Decreased gut short-chain fatty acids in cutaneous T-cell lymphoma: a novel insight

Short-chain fatty acids (SCFAs) are critical metabolites produced by gut microbiota that play a key role in modulating inflammation and regulating systemic immunity, including against cancer. Decreases in SCFAs can foster a permissive tumor immune environment. Recent studies have shown that cutaneous T-cell lymphoma (CTCL) patients exhibit increasing gut dysbiosis and loss of bacteria predicted to produce SCFAs with increasing disease severity. To investigate this functional connection, we collected stool swab samples from 15 individuals- 8 mycosis fungoides (MF) patients and 7 matched healthy controls (HC)- and quantified concentrations of four SCFAs (acetate, propionate, isovalerate, butyrate) via liquid chromatography-mass spectrometry. Our results demonstrated significantly reduced acetate and propionate concentrations in MF patients when compared to HC (both p = 0.027). Total measured SCFA concentrations were on average lower in MF versus HC, but did not achieve statistical significance (p = 0.063). Both propionate and acetate have been previously demonstrated to promote tumor apoptosis, inhibit tumor proliferation, and enhance antitumor immunity. Thus, dysbiosis-associated reductions in SCFAs may be another contributive factor in the immune dysfunction observed in CTCL. Our pilot findings add to the growing body of knowledge implicating the gut microbiota-SCFA axis in CTCL pathogenesis and offer potential new avenues for therapeutic intervention.