Nondigestible Fructans Alter Gastrointestinal Barrier Function, Gene Expression, Histomorphology, and the Microbiota Profiles of Diet-Induced Obese C57BL/6J Mice

J Nutr. 2016 May;146(5):949-56. doi: 10.3945/jn.115.227504. Epub 2016 Apr 6.

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-fed mice (5% and 10%: 109 μm). Inulin-fed mice had greater (P < 0.05) cecal transmural resistance (101 Ω × cm(2)) than 5% cellulose-fed controls (45 Ω × cm(2)). 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 gut microbiota and improved intestinal physiology in obese mice, but the mechanisms by which they affect gut integrity and inflammation in the obese are still unknown.

Keywords: fiber; gut microbiota; intestinal permeability; obesity; tight junctions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / growth & development
  • Cellulose / pharmacology
  • Diet, High-Fat
  • Dietary Fiber / pharmacology*
  • Feces / microbiology
  • Fructans / pharmacology*
  • Gastrointestinal Microbiome / drug effects*
  • Gene Expression
  • Inflammation / etiology
  • Intestinal Absorption
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology
  • Intestine, Large / drug effects*
  • Intestine, Large / metabolism
  • Intestine, Large / pathology
  • Intestine, Large / physiopathology
  • Inulin / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Mice, Obese
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism
  • Obesity* / complications
  • Obesity* / microbiology
  • Obesity* / physiopathology
  • Occludin / genetics
  • Occludin / metabolism
  • Oligosaccharides / pharmacology
  • Oligosaccharides / therapeutic use
  • RNA, Messenger / metabolism
  • Symporters / genetics
  • Symporters / metabolism
  • Weight Gain / drug effects

Substances

  • Dietary Fiber
  • Fructans
  • Monocarboxylic Acid Transporters
  • Occludin
  • Ocln protein, mouse
  • Oligosaccharides
  • RNA, Messenger
  • Symporters
  • monocarboxylate transport protein 1
  • Cellulose
  • Inulin