Table 1_The alteration of bile acids and gut microbiota is associated with intestinal barrier dysfunction and inflammaging in human.docx

BackgroundThe increasing prevalence of age-related chronic diseases, driven by the aging population, poses substantial medical and economic challenges. Emerging researches have underscored the crucial roles of gut microbiota and bile acids (BAs) in metabolic and physiological functions regulation.
Methods100 elderly and 100 young participants were enrolled in this study. Fecal and serum BAs were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), while gut microbiota composition was assessed through 16S rRNA gene sequencing. Cytokine levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA).
ResultsElderly participants exhibited significantly lower levels of primary fecal BAs, particularly cholic acid (CA) and chenodeoxycholic acid (CDCA), alongside an increase in secondary BAs such as lithocholic acid (LCA), leading to a marked reduction in the primary/secondary BAs ratio. Serum showed a decline in both conjugated and unconjugated BAs, primary/secondary BAs ratio, while a notable rise in 12α-OH/non-12α-OH BAs. Furthermore, increased levels of P21, LPS, IL-6, and TNF-α in the elderly were associated with specific BA changes, including reduced fecal unconjugated primary BAs and increased LCA. Significant differences in gut microbiota composition were observed, with the elderly displaying a higher abundance of microbiota capable of 7α-dehydroxylation. Correlations were observed among BAs, gut microbiota alterations, and markers of chronic inflammation and intestinal barrier dysfunction.
ConclusionAging is associated with significant changes in the BA pool, which are associated with gut microbiota dysbiosis. These alterations may be related to intestinal barrier dysfunction and chronic low-grade inflammation. Modulating BA metabolism presents a potential strategy for mitigating the aging process. Due to the cross-sectional design, causal relationships cannot be established.

研究背景：人口老龄化加剧导致年龄相关性慢性病患病率持续攀升，给医疗保健与经济发展带来了沉重负担。近年新兴研究已证实，肠道菌群（gut microbiota）与胆汁酸（bile acids, BAs）在代谢与生理功能调控中发挥关键作用。
研究方法：本研究共纳入100名老年受试者与100名青年受试者。采用液相色谱-串联质谱法（liquid chromatography-tandem mass spectrometry, LC-MS/MS）对粪便与血清中的胆汁酸进行定量检测；通过16S rRNA基因测序分析肠道菌群组成；采用酶联免疫吸附实验（Enzyme-Linked Immunosorbent Assay, ELISA）检测细胞因子水平。
研究结果：老年受试者粪便中初级胆汁酸水平显著降低，尤以胆酸（cholic acid, CA）与鹅脱氧胆酸（chenodeoxycholic acid, CDCA）为著；同时次级胆汁酸如石胆酸（lithocholic acid, LCA）水平升高，导致初级/次级胆汁酸比值显著下降。血清中结合型与非结合型胆汁酸、初级/次级胆汁酸比值均出现下降，而12α-羟基/非12α-羟基胆汁酸比值则显著升高。此外，老年受试者体内P21、脂多糖（lipopolysaccharide, LPS）、白细胞介素6（interleukin-6, IL-6）与肿瘤坏死因子α（tumor necrosis factor-α, TNF-α）水平升高，且这些变化与特定胆汁酸改变相关，包括粪便非结合型初级胆汁酸降低与石胆酸水平升高。肠道菌群组成存在显著差异，老年受试者中具备7α-脱羟活性的菌群丰度更高。胆汁酸、肠道菌群改变与慢性炎症及肠屏障功能障碍标志物之间存在显著相关性。
研究结论：衰老与胆汁酸池的显著改变密切相关，而该改变又与肠道菌群失调相关。上述异常变化可能与肠屏障功能障碍及慢性低度炎症有关。调控胆汁酸代谢或许是延缓衰老进程的潜在策略。由于本研究为横断面设计，无法确立因果关联。