The Iron-Sulfur Cluster Crisis: Why Your Mitochondria Can't Recover (And Why Practitioners Don't Talk About It) — The Dysbiosis-Iron-Sulfur Connection: A Two-Way Street

Here&#8217;s what conventional gastroenterology misses: dysbiosis doesn&#8217;t just produce problematic metabolites. It dismantles the host&#8217;s ability to assemble and maintain Fe-S clusters . This happens through two overlapping mechanisms. Mechanism 1: Iron Dysmetabolism Dysbiotic bacteria have evolved to compete for iron. Pathogenic organisms like Clostridioides difficile , pathogenic E. coli , and various Proteobacteria produce siderophores&#8212;iron-chelating compounds that scavenge iron from the mucosa and colonocyte cytoplasm. They literally steal iron that should be bound for Fe-S cluster assembly. Simultaneously, dysbiosis disrupts the microbiome&#8217;s ability to regulate iron absorption. Commensal bacteria maintain local pH and produce compounds that keep iron in an absorbable form. When dysbiosis takes hold, the gradient collapses. Iron bioavailability crashes. The colonocyte starves. But here&#8217;s the deeper problem: even if iron is available, the dysbiotic environment&#8212;particularly high sulfide production from sulfate-reducing bacteria and the altered fermentation profile&#8212;shifts intestinal pH and redox state. Iron becomes trapped in forms the colonocyte can&#8217;t transport. Bioavailability falls further. Mechanism 2: Sulfur Dysmetabolism and Cysteine Depletion Fe-S clusters require sulfur. The primary source is the amino acid cysteine, which