When Gut Microbiota Creep into Fat, the Fat Creeps Back

Abstract

Ha and colleagues describe a previously unappreciated diversity of microbes in the mesenteric adipose tissue (MAT) surrounding the GI tract. Viable bacteria that are mislocalized from the gut microbiota and metabolically adapted to the MAT contribute to the "creeping fat" of Crohn's disease.

Figure 1.

Microbial translocation into mesenteric adipose tissue contributes to Crohn’s disease “Creeping Fat”. (Left side) This study finds that the mesenteric adipose tissue (MAT) in Crohn’s disease (CD) is enriched for an immune infiltrate that includes: T cells, B cells and macrophages with a mixed tissue remodeling type 2 and an inflammatory type 1 program. They find the unique presence of five bacterial and two fungal species in CD MAT listed above. (Right side) Isolates of C. innocuum from CD MAT as compared to CD mucosa are enriched for metabolism of beta-hydroxybutyrate, a substrate from lipolysis abundant in fat, as well as expression of serpin B and arginase, enzymes that protect against neutrophil elastase and inhibit macrophage nitric oxide production, respectively. In vitro experiments revealed no significant response from primary MAT stromal and stem cells when Crohn’s MAT-specific bacteria are added, but do demonstrate expression of collagen genes when they are exposed to macrophage conditioned media, suggesting that translocated bacteria lead to tissue remodeling and fibrosis seen in Creeping Fat via macrophage activation. The direct response of adipocytes to bacterial stimuli remains untested and will be of interest going forward. Given the large T and B cell component present in CrF and inflamed MAT, it will be important to elucidate the role of adaptive immunity in this complex microbial-host dialogue.