@article{8b9bcb8587d9494baa09a6e69b046dd1,
title = "Dietary Fructose Alters the Composition, Localization, and Metabolism of Gut Microbiota in Association With Worsening Colitis",
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.",
keywords = "Bile Acids, Colitis, Fructose, Microbiota",
author = "Montrose, {David C.} and Ryohei Nishiguchi and Srijani Basu and Staab, {Hannah A.} and Zhou, {Xi Kathy} and Hanhan Wang and Lingsong Meng and Melanie Johncilla and Cubillos-Ruiz, {Juan R.} and Morales, {Diana K.} and Wells, {Martin T.} and Simpson, {Kenneth W.} and Shiying Zhang and Belgin Dogan and Chen Jiao and Zhangjun Fei and Akihiko Oka and Herzog, {Jeremy W.} and Sartor, {R. Balfour} and Dannenberg, {Andrew J.}",
note = "Funding Information: Funding Supported by Career Development Award from the Crohn{\textquoteright}s and Colitis Foundation (D.C.M.), New York Crohn{\textquoteright}s Foundation (D.C.M. & A.J.D.), The Jill Roberts IBD Research Fund in honor of Ellen J. Scherl, MD (A.J.D.), Tokyo Clinical Surgical Association (R.N.), Ovarian Cancer Academy -Early-Career Investigator Award W81XWH-16-1-0438 of the Department of Defense (J.C.R), the Mark Foundation ASPIRE Award (J.C.R), and the Pershing Square Sohn Cancer Research Alliance (J.C.R), Jill Roberts Center for Inflammatory Bowel Disease (K.W.S), NIHP01DK094779 (R.B.S), NIHP40OD010995 (R.B.S.), NIHP30DK034987 (R.B.S.), Research Fellowship Award (A.O.), and Gnotobiotic Facility Grant (R.B.S) from the Crohn{\textquoteright}s and Colitis Foundation. Funding Information: Funding Supported by Career Development Award from the Crohn's and Colitis Foundation (D.C.M.), New York Crohn's Foundation (D.C.M. & A.J.D.), The Jill Roberts IBD Research Fund in honor of Ellen J. Scherl, MD (A.J.D.), Tokyo Clinical Surgical Association (R.N.), Ovarian Cancer Academy-Early-Career Investigator Award W81XWH-16-1-0438 of the Department of Defense (J.C.R), the Mark Foundation ASPIRE Award (J.C.R), and the Pershing Square Sohn Cancer Research Alliance (J.C.R), Jill Roberts Center for Inflammatory Bowel Disease (K.W.S), NIHP01DK094779 (R.B.S), NIHP40OD010995 (R.B.S.), NIHP30DK034987 (R.B.S.), Research Fellowship Award (A.O.), and Gnotobiotic Facility Grant (R.B.S) from the Crohn's and Colitis Foundation. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2021",
month = jan,
doi = "10.1016/j.jcmgh.2020.09.008",
language = "English (US)",
volume = "11",
pages = "525--550",
journal = "CMGH Cellular and Molecular Gastroenterology and Hepatology",
issn = "2352-345X",
publisher = "Elsevier",
number = "2",
}