The Hidden Driver of SIBO and Chronic Gut Dysfunction: Bile Acid Malabsorption, Dysbiosis, and the Mitochondrial Cascade — Part IV: Pharmaceutical Interventions—Why They Cannot Solve the Problem Alone

Bile Acid Sequestrants: Binding Without Restoration Bile acid sequestrants (cholestyramine, colesevelam) are hydrophilic polymers that bind bile acids in the small intestinal lumen, preventing their reabsorption and increasing fecal loss. They are effective at reducing bile acid return to the circulation and are the standard treatment for bile acid diarrhea and elevated LDL cholesterol. However, in the context of dysbiosis-driven bile acid malabsorption, sequestrants have several critical limitations: 1. They Treat the Consequence, Not the Cause Sequestrants do nothing to restore the bacterial enzymes (BSH, bai operon) that are absent. They cannot re-establish secondary bile acid synthesis. They simply reduce the luminal concentration of unconjugated primary bile acids by preventing their reabsorption. This is symptomatic management. 2. They Worsen the Underlying Dysbiosis By further reducing the return of bile acids to the liver and the enteric circulation, sequestrants accelerate hepatic depletion of the bile acid pool. This triggers compensatory increases in hepatic bile acid synthesis de novo , but the newly synthesized bile acids&#8212;being primary&#8212;enter a dysbiotic small intestine incapable of converting them to secondary form. The dysbiosis becomes more chemically selective for dysbiotic organisms. 3. They Disrupt FXR and TGR5 Signaling Bile acid sequestrants redu