Why Butyrate Supplementation Makes Chronic Gut Dysfunction Worse: The Data They Don't Show You — What the Client Data Shows

I&#8217;ve worked with over a dozen clients with chronic SIBO, refractory IBS, and suspected colonocyte dysfunction. The pattern is consistent: Case Pattern: Pre-supplementation: Elevated fecal butyrate (GI-MAP or similar stool analysis): 2&#8211;4x normal range Elevated markers of oxidation failure: Low butyrate-to-acetate ratio, high phenylacetylglutamine (PAG&#8212;a marker of amino acid fermentation), elevated secondary bile acids (indicating dysbiosis) High fecal LPS activity (via LAL or LBP as proxy) Elevated inflammatory markers: Calprotectin, lysozyme, elevated elastase suggesting dysbiosis-driven intestinal inflammation After butyrate supplementation (high-dose prebiotic or SCFA supplement): Fecal butyrate increases further (4&#8211;6x normal) Butyrate oxidation biomarkers worsen: Continued low butyrate-to-acetate ratio, unchanged or worsening PAG, elevated butyric acid in urine (suggesting systemic exposure without utilization) Clinical symptoms: Bloating, brain fog, fatigue, histamine flare, anxiety, insomnia worsen significantly within 2&#8211;7 days Discontinuation of supplementation: Symptoms improve within 3&#8211;5 days The data is unambiguous: In these patients, butyrate oxidation capacity is the limiting factor, not butyrate production. Adding more butyrate doesn&#8217;t solve the problem. It worsens the HDAC inhibition-driven pathology.