Bugs, Stool, and the Irritable Bowel Syndrome: Too Much Is as Bad as Too Little?

Intestinal bacteria and IBS. Different people have distinct gut microbiota; the hypothesis is that the differences set in motion an inflammatory cascade in those who are genetically predisposed and subject to a specific environmental hit. A new insult (eg, acute infectious gastroenteritis) may damage intestinal permeability, leading to a cascade of microbes upregulating mast cells through the Th2 pathway. Toll-like receptors (TLR) on mast cells may interact directly with relevant microbes. Mast cells accumulate in the lamina propria and release histamine (that interacts with H1-4 receptors), proteases (PAR1 receptor), and probably serotonin (5HT3 and 5HT4 receptors). Chemical signaling via receptors results in neural excitation and smooth muscle contraction, leading to abdominal pain, abnormal intestino-abdominal reflex responses (that combined with fermentation by gas-producing bacteria in the lumen triggers bloating), and disturbed intestinal transit (manifest as diarrhea or constipation, or both, depending on the balance of up- and down-regulatory responses). Cytokines and chemokines are released into the circulation inducing extra-intestinal symptoms.