{"version":"v1","contradiction":{"id":"is-butyrate-always-therapeutic","question":"Is exogenous butyrate always beneficial in chronic gut disease?","summary":"Default narrative: butyrate is fuel, give more. Mechanistic concern: in epithelium with impaired β-oxidation (low SIRT3, H₂S burden, mitochondrial damage), exogenous butyrate may not be oxidised efficiently and could plausibly worsen symptoms.","positions":[{"id":"butyrate-universally-beneficial","label":"Butyrate is universally beneficial","thesis":"Increasing colonic butyrate availability improves epithelial function and reduces inflammation across patient groups.","predicts":["Symptom improvement on butyrate supplementation in most patients."],"supportingEvidence":["Butyrate's role as colonocyte fuel is established (Donohoe et al.).","PPAR-γ agonism by SCFA is protective in animal models."],"weakeningEvidence":["Clinical reports of symptom worsening on butyrate in subsets of chronic gut patients.","H₂S inhibition of SCAD predicts impaired butyrate utilisation in some patients."],"authorPosition":"treated-as-rival","evidenceLevel":"emerging"},{"id":"butyrate-context-dependent","label":"Butyrate is context-dependent","thesis":"In epithelium with impaired β-oxidation capacity, exogenous butyrate may accumulate as an unprocessed substrate and worsen symptoms; benefit requires intact mitochondrial throughput.","predicts":["Patients with H₂S overload, low SIRT3, or mitochondrial dysfunction tolerate or benefit less from butyrate.","Restoring β-oxidation capacity precedes meaningful butyrate response."],"supportingEvidence":["H₂S inhibits SCAD and complex IV in colonocytes.","Clinical reports of paradoxical worsening on butyrate."],"weakeningEvidence":["Lack of randomised trials stratifying butyrate response by bioenergetic phenotype."],"authorPosition":"preferred","evidenceLevel":"hypothesis"}],"unresolvedQuestions":["Can stool SCFA, H₂S, or biopsy SIRT3 predict butyrate-supplement response?","Does pre-treatment of sulfide burden change butyrate tolerance?"],"arbitratingExperiments":["Stratified RCT of butyrate supplementation by sulfide burden and biopsy bioenergetic markers."],"relatedConcepts":["butyrate-oxidation","colonocyte-bioenergetics"],"relatedArticles":["why-butyrate-supplementation-makes-chronic-gut-dysfunction-w"],"relatedClaims":["exogenous-butyrate-can-worsen-symptoms-in-energy-failed-epithelium","h2s-inhibits-colonocyte-beta-oxidation"],"lastReviewed":"2026-05-11"}}