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

in Archives of dermatological research by Zachary O Thomas, JoJo Holm, Morgan McCarthy, William Nguyen, Yanzhen Pang, Lauren P Chrisman, Joan Guitart, Michael B Burns, Xiaolong Alan Zhou

TLDR

  • The study found reduced concentrations of acetate and propionate in cutaneous T-cell lymphoma patients compared to healthy controls, suggesting a potential link between gut microbiota, short-chain fatty acids, and disease pathogenesis.

Abstract

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.

Overview

  • The study investigated the relationship between gut microbiota and cutaneous T-cell lymphoma (CTCL) by analyzing stool swab samples from 15 individuals, including 8 patients with mycosis fungoides (MF) and 7 healthy controls (HC).
  • The researchers quantified concentrations of four short-chain fatty acids (SCFAs) - acetate, propionate, isovalerate, and butyrate - in the stool samples using liquid chromatography-mass spectrometry.
  • The primary objective of the study was to explore the connection between SCFAs and CTCL, with potential implications for therapeutic interventions targeting the gut microbiota-SCFA axis.

Comparative Analysis & Findings

  • The study found significantly reduced concentrations of acetate and propionate in MF patients compared to HC (both p = 0.027).
  • Total measured SCFA concentrations were lower in MF patients compared to HC, but the difference did not achieve statistical significance (p = 0.063).
  • The findings suggest that dysbiosis-associated reductions in SCFAs may contribute to immune dysfunction in CTCL, highlighting the importance of the gut microbiota-SCFA axis in the disease's pathogenesis.

Implications and Future Directions

  • The study's findings offer potential new avenues for therapeutic intervention in CTCL by targeting the gut microbiota-SCFA axis.
  • Future research should explore the mechanisms underlying the decreased SCFA concentrations in MF patients and investigate the therapeutic potential of SCFA-targeted approaches.
  • The study's results also underscore the importance of understanding the relationship between the gut microbiota and systemic immunity in the context of cancer progression and treatment outcome.
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