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.

To cite: Jin X, lian J-s, hu Jh, et al. Gut epub ahead of print: [please include Day Month Year].

Liver cirrhosis is the pathologic end stage of chronic liver disease. Increasing evidence suggests that gut flora is implicated in the pathogenesis of liver cirrhosis complications. The aim of this study was to characterize the fecal microbial communities in patients with liver cirrhosis in comparison with healthy individuals. We recruited 36 patients with liver cirrhosis and 24 healthy controls. The fecal microbial community was analyzed by way of 454 pyrosequencing of the 16S ribosomal RNA V3 region followed by real-time quantitative polymerase chain reaction. Community-wide changes of fecal microbiota in liver cirrhosis were observed compared with healthy controls. The proportion of phylum Bacteroidetes was significantly reduced (P 5 0.008), whereas Proteobacteria and Fusobacteria were highly enriched in the cirrhosis group (P 5 0.001 and 0.002, respectively). Enterobacteriaceae (P 5 0.001), Veillonellaceae (P 5 0.046), and Streptococcaceae (P 5 0.001) were prevalent in patients with cirrhosis at the family level. A positive correlation was observed between Child-Turcotte-Pugh (CTP) score and Streptococcaceae (R 5 0.386, P 5 0.02). Lachnospiraceae decreased significantly in patients with cirrhosis (P 5 0.004) and correlated negatively with CTP score (R 5 20.49, P 5 0.002). Using partial least square discriminate analysis, we identified 149 operational taxonomic units (OTUs) as key phylotypes that responded to cirrhosis, most of which were Lachnospiraceae (65 OTUs), Streptococcaceae (23 OTUs), and Veillonellaceae (21 OTUs). Conclusion: Fecal microbial communities are distinct in patients with cirrhosis compared with healthy individuals. The prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae and Streptococcaceae, with the reduction of beneficial populations such as Lachnospiraceae in patients with cirrhosis may affect prognosis. (HEPATOLOGY 2011;54:562-572)

Background Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. Methods We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3–V4 region sequencing. Results Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94). Conclusions The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.

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