Isolithocholic acid is an isomer of lithocholic acid. Isolithocholic acid is a bile acid formed through microbial metabolism of lithocholic acid or its 3α-sulfate [1]. Isolithocholic acid can be used to regulate lipid metabolism and cholesterol homeostasis [2-3].
In vitro, Isolithocholic acid (0.625, 1.25, 2.5, 5, 10, 20 and 40μM; 18h) can dose-dependently inhibit the differentiation of initial CD4+ T cells into TH17 cells, and has no significant effect on cell viability or total cell number [4]. The treatment with isolithocholic acid (0.03mM, 0.15mM; 24h) significantly reduced the viability of Clostridium difficile, and at lower inhibitory concentrations, it also decreased the expression of the toxin (tcdA) [5].
In vivo, Isolithocholic acid (50mg/kg/day; 8 weeks) orally administered to a mouse model induced by high-fat diet for Nonalcoholic Steatohepatitis (NASH) reduces the levels of ALT, AST, TC and TG in mouse serum, alleviates the increase of inflammatory cells, lipid droplets and fibrosis. At the same time, the expression levels of IL-17 A, Act 1, TRAF 6, ERK, JUN, FOSB, IL-6, TNF-α, S100 A9, IL-23 R, RORγt, MMP-1, PPARγ and FABP 1 are decreased, while the expression levels of IL-2 R and Foxp 3 are increased [6]. B6Tac mice with a filamentous bacterial (SFB) host fed a powdered diet containing Isolithocholic acid (0.3% w/w; 4 days) have a reduced level of existing TH17 cells in the intestinal lamina propria of mice [7].
References:
[1] Batta, A.K., Salen, G., and Shefer, S.Transformation of bile acids into iso-bile acids by Clostridium perfringes: Possible transport of 3β-hydrogen via the coenzymeHepatology5(6)1126-1131(1985)
[2] Lu Y, Du J, Peng S, et al. Therapeutic potential of isoallolithocholic acid in methicillin-resistant Staphylococcus Aureus peritoneal infection[J]. The Journal of Antibiotics, 2025, 78(3): 166-180.
[3] Jiang J, Zhang H, Hussain M, et al. Novel Approaches in Glucose and Lipid Metabolism Disorder Therapy: Targeting the Gut Microbiota–Bile Acid Axis[J]. Biology, 2025, 14(7): 802.
[4] Hindson J. Bile acid metabolites produced by gut bacteria suppress TH17 cells[J]. Nature Reviews Gastroenterology & Hepatology, 2022, 19(5): 280-280.
[5] Kisthardt S C, Thanissery R, Pike C M, et al. The microbial-derived bile acid lithocholate and its epimers inhibit Clostridioides difficile growth and pathogenicity while sparing members of the gut microbiota[J]. Journal of Bacteriology, 2023, 205(9): e00180-23.
[6] Wang Y, Chen X, Huws S A, et al. Ileal microbial microbiome and its secondary bile acids modulate susceptibility to nonalcoholic steatohepatitis in dairy goats[J]. Microbiome, 2024, 12(1): 247. [7] Paik D, Yao L, Zhang Y, et al. Human gut bacteria produce ΤΗ17-modulating bile acid metabolites[J]. Nature, 2022, 603(7903): 907-912.
Isolithocholic acid是石胆酸的异构体。异石胆酸是一种胆汁酸，由石胆酸或石胆酸3α-硫酸盐的微生物代谢形成 [1]。Isolithocholic acid可用于调节脂质代谢 、 胆固醇稳态 [2-3]。
在体外，Isolithocholic acid（0.625, 1.25, 2.5, 5,10, 20 and 40μM; 18h）能够剂量依赖性地抑制初始CD4+ T细胞向TH17细胞的分化作用，且对细胞活力或总细胞数量没有显著影响 [4]。Isolithocholic acid（0.03mM, 0.15mM; 24h）处理显著降低了艰难梭菌的活力，并且在亚抑制浓度下，降低了毒素（tcdA）的表达 [5]。
在体内， Isolithocholic acid（50mg/kg/day; 8周）口服治疗高脂肪饮食诱导非酒精性脂肪性肝炎（NASH）的小鼠模型，降低了小鼠血清中ALT、AST、TC和TG水平，缓解了炎性细胞、脂滴和纤维化的增加。同时，检测到IL-17 A、Act 1、TRAF 6、ERK、JUN、FOSB、IL-6、TNF-α、S100 A9、IL-23 R、RORγt、MMP-1、PPARγ和FABP 1的表达水平降低，而IL-2 R和Foxp 3的表达水平升高 [6]。富含丝状细菌（SFB）宿主的B6Tac小鼠喂食含Isolithocholic acid（0.3% w/w; 4天）的粉状饲料，小鼠回肠固有层中已存在的TH17细胞水平降低 [7]。