Alterations of the human gut microbiome in liver cirrhosis

Abstract

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.

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

“…Case-control studies have associated microbial traits in individuals with patterns of diseases, thereby implicating gastrointestinal microbial communities in a range of human disorders [6][7][8][9][10] . Metagenomics is able to resolve differences in the functional potential of microbial communities and has revealed a surprisingly stable set of core functions, even though gastrointestinal community structures display great inter-individual variation 2 .…”

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist

“…Sequencing of DNA extracted from patient samples is the most commonly used approach for studying the human microbiome (2). Human cohort sequencing studies have found strong correlations between changes in bacterial populations and human pathophysiology (3)(4)(5)(6)(7). Mouse models have been used to show that native bacterial ecology is necessary for normal physiologic functions and dysbiosis causes diseases like obesity, cancer, diabetes, and colitis among others (8)(9)(10)(11).…”

Microbiome alterations observed in liver diseases present opportunities for potential fecal transplantation

“…A 2014 study noted that patients with cirrhosis and hepatic encephalopathy were demonstrated to have relatively reduced abundance of native taxa including Lachnospiraceae, Ruminococcaceae, and a Clostridial strain while having a relatively higher abundance of others such as Enterobacteriaceae and higher proportion of Firmicutes (5). Multiple studies have demonstrated this same trend across cirrhotics due to alcohol, HCV, and cryptogenic etiologies (6)(7)(8)(9). The ratio of native versus non-native bacterial strains in cirrhotic patients is referred to as cirrhosis dysbiosis ratio (CDR).…”