Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases. Invasion of the gut by oral bacteria in liver cirrhosis. Previous work has revealed an association between liver complications such as cirrhosis and the gut microbiome. Lanjuan Li and colleagues undertook a microbiome-wide association study of stool samples from 98 liver cirrhosis patients and 83 healthy controls. Quantitative metagenomics analysis revealed 75,245 genes that were significantly different in abundance between the two groups, many of which could be grouped into 66 clusters that represent cognate bacterial species. Of these, 28 species were enriched in liver cirrhosis patients and most were of buccal origin (mostly Veillonella and streptococci). The identified markers were unique liver cirrhosis-specific genes and the authors identify a set of just 15 of these genes that could form the basis of a highly accurate discrimination index that could be used as a diagnostic tool.

Alterations of the human gut microbiome in liver cirrhosis

Background: Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core o

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Changes of Intestinal Functions in Liver Cirrhosis

A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.

https://www.pnas.org/content/pnas/113/1/E7.full.pdf

Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip

Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions.

Author(s): Thung, I; Aramin, H; Vavinskaya, V; Gupta, S; Park, JY; Crowe, SE; Valasek, MA | Abstract: BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.

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Review article: the global emergence of Helicobacter pylori antibiotic resistance.

Gut microbiota and probiotics in chronic liver diseases

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori -infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naive to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

https://gut.bmj.com/content/gutjnl/59/11/1465.full.pdf

Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial

Intestinal permeability in patients with chronic liver diseases: Its relationship with the aetiology and the entity of liver damage.

A case of hepatotoxicity caused by green tea.

Background. During intesti - nal inflammation white blood cells are recruited from the blood, and they represent the major contributors to tissue perpetuation of inflamma - tion via their production of chemokines and pro- inflammatory cytokines. Objectives. Investigate the effect of a symbi - otic formulation containing Lactobacillus Paraca - sei B 20160 versus placebo, on serum levels of interleukin (IL)-6, tumor necrosis factor (TNF) α, IL-8, IL-1 β and IL-10 and on mRNA lymphomono - cyte expression of TNF α, IL-8 and IL-1 β in pa - tients with ulcerative colitis. Materials and Methods. Eighteen patients en - tered the study with histologically proven not complicated ulcerative colitis, treated with mesalazine. Patients were treated for 8 weeks (9 with symbiotic and 9 with placebo). Serum levels of IL-6, TNF α, IL-8, IL-1 β and IL-10 were measured using a commercially available sandwich ELISA kit. RT-PCR analysis was performed on total RNA isolated from peripheral lymphomonocytes. Results. In basal condition, there was an in - crease of serum levels of TNF α, IL-6, and IL-8. The treatment with symbiotic significantly de - creased serum levels of the last two cytokines (IL-6 and IL-8). In lymphocytes, the treatment with the symbiotic don't significantly reduced the mRNA expression of TNF α and IL-1 β, while that of IL-8 was strongly and significantly de - creased. Conclusion. Our preliminary results suggest that a symbiotic formulation containing Lacto - bacillus paracasei significantly improves the plasma and lymphocyte content of some proin - flammatory cytokines.

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The effect of a new symbiotic formulation on plasma levels and peripheral blood mononuclear cell expression of some pro-inflammatory cytokines in patients with ulcerative colitis: a pilot study.

A. Tiso

Papers

Gut microbiota and probiotics in chronic liver diseases

Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial

Intestinal permeability in patients with chronic liver diseases: Its relationship with the aetiology and the entity of liver damage.

A case of hepatotoxicity caused by green tea.

The effect of a new symbiotic formulation on plasma levels and peripheral blood mononuclear cell expression of some pro-inflammatory cytokines in patients with ulcerative colitis: a pilot study.