Diet and its microenvironment influence the health of colon

Abstract Ulcerative colitis (UC) is an autoimmune chronic inflammatory disease of the large intestine that greatly increases risks of colorectal cancer. UC is an idiopathic inflammatory disorder of the colonic mucosa, which starts in the rectum and generally extends proximally in a continuous manner through part of, or the entire, colon. A Western diet, smoking, alcohol abuse, altered circadian rhythm and a dysbiotic microbiome is thought to induce UC. However, it is still not completely understood the factors in the diet that triggers UC. Identification of the factors associated with the diet that induce UC will lead to healthier lifestyle that prevents UC. In animal models we show that standard diet and diet rich in fiber positively influenced the health of the colon. A high fat high protein diet negatively regulated the health of the colon. A high fat high protein diet caused obesity in animals, paradoxically it also reduced the colon length significantly in these animals. Animals feeding on a high fat high protein had no energy in the fecal pellet demonstrating peinosis [hunger-like-condition; peina (Greek) hunger; osis (Greek) condition] of the colon. A high fat high protein diet also induced peripheral neuropathy in animals; whereas animals on a high fiber diet was healthy and had longer colon and no peripheral neuropathy. Bacteria of the family Erysipelotrichaceae that is related to inflammation-related disorders of the gastrointestinal tract is also high in animals fed with a high fat high protein diet; these animals also had low levels of valeric acid and propionic acid in the colon. Overall, a high fat high protein diet negatively impacts the health of the colon due to poor energy metabolism and its associated dysbiotic microbiome and metabolome. Currently, anti-inflammatory drugs and immune suppressors are prescribed for UC treatment, side-effects and the risk of opportunistic infections limit the quality of treatment. Hence, there is a need for a new class of biologics for efficient UC treatment. Bin1 is a risk factor in UC as determined by the increase in Bin1 expression in the colon of UC patients. In animal models, we showed that attenuation of BIN1 gene protected against UC. We have developed an innovative therapeutic strategy to treat UC that acts by correcting the leaky colonic epithelial barrier function that drives chronic inflammation in this setting. Specifically, we recently showed that administration of our anti-Bin1 monoclonal antibody (Bin1 mAb 99D) is sufficient to mimic the effect of genetic downregulation of Bin1 to preserve the normal colonic mucosa in an established mouse model of UC, in comparison to control-treated mice which exhibited severe lesions and inflammatory cell influx throughout the mucosa. A diet that positively influence the colon may be beneficial during immunotherapeutic treatment of ulcerative colitis.