Colonic carcinogenesis: the microbial feast or famine mechanism.

A mechanism is presented which suggests that high-fat, high-protein, low-fiber diets can cause an unfavorable microbial environment in the human colon which predisposes some individuals towards large bowel diseases. The digesta leaving the ileum on high-fat, high-protein, low-fiber diets has a high proportion of mucins, malabsorbed carbohydrates and proteins, bile acids, and sloughed epithelial cells. The irregular (pulsatile) emptying of rapidly fermentable ileal digesta into the colon causes a massive surge in microbial activity. The sudden availability of rapidly fermentable substrate generates a large microbial population in the exponential growth phase that soon depletes its substrate. For microorganisms to perpetuate until the next high-fat, high-protein, low-fiber meal propels ileal digesta into the colon, they must induce enzymes to ferment dying or dead microbes (cannibalism) in addition to colonic epithelial mucosa and mucins. As the carbohydrate-to-nitrogen ratio of the colonic contents decreases, the fermentation becomes more proteolytic and subacute levels of fermentation products such as ammonia may be generated. Carcinogens are concentrated within a small colonic mass and the probability of precancerous lesions and polyps developing in the colonic mucosa is directly related to the severity, frequency, and duration of these microbial "feast or famine" situations in the colon.