Metabolites and Short-Chain Fatty Acids

Short-chain fatty acids (SCFAs) are produced by bacterial fermentation of dietary fiber and have profound effects on host physiology.

1 Butyrate

Butyrate is the most metabolically important SCFA, with multiple functions relevant to ME/CFS:

• Colonocyte energy: Primary fuel source for colonic epithelium
• Barrier function: Strengthens tight junctions, reduces permeability
• Anti-inflammatory: Inhibits NF-\(\kappa\)B, reduces pro-inflammatory cytokines
• Immune modulation: Promotes regulatory T cell differentiation
• Neuromodulation: Crosses blood-brain barrier, affects microglial function
• Epigenetic effects: Histone deacetylase inhibitor

Butyrate deficiency in ME/CFS (see Achievement Deficient Butyrate-Producing Capacity) may contribute to:

• Increased intestinal permeability
• Chronic low-grade inflammation
• Impaired immune regulation
• Neuroinflammation

2 Acetate and Propionate

• Acetate: Most abundant SCFA; enters systemic circulation; substrate for lipogenesis; appetite regulation
• Propionate: Gluconeogenic substrate; cholesterol-lowering effects; modulates immune function