Nondigestible fructans alter gastrointestinal barrier function, gene expression, histomorphology, and themicrobiota profiles of diet-induced obese C57BL/6J Mice

Abstract

Background: Obesity is associated with compromised intestinal barrier function and shifts in gastrointestinal microbiota that may contribute to inflammation. Fiber provides benefits, but impacts of fiber type are not understood. Objective: We aimed to determine the impact of cellulose compared with fructans on the fecal microbiota and gastrointestinal physiology in obese mice. Methods: Eighteen-wk-old male diet-induced obese C57BL/6J mice (n = 6/group; 40.5 g) were fed high-fat diets (45% kcal fat) containing 5% cellulose (control), 10% cellulose, 10% short-chain fructooligosaccharides (scFOS), or 10% inulin for 4 wk. Cecal and colon tissues were collected to assess barrier function, histomorphology, and gene expression. Fecal DNA extracts were subjected to 16S ribosomal RNA amplicon-based Illumina MiSeq sequencing to assess microbiota. Results: Body weight gain was greater (P < 0.05) in scFOS-fed than in 10% cellulose-fed mice. Both groups of fructan-fed mice had greater (P < 0.05) cecal crypt depth (scFOS: 141 μm; inulin: 145 μm) than both groups of cellulose-fedmice (5%and 10%: 109 μm). Inulin-fed mice had greater (P < 0.05) cecal transmural resistance (101 U 3 cm2) than 5% cellulose-fed controls (45 Ω 3 cm2). Inulin-fed mice had lower (P < 0.05) colonic mRNA abundance of Ocln (0.41) and Mct1 (0.35) than those fed 10% cellulose (Ocln: 1.28; Mct1: 0.90). Fructan and cellulose groups had different UniFrac distances of fecal microbiota (P < 0.05) and α diversity, which demonstrated lower (P < 0.01) species richness in fructan-fed mice. Mice fed scFOS had greater (P < 0.05) Actinobacteria (15.9%) and Verrucomicrobia (Akkermansia) (17.0%) than 5% controls (Actinobacteria: 0.07%; Akkermansia: 0.08%). Relative abundance of Akkermansia was positively correlated (r = 0.56, P < 0.01) with cecal crypt depth. Conclusions: Fructans markedly shifted gutmicrobiota and improved intestinal physiology in obesemice, but themechanisms by which they affect gut integrity and inflammation in the obese are still unknown.