The unfortunate combination of genetic background and colonization by certain inciting commensal bacteria, can result in the development of inflammatory bowel diseases (IBD) in genetically susceptible individuals. Because little can be done presently to correct genetic susceptibility, changing the gut flora of IBD patients in a predictable and sustainable way represents a tangible and practical solution. We believe this can be accomplished through dietary manipulation of the enteric microbiota. Two hypotheses will be tested: (1) that certain dietary fats which that are well represented in "Western diets" ar capable of either precipitating or preventing/ameliorating colonic inflammation through their actions on the enteric microbiome (Aim 1), and (2) that dietary intervention with fatty acid supplements or increased short chain fatty acid bioavailability can reshape disease-causing enteric microbiomes to reduce risk or ameliorate IBD, thus setting the stage for future clinical application. We show, for instance, that risk for developing colitis in IL-10 KO mice can be significantly increased by diets high in saturated, milk-derived fat, which promote the bloom of immunogenic Deltaproteobacteria that are part of the "rare biosphere" of the enteric microbiome. We also show that several forms of dietary supplementation can reshape and alter the immunogenicity of saturated fat-induced changes in the enteric microbiota. These studies will take advantage of cultivation-dependent and -independent approaches and the bioinformatic analysis services of DDRCC Host-Microbe Core. In addition, microbiota transfer and gnotobiotic animal technologies will be used to determine if there is causal role of diet-induced changes of the enteric microbiota in creating immune imbalances and adverse risk outcomes. In summary, we will determine how diet affects and can be used to manipulate the enteric microbiota to restore immune homeostasis and reduce risk and severity of complex immune-mediated disorders. The knowledge gained through these studies will provide fundamental insights into the cause of IBD and help define dietary strategies to prevent or ameliorate IBD through manipulation of the enteric microbiota.
We will investigate how specific dietary fats affect the composition of the intestinal microbes and what impact this has on host immune balance, health and development of IBD in genetically susceptible mice. We will also examine how certain dietary supplements can reshape disease-promoting gut microbial profiles to restore and maintain health. By doing so, we can develop effective and practical measures that can be used clinically to prevent and treat inflammatory bowel diseases.
|Ueno, Nobuhiro; Hasebe, Takumu; Kaneko, Atsushi et al. (2014) TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-?B suppression. PLoS One 9:e97456|
|Leone, Vanessa A; Cham, Candace M; Chang, Eugene B (2014) Diet, gut microbes, and genetics in immune function: can we leverage our current knowledge to achieve better outcomes in inflammatory bowel diseases? Curr Opin Immunol 31:16-23|
|Evans, Christian C; LePard, Kathy J; Kwak, Jeff W et al. (2014) Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS One 9:e92193|
|Dalal, Sushila R; Chang, Eugene B (2014) The microbial basis of inflammatory bowel diseases. J Clin Invest 124:4190-6|
|Zhang, Zhiyu; Du, Guang-Jian; Wang, Chong-Zhi et al. (2013) Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions. Int J Mol Sci 14:2980-95|
|Huang, Edmond Y; Leone, Vanessa A; Devkota, Suzanne et al. (2013) Composition of dietary fat source shapes gut microbiota architecture and alters host inflammatory mediators in mouse adipose tissue. JPEN J Parenter Enteral Nutr 37:746-54|
|Dennis, Kristen L; Wang, Yunwei; Blatner, Nichole R et al. (2013) Adenomatous polyps are driven by microbe-instigated focal inflammation and are controlled by IL-10-producing T cells. Cancer Res 73:5905-13|
|Leone, Vanessa; Chang, Eugene B; Devkota, Suzanne (2013) Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases. J Gastroenterol 48:315-21|