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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 09 Apr 2020 at 01:40 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: 2020-04-08

Boem F, Nannini G, A Amedei (2020)

Not just 'immunity': how the microbiota can reshape our approach to cancer immunotherapy.

Immunotherapy [Epub ahead of print].

Cancer immunotherapy refers to a set of approaches aiming at enhancing the immune system to fight cancer growth and spread. This variety of therapeutic approaches, especially those inhibiting immune checkpoints, have shown very promising results. Nevertheless, patients may respond differently to treatments and the efficacy of immunotherapy seems to be dependent on several factors that go beyond the molecular targeting of immune cells modulation. Here, we review how the activity of gut microbiota appears to be crucial in determining the effectiveness of some immunotherapeutic treatments, fostering or impeding the conditions under which treatments can work or not. Moreover, we discuss how these findings suggest not only extending the range of immunotherapeutic approaches but also reshaping our understanding of immunotherapy itself.

RevDate: 2020-04-08

Voth E, S Khanna (2020)

Fecal microbiota transplantation for treatment of patients with recurrent Clostridioides difficile infection.

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

Introduction: Recurrent Clostridiodes difficile infection (rCDI) is a growing public health burden, and is associated with poor patient outcomes. Fecal microbiota transplantation (FMT) is a novel therapy with an aim to restore the disrupted microbiota with demonstrated success in management of rCDI and a favorable safety profile.Areas covered: This review includes a comprehensive overview of a search of the literature including epidemiology of rCDI, basics of the gut microbiome, antibiotic therapy for rCDI along with rationale for, safety and efficacy of FMT for rCDI.Expert opinion: Patients exposed to risk factors, such as antimicrobial agents, are at risk for disruption of the gut microbiome resulting in reduction of microbial diversity and dysbiosis. Dysbiotic microbiota predispose to primary and rCDI. Strategies to improve the current and future management of rCDI are under clinical investigation, including narrow spectrum antibiotics, monoclonal antibodies, and FMT, which has shown a high success rate for rCDI. Further investigation is needed to determine optimal standardization of the methodological components of FMT including donor screening, stool preparation, storage and instillation, and patient follow-up. Newer methods of microbiota replacement therapies including enema- and capsule-based therapies are under investigation.

RevDate: 2020-04-08

Vendrik KEW, Ooijevaar RE, de Jong PRC, et al (2020)

Fecal Microbiota Transplantation in Neurological Disorders.

Frontiers in cellular and infection microbiology, 10:98.

Background: Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent Clostridioides difficile infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT. In addition, we provide suggestions for future directions. Methods: In July 2019, five main databases were searched for studies and case descriptions on FMT in neurological disorders in humans or animal models. In addition, the website was consulted for registered planned and ongoing trials. Results: Of 541 identified studies, 34 were included in the analysis. Clinical trials with FMT have been performed in patients with autism spectrum disorder and showed beneficial effects on neurological symptoms. For multiple sclerosis and Parkinson's disease, several animal studies suggested a positive effect of FMT, supported by some human case reports. For epilepsy, Tourette syndrome, and diabetic neuropathy some studies suggested a beneficial effect of FMT, but evidence was restricted to case reports and limited numbers of animal studies. For stroke, Alzheimer's disease and Guillain-Barré syndrome only studies with animal models were identified. These studies suggested a potential beneficial effect of healthy donor FMT. In contrast, one study with an animal model for stroke showed increased mortality after FMT. For Guillain-Barré only one study was identified. Whether positive findings from animal studies can be confirmed in the treatment of human diseases awaits to be seen. Several trials with FMT as treatment for the above mentioned neurological disorders are planned or ongoing, as well as for amyotrophic lateral sclerosis. Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Schmidt EKA, Torres-Espin A, Raposo PJF, et al (2020)

Fecal transplant prevents gut dysbiosis and anxiety-like behaviour after spinal cord injury in rats.

PloS one, 15(1):e0226128.

Secondary manifestations of spinal cord injury beyond motor and sensory dysfunction can negatively affect a person's quality of life. Spinal cord injury is associated with an increased incidence of depression and anxiety; however, the mechanisms of this relationship are currently not well understood. Human and animal studies suggest that changes in the composition of the intestinal microbiota (dysbiosis) are associated with mood disorders. The objective of the current study is to establish a model of anxiety following a cervical contusion spinal cord injury in rats and to determine whether the microbiota play a role in the observed behavioural changes. We found that spinal cord injury caused dysbiosis and increased symptoms of anxiety-like behaviour. Treatment with a fecal transplant prevented both spinal cord injury-induced dysbiosis as well as the development of anxiety-like behaviour. These results indicate that an incomplete unilateral cervical spinal cord injury can cause affective disorders and intestinal dysbiosis, and that both can be prevented by treatment with fecal transplant therapy.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Cao Z, Wang X, Pang Y, et al (2019)

Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment.

Nature communications, 10(1):5783.

The gut microbiota represents a huge community of microorganisms that play essential roles in immune modulation and homeostasis maintenance. Microbiota transplantation is an important approach to prevent and treat disease as it can inhibit pathogen colonization and positively modulate bacterial composition. However, the development of oral bacterial therapeutics has been restricted by low bioavailability and limited retention in the gastrointestinal tract. Here, we report a simple yet highly efficient method to coat gut microbes via biointerfacial supramolecular self-assembly. Coating can be performed within 15 min by simply vortexing with biocompatible lipids. Bacteria coated with an extra self-assembled lipid membrane exhibit significantly improved survival against environmental assaults and almost unchanged viability and bioactivity. We demonstrate their enhanced efficacies in oral delivery and treatment using two murine models of colitis. We suggest that biointerfacial supramolecular self-assembly may provide a unique platform to generate advanced bacterial therapeutics for the treatment of various diseases.

RevDate: 2020-04-08
CmpDate: 2020-04-06

Ahmad AF, Dwivedi G, O'Gara F, et al (2019)

The gut microbiome and cardiovascular disease: current knowledge and clinical potential.

American journal of physiology. Heart and circulatory physiology, 317(5):H923-H938.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and, with its associated genome, is known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension, and heart failure. Although there have been advances in the characterization and analysis of the gut microbiota and associated bacterial metabolites, the exact mechanisms through which they exert their action are not well understood. This review will focus on the role of the gut microbiome and associated functional components in the development and progression of atherosclerosis. Potential treatments to alter the gut microbiome to prevent or treat atherosclerosis and CVD are also discussed.

RevDate: 2020-04-08
CmpDate: 2020-04-08

Viennois E, Gewirtz AT, B Chassaing (2019)

Chronic Inflammatory Diseases: Are We Ready for Microbiota-based Dietary Intervention?.

Cellular and molecular gastroenterology and hepatology, 8(1):61-71.

The last 15 years have witnessed the emergence of a new field of research that focuses on the roles played by the intestinal microbiota in health and disease. This research field has produced accumulating evidence indicating that dysregulation of host-microbiota interactions contributes to a range of chronic inflammatory diseases, including inflammatory bowel diseases, colorectal cancer, and metabolic syndrome. Although dysregulation of the microbiota can take complex forms, in some cases, specific bacterial species that can drive specific clinical outcomes have been identified. Among the numerous factors influencing the intestinal microbiota composition, diet is a central actor, wherein numerous dietary factors can beneficially or detrimentally impact the host/microbiota relationship. This review will highlight recent literature that has advanced understanding of microbiota-diet-disease interplay, with a central focus on the following question: Are we ready to use intestinal microbiota composition-based personalized dietary interventions to treat chronic inflammatory diseases?

RevDate: 2020-04-08
CmpDate: 2020-04-06

Morris DJ, AS Brem (2019)

Role of gut metabolism of adrenal corticosteroids and hypertension: clues gut-cleansing antibiotics give us.

Physiological genomics, 51(3):83-89.

Intestinal bacteria can metabolize sterols, bile acids, steroid hormones, dietary proteins, fiber, foodstuffs, and short chain fatty acids. The metabolic products generated by some of these intestinal bacteria have been linked to a number of systemic diseases including obesity with Type 2 diabetes mellitus, some forms of inflammation, and more recently, systemic hypertension. In this review, we primarily focus on the potential role selected gut bacteria play in metabolizing the endogenous glucocorticoids corticosterone and cortisol. Those generated steroid metabolites, when reabsorbed in the intestine back into the circulation, produce biological effects most notably as inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2. Inhibition of the dehydrogenase actions of 11β-HSD, particularly in kidney and vascular tissue, allows both corticosterone and cortisol the ability to bind to and activate mineralocorticoid receptors with attended changes in sodium handling and vascular resistance leading to increases in blood pressure. In several animal models of hypertension, administration of gut-cleansing antibiotics results in transient resolution of hypertension and transfer of intestinal contents from a hypertensive animal to a normotensive animal produces hypertension in the recipient. Moreover, fecal samples from hypertensive humans transplanted into germ-free mice resulted in hypertension in the recipient mice. Thus, it appears that the intestinal microbiome may not just be an innocent bystander but certain perturbations in the type and number of bacteria may directly or indirectly affect hypertension and other diseases.

RevDate: 2020-04-07

Chen HT, Huang HL, Xu HM, et al (2020)

Fecal microbiota transplantation ameliorates active ulcerative colitis.

Experimental and therapeutic medicine, 19(4):2650-2660.

Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

RevDate: 2020-04-07

Du HX, Liu Y, Zhang LG, et al (2020)

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis-induced depressive-like behaviors in mice.

The Prostate [Epub ahead of print].

BACKGROUND: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).

METHODS: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria.

RESULTS: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation.

CONCLUSIONS: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.

RevDate: 2020-04-07

Hughes KR, Schofield Z, Dalby MJ, et al (2020)

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding.

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

The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation.

RevDate: 2020-04-06

Pickert G, Wirtz S, Matzner J, et al (2020)

Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor-mediated Dysbiosis.

Gastroenterology pii:S0016-5085(20)30447-9 [Epub ahead of print].

BACKGROUND & AIMS: Wheat has become the world´s major staple and its consumption correlates with prevalence of non-communicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice.

METHODS: C57BL/6 wildtype and Tlr4-/- mice were fed wheat- or ATI-containing diets or a wheat-free (control) diet and then given dextran sodium sulfate to induce colitis; we also studied Il10-/- mice, which develop spontaneous colitis. Changes in fecal bacteria were assessed by taxa-specific quantitative PCR and 16S ribosomal RNA metagenomic sequencing. Feces were collected from mice on wheat-containing, ATI-containing, control diets and transplanted to intestines of mice with and without colitis on control or on ATI-containing diets. Intestinal tissues were collected and analyzed by histology, immunohistochemistry and flow cytometry. Bacteria with reported immunomodulatory effects were incubated with ATIs and analyzed in radial diffusion assays.

RESULTS: The wheat- or ATI-containing diets equally increased inflammation in intestinal tissues of C57BL/6 mice with colitis, compared with mice on control diets. The ATI-containing diet promoted expansion of taxa associated with development of colitis comparable to the wheat-containing diet. ATIs inhibited proliferation of specific human commensal bacteria in radial diffusion assays. Transplantation of microbiota from feces of mice fed the wheat- or ATI-containing diets to intestines of mice on control diets increased the severity of colitis in these mice. The ATI-containing diet did not increase the severity of colitis in Tlr4-/- mice.

CONCLUSIONS: Consumption of wheat or wheat-ATIs increases intestinal inflammation in mice with colitis, via TLR4, and alters their fecal microbiota. Wheat-based, ATI-containing diets therefore activate TLR4 signaling and promote intestinal dysbiosis.

RevDate: 2020-04-06

Mennini M, Fierro V, Di Nardo G, et al (2020)

Microbiota in non-IgE-mediated food allergy.

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

PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy.

RECENT FINDINGS: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota.

SUMMARY: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

RevDate: 2020-04-04

Weir V, KR Reddy (2020)

Nonpharmacologic Management of Hepatic Encephalopathy: An Update.

Clinics in liver disease, 24(2):243-261.

Research increasingly shows that the gut-liver-brain axis is a crucial component in the pathophysiology of hepatic encephalopathy (HE). Due to the limitations of current standard-of-care medications, non-pharmacological treatments that target gut dysbiosis, including probiotics, nutritional management, and fecal microbiota transplants, are being considered as alternative and adjunct therapies. Meta-analyses note that probiotics could offer benefits in HE treatment, but have not shown superiority over lactulose. Emerging literature suggests that fecal microbiota transplants could offer a novel strategy to treat gut dysbiosis and favorably impact HE. Finally, liver support devices and liver transplantation could offer a last-resort treatment option for persistent HE.

RevDate: 2020-04-04

Mahpour NY, Pioppo-Phelan L, Reja M, et al (2020)

Pharmacologic Management of Hepatic Encephalopathy.

Clinics in liver disease, 24(2):231-242.

Pharmacologic management of hepatic encephalopathy includes a broad range of therapies. This article covers the specific mainstays of therapies, such as antimicrobials and laxatives, with an established evidence base. This article also covers newer modalities of therapies, such as fecal microbiota transplant, probiotics, bioartificial support systems, small molecular therapies such as l-ornithine l-aspartate, branched chain amino acids, l-carnitine, zinc, and other forms of therapy currently under review.

RevDate: 2020-04-03

Kumar AR (2020)

Continuing Medical Education Questions: April 2020: Understanding the Scope of Do-It-Yourself Fecal Microbiota Transplant.

The American journal of gastroenterology, 115(4):505.

RevDate: 2020-04-03
CmpDate: 2020-04-03

Ma Y, H Chen (2019)

Faecal microbiota transplantation, a promising way to treat colorectal cancer.

EBioMedicine, 49:13-14.

RevDate: 2020-04-02

Eltokhi A, Janmaat IE, Genedi M, et al (2020)

Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders.

Journal of neuroscience research [Epub ahead of print].

The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders.

RevDate: 2020-04-02

Zhu F, Ju Y, Wang W, et al (2020)

Metagenome-wide association of gut microbiome features for schizophrenia.

Nature communications, 11(1):1612 pii:10.1038/s41467-020-15457-9.

Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

RevDate: 2020-04-02

Liu J, Miyake H, Zhu H, et al (2020)

Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis.

Journal of pediatric surgery pii:S0022-3468(20)30163-9 [Epub ahead of print].

PURPOSE: Necrotizing Enterocolitis (NEC) is a devastating neonatal disease with a high mortality rate. Fecal Microbiota Transplantation (FMT) has been used to treat a variety of gastrointestinal diseases. We aimed to investigate the role of FMT in NEC.

METHODS: NEC was induced by hypoxia, LPS, and hyperosmolar gavage feeding between postnatal days P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). FMT (30 μl/g) was administered by gavage or enema at P6 during NEC induction. Distal ileum was harvested on P9. Disease severity was evaluated by H&E staining. Gene expression of inflammatory markers IL6 and TNFa was measured. Expression of intestinal barrier function was investigated by measuring Claudin-7. Microbiota composition in ileum and colon was analyzed by quantitative PCR.

RESULTS: FMT by gavage further increased terminal ileum inflammation and did not improve the histological damage owing to experimental NEC. Conversely, FMT by enema decreased intestinal inflammation and improved histology of the NEC-like injury in the ileum. In addition, compared with NEC alone, FMT by enema increased Claudin-7 expression indicating an improvement in barrier function. These beneficial effects occurred despite no change in microbiota.

CONCLUSION: Our results show that FMT by enema may be an effective strategy to reduce NEC progression as it attenuates intestinal inflammation and enhances intestinal barrier function. FMT by enema is a potential novel treatment for NEC.

LEVEL OF EVIDENCE: Level IV, Evidence from well-designed case-control or cohort studies.

RevDate: 2020-04-01

Trang-Poisson C (2019)

[Fecal transplantation].

La Revue du praticien, 69(7):792-793.

RevDate: 2020-04-01

Barbut F, J Couturier (2019)

[Interactions between intestinal microbiota and Clostridioides difficile].

La Revue du praticien, 69(7):784-791.

Interactions between intestinal microbiota and clostridioides difficile. Clostridioides difficile is a spore-forming anaerobic Gram-positive bacillus that is responsible for diarrhea and post-antibiotic colitis. Approximately 20,000 inpatients are infected by C. difficile in France per year. This bacterium is recognized as an emerging pathogen responsible for community-acquired diarrhea. Antibiotic therapy is the main risk factor for C. difficile infection (CDI) because it leads to intestinal dysbiosis and loss of "colonization resistance". C. difficile from endogenous or exogenous origin can then establish, multiply and produce its two toxins causing enterocyte lesions and a significant inflammatory reaction. The loss of colonization resistance has been associated with the loss of microbial diversity, particularly of some taxa that play a protective role. These variations of bacterial communities lead to changes in functions that can be explored by metabolomic or metagenomic approaches. Data from these experiments led to mechanistic assumptions about resistance or susceptibility to CDI. Microbiota studies have also pushed physicians to develop therapeutic approaches based on biotherapies. These therapies aim at repopulating the colon by a healthy microbiota either by fecal microbiota transplantation or by the administration of strains and cocktails of strains to restore the colonization resistance effect.

RevDate: 2020-04-01

Hiippala K, Kainulainen V, Suutarinen M, et al (2020)

Isolation of Anti-Inflammatory and Epithelium Reinforcing Bacteroides and Parabacteroides Spp. from A Healthy Fecal Donor.

Nutrients, 12(4): pii:nu12040935.

Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate Escherichia coli lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of Bacteroides and Parabacteroides isolates, which were identified as P.distasonis, B.caccae, B. intestinalis, B.uniformis, B. fragilis, B.vulgatus and B.ovatus using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The Bacteroides strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.

RevDate: 2020-04-01

Morissette A, Kropp C, Songpadith JP, et al (2020)

Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.

American journal of physiology. Endocrinology and metabolism [Epub ahead of print].

Blueberry consumption can prevent obesity-linked metabolic diseases and it has been proposed that its polyphenol content may contribute to these effects. Polyphenols have been shown to favourably impact metabolic health, but the role of specific polyphenol classes, and whether the gut microbiota is linked to these effects remains unclear. We aimed to evaluate the impact of whole blueberry and blueberry polyphenols against the development of obesity and insulin resistance, and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Seventy C57BL/6 male mice were assigned to one of the following diets for 12 weeks: balanced diet (Chow), high-fat high-sucrose (HFHS) diet, or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT) or proanthocyanidin (PAC)-rich extracts. After 8 weeks, mice were housed in metabolic cages and an oral glucose tolerance test (oGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups bi-weekly for 8 weeks, followed by an oGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC and ANT-treated mice showed improved insulin responses during oGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity, and that at least part of these beneficial effects are explained by modulation of the gut microbiota.

RevDate: 2020-03-30
CmpDate: 2020-03-30

Kachlíková M, Sabaka P, Koščálová A, et al (2020)

Comorbid status and the faecal microbial transplantation failure in treatment of recurrent Clostridioides difficile infection - pilot prospective observational cohort study.

BMC infectious diseases, 20(1):52.

BACKGROUND: Faecal microbial transplantation (FMT) is currently the most effective treatment of recurrent Clostridioides difficile infection (CDI). However, up to 20% of patients experience further recurrences after single FMT. The mechanisms that lead to FMT failure and its risk factors are poorly understood. Comorbidity is one of the risk factors of the failure of standard antibiotic therapy of recurrent CDI. It is not known if comorbidity is also associated with the risk of FMT failure.

METHODS: We conducted a prospective observational cohort study in order to elucidate if comorbid status is associated with FMT failure. Patients with microbiologically proven recurrent CDI were recruited and underwent FMT via retention enema. Patients were followed up for 12 weeks after FMT for signs and symptoms of CDI recurrence. Single FMT failure was defined as recurrence of diarrhoea and a positive stool test for the presence of C. difficile antigen or toxin at any time point during the 12 weeks of follow-up. We assessed the association of single FMT failure with possible manageable and unmanageable risk factors. As a surrogate of comorbid status, we used Charlson Comorbidity Index (CCI) ≥ 7.

RESULTS: A total of 60 patients that underwent single FMT (34 women, 26 men) were included in the study. Overall, 15 patients (25%) experienced single FMT failure. 24 patients (40%) had CCI ≥ 7, and 45.0% patients with CCI ≥ 7 experienced failure of single FMT. Patients who experienced single FMT failure had a significantly higher CCI and significantly lower albumin concentration as compared to patients who experienced single FMT success. There was no difference in age, C-reactive protein concentration, leukocyte count and time from FMT to first defecation. In multivariate analysis, CCI ≥ 7 was positively associated with the failure of single FMT. Analysis was controlled for sex, age, time from FMT to first defecation, concomitant PPI therapy, severe CDI, hospital-acquired infection and albumin concentration.

CONCLUSIONS: Comorbid status surrogated by CCI is positively associated with the failure of single FMT in the treatment of recurrent CDI.

RevDate: 2020-03-30
CmpDate: 2020-03-30

Bo TB, Zhang XY, Wen J, et al (2019)

The microbiota-gut-brain interaction in regulating host metabolic adaptation to cold in male Brandt's voles (Lasiopodomys brandtii).

The ISME journal, 13(12):3037-3053.

Gut microbiota play a critical role in orchestrating metabolic homeostasis of the host. However, the crosstalk between host and microbial symbionts in small mammals are rarely illustrated. We used male Brandt's voles (Lasiopodomys brandtii) to test the hypothesis that gut microbiota and host neurotransmitters, such as norepinephrine (NE), interact to regulate energetics and thermogenesis during cold acclimation. We found that increases in food intake and thermogenesis were associated with increased monoamine neurotransmitters, ghrelin, short-chain fatty acids, and altered cecal microbiota during cold acclimation. Further, our pair-fed study showed that cold temperature can alter the cecal microbiota independently of overfeeding. Using cecal microbiota transplant along with β3-adrenoceptor antagonism and PKA inhibition, we confirmed that transplant of cold-acclimated microbiota increased thermogenesis through activation of cAMP-PKA-pCREB signaling. In addition, NE manipulation induced a long-term alteration in gut microbiota structure. These data demonstrate that gut microbiota-NE crosstalk via cAMP signaling regulates energetics and thermogenesis during cold acclimation in male Brandt's voles.

RevDate: 2020-03-29

Dale HF, GA Lied (2020)

Gut microbiota and therapeutic approaches for dysbiosis in irritable bowel syndrome: Recent developments and future perspectives.

Turkish journal of medical sciences [Epub ahead of print].

Increased knowledge regarding the implications of gut microbiota in irritable bowel syndrome (IBS), suggest that a disturbed intestinal microenvironment (dysbiosis) might promote the development and maintenance of IBS symptoms and effects several pathways in the pathology of this multifactorial disease. Accordingly, manipulation of the gut microbiota in order to improve IBS symptoms has the last decade evolved as a novel treatment strategy. Several different approaches have been investigated in order to improve the gut microbiota composition. Dietary modifications including supplementation with fibers, prebiotics and probiotics are shown to improve symptoms and composition of gut microbiota in IBS, however the exact probiotic mixture beneficial for each individual remains to be identified. The use of antibiotics still needs confirmation, although promising results have been reported with use of rifaximin. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and several placebo-controlled trials investigating FMT pose promising results regarding symptom reduction and gut microbiota manipulation in IBS. However, more data regarding long-term effects is needed before FMT can be integrated as a customised treatment for IBS in the clinical routine.

RevDate: 2020-03-28

Polimeno L, Barone M, Mosca A, et al (2020)

Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions.

Microorganisms, 8(4): pii:microorganisms8040469.

BACKGROUND: Colorectal cancer (CRC) requires the presence of a variety of factors predisposing a tumorigenic milieu. Excluding familial clustering and hereditary CRC syndromes, the development of sporadic CRC from precancerous lesions is influenced by tissue inflammation, modulation of intestinal immunity, hormones, dietary habits and gut microbiota composition. As concerning the last two aspects, the intestinal presence of equol, the most biologically active metabolite of the soy isoflavone daidzein and the presence of a genetic determinant of gut microbiota able to metabolize daidzein, seem to lower the CRC risk. It has been hypothesized that the anaerobic microorganisms of the Bacteroides genus play a role in equol production.

AIM: To evaluate the presence of (i) anaerobic gut microbiota and (ii) the urinary levels of soy isoflavones (daidzein, genistein and equol) in patients with and without precancerous lesions, challenged with a daidzein-rich soy extract.

METHODS: Consecutive subjects undergoing colonoscopy participated to the study. Feces were collected from all patients one week before colonoscopy for gut microbiota studies. After the endoscopy examination and the histological evaluation, 40 subjects, 20 with sporadic colorectal adenomas (SCA/P group) and 20 without proliferative lesions (control group) were enrolled for the study. Urine levels of soy isoflavones daidzein, genistein and their metabolite equol, were determined by high performance liquid chromatographic (HPLC) analysis and gut microbiota analysis was performed by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) procedure.

RESULTS: Seventeen different bacterial species were identified in the fecal samples of the forty subjects participating to the study. Ten bacterial species resulted anaerobic Gram-negative bacteria, all belonging to the Bacteroides genus. A significant difference of bacteria species was evidenced in the fecal samples of the two groups of subjects. Particularly important was the evidence of Parabacteroidesdistasonis, Clostridiumclostridioforme and Pediococcuspentasaceus only in control fecal samples, such as the presence of Bacteroides fragilis and Prevotellamelaningenica only in SCA/P fecal samples. Concerning the soy isoflavones levels, no statistically significant differences were revealed in the genistein and daidzein urinary levels between the two groups of subjects. On the contrary, urinary equol levels were undetectable in ten SCA/P subjects and in two controls; moreover, when present, the levels of urinary equol were significantly lower in SCA/P subjects compared to controls (0.24 ± 0.27 mg/24 hrs vs. 21.25 ± 4.3 mg/24 hrs, respectively, p = 1.12 × 10-6).

CONCLUSIONS: Our results suggest that the presence of anaerobic Bacteroides in the colon, and the production of equol from soy, could determine a milieu able to contrast the development of colonic mucosa proliferative lesions.

RevDate: 2020-03-27

Kukla M, Adrych K, Dobrowolska A, et al (2020)

Guidelines for Clostridium difficile infection in adults.

Przeglad gastroenterologiczny, 15(1):1-21.

Clostridium difficile infection (CDI) has become a serious medical and epidemiological problem, especially in well developed countries. There has been evident increase in incidence and severity of CDI. Prevention, proper diagnosis and effective treatment are necessary to reduce the risk for the patients, deplete the spreading of infection and diminish the probability of recurrent infection. Antibiotics are the fundamental treatment of CDI. In patients who had recurrent CDI fecal microbiota transplantation seems to be promising and efficient strategy. These guidelines systematize existing data and include recent changes implemented in the management of CDI.

RevDate: 2020-03-24

Slomski A (2020)

"Superdonor" Fecal Microbiota Transplant Effective for IBS.

JAMA, 323(12):1124.

RevDate: 2020-03-24

Tsai MC, Liu YY, Lin CC, et al (2020)

Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan.

Nutrients, 12(3): pii:nu12030820.

The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus RuminococcaceaeUCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.

RevDate: 2020-03-23

Hui S, Liu Y, Huang L, et al (2020)

Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling.

International journal of obesity (2005) pii:10.1038/s41366-020-0566-y [Epub ahead of print].

OBJECTIVE: Current evidence has linked dietary resveratrol (RSV) intake to the activation of brown adipose tissue (BAT) and induction of white adipose tissue (WAT) browning, which may be a potential means of improving glucose homeostasis. However, the underlying mechanisms remain unclear.

METHODS: A diet containing RSV was fed to db/db mice for 10 weeks, following which the body weight, adipose tissue accumulation, bile acid (BA) profiles, and markers of BA metabolism were analyzed. Oral glucose tolerance testing, immunohistochemistry, and gut microbiota sequencing were also performed.

RESULTS: RSV intervention improved glucose homeostasis in db/db mice, which was linked to the enhanced BAT activity and WAT browning. Moreover, RSV-treated mice exhibited altered plasma and fecal BA compositions and significant remodeling of the gut microbiota, the latter confirmed by a higher level of lithocholic acid (LCA) in the plasma and feces. LCA was identified to be the agonist of Takeda G-protein coupled receptor 5 (TGR5), which mediated the BAT activation and WAT browning by upregulating uncoupling protein 1 (UCP1) expression. Furthermore, depletion of the gut microbiota using antibiotics partially abolished the beneficial effects of RSV against glucose intolerance. Finally, microbiota transplantation experiments demonstrated that the RSV-induced beneficial effects were transferable, indicating that these effects were largely dependent on the gut microbiota.

CONCLUSIONS: These data indicate that RSV administration improves glucose homeostasis by enhancing BAT activation and WAT browning, a mechanism that might partially be mediated by the gut microbiota-BA-TGR5/UCP1 pathway.

RevDate: 2020-03-23

Zybura J, Dyla A, W Mielnicki (2020)

Fecal microbiota transplantation is feasible even in critically ill patients with toxic megacolon due to Clostridium difficile infection.

Anaesthesiology intensive therapy pii:40108 [Epub ahead of print].

RevDate: 2020-03-21

Khoruts A, JS Bajaj (2020)

Intestinal microbiota transplantation: Naming a new paradigm.

RevDate: 2020-03-20

Ianiro G, Mullish BH, Kelly CR, et al (2020)

Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel.

The lancet. Gastroenterology & hepatology pii:S2468-1253(20)30082-0 [Epub ahead of print].

RevDate: 2020-03-19
CmpDate: 2020-03-19

Lleal M, Sarrabayrouse G, Willamil J, et al (2019)

A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis.

EBioMedicine, 48:630-641.

BACKGROUND: Faecal microbiota transplantation (FMT) is a novel potential therapy for inflammatory bowel diseases, but it is poorly characterised.

METHODS: We evaluated the performance of the mouse and rat as a pre-clinical model for human microbiota engraftment. We then characterised the effect of a single human stool transfer (HST) on a humanised model of DSS-induced colitis. Colonic and faecal microbial communities were analysed using the 16S rRNA approach and clinical manifestations were assessed in a longitudinal setting.

FINDINGS: The microbial community of rats showed greater similarity to that of humans, while the microbiome of mice showed less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated faecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These faecal and colonic microbial communities alterations led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by removing DSS before HST caused a faster and greater recovery of both microbiome and clinical manifestation features.

INTERPRETATION: Our results indicate that the rat outperforms the mouse as a model for human microbiota engraftment and show that the efficacy of HST can be enhanced when inflammation stimulation is withdrawn. Finally, our findings support a new therapeutic strategy based on the use FMT combined with anti-inflammatory drugs.

RevDate: 2020-03-18

Dorsaz S, Charretier Y, Girard M, et al (2020)

Changes in Microbiota Profiles After Prolonged Frozen Storage of Stool Suspensions.

Frontiers in cellular and infection microbiology, 10:77.

Introduction: Fecal microbiota transplantation (FMT) is recommended as safe and effective treatment for recurrent Clostridioides difficile infections. Freezing the FMT preparation simplifies the process, allowing a single stool sample to be used for multiple receivers and over an extended period of time. We aimed to assess the effect of long-term frozen storage on bacterial taxonomic profiles of a stool suspension prepared for FMT. Methods: DNA was extracted from a stool suspension before freezing and sequentially during the 18-month storage period at -80°C. Two different protocols were used for DNA extraction. The first relied on a classical mechanical and chemical cell disruption to extract both intra- and extracellular DNA; the second included specific pre-treatments aimed at removing free DNA and DNA from human and damaged bacterial cells. Taxonomic profiling of bacterial communities was performed by sequencing of V3-V4 16S rRNA gene amplicons. Results: Microbiota profiles obtained by whole DNA extraction procedure remained relatively stable during frozen storage. When DNA extraction procedure included specific pre-treatments, microbiota similarity between fresh and frozen samples progressively decreased with longer frozen storage times; notably, the abundance of Bacteroidetes decreased in a storage duration-dependent manner. The abundance of Firmicutes, the main butyrate producers in the colon, were not much affected by frozen storage for up to 1 year. Conclusion: Our data show that metataxonomic analysis of frozen stool suspensions subjected to specific pre-treatments prior to DNA extractions might provide an interesting indication of bacterial resistance to stress conditions and thus of chances of survival in FMT recipients.

RevDate: 2020-03-18

Liu X, Lv Q, Ren H, et al (2020)

The altered gut microbiota of high-purine-induced hyperuricemia rats and its correlation with hyperuricemia.

PeerJ, 8:e8664 pii:8664.

Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.

RevDate: 2020-03-17

Dang X, Xu M, Liu D, et al (2020)

Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis.

PloS one, 15(3):e0228846 pii:PONE-D-19-00488.

BACKGROUND: Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis.

PURPOSE: This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis.

METHODS: The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons.

RESULTS: Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles.

CONCLUSIONS: Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy.

RevDate: 2020-03-17

Ávila PRM, Michels M, Vuolo F, et al (2020)

Protective effects of fecal microbiota transplantation in sepsis are independent of the modulation of the intestinal flora.

Nutrition (Burbank, Los Angeles County, Calif.), 73:110727 pii:S0899-9007(20)30010-1 [Epub ahead of print].

OBJECTIVE: The aim of this study was to investigate the protective effects of probiotics and fecal transplantation on inflammatory and oxidative parameters in the intestines of two rat models of sepsis.

METHODS: Rats were treated with prebiotics, probiotics, or symbiotics and exposed to lipopolysaccharide (LPS) or zymosan after 15 d to induce endotoxemia. Oxidative damage and inflammation were analyzed, and histologic examination of the intestinal tissue was performed. Fecal microbiota transplantation (FMT) was carried out in LPS- and zymosan-induced rat models of sepsis.

RESULTS: Supplementation with symbiotics for 15 d effectively reduced the inflammatory parameters compared with supplementation for 7 d. Probiotics, prebiotics, and symbiotics exerted different effects on the evaluated parameters. In general, Lactobacillus rhamnosus and L. casei exerted better local protective effects. Evaluation of the role of the intestinal microbiota through FMT revealed its protective effects irrespective of the previous treatment with probiotics.

CONCLUSION: Probiotic strains significantly differ among themselves and exert different effects on the host's health. Symbiotics and FMT could offer additional immunomodulatory benefits to drug therapy, thus serving as a new therapeutic alternative in pediatric patients with sepsis.

RevDate: 2020-03-16

Chen Y, Zhang S, Zeng B, et al (2020)

Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria.

Aging, 12: pii:102872 [Epub ahead of print].

A close relationship between age and gut microbiota exists in invertebrates and vertebrates, including humans. Long-living people are a model for studying healthy aging; they also have a distinctive microbiota structure. The relationship between the microbiota of long-living people and aging phenotype remains largely unknown. Herein, the feces of long-living people were transplanted into mice, which were then examined for aging-related indices and beneficial bacteria. Mice transplanted with fecal matter from long-living people (L group) had greater α diversity, more probiotic genera (Lactobacillus and Bifidobacterium), and short-chain fatty acid producing genera (Roseburia, Faecalibacterium, Ruminococcus, Coprococcus) than the control group. L group mice also accumulated less lipofuscin and β-galactosidase and had longer intestinal villi. This study indicates the effects that the gut microbiota from long-living people have on healthy aging.

RevDate: 2020-03-14

Tamez-Torres KM, Ponce-de-Leon A, Torres-Gonzalez P, et al (2020)

High prevalence of MDR gram-negative bacteria in feces of healthy blood donors in Mexico.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-020-03858-z [Epub ahead of print].

During the initial stage of a study to recruit universal intestinal microbiota donors in Mexico City, we found multiple "healthy" subjects that colonized with MDRO (Multidrug-resistant organisms). We aimed to describe clinical and demographic characteristics of these individuals. This was a prospective observational study. Participants were consecutively recruited among blood donors. A fecal sample was collected from each subject and analyzed at the same day in search of MDRO through chromographic culture media and, if growth observed, later confirmed by MALDI-TOF and susceptibility testing in Vitek 2 system. From July 2018 to March 2019, 85 individuals were screened for fecal colonization. Median age was 35 years (IQR 27-46 years), and 48/85 (56.4%) were males. Seventy-two (84.7%) subjects harbored at least one MDRO. ESBL-producing microorganisms were found in 72/85 (84.3%) subjects, and E. coli was the most frequent (63/85, 74.1%). Four samples (2 E. coli, 2 P. aeruginosa, 2.4% each) harbored carbapenem-resistant Enterobacteriaceae (CRE), together with an ESBL-producing microorganism. Antibiotic use (p = 0.06) and PPIs or H2-blockers intake (p = 0.03) were more common in the colonized subjects during the previous 6-month period. We report a high incidence of enteric colonization of healthy subjects with MDRO, a condition that may be related to antibiotics or PPIs/H2-blockers consumption. This surprisingly high MDRO colonization rate in potential FMT donors emphasizes the need for careful screening of donors to avoid possible transmission to FMT recipients.

RevDate: 2020-03-14

Allegretti JR, Mehta SR, Kassam Z, et al (2020)

Risk Factors that Predict the Failure of Multiple Fecal Microbiota Transplantations for Clostridioides difficile Infection.

Digestive diseases and sciences pii:10.1007/s10620-020-06198-2 [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI); however, a small percentage of patients fail to achieve cure even after two FMTs. This high-risk cohort remains poorly understood.

METHODS: We performed a multicenter, multinational retrospective review of patients that underwent at least one FMT for a CDI indication at four academic FMT referrals. Patients' data including CDI, FMT, and FMT variables were assessed. The primary outcome was FMT failure after a second FMT defined as persistent diarrhea and positive laboratory test for C. difficile (PCR or toxin) despite a second FMT within 8 weeks of the first FMT. A multivariable logistic regression model was performed to determine predictors of second FMT failure.

RESULTS: A total of 540 patients received at least one FMT during the study period, of which 432 patients had success following the first FMT, 108 had documented failure (25%). Among those who failed the first FMT, 63 patients received a second FMT, of which 36 achieved cure, and 24 had documented failure after the second FMT. Patients that failed the first FMT but did not receive a second FMT and those lost to follow-up were excluded leaving 492 patients included in the analysis. The second FMT failure rate was 4.8% (24/492). Risk factors for second FMT failure identified by multivariable logistic regression included: inpatient status (OR 7.01, 95% CI: 2.37-20.78), the presence of pseudomembranes (OR 3.53, 95% CI: 1.1-11.33), and immunocompromised state (OR 3.56, 95% CI: 1.45-8.72) at the time of first FMT.

CONCLUSION: This study identifies clinically relevant risk factors predictive of failing a second FMT. Clinicians can use these variables to help identify high-risk patients and provide a better-informed consent regarding the possibility of needing multiple FMTs.

RevDate: 2020-03-14

Li Y, Su X, Gao Y, et al (2020)

The potential role of the gut microbiota in modulating renal function in experimental diabetic nephropathy murine models established in same environment.

Biochimica et biophysica acta. Molecular basis of disease pii:S0925-4439(20)30109-5 [Epub ahead of print].

Recent studies have shown that laboratory murine autoimmunity models under the same environment display different outcomes. We established diabetic nephropathy model mice under the same environment using the classic streptozotocin method. Renal dysfunction was different among the mice. Proteinuria was more significant in the severe proteinuria group (SP) than in the mild proteinuria group (MP). We hypothesized a role for the gut microbiota in the outcome and reproducibility of induced DN models. 16S rDNA gene sequencing technology was used to analyze the differences in the gut microbiota between the two groups. Here, through fecal microbiota transplantation (FMT) and gas chromatography mass spectrometry (GC-MS), we verified the role of the gut microbiota and its short-chain fatty acid (SCFA) generation in DN mouse renal dysfunction. In the SP group, there was a reduced abundance of Firmicutes (P < 0.0001), and the dominant genus Allobaculum [linear discriminant analysis (LDA) >3, P < 0.05] was positively correlated with body weight (Rho = 0.767, P < 0.01) and blood glucose content (Rho = 0.648, P < 0.05), while the dominant genus Anaerosporobacter (LDA > 3, P < 0.05) was positively correlated with 24-hour urinary protein content (Rho = 0.773, P < 0.01). In the MP group, the dominant genus Blautia (LDA > 3, P < 0.05) was negatively correlated with 24-hour urinary protein content (Rho = -0.829, P < 0.05). The results indicated that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. These findings suggested that the gut microbiota may contribute to the heterogeneity of the induced response since we observed potential disease-associated microbial taxonomies and correlations with DN.

RevDate: 2020-03-14

Jo YJ, Tagele SB, Pham HQ, et al (2020)

In Situ Profiling of the Three Dominant Phyla Within the Human Gut Using TaqMan PCR for Pre-Hospital Diagnosis of Gut Dysbiosis.

International journal of molecular sciences, 21(6): pii:ijms21061916.

A microbial imbalance called dysbiosis leads to inflammatory bowel disease (IBD), which can include ulcerative colitis (UC). Fecal microbiota transplantation (FMT), a novel therapy, has recently been successful in treating gut dysbiosis in UC patients. For the FMT technique to be successful, the gut microbiota of both the healthy donors and UC patients must be characterized. For decades, next-generation sequencing (NGS) has been used to analyze gut microbiota. Despite the popularity of NGS, the cost and time constraints make it difficult to use in emergency services and activities related to the periodic monitoring of microbiota profile alterations. Hence, in this study, we developed a multiplex TaqMan qPCR assay (MTq-PCR) with novel probes to simultaneously determine the relative proportions of the three dominant microbial phyla in the human gut: Bacteroidetes, Firmicutes, and Proteobacteria. The relative proportions of the three phyla in fecal samples of either healthy volunteers or UC patients were similar when assessed NGS and the MTq-PCR. Thus, our MTq-PCR assay could be a practical microbiota profiling alternative for diagnosing and monitoring gut dysbiosis in UC patients during emergency situations, and it could have a role in screening stool from potential FMT donors.

RevDate: 2020-03-13

Yu L, Wang L, Yi H, et al (2020)

Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model.

Gut microbes [Epub ahead of print].

Alcohol intake can modify gut microbiota composition, increase gut permeability, and promote liver fibrogenesis. LRP6 is a signal transmembrane protein and a co-receptor for the canonical Wnt signaling pathway. This study compared the curative effect of LRP6-CRISPR on alcohol-related liver injury with that of traditional fecal microbiota transplant (FMT) and investigated the alteration of the gut microbiome following the treatment. A rat model of alcohol-related liver injury was established and injected with lentiviral vectors expressing LRP6-CRISPR or administered with fecal filtrate from healthy rats, with healthy rat served as the control. Liver tissues of rats were examined by HE staining, Sirius staining, and Oil red O staining, respectively. The expression of LRP6 and fibrosis biomarkers were tested by PCR. The fecal sample of rats was collected and examined by 16S rRNA sequencing. Our data indicated that LRP6-CRISPR was more efficient in the prevention of alcohol-related liver injury than FMT. Microbiome analysis showed that alcohol-related liver injury related to gut microbiota dysbiosis, while treatment with LRP6-CRISPR or FMT increased gut microflora diversity and improved gut symbiosis. Further, bacteria specific to the disease stages were identified. Genera Romboutsia, Escherichia-Shigella, Pseudomonas, Turicibacter, and Helicobacter were prevalent in the intestine of rats with alcohol-related liver injury, while the domination of Lactobacillus was found in rats treated with LRP6-CRISPR or FMT. Besides, Lactobacillus and genera belonging to family Lachnospiraceae, Bacteroidales S24-7 group, and Ruminococcaceae were enriched in healthy rats. LRP6-CRISPR and FMT have beneficial effects on the prevention of alcohol-related liver injury, and correspondently, both treatments altered the disrupted gut microflora to a healthy one.

RevDate: 2020-03-13

Ramai D, Zakhia K, Fields PJ, et al (2020)

Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

Digestive diseases and sciences pii:10.1007/s10620-020-06185-7 [Epub ahead of print].

BACKGROUND: Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules.

AIM: To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI.

METHODS: We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design.

RESULTS: Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4-96.8%; I2 15.6%), capsule 92.1% (CI 88.6-95.0%; I2 7.1%), enema 87.2% (CI 83.4-90.5%; I2 0%), and NGT/NDT 78.1% (CI 71.6-84.1%; I2 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%.

CONCLUSION: CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.

RevDate: 2020-03-11

AlQahtani H, Baloch S, D Tabb (2020)

Treatment of Recurrent Clostridium difficile Infection in an Immunocompromised Patient with Severe Neutropenia Not Responding to Standard Therapy.

Case reports in infectious diseases, 2020:3089023.

One of the most effective strategies in reducing the risk of Clostridium difficile infection (CDI) recurrence is fecal microbiota transplantation (FMT). However, several adverse events have been reported post FMT, and data on the efficacy and safety of FMT in immunocompromised patients with hematological malignancies are rare. This report presents FMT treatment for refractory CDI in a severely immunocompromised patient. A 69-year-old female presented to the emergency department complaining of foul smelling, intractable, watery diarrhea and generalized abdominal pain. She was recently diagnosed with high-risk myelodysplastic Syndrome (MDS) requiring daily blood transfusions and reported multiple CDI episodes in the past treated successfully with metronidazole and vancomycin as mono- or combotherapy. During this admission, treatment with oral vancomycin (high dose) and intravenous metronidazole was unsuccessful, so FMT was administered. The patient recovered well despite an absolute neutrophil count (ANC) < 0.25 × 109/L, and chemotherapy was initiated soon after. FMT was successful and safe in this patient, with no relapse and adverse events seen in 8 weeks of follow-up via phone calls and office visits.

RevDate: 2020-03-11

Ren K (2020)

Commentary on Ma et al. Resveratrol brings back happy bug's harmony.

Brain, behavior, and immunity pii:S0889-1591(20)30298-1 [Epub ahead of print].

RevDate: 2020-03-10

McKinney CA, Oliveira BCM, Bedenice D, et al (2020)

The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea.

PloS one, 15(3):e0230148 pii:PONE-D-19-33915.

BACKGROUND AND AIMS: Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity.

METHODS: To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing.

RESULTS AND CONCLUSIONS: In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor.

RevDate: 2020-03-10

Keen EC, Tasoff P, Hink T, et al (2020)

Microbiome Restoration by RBX2660 Does Not Preclude Recurrence of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report.

Open forum infectious diseases, 7(3):ofaa042 pii:ofaa042.

A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.

RevDate: 2020-03-10
CmpDate: 2020-03-10

Durgan DJ (2019)

Evidence for a gut-immune-vascular axis in the development of hypertension.

Acta physiologica (Oxford, England), 227(1):e13338.

RevDate: 2020-03-09

Yu EW, Gao L, Stastka P, et al (2020)

Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial.

PLoS medicine, 17(3):e1003051 pii:PMEDICINE-D-19-02285.

BACKGROUND: There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity.

METHODS AND FINDINGS: FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention.

CONCLUSIONS: Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study.


RevDate: 2020-03-09

Gupta A, Saha S, S Khanna (2020)

Therapies to modulate gut microbiota: Past, present and future.

World journal of gastroenterology, 26(8):777-788.

The human gut microbiota comprises of a complex and diverse array of microorganisms, and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest. Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection (CDI). Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI. There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation (FMT) across different centers globally, and standardized microbioal replacement therapies offer an attractive alternative. The adverse effects associated with FMT are usually mild. However, there is paucity of data on long term safety of FMT and there is a need for further studies in this regard. With our increasing understanding of the host-microbiome interaction, there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases. The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease, irritable bowel syndrome, obesity, multidrug resistant infections, and neuropsychiatric illnesses. Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.

RevDate: 2020-03-09

Giuffrè M, Campigotto M, Campisciano G, et al (2020)

A Story of Liver and Gut Microbes: How Does the Intestinal Flora Affect Liver Disease? A Review of the Literature.

American journal of physiology. Gastrointestinal and liver physiology [Epub ahead of print].

Each individual is endowed with a unique gut microbiota (GM) footprint, which mediates numerous host-related physiological functions such as nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. The rapid scientific interest in GM has recognized its central role in the pathophysiology of many intestinal and extra-intestinal conditions. Given the close relationship between the gastro-intestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review, we want to introduce to neophytes the vast world of gut microbes - including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge on the role of GM in liver diseases pathophysiology. Besides, we highlight the potentials and downsides of GM-based therapy.

RevDate: 2020-03-05

Zhang F, Zhai M, Wu Q, et al (2020)

Protective effect of Tong-Qiao-Huo-Xue Decoction on inflammatory injury caused by intestinal microbial disorders in stroke rats.

Biological & pharmaceutical bulletin [Epub ahead of print].

Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classic traditional Chinese medicine prescription for treating cerebral ischemia. The purpose of this study was to investigate the effect of TQHXD on intervening inflammatory response of ischemic stroke by regulating intestinal flora and repairing the intestinal barrier. A rat model of cerebral ischemia was established using middle cerebral artery occlusion (MCAO) and behavioral scores were performed. Additionally, the high throughput 16S rDNA sequence of intestinal bacteria in fecal samples of rat was also carried out. Our results showed that TQHXD could change the main components of intestinal flora in stroke rats, and reduced the excessive increase of Bacteroidetes, and also regulated the abnormal changes of abundance of some flora as well. In addition, the intestinal epithelial barrier was damaged after stroke, allowing bacterial metabolites to enter the blood, while TQHXD had an improved effect on this phenomenon. Meanwhile, pathological changes in the brain tissue and infarct volume was also alleviated by TQHXD. Due to the disorder of the intestinal flora and the destruction of the barrier, the peripheral immune imbalance caused an inflammatory reaction. TQHXD improved the imbalance of T cells, and inhibited the inflammatory response. Finally, the therapeutic transplantation of fecal microbiota also improved the outcome of stroke in rats. Our presented results suggest that TQHXD may improve the gut microbiota disorder and its induced inflammatory response after stroke, which could be a new target and mechanism for the treatment of stroke.

RevDate: 2020-03-04

Baffy G (2020)

Gut Microbiota and Cancer of the Host: Colliding Interests.

Advances in experimental medicine and biology, 1219:93-107.

Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that live on the external and internal epithelial surfaces of the body. The largest community of human microbiota resides in the gastrointestinal tract where commensal, symbiotic and pathogenic microorganisms interact with the intestinal barrier and gut mucosal lymphoid tissue, creating a tumor microenvironment in which cancer cells thrive or perish. Aberrant composition and function of the gut microbiota (dysbiosis) has been associated with tumorigenesis by inducing inflammation, promoting cell growth and proliferation, weakening immunosurveillance, and altering food and drug metabolism or other biochemical functions of the host. However, recent research has also identified several mechanisms through which gut microbiota support the host in the fight against cancer. These mechanisms include the use of antigenic mimicry, biotransformation of chemotherapeutic agents, and other mechanisms to boost anti-cancer immune responses and improve the efficacy of cancer immunotherapy. Further research in this rapidly advancing field is expected to identify additional microbial metabolites with tumor suppressing properties, map the complex interactions of host-microbe 'transkingdom network' with cancer cells, and elucidate cellular and molecular pathways underlying the impact of specific intestinal microbial configurations on immune checkpoint inhibitor therapy.

RevDate: 2020-03-08

Ebrahimzadeh Leylabadlo H, Sanaie S, Sadeghpour Heravi F, et al (2020)

From role of gut microbiota to microbial-based therapies in type 2-diabetes.

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 81:104268 pii:S1567-1348(20)30099-X [Epub ahead of print].

The incidence of type 2 diabetes mellitus (T2DM) has increased dramatically at an alarming level around the world.T2DM is associated with changeable risk factors in lifestyle as well as genetic and family associated risk factors. More importantly, imbalanced or impaired gut microbial distribution (dysbiosis) has been reported as a contributing risk factor in insulin resistance progression in T2DM. Dysbiosis may restructure the metabolic and functional pathways in the intestine which are involved in the development of T2DM. However, several studies have indicated the constructive and helpful effect of prebiotics, probiotics, and fecal microbiota transplantation (FMT) on the improvement of gut microbiota (GM) and accordingly host metabolism. In this review, the association between GM and T2DM have been evaluated and the role of prebiotics, probiotics and FMT, as potential therapeutic approaches have been discussed. Relevant studies were obtained randomly from online databases such as PubMed/Medline and ISI Web of Science.

RevDate: 2020-03-05

Adamberg K, Raba G, S Adamberg (2020)

Use of Changestat for Growth Rate Studies of Gut Microbiota.

Frontiers in bioengineering and biotechnology, 8:24.

Human colon microbiota, composed of hundreds of different species, is closely associated with several health conditions. Controlled in vitro cultivation and up-to-date analytical methods make possible the systematic evaluation of the underlying mechanisms of complex interactions between the members of microbial consortia. Information on reproducing fecal microbial consortia can be used for various clinical and biotechnological applications. In this study, chemostat and changestat cultures were used to elucidate the effects of the physiologically relevant range of dilution rates on the growth and metabolism of adult fecal microbiota. The dilution rate was kept either at D = 0.05 or D = 0.2 1/h in chemostat cultures, while gradually changing from 0.05 to 0.2 1/h in the A-stat and from 0.2 to 0.05 1/h in the De-stat. Apple pectin as a substrate was used in the chemostat experiments and apple pectin or birch xylan in the changestat experiments, in the presence of porcine mucin in all cases. The analyses were comprised of HPLC for organic acids, UPLC for amino acids, GC for gas composition, 16S-rDNA sequencing for microbial composition, and growth parameter calculations. It was shown that the abundance of most bacterial taxa was determined by the dilution rate on both substrates. Bacteroides ovatus, Bacteroides vulgatus, and Faecalibacterium were prevalent within the whole range of dilution rates. Akkermansia muciniphila and Ruminococcaceae UCG-013 were significantly enriched at D = 0.05 1/h, while Bacteroides caccae, Lachnospiraceae unclassified and Escherichia coli clearly preferred D = 0.2 1/h. In the chemostat cultures, the production of organic acids and gases from pectin was related to the dilution rate. The ratio of acetate, propionate and butyrate was 5:2:1 (D = 0.05 1/h) and 14:2:1 (D = 0.2 1/h). It was shown that the growth rate-related characteristics of the fecal microbiota were concise in both directions between D = 0.05 and 0.2 1/h. Reproducible adaptation of the fecal microbiota was shown in the continuous culture with a changing dilution rate: changestat. Consortia cultivation is a promising approach for research purposes and several biotechnological applications, including the production of multi-strain probiotics and fecal transplantation mixtures.

RevDate: 2020-03-05

Tsigalou C, Konstantinidis T, Stavropoulou E, et al (2020)

Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods.

Frontiers in microbiology, 11:50.

Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the "gut resistome." ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.

RevDate: 2020-03-02

Neff AS (2020)

Technical and Theoretic Limitations of the Experimental Evidence Supporting a Gut Bacterial Etiology in Mental Illness.

Clinical therapeutics pii:S0149-2918(20)30077-1 [Epub ahead of print].

The impact of gut bacteria on the brain and behavior has become the subject of intense research. The brain is sensitive to biochemical and physiologic changes in the body, for example, changes in blood oxygenation or nutritional status. The collection of microorganisms residing within the digestive tract (the gut microbiome) is increasingly considered a major contributor to human physiology. These 2 considerations have led to the hypothesis that human psychology, including complex constructs like emotion and mental illness, could be influenced by the composition or function of gut bacteria. Five lines of evidence have been used to support the concept, including human correlational research, probiotic supplementation, antibiotic use, germ-free animal research, and fecal transplantation. Results from these experiments do not provide substantial support for the theory that complex human psychology is under the influence of gut bacteria. Placebo-controlled interventional research in humans, in particular fecal microbiota transplantation, will be required before a stronger conclusion can be reached. (Clin Ther. 2020;42:XXX-XXX) © 2020 Elsevier Inc.

RevDate: 2020-03-02

Jiménez-Avalos JA, Arrevillaga-Boni G, González-López L, et al (2020)

Classical methods and perspectives for manipulating the human gut microbial ecosystem.

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

A healthy Human Gut Microbial Ecosystem (HGME) is a necessary condition for maintaining the orderly function of the whole body. Major alterations in the normal gut microbial composition, activity and functionality (dysbiosis) by an environmental or host-related disruptive event, can compromise metabolic, inflammatory, and neurological processes, causing disorders such as obesity, inflammatory bowel disease, colorectal cancer, and depressive episodes. The restore or the maintaining of the homeostatic balance of Gut Microbiota (GM) populations (eubiosis) is possible through diet, the use of probiotics, prebiotics, antibiotics, and even Fecal Microbiota Transplantation (FMT). Although these "classic methods" represent an effective and accepted way to modulate GM, the complexity of HGME requires new approaches to control it in a more appropriate way. Among the most promising emergent strategies for modulating GM are the use of engineered nanomaterials (metallic nanoparticles (NP), polymeric-NP, quantum dots, micelles, dendrimers, and liposomes); phagotherapy (i.e., phages linked with the CRISPR/Cas9 system), and the use of antimicrobial peptides, non-antibiotic drugs, vaccines, and immunoglobulins. Here we review the current state of development, implications, advantages, disadvantages, and perspectives of the different approaches for manipulating HGME.

RevDate: 2020-03-02

Zhao X, Jiang Y, Xi H, et al (2020)

Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): a Review.

Geburtshilfe und Frauenheilkunde, 80(2):161-171.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic syndrome (MS) with a complex etiology, and its pathogenesis is not yet clear. In recent years, the correlation between gut microbiota (GM) and metabolic disease has become a hot topic in research, leading to a number of new ideas about the etiology and pathological mechanisms of PCOS. The literature shows that GM can cause insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome (obesity, diabetes) and may contribute to the development of PCOS by influencing energy absorption, the pathways of short chain fatty acids (SCFA), lipopolysaccharides, choline and bile acids, intestinal permeability and the brain-gut axis. As part of the treatment of PCOS, fecal microbiota transplantation, supplementation with prebiotics and traditional Chinese medicine can be used to regulate GM and treat disorders. This article reviews possible mechanisms and treatment options for PCOS, based on methods which target the GM, and offers new ideas for the treatment of PCOS.

RevDate: 2020-02-28

Merli P, Putignani L, Ruggeri A, et al (2020)

Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.

Haematologica pii:haematol.2019.244210 [Epub ahead of print].

RevDate: 2020-02-27

Yan PG, JN Li (2020)

Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease.

Chinese medical journal [Epub ahead of print].

The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.

RevDate: 2020-03-01

Cheng YW, M Fischer (2020)

Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection.

Clinics in colon and rectal surgery, 33(2):92-97.

Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as " Clostridioides difficile ") infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.

RevDate: 2020-03-02

Peled JU, Gomes ALC, Devlin SM, et al (2020)

Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.

The New England journal of medicine, 382(9):822-834.

BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable.

METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death.

RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival.

CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).

RevDate: 2020-02-26

Chen K, Fu Y, Wang Y, et al (2020)

Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder.

Microbial ecology pii:10.1007/s00248-020-01494-w [Epub ahead of print].

Autism spectrum disorder (ASD) is a brain-based neurodevelopmental disorder characterized by behavioral abnormalities. Accumulating studies show that the gut microbiota plays a vital role in the pathogenesis of ASD, and gut microbiota transplantation (GMT) is a promising technique for the treatment of ASD. In clinical applications of GMT, it is challenging to obtain effective transplants because of the high costs of donor selection and heterogeneity of donors' gut microbiota, which can cause different clinical responses. In vitro batch culture is a fast, easy-to-operate, and repeatable method to culture gut microbiota. Thus, the present study investigates the feasibility of treating ASD with in vitro cultured gut microbiota as transplants. We cultured gut microbiota via the in vitro batch culture method and performed GMT in the maternal immune activation (MIA)-induced ASD mouse model with original donor microbiota and in vitro cultured microbiota. Open field, three-chamber social, marble burying, and self-grooming tests were used for behavioral improvement assessment. Serum levels of chemokines were detected. Microbial total DNA was extracted from mouse fecal samples, and 16S rDNA was sequenced using Illumina. Our results showed that GMT treatment with original and cultured donor gut microbiota significantly ameliorated anxiety-like and repetitive behaviors and improved serum levels of chemokines including GRO-α (CXCL1), MIP-1α (CCL3), MCP-3 (CCL7), RANTES (CCL5), and Eotaxin (CCL11) in ASD mice. Meanwhile, the gut microbial communities of the two groups that received GMT treatment were changed compared with the ASD mice groups. In the group treated with in vitro cultured donor gut microbiota, there was a significant decrease in the relative abundance of key differential taxa, including S24-7, Clostridiaceae, Prevotella_other, and Candidatus Arthromitus. The relative abundance of these taxa reached close to the level of healthy mice. Prevotella_other also decreased in the group treated with original donor gut microbiota, with a significant increase in Ruminococcaceae and Oscillospira. The present study demonstrated that GMT with in vitro cultured microbiota also improved behavioral abnormalities and chemokine disorders in an ASD mouse model compared with GMT with original donor gut microbiota. In addition, it significantly modified several key differential taxa in gut microbial composition.

RevDate: 2020-02-28

Ueckermann V, Hoosien E, De Villiers N, et al (2020)

Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient.

Case reports in infectious diseases, 2020:8462659.

Dysbiosis of the microbiome is a common finding in critically ill patients, who receive broad-spectrum antibiotics and various forms of organ support. Multidrug-resistant (MDR) organisms are a growing threat in all areas of medicine, but most markedly in the critically ill, where there is both loss of host defences and widespread use of broad spectrum antibiotics. We present a case of a critically ill patient with persistent MDR Klebsiella pneumoniae infection, successfully treated with fecal microbiota transplantation (FMT), using stool of a rigorously-screened, healthy donor. FMT for Clostridium difficile colitis has been well described in the literature and is an established therapy for recurrent infections with Clostridium difficile. The use of FMT for other multidrug-resistant organisms is less frequently described, particularly in the context of critically ill patients. In our case, we have culture-documented clearance of the MDR Klebsiella pneumoniae form a patient of FMT.

RevDate: 2020-02-27

Mazzawi T, Eikrem Ø, Lied GA, et al (2020)

Abnormal Uroguanylin Immunoreactive Cells Density in the Duodenum of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Changes following Fecal Microbiota Transplantation.

Gastroenterology research and practice, 2020:3520686.

Altered densities of enteroendocrine cells play an important role in patients with irritable bowel syndrome (IBS). Uroguanylin activates guanylate cyclase-C to regulate intestinal electrolyte and water transport. Aim. To quantify uroguanylin immunoreactive cells density in the duodenum of diarrhea-predominant IBS (IBS-D) patients compared to controls and to investigate the effect of fecal microbiota transplantation (FMT) on these cell densities. Method. Twelve patients with IBS-D according to Rome III criteria were included. The cause was identified as post infectious (PI, n = 6) or idiopathic (n = 6). They completed the IBS-symptom questionnaire before and 3 weeks after FMT. Thirty grams of fresh feces donated from healthy relatives were diluted with 60 ml normal saline and instilled via endoscope into the duodenum. Biopsies were taken from the patients' duodenum before and 3 weeks after FMT. Duodenal biopsies taken from eight healthy controls were also included. The biopsies were immunostained for uroguanylin and quantified using computerized image analysis. Results. Uroguanylin immunoreactive cells were found both in duodenal villi and crypts in both controls and IBS-D patients. The densities of uroguanylin immunoreactive cells were significantly lower in the villi (P < 0.0001) and higher in the crypts (P < 0.0001) for the patients than the controls. Following FMT, the densities of uroguanylin immunoreactive cells for the total group and idiopathic subgroup decreased significantly in the duodenal crypts (P = 0.049 and 0.04, respectively) but not in the villi. No significant changes were shown in the PI-IBS subgroups. The cells density in only the crypts correlated with diarrhea (r = 0.97, P = 0.001) and bloating (r = -0.91, P = 0.01) in the PI-IBS subgroup before FMT and with abdominal pain (r = 0.63, P = 0.03) in the total group of IBS-D patients after FMT. Conclusion. Altered uroguanylin immunoreactive cells density was found in IBS-D patients compared to controls. Changes in these cells density following FMT correlated with IBS symptoms (diarrhea, bloating, and abdominal pain).

RevDate: 2020-02-24

Chen EB, Shapiro KE, Wun K, et al (2020)

Microbial Colonization of Germ-Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury.

Journal of the American Heart Association, 9(5):e013496.

Background The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.

RevDate: 2020-03-09

Lopetuso LR, Ianiro G, Allegretti JR, et al (2020)

Fecal transplantation for ulcerative colitis: current evidence and future applications.

Expert opinion on biological therapy, 20(4):343-351.

Introduction: Established evidence suggests that gut microbiota plays a role in ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is clearly recognized as a highly effective treatment for patients with recurrent Clostridium difficile infection and has been investigated also in patients with UC, with promising results.Areas covered: Literature review was performed to select publications concerning current evidence on the role of gut microbiota in the pathogenesis of UC, and on the effectiveness of FMT in this disorder.Expert opinion: The randomized controlled trials published investigating the use of FMT suggested a potential role for FMT in the treatment of mild to moderate UC. However, given several unanswered questions regarding donor selection, dose, route of administration and duration of therapy, this is not yet recommended as a viable therapy option. FMT has allowed for more in depth investigation with regards to the role the gut microbiota may be playing in UC. This knowledge is critical to identifying where FMT may appropriately fit in the UC treatment paradigm. As our understanding of the role the microbiome plays in this chronic disease, FMT, and then eventually defined microbes, will hopefully serve in a complementary role to conventional IBD therapies.

RevDate: 2020-02-21

Pilmis B, Le Monnier A, JR Zahar (2020)

Gut Microbiota, Antibiotic Therapy and Antimicrobial Resistance: A Narrative Review.

Microorganisms, 8(2): pii:microorganisms8020269.

Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed.

RevDate: 2020-02-20

Luo Y, Tixier EN, AM Grinspan (2020)

Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults Is Associated with Early Recurrence.

Digestive diseases and sciences pii:10.1007/s10620-020-06147-z [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI). CDI disproportionately affects the elderly; however, there is a paucity of data on FMT effectiveness in older adults, especially subpopulations at highest risk for CDI-related morbidity and mortality.

AIM: To assess the efficacy and safety of FMT for CDI in older adults.

METHODS: A retrospective, long-term follow-up study was performed. The high-risk subpopulation included patients who were immunocompromised, patients with inflammatory bowel disease, and patients presenting with severe or fulminant colitis. Outcome measures included primary cure rates, early (< 12 weeks) and late (> 12 weeks) recurrence rates, adverse events, and subgroup analysis of higher-risk populations.

RESULTS: Our cohort included 75 patients (72% female) with a mean age of 76.4 and Charlson comorbidity index score of 5.4. There were 34 patients in our higher-risk subpopulation as defined above with an adjusted recurrence rate of 32.1%. FMT was performed for severe or fulminant disease in 30.6% of patients with a 3-month survival rate of 73.9%. Overall, the adjusted primary cure rate was 67.2% and the adjusted CDI recurrence was 29.9% in our cohort (90% of recurrences occurred early). Most adverse events in our study were rehospitalizations for recurrent CDI.

CONCLUSION: Compared with previous studies of FMT efficacy, our cohort had a lower primary cure rate and higher CDI recurrence rate than previously reported, likely driven by our higher-risk subpopulations. Nevertheless, FMT should be considered early to prevent progression of CDI severity and recurrence, especially in patients who present with severe and fulminant disease.

RevDate: 2020-02-20

Yan X, Jin J, Su X, et al (2020)

Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.

Circulation research [Epub ahead of print].

Rationale: High-salt diet (HSD) is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. Objective: To reveal the roles and mechanisms of intestinal flora in hSIH development. Methods and Results: The above-mentioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture and fecal microbiota transplantation (FMT). We found that HSD induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, while the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid (AA) levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis (B. fragilis) could inhibit the production of intestinal-derived corticosterone induced by HSD through its metabolite AA. Conclusions: hSIH could be transferred by FMT, indicating the pivotal roles of intestinal flora in hSIH development. HSD reduced the levels of B. fragilis and AA in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.

RevDate: 2020-03-05

Liu X, Liu Y, Chen X, et al (2020)

Multi-walled carbon nanotubes exacerbate doxorubicin-induced cardiotoxicity by altering gut microbiota and pulmonary and colonic macrophage phenotype in mice.

Toxicology, 435:152410 pii:S0300-483X(20)30049-4 [Epub ahead of print].

Epidemiologic studies show that the levels of air pollutants and particulate matter are positively associated with the morbidity and mortality of cardiovascular diseases. Here we demonstrate that the intratracheal instillation of multi-walled carbon nanotubes (MWCNTs), a standard fine particle, exacerbate doxorubicin (DOX)-induced cardiotoxicity in mice through altering gut microbiota and pulmonary and colonic macrophage phenotype. MWCNTs (25 μg/kg per day, 5 days a week for 3 weeks) promoted cardiotoxicity and apoptosis in the DOX (2 mg/kg, twice a week for 5 weeks)-treated C57BL/6 mice. MWCNTs exaggerated DOX-induced gut microbiota dysbiosis characterized by the increased abundances of Helicobacteraceae and Coriobacteriaceae. In addition, MWCNTs promoted DOX-induced M1-like polarization of colonic macrophages with an increase in TNF-α, IL-1β and CC chemokine ligand 2 in peripheral blood. Importantly, treatment with the antibiotics attenuated MWCNTs plus DOX-induced apoptosis of cardiomyocytes and M1-like polarization of colonic macrophages. The fecal microbiota transplantation demonstrated that MWCNTs exaggerated DOX-induced cardiotoxicity with M1-like polarization of colonic macrophages. The conditioned medium from MWCNTs-treated pulmonary macrophages promoted DOX-induced gut microbiota dysbiosis and colonic macrophage polarization. Furthermore, the co-culture of macrophages and fecal bacteria promoted M1-like macrophage polarization and their production of TNF-α and IL-1β, and thereby exacerbated the effects of MWCNTs. Moreover, IL-1β and TNF-α blockade, either alone or in combination attenuated MWCNTs-exacerbated cardiotoxicity. In summary, MWCNTs exacerbate DOX-induced cardiotoxicity in mice through gut microbiota and pulmonary and colonic macrophage interaction. Our findings identify a novel mechanism of action of inhaled particle-driven cardiotoxicity.

RevDate: 2020-03-04

Xiao J, Wang T, Xu Y, et al (2020)

Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats.

Translational psychiatry, 10(1):25.

Chronic lead exposure is associated with the development of neurodegenerative diseases, characterized by the long-term memory decline. However, whether this pathogenesis could be prevented through adjusting gut microbiota is not yet understood. To address the issue, pregnant rats and their female offspring were treated with lead (125 ppm) or separately the extra probiotics (1010 organisms/rat/day) till adulthood. For results, memory dysfunction was alleviated by the treatment of multispecies probiotics. Meanwhile, the gut microbiota composition was partially normalized against lead-exposed rats, which in turn mediated the memory repairment via fecal transplantation trials. In the molecular aspect, the decreased H3K27me3 (trimethylation of histone H3 Lys 27) in the adult hippocampus was restored with probiotic intervention, an epigenetic event mediated by EZH2 (enhancer of zeste homolog 2) at early developmental stage. In a neural cellular model, EZH2 overexpression showed the similar rescue effect with probiotics, whereas its blockade led to the neural re-damages. Regarding the gut-brain inflammatory mediators, the disrupted IL-6 (interleukin 6) expression was resumed by probiotic treatment. Intraperitoneal injection of tocilizumab, an IL-6 receptor antagonist, upregulated the hippocampal EZH2 level and consequently alleviated the memory injuries. In conclusion, reshaping gut microbiota could mitigate memory dysfunction caused by chronic lead exposure, wherein the inflammation-hippocampal epigenetic pathway of IL-6-EZH2-H3K27me3, was first proposed to mediate the studied gut-brain communication. These findings provided insight with epigenetic mechanisms underlying a unique gut-brain interaction, shedding light on the safe and non-invasive treatment of neurodegenerative disorders with environmental etiology.

RevDate: 2020-02-21

Wu H, Rao Q, Ma GC, et al (2019)

Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice.

Frontiers in pharmacology, 10:1652.

Triptolide is beneficial for the treatment of ulcerative colitis (UC), which is closely related to the gut microbiota. However, whether the therapeutic effects of triptolide involve the regulation of the gut microbiota is still unclear. In the present study, animal models of UC mice induced by dextran sodium sulfate (DSS) were established, the changes of gut microbiota in mice were detected by high-throughput sequencing. The effects of triptolide on DSS-induced UC mouse and its gut microbiota were studied. As a result, we found that triptolide exerted anti-inflammatory and therapeutic effects on UC mice. Sequencing results for the gut microbiota showed that the composition of the gut microbiota from DSS group was disordered as compared with that from the control group, consistent with a decrease in the abundance of flora. Triptolide treatment accelerated the recovery of the population of the gut microbiota and significantly improved the microbial diversity. At the phylum level, the population of Bacteroidetes decreased and that of Firmicutes increased. At the genus level, Bacteroides and Lachnospiraceae counts decreased. Thus, triptolide could regulate the composition of the gut microbiota, accelerate the recovery of microbiota, and exert good therapeutic effects in UC mice. Our results also revealed that fecal transplantation from triptolide-treated mice could relieve UC. This study provides a reference for the rational use of triptolide for the treatment of UC.

RevDate: 2020-02-19

Cheng YW, M Fischer (2020)

Clinical management of severe, fulminant, and refractory Clostridioides difficile infection.

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

Introduction: Up to 15% of hospitalized patients with Clostridioides difficile infection (CDI) develop severe CDI (SCDI) or Fulminant CDI (FCDI). Due to high rates of mortality in medically-refractory CDI cases, 30% of patients with severe infection historically require surgical intervention. However, colectomy itself is an imperfect solution because it is difficult to predict who will fail medical therapy, patients with SCDI are more likely to have underlying medical conditions that make them poor surgical candidates, and post-surgical mortality still approaches 30-50%.Areas covered: This review will serve as a clinically-based review of severe and fulminant CDI management including discussion of models to predict severe infection, emerging treatments, novel targets for therapy, and innovations in surgical management.Expert opinion: Among the most promising studies to emerge in the last decade have involved fecal microbiota transplantation (FMT), which is already recommended by multiple society guidelines for recurrent CDI (RCDI). In the case of SCDI/FCDI, multiple studies have safely and successfully utilized FMT to produce rates of cure in the 70-90% range. Additionally, patients who have FCDI refractory to medical therapy and are poor candidates for colectomy may benefit from FMT as salvage therapy.

RevDate: 2020-02-28

Saurman V, Margolis KG, RA Luna (2020)

Autism Spectrum Disorder as a Brain-Gut-Microbiome Axis Disorder.

Digestive diseases and sciences, 65(3):818-828.

While there are numerous medical comorbidities associated with ASD, gastrointestinal (GI) issues have a significant impact on quality of life for these individuals. Recent findings continue to support the relationship between the gut microbiome and both GI symptoms and behavior, but the heterogeneity within the autism spectrum requires in-depth clinical characterization of these clinical cohorts. Large, diverse, well-controlled studies in this area of research are still needed. Although there is still much to discover about the brain-gut-microbiome axis in ASD, microbially mediated therapies, specifically probiotics and fecal microbiota transplantation have shown promise in the treatment of GI symptoms in ASD, with potential benefit to the core behavioral symptoms of ASD as well. Future research and clinical trials must increasingly consider complex phenotypes in ASD in stratification of large datasets as well as in design of inclusion criteria for individual therapeutic interventions.

RevDate: 2020-02-14

Shin JH, Lee YK, Shon WJ, et al (2020)

Gut microorganisms and their metabolites modulate the severity of acute colitis in a tryptophan metabolism-dependent manner.

European journal of nutrition pii:10.1007/s00394-020-02194-4 [Epub ahead of print].

PURPOSE: Growing evidence shows that nutrient metabolism affects inflammatory bowel diseases (IBD) development. Previously, we showed that deficiency of indoleamine 2,3-dioxygenase 1 (Ido1), a tryptophan-catabolizing enzyme, reduced the severity of dextran sulfate sodium (DSS)-induced colitis in mice. However, the roles played by intestinal microbiota in generating the differences in disease progression between Ido1+/+ and Ido1-/- mice are unknown. Therefore, we aimed to investigate the interactions between the intestinal microbiome and host IDO1 in governing intestinal inflammatory responses.

METHODS: Microbial 16s rRNA sequencing was conducted in Ido1+/+ and Ido1-/- mice after DSS treatment. Bacteria-derived tryptophan metabolites were measured in urine. Transcriptome analysis revealed the effects of the metabolite and IDO1 expression in HCT116 cells. Colitis severity of Ido1+/+ was compared to Ido1-/- mice following fecal microbiota transplantation (FMT).

RESULTS: Microbiome analysis through 16S-rRNA gene sequencing showed that IDO1 deficiency increased intestinal bacteria that use tryptophan preferentially to produce indolic compounds. Urinary excretion of 3-indoxyl sulfate, a metabolized form of gut bacteria-derived indole, was significantly higher in Ido1-/- than in Ido1+/+ mice. Transcriptome analysis showed that tight junction transcripts were significantly increased by indole treatment in HCT116 cells; however, the effects were diminished by IDO1 overexpression. Using FMT experiments, we demonstrated that bacteria from Ido1-/- mice could directly attenuate the severity of DSS-induced colitis.

CONCLUSIONS: Our results provide evidence that a genetic defect in utilizing tryptophan affects intestinal microbiota profiles, altering microbial metabolites, and colitis development. This suggests that the host and intestinal microbiota communicate through shared nutrient metabolic networks.

RevDate: 2020-02-28

Carlson PE (Jr) (2020)

Regulatory Considerations for Fecal Microbiota Transplantation Products.

Cell host & microbe, 27(2):173-175.

Fecal microbiota for transplantation (FMT) is being studied as a potential intervention for numerous conditions. The regulation of FMT by the FDA is discussed along with FMT donor screening and manufacturing considerations. The FDA is committed to ensuring that FMT products can be safely tested in clinical trials.

RevDate: 2020-03-02
CmpDate: 2020-03-02

Markey KA, van den Brink MRM, JU Peled (2020)

Therapeutics Targeting the Gut Microbiome: Rigorous Pipelines for Drug Development.

Cell host & microbe, 27(2):169-172.

Restoration of the gut microbiome is a promising preventive and therapeutic strategy in a number of clinical scenarios. We discuss here the scientific and clinical challenges of engineering and implementing these strategies.

RevDate: 2020-02-19

Meighani A, Alimirah M, Ramesh M, et al (2020)

Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.

International journal of hepatology, 2020:1874570.

Background: Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive.

Aims: We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center.

Methods: A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD.

Results: A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%).

Conclusion: FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.

RevDate: 2020-02-19

Quigley EMM, P Gajula (2020)

Recent advances in modulating the microbiome.

F1000Research, 9:.

We are in the midst of "the microbiome revolution"-not a day goes by without some new revelation on the potential role of the gut microbiome in some disease or disorder. From an ever-increasing recognition of the many roles of the gut microbiome in health and disease comes the expectation that its modulation could treat or prevent these very same diseases. A variety of interventions could, at least in theory, be employed to alter the composition or functional capacity of the microbiome, ranging from diet to fecal microbiota transplantation (FMT). For some, such as antibiotics, prebiotics, and probiotics, an extensive, albeit far from consistent, literature already exists; for others, such as other dietary supplements and FMT, high-quality clinical studies are still relatively few in number. Not surprisingly, researchers have turned to the microbiome itself as a source for new entities that could be used therapeutically to manipulate the microbiome; for example, some probiotic strains currently in use were sourced from the gastrointestinal tract of healthy humans. From all of the extant studies of interventions targeted at the gut microbiome, a number of important themes have emerged. First, with relatively few exceptions, we are still a long way from a precise definition of the role of the gut microbiome in many of the diseases where a disturbed microbiome has been described-association does not prove causation. Second, while animal models can provide fascinating insights into microbiota-host interactions, they rarely recapitulate the complete human phenotype. Third, studies of several interventions have been difficult to interpret because of variations in study population, test product, and outcome measures, not to mention limitations in study design. The goal of microbiome modulation is a laudable one, but we need to define our targets, refine our interventions, and agree on outcomes.

RevDate: 2020-02-11

Ding X, Li Q, Li P, et al (2020)

Fecal microbiota transplantation: A promising treatment for radiation enteritis?.

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology pii:S0167-8140(20)30023-2 [Epub ahead of print].

BACKGROUND: Increasing evidence has indicated that gut microbiota is closely associated with radiation-induced bowel injury. We aimed to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in patients with chronic radiation enteritis (CRE).

METHODS: A pilot study of FMT for CRE was performed. The primary outcomes were safety and response to FMT which was defined as a ≥1-grade reduction in Radiation Therapy Oncology Group (RTOG/EORTC) late toxicity grade from baseline, by 8 weeks post-FMT. The secondary outcomes included a decrease in the severity of four common symptoms (diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence) in CRE and changes in Karnofsky Performance Status (KPS) score. Microbial analyses were performed by 16S rRNA sequencing.

RESULTS: Five female patients underwent FMT from January to November 2018 with a median age of 58 (range 45-81) years. The median baseline RTOG/EORTC grade was 2 (range 2-4). Three patients responded to FMT and experienced improvement in diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence as well as a decrease in KPS score. No FMT-related death and infectious complications occurred. One mild FMT-related AE was observed during a follow-up ranged from 8 to 18 months. 16S rRNA sequencing indicated that FMT altered the composition of gut microbiota of patients.

CONCLUSION: The present case series first demonstrated that FMT might be safe and effective to improve intestinal symptoms and mucosal injury in patients with CRE for a period of time. Trial registration ID: NCT03516461.

RevDate: 2020-02-11

Han J, Wang X, Tang S, et al (2020)

Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota.

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

Recently, interest in using whole food-derived mixtures to alleviate chronic metabolic syndrome through potential synergistic interactions among different components is increasing. In this study, the effects and mechanisms of tuna meat oligopeptides (TMOP) on hyperuricemia and associated renal inflammation were investigated in mice. Dietary administration of TMOP alleviated hyperuricemia and renal inflammation phenotypes, reprogramed uric acid metabolism pathways, inhibited the activation of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways, and suppressed the phosphorylation of p65-NF-κB. In addition, TMOP treatments repaired the intestinal epithelial barrier, reversed the gut microbiota dysbiosis and increased the production of short-chain fatty acids. Moreover, the antihyperuricemia effects of TMOP were transmissible by transplanting the fecal microbiota from TMOP-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, for the first time, we clarify the potential effects of TMOP as a whole food derived ingredient on alleviating hyperuricemia and renal inflammation in mice, and additional efforts are needed to confirm the beneficial effects of TMOP on humans.

RevDate: 2020-02-28

Abu-Sbeih H, Y Wang (2020)

Gut Microbiome and Immune Checkpoint Inhibitor-Induced Enterocolitis.

Digestive diseases and sciences, 65(3):797-799.

The gut microbiome is increasingly being described as one of the underlying mechanisms for development of immune checkpoint inhibitor (ICI)-induced colitis. Similarities in gut microbiome profiles have been found among various diseases associated with intestinal inflammation, including inflammatory bowel disease. Certain bacterial species have been reported to be preventive for colitis, as well as beneficial for cancer outcome, in patients receiving ICI therapy. Alternatively, other bacterial classes have been shown to be associated with immunologic alterations causing intestinal inflammation with subsequent increase in the risk of ICI-related colitis. Gut microbiome manipulation by fecal transplantation has been proposed as one of the modalities to ameliorate inflammation in patients with ICI-related colitis refractory to immunosuppressive therapy. Additional investigations are needed to clarify the role of gut microbiome in the pathogenesis of ICI-related colitis.

RevDate: 2020-02-10

Guo XY, Liu XJ, JY Hao (2020)

Gut Microbiota in Ulcerative Colitis: Insights on Pathogenesis and Treatment.

Journal of digestive diseases [Epub ahead of print].

Gut microbiota constitute the largest reservoir of the human microbiome, and is an abundant and stable ecosystem - based on its diversity, complexity, redundancy, and host interactions. This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease(IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.

RevDate: 2020-03-04

Schwenger KJ, Clermont-Dejean N, JP Allard (2019)

The role of the gut microbiome in chronic liver disease: the clinical evidence revised.

JHEP reports : innovation in hepatology, 1(3):214-226.

Recent research has suggested a role for the intestinal microbiota in the pathogenesis and potential treatment of a wide range of liver diseases. The intestinal microbiota and bacterial products may contribute to the development of liver diseases through multiple mechanisms including increased intestinal permeability, chronic systemic inflammation, production of short-chain fatty acids and changes in metabolism. This suggests a potential role for pre-, pro- and synbiotic products in the prevention or treatment of some liver diseases. In addition, there is emerging evidence on the effects of faecal microbial transplant. Herein, we discuss the relationship between the intestinal microbiota and liver diseases, as well as reviewing intestinal microbiota-based treatment options that are currently being investigated.

RevDate: 2020-03-04

Wang Y, Xu L, Sun X, et al (2020)

Characteristics of the fecal microbiota of high- and low-yield hens and effects of fecal microbiota transplantation on egg production performance.

Research in veterinary science, 129:164-173.

The microbiota that resides in the digestive tract plays pivotal role in maintaining intestinal environmental stability by promoting nutrition digestion and intestinal mucosal immunity. However, whether the intestinal microbiota in laying hens affects egg laying- performance is not known. In this study, 16S rDNA gene sequencing and fecal microbiota transplantation were used to determine the structure of the intestinal microbiota and the effect of the intestinal microbiota on egg production. The results revealed that Firmicutes were dominant in both the H (high egg laying rates) and L (low egg laying rates) groups, while Bacteroides, Actinobacteria and Proteobacteria were significantly enriched in the L group compared to the H group. The laying rates were weakly affected in H hens transplanted with the fecal microbiota from L hens, except for temporary fluctuation, while the egg laying rates were significantly increased in L hens transplanted with the fecal microbiota from H hens. Therefore, we concluded that the population structure of the intestinal microbiota varied between the H and L groups, and the intestinal microbiota of high-yield laying hens had significant effects on low-yield laying hens performance.

RevDate: 2020-02-06

Park S, Kang Y, Koh H, et al (2020)

Increasing incidence of inflammatory bowel disease in children and adolescents: the significance of the environmental factors.

Clinical and experimental pediatrics pii:cep.2019.00500 [Epub ahead of print].

Inflammatory bowel disease is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is investigated to be lower in Asia than in Western countries, the rapid increase in the incidence rate of inflammatory bowel disease has drawn attention to the etiology of inflammatory bowel disease, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may interact with the immune system, and the imbalance of this relationship may lead to the immune dysregulation in inflammatory bowel disease. The changes in diet or alteration in the composition of intestinal microbiota may be associated with the increasing incidence of inflammatory bowel disease in Asia. Here, we aim to review the recent studies on the role of the diet and intestinal microbiota in inflammatory bowel disease pathogenesis and the results of the investigations performed to modulate these factors.

RevDate: 2020-02-11

Swarte JC, Douwes RM, Hu S, et al (2020)

Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients.

Journal of clinical medicine, 9(2): pii:jcm9020386.

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.

RevDate: 2020-02-11

Kachrimanidou M, E Tsintarakis (2020)

Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection.

Microorganisms, 8(2): pii:microorganisms8020200.

Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut's metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut's microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.

RevDate: 2020-02-28

Lechner S, Yee M, Limketkai BN, et al (2020)

Fecal Microbiota Transplantation for Chronic Liver Diseases: Current Understanding and Future Direction.

Digestive diseases and sciences, 65(3):897-905.

Chronic liver disease is a major cause of morbidity and mortality worldwide. Even though effective treatments are now available for most chronic viral hepatitis, treatment options for other causes of chronic liver disease remain inadequate. Recent research has revealed a previously unappreciated role that the human intestinal microbiome plays in mediating the development and progression of chronic liver diseases. The recent remarkable success of fecal microbiota transplantation (FMT) in treating Clostridioides difficile demonstrates that the intestinal microbiota can be manipulated to obtain favorable therapeutic benefits and that FMT may become an important component of a total therapeutic approach to effectively treat hepatic disorders.

RevDate: 2020-02-25

Ghimire S, Roy C, Wongkuna S, et al (2020)

Identification of Clostridioides difficile-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly.

mSystems, 5(1):.

A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious levels. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1,590 isolates belonging to 102 species. This culture collection represents 34.57% of the taxonomic diversity and 70% functional capacity, as estimated by metagenomic sequencing of the fecal samples used for culture. Using whole-genome sequencing, we characterized species representatives from this collection and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profiles and short-chain fatty acid production. When screened with a coculture assay, 66 species in our culture collection inhibited Clostridioides difficile Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol, or succinate, correlated with C. difficile inhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory to C. difficile We tested 256 combinations and found that both species composition and blend size were important in inhibition. Our results show that the interaction of bacteria with one another in a mix and with other members of gut commensals must be investigated to design defined bacterial mixes for inhibiting C. difficilein vivoIMPORTANCE Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, thus allowing pathogens such as Clostridioides difficile to colonize and causing recurrent infection and mortality. Although fecal microbiome transplantation has been shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. The C. difficile-inhibiting species and bacterial combinations identified herein improve the understanding of the ecological interactions controlling colonization resistance against C. difficile and could aid in the design of defined bacteriotherapy as a nonantibiotic alternative against CDI.

RevDate: 2020-02-20

You JHS, Jiang X, Lee WH, et al (2020)

Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with inflammatory bowel disease.

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

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) patients are at risk for recurrent Clostridium difficile infection (RCDI). We aimed to evaluate the potential health economic and clinical outcomes of four strategies for management of RCDI in IBD patients from the perspective of public health-care provider in Hong Kong.

METHODS: A decision-analytic model was designed to simulate outcomes of adult IBD patients with first RCDI treated with vancomycin, vancomycin plus bezlotoxumab, fidaxomicin and fecal microbiota transplantation (FMT). Model inputs were derived from literature and public data. Primary model outcomes were C. difficile infection (CDI)-related direct medical cost and quality-adjusted life-years (QALYs) loss. Base-case and sensitivity analysis were performed.

RESULTS: Comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab, FMT saved 0.00318, 0.00149 and 0.00306 QALYs and reduced cost by USD3180, USD3790 and USD5514, respectively, in base-case analysis. In probabilistic sensitivity analysis, FMT was cost-saving when comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab by USD3765 (95% confidence interval [CI] 3732-3798; P < 0.001), USD3854 (95%CI 3827-3883; P < 0.001) and USD6501 (95%CI 6465-6,536; P < 0.001), respectively. The QALYs saved by FMT (vs vancomycin) were 0.00386 QALYs (95%CI 0.00384-0.00388; P < 0.001), (vs fidaxomicin) 0.00179 QALYs (95%CI 0.00177-0.00180; P < 0.001) and (vs vancomycin plus bezlotoxumab) 0.00376 QALYs (95%CI 0.00374-0.00378; P < 0.001). FMT was found to save QALYs at lower cost in 99.3% (vs vancomycin), 99.7% (vs fidaxomicin) and 100.0% (vs vancomycin plus bezlotoxumab) of the 10 000 Monte Carlo simulations.

CONCLUSIONS: FMT for IBD patients with RCDI appeared to save both direct medical cost and QALYs when comparing to vancomycin (with or without bezlotoxumab) and fidaxomicin.

RevDate: 2020-03-04

Peng Y, Thomas AS, Wei D, et al (2020)

An Aggressive Approach Toward a Case of Refractory Ulcerative Colitis With Uncertain Etiology in the Context of Chronic Myeloid Leukemia.

Inflammatory bowel diseases, 26(4):e26-e27.

RevDate: 2020-02-14

Li B, Yin GF, Wang YL, et al (2020)

Impact of fecal microbiota transplantation on TGF-β1/Smads/ERK signaling pathway of endotoxic acute lung injury in rats.

3 Biotech, 10(2):52.

Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Studies have shown that intestinal microbiota affect the pathology and immune function of respiratory diseases through the "gut-lung axis". The authors investigated the therapeutic effect of fecal microbiota transplantation (FMT) in rats with ALI induced by lipopolysaccharide (LPS). Rats were treated with FMT, and then measured lung wet/dry ratio, PaO2 in artery, proinflammatory marker, and TGF-β1, Smad3, Smad7, and phosphorylated ERK (p-ERK) protein levels, as well as a histopathologic analysis and high-throughput sequencing of intestinal microbiota. FMT significantly reduced lung wet/dry ratio and TNF-α, IL-1β, and IL-6 levels, but increased the levels of PaO2 in artery. In addition, FMT significantly decreased the expression of TGF-β1, Smad3, and p-ERK, while increased the levels of Smad7. Lung histopathological analyses showed that FMT reduced the inflammatory cell infiltration and interstitial lung exudates. High-throughput sequencing of intestinal microbiota analyses showed that FMT reconstructed the structure of intestinal microbiota, and increased the gene abundance of the bacterial community. Therefore, FMT may act on the TGF-β1/Smads/ERK pathway by regulating intestinal microbiota, inhibiting immune inflammation, reducing the production of inflammatory markers in the body and release, and reducing alveolar epithelial damage and repair, thereby improving the endotoxic ALI in rats induced by LPS.

RevDate: 2020-02-11

Sokol H, Landman C, Seksik P, et al (2020)

Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study.

Microbiome, 8(1):12.

BACKGROUND: The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD.

METHOD: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6).

RESULTS: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified.

CONCLUSION: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797). Video abstract.


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.

Electronic Scholarly Publishing
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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).


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


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 )