Why Dysbiosis, SIBO, Hydrogen Sulfide Intolerance, MCAS, and Long COVID May All Be Downstream of a Single Event — SLC5A8 silencing: the self-reinforcing lock

Remember SLC5A8, the gene for the SMCT1 transporter that carries butyrate into the colonocyte? It closes one of the cruelest loops in the entire model. In inflamed and metabolically stressed colonic tissue, SLC5A8 is frequently epigenetically silenced — switched off by chemical marks (DNA methylation) on its promoter, the same way it is silenced in colon cancer. And here's the trap: one of the things that normally keeps SLC5A8 switched on is butyrate itself, acting through its HDAC-inhibitor activity. Trace the circle: a stressed cell can't use butyrate well, so it gets less of butyrate's gene-regulating, HDAC-inhibiting signal, so SLC5A8 gets silenced, so even less butyrate can be transported into the cell, so the cell uses even less butyrate, and the silencing deepens. The cell locks the door to its own fuel supply, and butyrate — the molecule that could have kept the door open — can no longer get in to do it. This is a textbook example of why these conditions become self-perpetuating at the molecular level, and why simply raising luminal butyrate doesn't always reach the cell that needs it most.