Why Butyrate Supplementation Makes Chronic Gut Dysfunction Worse: The Data They Don't Show You — What Butyrate Actually Is (And What It’s Supposed to Do)

Butyrate is a short-chain fatty acid (SCFA)&#8212;a 4-carbon molecule produced when your gut bacteria ferment dietary fiber. It&#8217;s one of three major SCFAs, along with acetate and propionate. In a healthy system, butyrate has genuine biological roles: Energy substrate : Colonocytes (the cells lining your colon) preferentially oxidize butyrate for energy, using it in mitochondrial beta-oxidation to generate ATP. Histone deacetylase (HDAC) inhibition : Butyrate inhibits a family of enzymes that remove acetyl groups from histone proteins, keeping chromatin more &#8220;open&#8221; and affecting gene expression. Tight junction support : It upregulates claudins and other tight junction proteins, theoretically strengthening the intestinal barrier. Anti-inflammatory signaling : Through GPR43 and other GPCRs, butyrate activates pathways associated with regulatory T cells and immune tolerance. This is the model taught in every gastroenterology course. More butyrate = healthier gut. Simple. Except in chronically dysfunctional systems, it&#8217;s not simple at all.