The Real Cause of SIBO — Why Everything You’ve Been Told Is Incomplete — Bile Acids: The Forgotten Antimicrobial System and What Happens When They Turn Toxic

Bile acids are potent antimicrobials in the small intestine and signaling molecules that regulate the small intestinal microbiome through the FXR-FGF19 axis. Bile acid activation of FXR in the ileal epithelium drives FGF19 secretion and directly stimulates production of Angiogenin-4 &#8212; an antimicrobial peptide that suppresses bacterial growth in the small intestinal lumen. Post-cholecystectomy patients lose the episodic bile bolus and have continuous low-level bile trickle that never reaches the FXR activation threshold. Genetic variants in SLC10A2, CYP7A1, and FGFR4 modulate individual bile acid pool size and antimicrobial competence. But there is a second side of this story that almost no one discusses: what happens to bile acids once SIBO is established. When bacteria overgrow the small intestine, they express bile salt hydrolase enzymes that prematurely deconjugate bile acids in the small intestinal lumen. Conjugated bile acids &#8212; glycocholate, taurocholate &#8212; are water-soluble, efficiently reabsorbed in the ileum via the SLC10A2 transporter, and recirculated in the enterohepatic cycle. Deconjugated bile acids are a completely different story. Free deconjugated bile acids are poorly water-soluble. They precipitate in the small intestinal lumen. They are directly cytotoxic to enterocytes &#8212; intercalating into membrane phospholipid bilayers, disrupting tig