A mysterious feature of Crohn’s disease (CD) is the extra-intestinal manifestation of “creeping fat” (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

克罗恩病 (CD) 的一个神秘特征是“蠕动脂肪”(CrF) 的肠外表现，定义为发炎和纤维化肠道周围肠系膜脂肪组织的扩张。在当前的研究中，我们探讨 CD 中的微生物易位是否是 CrF 发育的中心线索。我们发现了粘膜相关肠道细菌的一个子集，在 CD 回肠手术切除的 CrF 中持续易位并保持活力，并确定无害梭状芽孢杆菌 ( Clostridium innocuum)为该菌群的标志，其粘膜和脂肪分离株之间存在菌株差异，表明对富含脂质的环境的偏好。单细胞 RNA 测序表明 CrF 具有促纤维化和促脂肪生成的特性，具有丰富的激活免疫细胞对微生物刺激做出反应的环境，我们在感染无害梭菌的无菌小鼠中证实了这一点。表达模式的离体验证表明， C. innocuum通过 M2 巨噬细胞刺激组织重塑，形成脂肪组织屏障，从而防止细菌的全身传播。