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Team Sees Gut Microbial Genes, Metagenomic Species Associated with Liver Cirrhosis

NEW YORK (GenomeWeb) – In a study appearing online today in Nature, researchers from China, France, and the UK described a gut microbiome signature for identifying individuals with liver cirrhosis, a form of advanced liver disease that can stem from a range of acute or chronic liver conditions or injuries.

The team began by developing the same type of gut microbial gene catalog described by researchers involved in the European MetaHIT project. In fecal samples from 98 Chinese individuals with liver cirrhosis and 83 unaffected individuals from the same population, it narrowed in on almost 2.7 million microbial genes, including many predicted protein-coding sequences not seen before.

When they used the new reference gene set — and similar gene catalogs from MetaHIT and other studies — to look more closely at microbial genes with especially high or low abundance in the guts of those with liver cirrhosis, the researchers narrowed in on 75,000 such genes, which fell into co-abundance gene clusters representing 66 metagenomic species.

Twenty-eight of the metagenomic species were more apt to appear in gut microbial communities from those with liver cirrhosis. More than half of those species seemingly originated in the mouth microbiome, hinting that bile production shifts associated with liver cirrhosis might make the gut more accessible to oral bugs.

"Use of the liver cirrhosis gene catalog, in conjunction with the quantitative metagenomics approach, revealed a major change of the gut microbiota in the patients with liver cirrhosis, mainly because of a massive invasion of the gut by oral bacterial species," the study's authors wrote. "Correlation of the severity of the disease with the abundance of the invading species suggests that they may play an active role in the pathology."

After tossing out gut microbial community members that seemed to be shared between individuals with liver cirrhosis and other conditions such as type 2 diabetes and inflammatory bowel disease, the investigators were left with 15 bacterial species suspected of being specific to liver cirrhosis.

That "patient discrimination index," or PDI, proved useful for accurately classifying liver cirrhosis cases in their analysis of samples from additional liver cirrhosis cases and controls.

"None of the 15 markers found in the liver cirrhosis study overlapped with the 50 markers found in the T2D study," they noted, "indicating that diagnosis of different diseases with microbiota-targeted biomarkers may be a powerful tool for disease detection."

Conversely, the study's authors saw hints that more severe liver cirrhosis cases coincided with declines in the presence of metagenomic species that dominated gut microbiomes from healthy Chinese individuals, pointing to potential probiotic candidates.

For instance, those healthy gut microbiomes tended to be home to species such as Faecalibacterium prausnitzii and Coprococcus comes, along with higher levels of bacteria from Bacteroidetes, Firmicutes, and Clostridiales phyla.

As in studies of obesity and inflammatory bowel disease, the overall diversity and gene richness was higher in the gut microbial communities from healthy individuals than it was in the gut microbiomes from those with disease.