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.

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)

The human gut microbiota is a complex system that is essential to the health of the host. Increasing evidence suggests that the gut microbiota may play an important role in the pathogenesis of colorectal cancer (CRC). In this study, we used pyrosequencing of the 16S rRNA gene V3 region to characterize the fecal microbiota of 19 patients with CRC and 20 healthy control subjects. The results revealed striking differences in fecal microbial population patterns between these two groups. Partial least-squares discriminant analysis showed that 17 phylotypes closely related to Bacteroides were enriched in the gut microbiota of CRC patients, whereas nine operational taxonomic units, represented by the butyrate-producing genera Faecalibacterium and Roseburia, were significantly less abundant. A positive correlation was observed between the abundance of Bacteroides species and CRC disease status (R = 0.462, P = 0.046 < 0.5). In addition, 16 genera were significantly more abundant in CRC samples than in controls, including potentially pathogenic Fusobacterium and Campylobacter species at genus level. The dysbiosis of fecal microbiota, characterized by the enrichment of potential pathogens and the decrease in butyrate-producing members, may therefore represent a specific microbial signature of CRC. A greater understanding of the dynamics of the fecal microbiota may assist in the development of novel fecal microbiome-related diagnostic tools for CRC.

The beneficial effects of Bifidobacteria on health have been widely accepted. Patients with chronic liver disease have varying degrees of intestinal microflora imbalance with a decrease of total Bifidobacterial counts. Since different properties have been attributed to different Bifidobacterium species and there is no information available for the detailed changes in the genus Bifidobacterium in patients with chronic liver disease heretofore, it is meaningful to investigate the structure of this bacterium at the species level in these patients. The aim of this study was to characterize the composition of intestinal Bifidobacterium in patients with hepatitis B virus-induced chronic liver disease. Nested-PCR-based denaturing gradient gel electrophoresis (PCR-DGGE), clone library, and real-time quantitative PCR were performed on the fecal samples of 16 patients with chronic hepatitis B (CHB patients), 16 patients with hepatitis B virus-related cirrhosis (HBV cirrhotics), and 15 healthy subjects (Controls). Though there was no significant difference in the diversity among the three groups (P = 0.196), Bifidobacterium dentium seems to be specifically enhanced in patients as the PCR-DGGE profiles showed, which was further validated by clone library and real-time quantitative PCR. In contrast to the B. dentium, Bifidobacterium catenulatum/Bifidobacterium pseudocatenulatum were detected less frequently in the predominant profile and by quantitative PCR in HBV cirrhotics than in the controls, and the level of this species was also significantly different between these two groups (P = 0.023). Although having no quantitative difference among the three groups, Bifidobacterium longum was less commonly detected in HBV cirrhotics than in CHB patients and Controls by quantitative PCR (P = 0.011). Thus, the composition of intestinal Bifidobacterium was deeply altered in CHB and HBV cirrhotic patients with a shift from beneficial species to opportunistic pathogens. The results provide further insights into the dysbiosis of the intestinal microbiota in patients with hepatitis B virus-induced chronic liver disease and might potentially serve as guidance for the probiotics interventions of these diseases.

Early detection and effective interventions for liver cirrhosis (LC) remain an urgent unmet clinical need. Inspired from intestinal disorders in LC patients, we investigated the associations between gut microbiome and disease progression based on a raw metagenomic dataset of 47 healthy controls, 49 compensated, and 46 decompensated LC patients from our previous study, and a metabolomic dataset of urine samples from the same controls/patients using ultra-performance liquid chromatography/mass spectrophotometry system. It was found that the combination and relative abundance of gut microbiome, the inter-microbiome regulatory networks, and the microbiome-host correlation patterns varied during disease progression. The significant reduction of bacteria involved in fermentation of plant cell wall polysaccharides and resistant starch (such as Alistipes sp. HG5, Clostridium thermocellum) contributed to the reduced supply of energy sources, the disorganized self-feeding and cross-feeding networks and the thriving of some opportunistic pathogens in genus Veillonella. The marked decrease of butyrate-producing bacteria and increase of Ruminococcus gnavus implicated in degradation of elements from the mucus layer provided an explanation for the impaired intestinal barrier function and systematic inflammation in LC patients. Our results pave the way for further developments in early detection and intervention of LC targeting on gut microbiome.