177_1756284819869144.

Background: Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it.

Methods: A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed.

Results: A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p = 0.000 and 56.80% vs. 41.45%, p = 0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT.

Conclusions: This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.

RevDate: 2019-09-12

Schepici G, Silvestro S, Bramanti P, et al (2019)

The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials.

Cell transplantation [Epub ahead of print].

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing-remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.

RevDate: 2019-09-12

Prochazkova P, Roubalova R, Dvorak J, et al (2019)

Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation.

Microorganisms, 7(9): pii:microorganisms7090338.

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

RevDate: 2019-09-12
CmpDate: 2019-09-12

Enck P, N Mazurak (2019)

[Microbiota and irritable bowel syndrome: A critical inventory].

Zeitschrift fur Gastroenterologie, 57(7):859-870.

This narrative review critically explores the role of the gut microbiota in functional bowel disorders of IBS-type. Starting with changes in the microbiota composition and diversity, as they have been often found in correlative IBS studies, it raises the question of cause and consequence, of sensitivity and specificity of findings in comparison to other diseases, and of the scientific and clinical options to manipulate the microbiota. This includes a discussion of pre- and probiotics and antibiotics as well as the role of nutrition and the microbiota exchange with fecal microbiota transfer (FMT). For IBS, most of these strategies have not been found to be successful therapies. This may be due to the heterogeneity of the disease itself, but eventually also due to the concepts of microbiological research, e. g., the term dysbiosis, or in methodological differences of the molecular-genetic research that are not visible in the published papers. Future studies should aim to identify those factors that may explain and predict the response to such therapies.

RevDate: 2019-09-12
CmpDate: 2019-09-12

Mullish BH, Quraishi MN, Segal JP, et al (2018)

Introduction to the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) faecal microbiota transplant guidelines.

The Journal of hospital infection, 100(2):130-132.

RevDate: 2019-09-10

Lee H, Kim J, An J, et al (2019)

Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation.

Immune network, 19(4):e28 pii:2019190406.

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.

RevDate: 2019-09-09

Philips CA, Augustine P, Yerol PK, et al (2019)

Severe alcoholic hepatitis: current perspectives.

Hepatic medicine : evidence and research, 11:97-108 pii:197933.

Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options - past, present, and future, in patients with severe alcoholic hepatitis.

RevDate: 2019-09-09

Hu Y, B Lyu (2019)

[Development and prospects of fecal microbiota transplantation].

Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 48(3):342-346.

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

Endres K, KH Schäfer (2018)

Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases.

Journal of innate immunity, 10(3):172-180.

When thinking about neurodegenerative diseases, the first symptoms that come to mind are loss of memory and learning capabilities, which all resemble hallmarks of manifestation of such diseases in the central nervous system (CNS). However, the gut comprises the largest nervous system outside the CNS that is autonomously active and in close interplay with its microbiota. Therefore, the enteric nervous system (ENS) might serve as an indicator of degenerative pathomechanisms that also affect the CNS. On the other hand, it might offer an entry point for devastating influences from the microbial community or - conversely - for therapeutic approaches via gut commensals. Within the last years, the ENS and gut microbiota therefore have sparked the interest of researchers of CNS diseases and we here report on recent findings and open questions, especially with regard to Alzheimer and Parkinson diseases.

RevDate: 2019-09-07

Madoff SE, Urquiaga M, Alonso CD, et al (2019)

Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials.

Anaerobe pii:S1075-9964(19)30158-1 [Epub ahead of print].

Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next.

RevDate: 2019-09-07

Luo Y, Lucas AL, AM Grinspan (2019)

Fecal Transplants by Colonoscopy and Capsules Are Cost-Effective Strategies for Treating Recurrent Clostridioides difficile Infection.

Digestive diseases and sciences pii:10.1007/s10620-019-05821-1 [Epub ahead of print].

BACKGROUND: Recurrent Clostridioides difficile infections (CDIs) occur frequently and pose a substantial economic burden on the US healthcare system. The landscape for the treatment of CDI is evolving.

AIM: To elucidate the most cost-effective strategy for managing recurrent CDI.

METHODS: A decision tree analysis was created from a modified third-party payer's perspective to compare the cost-effectiveness of five strategies for patients experiencing their first CDI recurrence: oral vancomycin, fidaxomicin, fecal microbiota transplant (FMT) via colonoscopy, FMT via oral capsules, and a one-time infusion of bezlotoxumab with vancomycin. Effectiveness measures were quality-adjusted life years (QALY). A willingness-to-pay (WTP) threshold of $100,000 per QALY was set. One-way and probabilistic sensitivity analyses were performed.

RESULTS: Base-case analysis showed that FMT via colonoscopy was associated with the lowest cost at $5250 and that FMT via capsules was also a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $31205/QALY. Sensitivity analyses demonstrated that FMT delivered by oral capsules and colonoscopy was comparable cost-effective modalities. At its current cost and effectiveness, bezlotoxumab was not a cost-effective strategy.

CONCLUSIONS: FMT via oral capsules and colonoscopy is both cost-effective strategies to treat the first recurrence of CDI. Further real-world economic studies are needed to understand the cost-effectiveness of all available strategies.

RevDate: 2019-09-07

Chong PP, AY Koh (2019)

The gut microbiota in transplant patients.

Blood reviews pii:S0268-960X(19)30030-X [Epub ahead of print].

Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at increased risk for developing infections due to underlying immunosuppression. Antibiotic use, and in HSCT recipients, the use of preparative regimens prior to transplantation can deplete gut commensal bacteria, resulting in intestinal dysbiosis. Emerging evidence in transplant patients, particularly HSCT, suggest that disturbances in gut microbiota populations are associated with a number of adverse outcomes. Here, we review the outcomes of HSCT and SOT recipients with gut microbiota imbalance or dysbiosis, explore the nascent field of gut microbiome therapeutic approaches including fecal microbiota transplantation and the use of precision probiotics in HSCT and SOT recipients.

RevDate: 2019-09-06

Mashaqi S, D Gozal (2019)

Obstructive Sleep Apnea and Systemic Hypertension: Gut Dysbiosis as the Mediator?.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine pii:jc-18-00726 [Epub ahead of print].

INTRODUCTION: Obstructive sleep apnea (OSA) and systemic hypertension (SH) are common and interrelated diseases. It is estimated that approximately 75% of treatment-resistant hypertension cases have an underlying OSA. Exploration of the gut microbiome is a new advance in medicine that has been linked to many comorbid illnesses, including SH and OSA. Here, we will review the literature in SH and gut dysbiosis, OSA and gut dysbiosis, and whether gut dysbiosis is common in both conditions.

METHODS: We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central. We identified a total of 230 articles. The literature search was conducted using the phrase "obstructive sleep apnea and gut dysbiosis." Only original research articles were included. This yielded a total of 12 articles.

RESULTS: Most of the research conducted in this field was on animal models, and almost all trials confirmed that intermittent hypoxia models resulted in gut dysbiosis. Gut dysbiosis, however, can cause a state of low-grade inflammation through damage to the gut wall barrier resulting in "leaky gut." Neuroinflammation is a hallmark of the pathophysiology of OSA-induced SH.

CONCLUSIONS: Gut dysbiosis seems to be an important factor in the pathophysiology of OSA-induced hypertension. Reversing gut dysbiosis at an early stage through prebiotics and probiotics and fecal microbiota transplantation combined with positive airway pressure therapy may open new horizons of treatment to prevent SH. More studies are needed in humans to elicit the effect of positive airway pressure therapy on gut dysbiosis.

RevDate: 2019-09-06
CmpDate: 2019-09-06

Sircana A, Framarin L, Leone N, et al (2018)

Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?.

Current diabetes reports, 18(10):98.

PURPOSE OF REVIEW: In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota.

RECENT FINDINGS: In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance. Different strategies that reduce dysbiosis can improve glycemic control. Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.

RevDate: 2019-09-05

Martínez JV, Raush A, Efrón ED, et al (2019)

[Refractory colitis by Clostridium difficile treated with fecal microbiota transplant].

Medicina, 79(4):291-294.

Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.

RevDate: 2019-09-04

Mishima Y, RB Sartor (2019)

Manipulating resident microbiota to enhance regulatory immune function to treat inflammatory bowel diseases.

Journal of gastroenterology pii:10.1007/s00535-019-01618-1 [Epub ahead of print].

Altered intestinal microbial composition (dysbiosis) and metabolic products activate aggressive mucosal immune responses that mediate inflammatory bowel diseases (IBD). This dysbiosis impairs the function of regulatory immune cells, which normally promote mucosal homeostasis. Normalizing and maintaining regulatory immune cell function by correcting dysbiosis provides a promising approach to treat IBD patients. However, existing microbe-targeted therapies, including antibiotics, prebiotics, probiotics, and fecal microbial transplantation, provide variable outcomes that are not optimal for current clinical application. This review discusses recent progress in understanding the dysbiosis of IBD and the basis for therapeutic restoration of homeostatic immune function by manipulating an individual patient's microbiota composition and function. We believe that identifying more precise therapeutic targets and developing appropriate rapid diagnostic tools will guide more effective and safer microbe-based induction and maintenance treatments for IBD patients that can be applied in a personalized manner.

RevDate: 2019-09-02

Monaghan TM, Pučić-Baković M, Vučković F, et al (2019)

Decreased Complexity of Serum N-glycan Structures Associates with Successful Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

Gastroenterology pii:S0016-5085(19)41259-6 [Epub ahead of print].

RevDate: 2019-08-31

Tan X, S Johnson (2019)

Fecal Microbiota Transplantation (FMT) for C. difficile Infection, just say 'No'.

Anaerobe pii:S1075-9964(19)30152-0 [Epub ahead of print].

Despite lack of regulatory approval, fecal microbiota transplantation (FMT) is widely performed to manage C. difficile infection (CDI), particularly recurrent CDI. Herein, we critically review the available randomized controlled trials of FMT and address the following questions: Is FMT better than drug management of recurrent CDI?; Is FMT treatment per se or adjunctive treatment to antibiotics for CDI?; and, Is FMT safe? Finally, we elaborate non-FMT options for the management of recurrent CDI. Although promising, FMT should be reserved for patients who have failed appropriate antibiotic management of recurrent CDI.

RevDate: 2019-08-31

Kim MS, Kim Y, Choi H, et al (2019)

Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model.

Gut pii:gutjnl-2018-317431 [Epub ahead of print].

OBJECTIVE: Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer's disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive.

DESIGN: Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.

RESULTS: Composition of the gut microbiota in ADLPAPT mice differed from that of healthy wild-type (WT) mice. Besides, ADLPAPT mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLPAPT mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLPAPT recipient mice.

CONCLUSION: These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLPAPT mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.

RevDate: 2019-08-30

Yoon YK, Suh JW, Kang EJ, et al (2019)

Efficacy and safety of fecal microbiota transplantation for decolonization of intestinal multidrug-resistant microorganism carriage: Beyond Clostridioides difficile infection.

Annals of medicine [Epub ahead of print].

Persistent reservoirs of multidrug-resistant microorganisms (MDRO) that are prevalent in hospital settings and communities can lead to the spread of MDRO. Currently, there are no effective decolonization strategies, especially non-pharmacological strategies without antibiotic regimens. Our aim was to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the eradication of MDRO. A systematic literature search was performed to identify studies on the use of FMT for the decolonization of MDRO. PubMed, EMBASE, Web of Science, and Cochrane Library were searched from inception through January 2019. Of the 1,395 articles identified, 20 studies met the inclusion and exclusion criteria. Overall, the efficacy of FMT for the eradication of each MDRO was 70.3% (102/146) in 121 patients from the 20 articles. The efficacy rates were 68.2% (30/44) for gram-positive bacteria and 70.6% (72/102) for gram-negative bacteria. Minor adverse events, including vomiting, diarrhea, abdominal pain, and ileus, were reported in patients who received FMT. FMT could be a promising strategy to eradicate MDRO in patients. Further studies are needed to confirm these findings and establish a comprehensive FMT protocol for standardized treatment. Key messages: The development of new antibiotics lags behind the emergence of multidrug-resistant microorganisms (MDRO). New strategies are needed. Theoretically, fecal microbiota transplantation (FMT) might recover the diversity and function of commensal microbiota from dysbiosis in MDRO carriers and help restore colonization resistance to pathogens. A literature review indicated that FMT could be a promising strategy to eradicate MDRO in patients.

RevDate: 2019-09-01

Zhou Y, Xu H, Huang H, et al (2019)

Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders?.

BioMed research international, 2019:3469754.

Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.

RevDate: 2019-08-29

Liu Z, Li N, Fang H, et al (2019)

Enteric dysbiosis is associated with sepsis in patients.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [Epub ahead of print].

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to microbial infection. For decades, the potential role of gut microbiota in sepsis pathogenesis has been revealed. However, the systemic and functional link between gut microbiota and sepsis has remained unexplored. To address this gap in knowledge, we carried out systematic analyses on clinical stool samples from patients with sepsis, including 16S rDNA sequencing, metabolomics, and metaproteomics analyses. In addition, we performed fecal microbiota transplantation from human to mice to validate the roles of gut microbiota on sepsis progression. We found that the composition of gut microbiota was significantly disrupted in patients with sepsis compared with healthy individuals. Besides, the microbial functions were significantly altered in septic feces as identified by metabolomics and metaproteomics analyses. Interestingly, mice that received septic feces exhibited more severe hepatic inflammation and injury than mice that received healthy feces after cecal ligation and puncture. Finally, several strains of intestinal microbiota and microbial metabolites were corelated with serum total bilirubin levels in patients with sepsis. Taken together, our data indicated that sepsis development is associated with the disruption of gut microbiota at both compositional and functional levels, and such enteric dysbiosis could promote organ inflammation and injury during sepsis.-Liu, Z., Li, N., Fang, H., Chen, X., Guo, Y., Gong, S., Niu, M., Zhou, H., Jiang, Y., Chang, P., Chen, P. Enteric dysbiosis is associated with sepsis in patients.

RevDate: 2019-09-05

Zhong S, Zeng J, Deng Z, et al (2019)

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report.

Italian journal of pediatrics, 45(1):116 pii:10.1186/s13052-019-0708-9.

BACKGROUND: Immunocompromised (IC) patients have an increased risk of refractory diarrhea. Fecal microbiota transplantation (FMT) is a safe and effective therapy for infection-related diarrhea which are mainly mediated by the loss of the microbial colonization, although there is concern that IC patients may be at higher risk of infectious complications related to FMT. And reports of FMT in IC children are limited.

CASE PRESENTATION: We describe two cases of FMT in IC children with refractory diarrhea. One IC child had polyendocrinopathy, enteropathy, X-linked syndrome and the other child had graft-versus-host disease. Both of the children had a long course of diarrhea and no response to traditional treatment. FMT was performed on both patients via nasojejunal tubes under guidance of gastroduodenoscopy. After FMT, the patients achieved remission of symptoms and neither of them had related infectious complications. Microbiota analysis showed that FMT resulted in reconstruction of a diverse microbiota.

CONCLUSIONS: Use of FMT is safe and effective in treatment of refractory diarrhea in IC children with a damaged microbiota.

RevDate: 2019-08-26

Brüssow H (2019)

Problems with the concept of gut microbiota dysbiosis.

Microbial biotechnology [Epub ahead of print].

The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.

RevDate: 2019-08-25

Hasan N, H Yang (2019)

Factors affecting the composition of the gut microbiota, and its modulation.

PeerJ, 7:e7502 pii:7502.

Gut microbiota have important functions in the body, and imbalances in the composition and diversity of those microbiota can cause several diseases. The host fosters favorable microbiota by releasing specific factors, such as microRNAs, and nonspecific factors, such as antimicrobial peptides, mucus and immunoglobulin A that encourage the growth of specific types of bacteria and inhibit the growth of others. Diet, antibiotics, and age can change gut microbiota, and many studies have shown the relationship between disorders of the microbiota and several diseases and reported some ways to modulate that balance. In this review, we highlight how the host shapes its gut microbiota via specific and nonspecific factors, how environmental and nutritional factors affect it, and how to modulate it using prebiotics, probiotics, and fecal microbiota transplantation.

RevDate: 2019-08-29

Zhang Y, Huang R, Cheng M, et al (2019)

Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2.

Microbiome, 7(1):116 pii:10.1186/s40168-019-0733-3.

BACKGROUND: Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail.

RESULTS: The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes, Proteobacteria, and Bacteroidetes. Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression.

CONCLUSIONS: Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.

RevDate: 2019-08-27

Chang CS, CY Kao (2019)

Current understanding of the gut microbiota shaping mechanisms.

Journal of biomedical science, 26(1):59 pii:10.1186/s12929-019-0554-5.

Increasing evidences have shown strong associations between gut microbiota and many human diseases, and understanding the dynamic crosstalks of host-microbe interaction in the gut has become necessary for the detection, prevention, or therapy of diseases. Many reports have showed that diet, nutrient, pharmacologic factors and many other stimuli play dominant roles in the modulation of gut microbial compositions. However, it is inappropriate to neglect the impact of host factors on shaping the gut microbiota. In this review, we highlighted the current findings of the host factors that could modulate the gut microbiota. Particularly the epithelium-associated factors, including the innate immune sensors, anti-microbial peptides, mucus barrier, secretory IgAs, epithelial microvilli, epithelial tight junctions, epithelium metabolism, oxygen barrier, and even the microRNAs are discussed in the context of the microbiota shaping. With these shaping factors, the gut epithelial cells could select the residing microbes and affect the microbial composition. This knowledge not only could provide the opportunities to better control many diseases, but may also be used for predicting the success of fecal microbiota transplantation clinically.

RevDate: 2019-08-22
CmpDate: 2019-08-22

Guery B, Galperine T, F Barbut (2019)

Clostridioides difficile: diagnosis and treatments.

BMJ (Clinical research ed.), 366:l4609.

Clostridioides difficile (formerly Clostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis of C difficile infection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treat C difficile infection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment of C difficile infection based on the most recent data available.

RevDate: 2019-09-03

Chen R, Xu Y, Wu P, et al (2019)

Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota.

Pharmacological research, 148:104403 pii:S1043-6618(19)30911-9 [Epub ahead of print].

The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.

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: 2019-09-02

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

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).

Journal of gastroenterology and hepatology [Epub ahead of print].

BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant.

METHODS: A retrospective analysis of patients with active UC (Mayo clinic score ≥ 4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed.

RESULTS: Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27 ± 1.06 h for the first session vs 5.12 ± 0.5 h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n = 2, 4.3%), arthritis/arthralgia (n = 3, 6.5%), depression (n = 1, 2.2%), partial sensorineural hearing loss (n = 1, 2.2%), and allergic bronchitis (n = 1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events.

CONCLUSION: Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.

RevDate: 2019-08-15

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: 2019-08-09

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: 2019-08-11

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: 2019-08-11

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: 2019-08-07

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: 2019-08-08

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: 2019-08-09

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: 2019-08-08

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: 2019-08-26
CmpDate: 2019-08-26

Allegretti JR, Mullish BH, Kelly C, et al (2019)

The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications.

Lancet (London, England), 394(10196):420-431.

Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation-the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients-is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications.

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: 2019-09-04

Shin JH, CA Warren (2019)

Prevention and treatment of recurrent Clostridioides difficile infection.

Current opinion in infectious diseases, 32(5):482-489.

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: 2019-08-30

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: 2019-08-08

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: 2019-08-31

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

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

Nature medicine, 25(8):1225-1233.

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: 2019-08-10

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

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

Nature medicine, 25(8):1234-1242.

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: 2019-08-12

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

Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation 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].

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. Within a prospective cohort study of children (age <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 the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient 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 of 17 days (range, 6 to 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 β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before 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 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: 2019-08-20

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: 2019-08-08

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, 17(8):557-569.

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: 2019-09-02
CmpDate: 2019-09-02

Lo GH (2019)

The Transplantation of Fecal Microbiota for Cirrhotic Patients.

Gastroenterology, 157(3):902.

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: 2019-08-16
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: 2019-09-02
CmpDate: 2019-09-02

Bajaj JS, PM Gillevet (2019)

Reply.

Gastroenterology, 157(3):902-903.

RevDate: 2019-08-11

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] ≥5 kg/m2) without a diagnosis of diabetes, nonalcoholic steatohepatitis, or metabolic syndrome. Participants were assigned randomly (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 up 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 the 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 resemble those of the donor more closely. 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. ClinicalTrials.gov number: NCT02741518.

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: 2019-08-17

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: 2019-08-16

Martel B, G Saint-Lorant (2019)

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

Annales pharmaceutiques francaises, 77(5):435-442.

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: 2019-08-31

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, 87(9): pii:IAI.00206-19.

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. We collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multiparallel 16S rRNA gene sequencing as well as the density of bacteria in stool by quantitative PCR (qPCR). We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics. 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. 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: 2019-09-04

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

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

Transfusion, 59(9):2776-2782.

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.

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ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

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Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).

Timelines

ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.

Biographies

Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )