南方医科大学左大明小组的一项最新研究揭示了肠道生态失调通过微生物代谢物驱动的Th2细胞分化加剧皮肤炎症。相关论文于2026年4月16日发表在《免疫学》杂志上。

研究组证明了肠道上皮Toll样受体（TLR）4缺陷重塑了肠道微生物群，随后加重了小鼠的特应性皮炎（AD）。从机制上讲，TLR4缺失降低了嗜粘阿克曼氏菌的丰度，并使表达胆碱三甲胺裂解酶（CutC）的细菌富集。这增强了微生物胆碱到三甲胺的转化和循环三甲胺氧化物（TMAO）水平的升高。临床上，AD患者血浆TMAO水平升高，与疾病严重程度和免疫球蛋白E （IgE）水平呈正相关。

英国生物银行的数据还显示，较高的饮食胆碱摄入量与阿尔茨海默病风险增加有关。TMAO通过直接与蛋白磷酸酶5 （PPP5）相互作用，增强PPP5介导的PPARγ去磷酸化，促进辅助性T (Th)2分化。CD4⁺ T细胞特异性PPARγ缺失可消除AD小鼠TMAO驱动的皮肤病理。他们的研究结果揭示了肠道生态失调，作为先天免疫缺陷的结果，是炎症性Th2细胞和AD病理的驱动因素，突出了肠道免疫环境、微生物代谢物和皮肤病之间的联系。

研究人员表示，肠道微生物群和粘膜免疫系统之间的相互作用对全身免疫和疾病易感性具有重要的调节作用。

附：英文原文

Title: Intestinal dysbiosis exacerbates skin inflammation via microbial metabolite-driven Th2 cell differentiation

Author: Lu Yu, Shuying Peng, Xi Chen, Tianxing Wu, Lijun Dong, Jialiang Luo, Shuangbin Xu, Jia Zhou, Xiaoshan Zhao, Lei Zheng, Gang Shu, Xuemin Wang, Liping Huang, Qingyun Chen, Deke Jiang, Liang-Dan Sun, Phillip Hylemon, Xiang-Yang Wang, Ledong Sun, Li Ma, Daming Zuo

Issue&Volume: 2026-04-16

Abstract: The interplay between gut microbiota and the mucosal immune system critically regulates systemic immunity and disease susceptibility. Here, we demonstrate that intestinal epithelial Toll-like receptor (TLR)4 deficiency reshaped the gut microbiome and subsequently exacerbated atopic dermatitis (AD) in mice. Mechanistically, TLR4 deficiency reduced Akkermansia muciniphila abundance and enriched choline trimethylamine-lyase (CutC)-expressing bacteria. This enhanced microbial choline-to-trimethylamine conversion and elevated circulating trimethylamine oxide (TMAO) levels. Clinically, AD patients exhibited increased plasma TMAO levels that positively correlated with disease severity and immunoglobulin E (IgE) levels. UK Biobank data also showed that higher dietary choline intake was associated with increased AD risk. TMAO promoted T helper (Th)2 differentiation by directly interacting with protein phosphatase 5 (PPP5) and enhancing PPP5-mediated dephosphorylation of PPARγ. CD4+ T cell-specific PPARγ deletion abolished TMAO-driven skin pathology in AD mice. Our results reveal intestinal dysbiosis, as a result of innate immune deficiency, as a driver of inflammatory Th2 cells and AD pathology, highlighting a link among the gut immune environment, microbial metabolites, and skin disease.

DOI: 10.1016/j.immuni.2026.03.019

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00130-5