Causal relationships between gut microbrome and digestive system diseases: A two-sample Mendelian randomization study.

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs.

Modulating host gene expression via gut microbiome-microRNA interplay to treat human diseases.

The human gastrointestinal (GI) tract hosts trillions of microbial inhabitants involved in maintaining intestinal homeostasis, dysbiosis of which provokes a motley of pathogenic and autoimmune disorders. While the mechanisms by which the microbiota modulates human health are manifold, their liberated metabolites from ingested dietary supplements play a crucial role by bidirectionally regulating the expression of micro-ribonucleic acids (miRNAs). miRNAs are small endogenous non-coding RNAs (ncRNAs) that have been confirmed to be involved in an interplay with microbiota to regulate host gene expression. This comprehensive review focuses on key principles of miRNAs, their regulation, and crosstalk with gut microbiota to influence host gene expression in various human disorders, by bringing together important recent findings centric around miRNA-microbiota interactions in diseases along various axis of the gut with other organs. We also attempt to lay emphasis on exploiting the avenues of gut-directed miRNA therapeutics using rudimentary dietary supplements to regulate abnormal host gene expression in diseases, opening doors to an accessible and economical therapeutic strategy.

Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection.

Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15-1.36; P = 1.8 × 10-7), including sepsis (HR 2.68; 95% CI = 2.25-3.19; P = 3.1 × 10-28), pneumonia (HR 1.76; 95% CI = 1.53-2.03; P = 2.3 × 10-15), digestive system infections (HR 1.51; 95% CI = 1.32-1.73; P = 2.2 × 10-9) and genitourinary infections (HR 1.25; 95% CI = 1.11-1.41; P = 3.7 × 10-4). A genome-wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections.

Efficacy of Single-Strain Probiotics Versus Multi-Strain Mixtures: Systematic Review of Strain and Disease Specificity.

The diversity of probiotic products makes choosing an appropriate probiotic challenging. One unanswered question is whether single-strain probiotics are more effective than multi-strain mixtures. The aim of this review is to account for both disease and strain specificity to determine whether single strains or multiple strains are equivalent or more effective. This literature review of randomized controlled trials from 1973 to 2019 was used to compare the pooled efficacy of trials with a single strain versus the probiotic mixture with same matched strain within the same type of disease indication. A total of 65 RCTs were included (41 with single strains, 22 multi-strain mixtures and 2 comparing single strain to mixture arms) for eight different disease indications (N = 10,863). Only three strains (L. rhamnosus GG, L. helveticus R52 and B. lactis Bb12) had corresponding trials with matching mixtures. Use of L. rhamnosus GG only was significantly more protective for necrotizing enterocolitis compared to two mixtures also containing different strains of B. lactis. The mixture of L. rhamnosus GG and B. lactis Bb12 was significantly more effective than L. rhamnosus GG alone for the eradication of H. pylori. In most cases, single strains were equivalent to mixtures. Choice of an appropriate probiotic should be based, not on the number of strains in the product, rather based on evidence-based trials of efficacy. In most cases, multi-strain mixtures were not significantly more effective than single-strain probiotics.

Analysis of biliary MICRObiota in hepatoBILIOpancreatic diseases compared to healthy people [MICROBILIO]: Study protocol.

BACKGROUND: The performance of the microbiota is observed in several digestive tract diseases. Therefore, reaching the biliary microbiota may suggest ways for studies of biomarkers, diagnoses, tests and therapies in hepatobiliopancreatic diseases. METHODS: Bile samples will be collected in endoscopic retrograde cholangiopancreatography patients (case group) and living liver transplantation donors (control group). We will characterize the microbiome based on two types of sequence data: the V3/V4 regions of the 16S ribosomal RNA (rRNA) gene and total shotgun DNA. For 16S sequencing data a standard 16S processing pipeline based on the Amplicon Sequence Variant concept and the qiime2 software package will be employed; for shotgun data, for each sample we will assemble the reads and obtain and analyze metagenome-assembled genomes. RESULTS: The primary expected results of the study is to characterize the specific composition of the biliary microbiota in situations of disease and health. In addition, it seeks to demonstrate the existence of changes in the case of illness and also possible disease biomarkers, diagnosis, interventions and therapies in hepatobiliopancreatic diseases. TRIAL REGISTRATION: NCT04391426. Registered 18 May 2020, https://clinicaltrials.gov/ct2/show/NCT04391426.

Epidemiological Profile of Helicobacter pylori Infection in Patients with Digestive Symptoms in Algeria.

BACKGROUND: The purpose of this study was to assess the prevalence of Helicobacter pylori infection in Algerian patients with peptic disorders and evaluate the impact of different epidemiological factors (age, sex, sampling site, presence or absence of H. pylori, and type of pathology related to this bacterium). METHODS: We undertook a retrospective and descriptive study on a series of 735 symptomatic patients identified in the laboratory of pathological anatomy at Hassani Abdelkader University Hospital Center of Sidi Bel Abbes, Algeria, over a period of 16 years from January 2002 to December 2017. All patients had benefited from a high gastroscopic fibroscopy and the diagnosis was made by histological examination (hematoxylin-eosin staining). The epidemiological factors, as well as the main gastric diseases related to this bacterium, were studied. RESULTS: The prevalence of H. pylori infection was 66.12%. The infection was more important in the age group 60-69 years (71.43%). The prevalence of H. pylori infection was statistically higher in women than in men (69.3% vs. 60.7%, p < 0.01).The antral region was most colonized by H. pylori (71.73%). In addition, the infection was associated mainly with atrophic gastritis (69.65%). CONCLUSION: In this context, the identification of epidemiological data would be of great value in guiding strategies to control the spread of this bacterium.

Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective.

An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, now known as coronavirus disease 2019 (COVID-19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID-19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal-oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID-19; (b) microbiological and virological investigations; (c) the role of fecal-oral transmission; and (d) prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.

Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders.

Gut microbiota dysbiosis has been repeatedly observed in obesity and type 2 diabetes mellitus, two metabolic diseases strongly intertwined with non-alcoholic fatty liver disease (NAFLD). Animal studies have demonstrated a potential causal role of gut microbiota in NAFLD. Human studies have started to describe microbiota alterations in NAFLD and have found a few consistent microbiome signatures discriminating healthy individuals from those with NAFLD, non-alcoholic steatohepatitis or cirrhosis. However, patients with NAFLD often present with obesity and/or insulin resistance and type 2 diabetes mellitus, and these metabolic confounding factors for dysbiosis have not always been considered. Patients with different NAFLD severity stages often present with heterogeneous lesions and variable demographic characteristics (including age, sex and ethnicity), which are known to affect the gut microbiome and have been overlooked in most studies. Finally, multiple gut microbiome sequencing tools and NAFLD diagnostic methods have been used across studies that could account for discrepant microbiome signatures. This Review provides a broad insight into microbiome signatures for human NAFLD and explores issues with disentangling these signatures from underlying metabolic disorders. More advanced metagenomics and multi-omics studies using system biology approaches are needed to improve microbiome biomarkers.

Use of steroids for abdominal tuberculosis: a systematic review and meta-analysis.

BACKGROUND: The role of adjunctive steroids in abdominal tuberculosis is unclear. OBJECTIVE: To evaluate effect of adjunctive use of steroids for abdominal tuberculosis in reducing/preventing complications. METHODS: We searched electronic databases (Medline, Embase, CENTRAL, Scopus, Web of Science, CINAHL) from inception to 25th June 2018 using the terms "abdominal tuberculosis" OR "intestinal tuberculosis" OR "peritoneal tuberculosis" OR "tuberculous peritonitis" AND steroids OR methylprednisolone OR prednisolone. Bibliography of potential articles was also searched. We included studies comparing adjunctive steroids to antitubercular therapy (ATT) alone. We excluded non-English articles, case reports, reviews and unrelated papers. The primary outcome was a comprehensive clinical outcome including need for surgery or the presence of symptomatic stricture (abdominal pain or intestinal obstruction). Quality assessment of included studies was done using ROBINS-I tool. Random-effects model was used to calculate the summary effect for all the outcomes. RESULTS: Of total 633 records, three studies on peritoneal tuberculosis were included in meta-analysis. These papers were of poor quality (one quasi-randomised study and two retrospective cohort studies). Meta-analyses showed adjunctive steroids, with ATT is more effective than ATT alone in tuberculous peritonitis patients for the prevention of composite end point (RR 0.15 [0.04, 0.62], p = 0.008), symptomatic stricture(RR 0.15 [0.04-0.62] p = 0.008) and intestinal obstruction (RR 0.18 [0.03-0.99] p = 0.05). CONCLUSION: The data on use of steroids for abdominal tuberculosis are limited to peritoneal tuberculosis. Although steroids seem to have some benefit in patients of tubercular peritonitis, the poor quality of studies limits the generalisability of the findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42016047347.

Digestive disorders and Intestinal microbiota.

In the last decade, a barge body of scientific literature has suggested that specific alterations of the gut microbiota may be associated with ther development and clinical course of several gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, gastrointestinal cancer and Clostridium difficile infection. These alterations are often referred to as "dysbiosis", a generic term designing reduction of gut microbiota biodiversity and alterations in its composition. Here, we provide a synthetic overview of the key concepts on the relationship between intestinal microbiota and gastrointestinal diseases, focusing on the translation of these concepts into clinical practice.

[Research progress on the relationship between oral microbes and digestive system diseases].

The human microbiome project promoted further understanding on human oral microbes. Besides oral diseases such as dental caries, periodontal disease, and oral cancer, oral microbes are closely associated with systematic diseases. They have a close connection with digestive system diseases and even contribute to the origination and progression of colorectal cancer. By reviewing recent studies involving oral microbe-related digestive systemic diseases, we aim to propose the considerable role of oral microbes in relation to digestive systemic diseases and the way of oral microbes to multiple organs of digestive system.

Interplay between gut microbiota metabolism and inflammation in HIV infection.

HIV infection causes a disruption of gut-associated lymphoid tissue, driving a shift in the composition of gut microbiota. A deeper understanding of the metabolic changes and how they affect the interplay with the host is needed. Here, we assessed functional modifications of HIV-associated microbiota by combining metagenomic and metatranscriptomic analyses. The transcriptionally active microbiota was well-adapted to the inflamed environment, overexpressing pathways related to resistance to oxidative stress. Furthermore, gut inflammation was maintained by the Gram-negative nature of the HIV-associated microbiota and underexpression of anti-inflammatory processes, such as short chain fatty acid biosynthesis or indole production. We performed co-occurrence and metabolic network analyses that showed relevance in the microbiota structure of both taxonomic and metabolic HIV-associated biomarkers. The Bayesian network revealed the most determinant pathways for maintaining the structure stability of the bacterial community. In addition, we identified the taxa's contribution to metabolic activities and their interactions with host health.

Digestive decontamination in burn patients: A systematic review of randomized clinical trials and observational studies.

OBJECTIVE: The objective of this systematic review is to assess the effect of selective digestive decontamination (SDD) or non-absorbable enteral antibiotics (EA) on mortality, the incidence of infection and its adverse effects in burn patients. MATERIAL AND METHODS: Systematic review of randomized clinical trials (RCT) or observational studies enrolling burn patients, and comparing SDD or EA prophylaxis with placebo or no treatment. The search includes Pubmed/Medline, EMBASE, WOS, Cochrane Library (1970-2015). Bibliographic references were also reviewed, as well as communications presented at conferences (2012-2015), without language restrictions. Two reviewers inspected each reference identified by the search independently; the risk of bias was assessed with the Cochrane Collaboration method for RCT and the Newcastle Ottawa Scale for observational studies. RESULTS: Five RCT and 5 observational studies were identified enrolling a total of 1680 patients. The overall methodological quality of the studies was poor. The pooled effect of RCT using EA was OR: 0.62 (95% CI: 0.20-1.94). The only RCT using SDD reported OR 0.20 (95% CI: 0.09-0.81). The incidence of Enterobacteriaceae bloodstream was lower in cases treated with SDD or EA. The incidence of pneumonia was only reduced in the studies using SDD. None of the studies reported an increase in antibiotic resistance but in one RCT SDD was associated to an increase in methicillin-resistant Staphylococcus aureus infections, that was controlled with enteral vancomycin. CONCLUSIONS: SDD and EA have shown a beneficial effect in burn patients. Both practices are safe. Higher quality RCTs should be conducted to properly assess the efficacy and safety of SDD in this population.

Resistance profiles and risk factors of resistant microorganisms in bacteraemia of abdominal origin. / Perfiles de resistencia y factores de riesgo de microorganismos resistentes en bacteriemia de origen abdominal.

OBJECTIVE: The presence of resistant microorganisms is a major cause of failure in initial empirical antimicrobial therapy. The objectives of this study are to determine the resistance profile of microorganisms that cause bacteraemia of abdominal origin and to identify whether the previous use of antibiotics and the place of acquisition of bacteraemia are risk factors associated with the presence of resistant organisms. MATERIAL AND METHODS: A clinical, observational, epidemiological, retrospective cohort study was conducted with all the adult patients admitted to a university hospital from 2011-2013. Antimicrobial resistance profiles were described and a 95% confidence interval chi-square test was used to determine whether the variables studied were risk factors in the isolation of resistant microorganisms. RESULTS: Of the 1245 patients with bacteraemia, 212 (17%) presented bacteraemia of abdominal origin. The resistance profile highlights the incidence of methicillin resistant Staphylococcus aureus (50%), coagulase-negative staphylococci resistant to linezolid (20.58%), enterococci resistant to vancomycin (3.12%), Escherichia coli resistant to third-generation cephalosporins (9.9%) and fluoroquinolones (35.64%), Klebsiella pneumoniae resistant to third-generation cephalosporins (8.33%), Pseudomonas aeruginosa resistant to fluoroquinolones and carbapenem (25% and 25% respectively) and Acinetobacter baumanii resistant to fluoroquinolones and carbapenem (100% and 100% respectively), Candida albicans resistant to fluconazole (11.11%), single Candida krusei isolate resistant to fluconazole and Candida parapsilosis resistant to echinocandins (12.5%). In our study, previous use of antibiotics had a statistically significant association with the isolation of resistant microorganisms (P=.013) but not the place of acquisition of bacteraemia (P=.239). CONCLUSION: Establishing the incidence of resistant organisms can improve empirical antimicrobial therapy in patients with bacteraemia of abdominal origin. Previous use of antibiotics was statistically significantly related to the isolation of resistant microorganisms.

An update on probiotics, prebiotics and symbiotics in clinical nutrition. / Actualización de probióticos, prebióticos y simbióticos en nutrición clínica.

The concept of prebiotics, probiotics, and symbiotics and their use in different situations of daily clinical practice related to clinical nutrition is reviewed, as well as their role in the treatment/prevention of diarrhea (acute, induced by antibiotics, secondary to radiotherapy), inflammatory bowel disease (ulcerative colitis and pouchitis), in colonic health (constipation, irritable bowel), in liver disease (steatosis and minimum encephalopathy), and in intensive care, surgical, and liver transplantation. While their effectiveness for preventing antibiotic-induced diarrhea and pouchitis in ulcerative colitis appears to be shown, additional studies are needed to establish recommendations in most clinical settings. The risk of infection associated to use of probiotics is relatively low; however, there are selected groups of patients in whom they should be used with caution (as jejunum infusion).

Human Microbiome and its Association With Health and Diseases.

Human microbiota are distinct communities of microorganisms that resides at different body niches. Exploration of the human microbiome has become a reality due to the availability of powerful metagenomics and metatranscriptomic analysis technologies. Recent advances in sequencing and bioinformatics over the past decade help provide a deep insight into the nature of the host-microbial interactions and identification of potential deriver genes and pathways associated with human health, well-being, and predisposition to different diseases. In the present review, we outline recent studies devoted to elucidate the possible link between the microbiota and various type of diseases. The present review also highlights the potential utilization of microbiota as a potential therapeutic option to treat a wide array of human diseases. J. Cell. Physiol. 231: 1688-1694, 2016. © 2015 Wiley Periodicals, Inc.

Advances in molecular diagnosis of parasitic enteropathogens.

Here, recent developments in the detection and identification of parasites causing enteric infection are reviewed including the utility and challenges of multi-target molecular assays. Difficulties in clinical interpretation arising from increased detection of parasites, of co-infection with other enteropathogens and of asymptomatic carriage are discussed. Published approaches for detection across a broad range of organisms are described, including commercial assays available to Australian laboratories. Using local data, the impact of introduction of modern molecular assays is assessed. In addition, recent advances in high density multi-target molecular platforms are discussed as potential platforms for increasing the scope of enteric pathogens to be detected whilst maintaining appropriate costs.