Elucidating the molecular mechanism of gut microbiome response to the Specific Carbohydrate Diet in pediatric patients with inflammatory bowel disease
EMSL Project ID
50720
Abstract
Pediatric Inflammatory Bowel Disease (IBD) is a debilitating condition that includes ulcerative colitis (UC) and Crohn's disease (CD). It affects 1.4 million children and adults in the US, at an overall annual cost of more than $1.7 billion, and is becoming more prevalent in other developed and developing countries. The Specific Carbohydrate Diet (SCD) is a carbohydrate exclusion diet that shows promise for reducing symptoms of IBD and inducing remission. This diet removes all grains, sweeteners except for honey, most processed foods, and all milk products except for hard cheeses and yogurt fermented longer than 24 hours. A preliminary prospective study of the SCD in pediatric patients with mild to moderate CD or UC, showed that the SCD diet was associated with clinical remission in 8 of 10 patients that completed the study. However, the mechanism of action of exclusionary diets in reduction of clinical symptoms and intestinal inflammation remains unclear. A current hypothesis of IBD pathogenesis is that pathologic alterations in the intestinal microbiome (dysbiosis) trigger an aberrant mucosal immune response in genetically predisposed individuals, leading to the development of chronic intestinal inflammation. Therefore, we postulate that the mode of action of the SCD is mediated through prebiotic modification of the gut microbiome and the functions they carry out. A fundamental question is given the variability between patients in terms of genetic background, microbiome structure and baseline diet, what is the common molecular mechanism by which the SCD diet influences the gut microbiome, and how does this translate to health impacts on the host? We hypothesize that alterations in gut functionality in response to the carbohydrate limitation imposed by the SCD diet result in an intestinal metabolite profile that confers positive health outcomes on the host. We are proposing to perform a preliminary, limited-scale study on a stool sample collection obtained by Co-PI Suskind. We will collect proteomic and metabolomic data and evaluate the effect of the dietary shift on the on gut microbiome function. This information will be used to identify the molecular mechanisms underlying the observed impacts through metabolic reconstruction, network analysis and functional enrichment. Successful completion of this project will provide a general mechanistic understanding of the gut microbiome response to the SCD, and elucidate how this response contributes to amelioration of symptoms of IBD.
Project Details
Start Date
2019-03-11
End Date
2021-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Kimberly Braly, Janet K. Jansson, Young-Mo Kim, Dale Lee, Mary S. Lipton, William C. Nelson, Carrie D. Nicora, Mason Nuding, Samuel O. Purvine, Namita Singh, David L. Suskind, Ghassan Wahbeh. 2020. "The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial." Nutrients 12 (12):3749. 10.3390/nu12123749