Recent epidemiological and molecular studies have linked the disruption of cholesterol homeostasis to increased risk for developing Alzheimer's disease (AD). Emerging evidence also suggests that brain cholesterol accumulation contributes to the progression of hepatic encephalopathy (HE) via bile acid (BA)‐mediated effects on the farnesoid X receptor. In this perspective paper, we reviewed several recently published studies that suggested a role for the gut microbiota transformation of BAs as a factor in AD and HE development/progression. We hypothesize that in addition to cholesterol elimination pathways, alteration of the gut microbiota and subsequent changes in both the serum and brain BA profiles are mechanistically involved in the development of both AD and HE, and thus, are a potential target for the prevention and treatment of the two diseases. Our understanding of the microbiome‐BAs‐brain axis in central nervous system disease is still evolving, and critical questions regarding the emerging links among central, peripheral, and intestinal metabolic failures contributing to brain health and disease during aging have yet to be addressed.

中文翻译：

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专家见解：肠道微生物组-胆汁酸-脑轴在阿尔茨海默病和肝性脑病的发展和进展中的潜在作用。

最近的流行病学和分子研究将胆固醇稳态的破坏与患阿尔茨海默病 (AD) 的风险增加联系起来。新出现的证据还表明，脑胆固醇积累通过胆汁酸 (BA) 介导的法尼醇 X 受体作用促进肝性脑病 (HE) 的进展。在这篇前瞻性论文中，我们回顾了最近发表的几项研究，这些研究表明 BA 的肠道微生物群转化是 AD 和 HE 发展/进展的一个因素。我们假设除了胆固醇消除途径外，肠道微生物群的改变以及随后血清和大脑 BA 谱的变化在机制上都参与了 AD 和 HE 的发展，因此，是预防和治疗这两种疾病的潜在靶点。我们对中枢神经系统疾病中微生物组-BAs-脑轴的理解仍在不断发展，关于中枢、外周和肠道代谢衰竭之间新出现的联系导致衰老过程中大脑健康和疾病的关键问题尚未得到解决。