波士顿儿童医院Talal A. Chatila研究团队证实菌群疗法通过调节性T细胞MyD88/RORγt途径抑制食物过敏。相关成果于2019年7月发表在《自然—医学》杂志上。

研究小组发现FA婴儿的粪便微生物群中的微生物群随着时间的推移而进化，并且在小鼠中未能防止FA。FA婴儿和老鼠的粪便细菌中IgA降低、IgE增加, 表明口服免疫耐受比迄今为止所理解的更广泛。采用受到菌群失调影响的梭菌属物种进行治疗，无论作为联合体或用Subdoligranulum variabile的单一疗法，同单独免疫调节性的拟杆菌目联合体一样可以抑制小鼠食物过敏。细菌疗法通过调节性T（Treg）细胞以MyD88依赖性方式诱导转录因子ROR-γt的表达，其在FA婴儿和小鼠中缺乏并且无法由微生物群有效诱导。Treg细胞中Myd88或Rorc的缺失消除了细菌疗法的作用。因此，正常菌丛激活新生Treg细胞中的MyD88 / ROR-γt途径以防止FA，而菌群失调损害了这种调节反应以促进疾病。

目前，菌群失调在食物过敏（FA）中的作用仍不清楚。

附：英文原文

Title: Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy

Author: Azza Abdel-Gadir, Emmanuel Stephen-Victor, Georg K. Gerber, Magali Noval Rivas, Sen Wang, Hani Harb, Leighanne Wang, Ning Li, Elena Crestani, Sara Spielman, William Secor, Heather Biehl, Nicholas Dibendetto, Xiaoxi Dong, Dale T. Umetsu, Lynn Bry, Rima Rachid, Talal A. Chatila

Issue&Volume: Volume 25 Issue 7, July 2019

Abstract: The role of dysbiosis in food allergy (FA) remains unclear. We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated. Therapy with Clostridiales species impacted by dysbiosis, either as a consortium or as monotherapy with Subdoligranulum variabile, suppressed FA in mice as did a separate immunomodulatory Bacteroidales consortium. Bacteriotherapy induced expression by regulatoryT (Treg) cells of the transcription factor ROR-t in a MyD88-dependent manner, which was deficient in FA infants and mice and ineffectively induced by their microbiota. Deletion of Myd88 or Rorc in Treg cells abrogated protection by bacteriotherapy. Thus, commensals activate a MyD88/ROR-t pathway in nascent Treg cells to protect against FA, while dysbiosis impairs this regulatory response to promote disease.

DOI: 10.1038/s41591-019-0461-z

Source:https://www.nature.com/articles/s41591-019-0461-z