TY - JOUR
T1 - Dietary simple sugars alter microbial ecology in the gut and promote colitis in mice
AU - Khan, Shahanshah
AU - Waliullah, Sumyya
AU - Godfrey, Victoria
AU - Khan, Md Abdul Wadud
AU - Ramachandran, Rajalaksmy A.
AU - Cantarel, Brandi L.
AU - Behrendt, Cassie
AU - Peng, Lan
AU - Hooper, Lora V.
AU - Zaki, Hasan
N1 - Funding Information:
We thank J. S. Malter for reviewing this manuscript. We would like to thank the UT Southwestern Animal Resource Center (ARC) for maintenance and care of our mouse colony. We acknowledge the assistance of the UT Southwestern Tissue Management and Resource Center, a shared resource at the Simmons Comprehensive Cancer Center supported by the National Cancer Institute (5P30CA142543), for histopathology. We also thank the Bioinformatics Core Facility of UT Southwestern supported by Cancer Prevention and Research Institute of Texas (CPRIT) award (RP150596) for supporting the bioinformatics analysis. This work was supported by CPRIT Individual Investigator Award RP200184 to H.Z., Careers in Immunology Fellowship of American Association of Immunologists (AAI), UT Southwestern funding to H.Z., and NIH grant R01 DK070855 to L.V.H. S.K. was supported by AAI Careers in Immunology Fellowship.
PY - 2020/10/28
Y1 - 2020/10/28
N2 - The higher prevalence of inflammatory bowel disease (IBD) in Western countries points to Western diet as a possible IBD risk factor. High sugar, which is linked to many noncommunicable diseases, is a hallmark of the Western diet, but its role in IBD remains unknown. Here, we studied the effects of simple sugars such as glucose and fructose on colitis pathogenesis in wild-type and Il10−/− mice. Wild-type mice fed 10% glucose in drinking water or high-glucose diet developed severe colitis induced by dextran sulfate sodium. High-glucose–fed Il10−/− mice also developed a worsened colitis compared to glucose-untreated Il10−/− mice. Short-term intake of high glucose or fructose did not trigger inflammatory responses in healthy gut but markedly altered gut microbiota composition. In particular, the abundance of the mucus-degrading bacteria Akkermansia muciniphila and Bacteroides fragilis was increased. Consistently, bacteria-derived mucolytic enzymes were enriched leading to erosion of the colonic mucus layer of sugar-fed wild-type and Il10−/− mice. Sugar-induced exacerbation of colitis was not observed when mice were treated with antibiotics or maintained in a germ-free environment, suggesting that altered microbiota played a critical role in sugar-induced colitis pathogenesis. Furthermore, germ-free mice colonized with microbiota from sugar-treated mice showed increased colitis susceptibility. Together, these data suggest that intake of simple sugars predisposes to colitis and enhances its pathogenesis via modulation of gut microbiota in mice.
AB - The higher prevalence of inflammatory bowel disease (IBD) in Western countries points to Western diet as a possible IBD risk factor. High sugar, which is linked to many noncommunicable diseases, is a hallmark of the Western diet, but its role in IBD remains unknown. Here, we studied the effects of simple sugars such as glucose and fructose on colitis pathogenesis in wild-type and Il10−/− mice. Wild-type mice fed 10% glucose in drinking water or high-glucose diet developed severe colitis induced by dextran sulfate sodium. High-glucose–fed Il10−/− mice also developed a worsened colitis compared to glucose-untreated Il10−/− mice. Short-term intake of high glucose or fructose did not trigger inflammatory responses in healthy gut but markedly altered gut microbiota composition. In particular, the abundance of the mucus-degrading bacteria Akkermansia muciniphila and Bacteroides fragilis was increased. Consistently, bacteria-derived mucolytic enzymes were enriched leading to erosion of the colonic mucus layer of sugar-fed wild-type and Il10−/− mice. Sugar-induced exacerbation of colitis was not observed when mice were treated with antibiotics or maintained in a germ-free environment, suggesting that altered microbiota played a critical role in sugar-induced colitis pathogenesis. Furthermore, germ-free mice colonized with microbiota from sugar-treated mice showed increased colitis susceptibility. Together, these data suggest that intake of simple sugars predisposes to colitis and enhances its pathogenesis via modulation of gut microbiota in mice.
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U2 - 10.1126/scitranslmed.aay6218
DO - 10.1126/scitranslmed.aay6218
M3 - Article
C2 - 33115951
AN - SCOPUS:85094860790
VL - 12
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 567
M1 - eaay6218
ER -