Why It's Impossible to Treat Chronic Gut Dysfunction at the Bacterial Level — What Actually Has to Happen

If the mechanism is host capacity collapse, the intervention sequence has to target the host. Not the microbes. Not primarily. The sequence that my data and the mechanism both support: First, stabilize immune signaling. Restore IAP function &#8212; zinc is the essential cofactor, and PPAR-&#947; activation supports transcription. Reduce LPS-TLR4 drive by supporting barrier integrity and, where appropriate, binding luminal LPS. Modulate CD38 to preserve NAD&#8314; (quercetin, apigenin have the strongest evidence) rather than flooding NAD&#8314; precursors into a system that will burn them before they reach SIRT3. This is the step that stops the bleeding. Second, restore mitochondrial bioenergetics. NAD&#8314; precursors only after CD38 drive is reduced &#8212; otherwise they are consumed before they can be used. Ubiquinol (not ubiquinone) in patients with NQO1 polymorphisms. Riboflavin in its active R5P form to support flavin-dependent dehydrogenases. Alpha-ketoglutarate as a TCA cycle fuel and TET2/KDM4 cofactor that simultaneously supports mitochondrial function and epigenetic flexibility. In select cases, compounds like SS-31 for cardiolipin and urolithin A for mitophagy have mechanism-of-action traction that matches the pathology. Third, fix the bile acid&#8211;mitochondrial axis. Reduce primary bile acid toxicity where indicated. Support the ecological recovery of secondary