Camilleri Michael
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Am J Physiol Gastrointest Liver Physiol. 2022 May 1;322(5):G480-G488. doi: 10.1152/ajpgi.00011.2022. Epub 2022 Mar 8.
Bile acids are amphipathic, detergent molecules. The detergent effects of di-α-hydroxy-bile acids are relevant to several colonic diseases. The aims were to review the concentrations of bile acids reaching the human colon in health and disease, the molecular structure of bile acids that determine detergent functions and the relationship to human diseases (neuroendocrine tumors, microscopic colitis, active celiac disease, and ulcerative colitis, Crohn's disease and ileal resection), the relationship to bacterial uptake into the mucosa, mucin depletion, and epithelial damage, the role of bile acids in mucosal inflammation and microscopic colitis, and the role of sulfation of bile salts in detoxification or prevention of the detergent effects of bile acids. The concentrations of bile acids reaching the human colon range from 2 to 10 mM; di-α-hydroxy bile acids are the only bile acids with detergent effects that include mucin depletion, mucosal damage, bacterial uptake, and microscopic inflammation that may be manifest in diseases associated with no overt inflammation of the mucosa, such as bile acid diarrhea, ileal diseases such as neuroendocrine tumors, ileal resection, and nonalcoholic steatohepatitis. Sulfation inactivates colonic secretion due to primary bile acids, but it may render secondary bile acids proinflammatory in the colon. Other evidence in preclinical models of inflammatory bowel disease (IBD) suggests reduced sulfation causes barrier dysfunction, inflammation, or carcinogenesis. These advances emphasize relevance and opportunities afforded by greater understanding of the chemistry and metabolism of bile acids, which stands to be further enhanced by research into the metabolic interactions of microbiota with bile acids.
胆汁酸是具有两亲性的去污剂分子。二-α-羟基胆汁酸的去污剂作用与多种结肠疾病相关。本文旨在综述健康和疾病状态下到达人类结肠的胆汁酸浓度、决定去污剂功能的胆汁酸分子结构及其与人类疾病(神经内分泌肿瘤、显微镜下结肠炎、活动性乳糜泻、溃疡性结肠炎、克罗恩病和回肠切除术)的关系、与细菌向黏膜内摄取、黏蛋白消耗及上皮损伤的关系、胆汁酸在黏膜炎症和显微镜下结肠炎中的作用,以及胆汁酸盐硫酸化在胆汁酸解毒或防止其去污剂作用方面的作用。到达人类结肠的胆汁酸浓度范围为2至10 mM;二-α-羟基胆汁酸是唯一具有去污剂作用的胆汁酸,其作用包括黏蛋白消耗、黏膜损伤、细菌摄取以及显微镜下炎症,这些作用可能在与黏膜无明显炎症相关的疾病中表现出来,如胆汁酸腹泻、回肠疾病(如神经内分泌肿瘤、回肠切除术和非酒精性脂肪性肝炎)。硫酸化可使初级胆汁酸引起的结肠分泌失活,但它可能使次级胆汁酸在结肠中具有促炎作用。炎症性肠病(IBD)临床前模型中的其他证据表明,硫酸化减少会导致屏障功能障碍、炎症或致癌作用。这些进展强调了深入了解胆汁酸化学和代谢所带来的相关性和机遇,而微生物群与胆汁酸代谢相互作用的研究有望进一步加强这方面的认识。