Integrative metagenomic and metabolomic analyses reveal the potential of gut microbiota to exacerbate acute pancreatitis

作者：Jianjun Liu, Qiulong Yan, Shenghui Li, Juying Jiao, Yiming Hao, Guixin Zhang, Qingkai Zhang, Fei Luo, Yue Zhang, Qingbo Lv, Wenzhe Zhang, Aiqin Zhang, Huiyi Song, Yi Xin, Yufang Ma, Lawrence Owusu, Xiaochi Ma, Peiyuan Yin, Dong Shang · 发表于：npj Biofilms and Microbiomes · 年份：2024 · DOI：10.1038/s41522-024-00499-4 · 被引用次数：44 · 研究领域：Pancreatitis Pathology and Treatment、Pancreatic and Hepatic Oncology Research、Gut microbiota and health

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In con...