Importance of the Microbiota Inhibitory Mechanism on the Warburg Effect in Colorectal Cancer Cells.

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world. Genetic backgrounds, lifestyle, and diet play an important role in CRC risk. The human gut microbiota has an influence on many features of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including CRC. It seems Warburg effect hypothesis corresponds to the early beginning of carcinogenesis because of eventual failure in the synthesis of a pyruvate dehydrogenase complex in cooperation with a supply of glucose in carbohydrates rich diets. From investigation among previous publications, we attempted to make it clear importance of Warburg effect in tumors; it also discusses the mechanisms of probiotics in inhibiting tumor progression and reverse Warburg effect of probiotics in modulating the microbiota and CRC therapies. These effects were observed in some clinical trials, the application of probiotics as a therapeutic agent against CRC still requirements further investigation. Fiber is fermented by colonic bacteria into SCFAs such as butyrate/acetate, which may play a vital role in normal homeostasis by promoting turnover of the colonic epithelium. Butyrate enters the nucleus and functions as a histone deacetylase inhibitor (HDACi). Because cancerous colonocytes undertake the Warburg effect pathway, their favored energy source is glucose instead of butyrate. Therefore, accumulation of moderate concentrations of butyrate in cancerous colonocytes and role as HDACi. Probiotics have been shown to play a protective role against cancer development by modulating intestinal microbiota and immune response.