1. Dietary Fructose Alters the Composition, Localization, and Metabolism of Gut Microbiota in Association With Worsening Colitis
- Author
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Kenneth W. Simpson, Andrew J. Dannenberg, David C. Montrose, Chen Jiao, Lingsong Meng, Martin T. Wells, Srijani Basu, Hanhan Wang, Akihiko Oka, Juan R. Cubillos-Ruiz, Melanie Johncilla, Jeremy Herzog, Xi Kathy Zhou, Belgin Dogan, Zhangjun Fei, Shiying Zhang, Diana K. Morales, R. Balfour Sartor, Ryohei Nishiguchi, and Hannah A Staab
- Subjects
Male ,0301 basic medicine ,Dietary Sugars ,Gut flora ,Severity of Illness Index ,Bile Acids ,Feces ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Citrobacter rodentium ,FISH, fluorescent in situ hybridization ,DSS, dextran sodium sulfate ,Intestinal Mucosa ,Original Research ,Mice, Knockout ,SPF, specific pathogen-free ,biology ,HGD, high glucose diet ,Microbiota ,Dextran Sulfate ,Gastroenterology ,qRT-PCR, quantitative real-time polymerase chain reaction ,Colitis ,Interleukin-10 ,BA, bile acid ,Female ,030211 gastroenterology & hepatology ,NASH, nonalcoholic steatohepatitis ,Colon ,PBS, phosphate-buffered saline ,Il, interleukin ,Fructose ,Microbiology ,03 medical and health sciences ,Genetic model ,OTU, operational taxonomic unit ,medicine ,Animals ,Humans ,IBD, inflammatory bowel diseases ,ABx, antibiotics ,Hepatology ,Metabolism ,biology.organism_classification ,medicine.disease ,WT, wild-type ,Mucus ,Gastrointestinal Microbiome ,GF, germ-free ,UPLC-MS/MS, ultra-high performance liquid chromatography-tandem mass spectrometry ,Disease Models, Animal ,AB/PAS, alcian blue/periodic-acid Schiff ,030104 developmental biology ,chemistry ,BSH, bile salt hydrolase ,HFrD, high fructose diet - Abstract
Background & Aims The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance dextran sodium sulfate (DSS)-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially driven and genetic models of colitis. Methods Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histologic analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses, and fecal metabolomics were used to determine microbial composition, spatial distribution, and metabolism. The significance of HFrD on pathogen and genetic-driven models of colitis was determined by using Citrobacter rodentium infection and Il10-/- mice, respectively. Results Reducing or eliminating bacteria attenuated HFrD-mediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa by reducing thickness and altering the quality of colonic mucus. Feeding an HFrD also altered gut microbial populations and metabolism including reduced protective commensal and bile salt hydrolase-expressing microbes and increased luminal conjugated bile acids. Administration of conjugated bile acids to mice worsened DSS-induced colitis. The HFrD also worsened colitis in Il10-/- mice and mice infected with C rodentium. Conclusions Excess dietary fructose consumption has a pro-colitic effect that can be explained by changes in the composition, distribution, and metabolic function of resident enteric microbiota., Graphical abstract
- Published
- 2021