Why Some People Never Recover From Gut Disorders: The Overlooked Genetic Architecture Driving Butyrate Failure, Dysbiosis, and Chronic Symptoms — Why These SNPs Matter More Than People Realize

These variants do not cause disease alone. They determine susceptibility and recovery trajectory . Here is the mechanistic chain that explains everything: Genetic variants reduce butyrate absorption or oxidation. Colonocyte mitochondria shift toward glycolysis. Oxygen leaks into the lumen, disrupting anaerobes. Opportunistic bacteria (Klebsiella, Enterobacter, Citrobacter, Bilophila) expand. LPS signaling spikes in genetically sensitive individuals. H&#8322;S detox pathways become overwhelmed. Mucosal inflammation suppresses mitochondrial enzymes even more. A self-perpetuating loop forms: low butyrate &#8594; high oxygen &#8594; dysbiosis &#8594; inflammation &#8594; further butyrate failure. This is why two people with the same infection or same stool test recover completely differently. Their genomic terrain determines whether the system rebounds or collapses.