Abstract
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.
Highlights
Cirrhosis is an advanced liver disease with high mortality and morbidity resulting from multiple liver injuries
Gut Microbial Dysbiosis Is Associated With liver cirrhosis (LC) Progression
To delineate the gut microbiome variations associated with LC progression, we retrieved 142 samples from the metagenomic shotgun sequencing data obtained previously (Qin et al, 2014) and acquired taxonomy information using MyTaxa with a likelihood cutoff of 0.8
Summary
Cirrhosis is an advanced liver disease with high mortality and morbidity resulting from multiple liver injuries. Determined as the 14th most common cause of death worldwide and fourth most frequent in central Europe, the morbidity and mortality rates due to cirrhosis continue to increase in more developed countries (Tsochatzis et al, 2014). Regarded as a single disease entity leading to death, cirrhosis is increasingly accepted as a dynamic process with the 1 year mortality rate ranging from 1 to 57% for patients at distinct clinical prognostic stages (Tsochatzis et al, 2014). Development of early interventions to stabilize disease progression and to avoid or delay decompensation of patients is of vital importance. Few clinical examinations are currently available for diagnosis of cirrhosis, except liver biopsy, which is not applicable to all patients and can lead to various complications in 2–3% patients (Schuppan and Afdhal, 2008). Clarification of the mechanisms underlying disease progression and identification of appropriate clinical factors that could be utilized as targets for disease monitoring and treatment remain an urgent medical requirement
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