Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.
Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.
复制标题
DOI：
10.1016/j.cell.2020.09.009
复制
发表时间：
2020-10-29
期刊：
影响因子：
64.5
通讯作者：
Devkota S
中科院分区：
文献类型：
--
作者：
Ha CWY;Martin A;Sepich-Poore GD;Shi B;Wang Y;Gouin K;Humphrey G;Sanders K;Ratnayake Y;Chan KSL;Hendrick G;Caldera JR;Arias C;Moskowitz JE;Ho Sui SJ;Yang S;Underhill D;Brady MJ;Knott S;Kaihara K;Steinbaugh MJ;Li H;McGovern DPB;Knight R;Fleshner P;Devkota S
克罗恩病（CD）的一个神秘特征是“蠕动脂肪”（CrF）的肠外表现，定义为炎症和纤维化肠道周围肠系膜脂肪组织的扩张。在目前的研究中，我们探讨是否微生物易位在CD作为一个中央线索CrF的发展。我们发现了一个粘膜相关肠道细菌的子集，这些细菌在CD回肠手术切除术中始终易位并在CrF中保持活力，并将无害梭菌鉴定为该财团的特征，粘膜和脂肪分离株之间存在菌株变异，表明偏好富含脂质的环境。单细胞RNA测序的特征是CrF具有促纤维化和促脂肪形成的作用，并且具有丰富的对微生物刺激做出反应的激活免疫细胞环境，我们在定植了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无害梭菌通过M2巨噬细胞刺激组织重塑，导致脂肪组织屏障，用于防止细菌的全身传播。肠道细菌移位至肠系膜脂肪组织（MAT）自然发生来自克罗恩病（CD）的MAT具有由无害梭菌（C. innocuum）定义的细菌聚生体。CD中的这些细菌促进MAT的重组和“蠕动脂肪”的形成蠕动脂肪膨胀和纤维化防止肠道细菌的系统移位。提供证据表明，在患有炎症性肠病的人中，称为“蠕动脂肪”的现象是一种保护性反应，其中肠系膜脂肪组织迁移（或“蠕动”）到肠屏障功能障碍的部位，以防止从肠腔易位穿过屏障的潜在有害细菌抗原的全身传播。
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. Gut bacterial translocation to mesenteric adipose tissue (MAT) naturally occurs MAT from Crohn’s disease (CD) harbors a bacterial consortium defined by C. innocuum These bacteria in CD promote restructuring of MAT and formation of “creeping fat” Creeping fat expansion and fibrosis prevent systemic translocation of gut bacteria Ha et al. provide evidence that, in humans with inflammatory bowel disease, the phenomenon known as “creeping fat” is a protective response where mesenteric adipose tissue migrates (or “creeps”) to sites of gut barrier dysfunction to prevent systemic dissemination of potentially harmful bacterial antigens that have translocated across the barrier from the gut lumen.
登录
查看更多内容
影响因子：
3.8
作者：
Huh JY;Park YJ;Ham M;Kim JB
通讯作者：
Kim JB
影响因子：
2.7
作者：
Didion JP;Martin M;Collins FS
通讯作者：
Collins FS
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
11.1
作者：
Amar, Jacques;Chabo, Chantal;Waget, Aurelie;Klopp, Pascale;Vachoux, Christelle;Bermudez-Humaran, Luis G.;Smirnova, Natalia;Berge, Mathieu;Sulpice, Thierry;Lahtinen, Sampo;Ouwehand, Arthur;Langella, Philippe;Rautonen, Nina;Sansonetti, Philippe J.;Burcelin, Remy
通讯作者：
Burcelin, Remy
DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W