Keystone Species in the Pathogenic Process of NAFLD

Abstract

BackgroundThe role of gut microbiome in the pathogenic process of NAFLD has been increasingly recognized. However, the keystone species in the gut of NAFLD, the critical factor(s) in maintaining the stability of the entire gut microbiome, has not been reported.MethodSparCC method was used to construct the microbial interaction ecosystem of human gut microbiome in healthy condition. PageRank algorithm was used to evaluate the importance of each bacterial species in healthy gut micro‐ecology system. Subsequently, the keystone species required for maintaining the stability of gut micro‐ecological system was identified on the basis of network stability assessment. Finally, the keystone species specific for NAFLD was determined by the quantitative analysis of gut microbiome between NAFLD patients and healthy people. And the relevant OTUs were annotated at species‐level based on phylogenetic trees. Furthermore, the same keystone species identification analysis was also conducted in NAFLD rats induced by high‐fat diet.ResultsHere we reconstructed the microbial interaction ecosystem of healthy human gut microbiome, consisting of 61 bacterial species and 90 pairwise interactions. Wherein, Bacteroides ovatus, Faecalibacterium prausnitzii, Barnesiella intestinihominis, Odoribacter splanchnicus, Roseburia faecis, Eubacterium ventriosum, Clostridium leptum were the seven keystone species that maintained the stability of the gut micro‐ecological system. The results of quantitative analysis indicated that the abundance of B. intestinihominis, E. ventriosum and C. leptum decreased significantly in the gut of NAFLD patients, and they were identified as the keystone species specific for NAFLD. These species could participate in the initiation and development of NAFLD by regulating the metabolic process of bile acid signaling and the activity of inflammasome. In addition, similar results were observed in the gut microbiome of NAFLD rats.ConclusionThis research identifies the keystone species specific for NAFLD, and highlights a novel target for the precise prevention and treatment of NAFLD based on gut microbiome. Importantly, our strategy for the identification of the keystone species can be extended to other ecological systems.Support or Funding InformationThis work was supported by National Natural Science Foundation of China 81770571 (to LZ), 81774152(to RZ), 41530105 (to RZ).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.