Protonophore activity of short‐chain fatty acids induces their intracellular accumulation and acidification

2025/05/05 by M. Jiang, Frans Bianchi, Geert van den Bogaart · 1 voice
Medicine · Nursing · #Diet and metabolism studies #Food composition and properties #Fatty Acid Research and Health

paper · pdf · doi:10.1002/1873-3468.70064

openalex publication_date 2025/05/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Short-chain fatty acids (SCFAs), produced by dietary fiber fermentation in the colon, play essential roles in cellular metabolism, with butyrate notably modulating immune responses and epigenetic regulation. Their production contributes to an acidic colonic environment where protonated SCFAs permeate membranes, leading to intracellular acidification and SCFA accumulation. Using our method to measure intracellular pH, we investigated how extracellular pH influences butyrate-induced acidification and immunomodulatory effects in human macrophages. Our data show that butyrate accumulates and acidifies cells at acidic extracellular pH due to the permeability of its protonated form. While inflammatory cytokine production was mildly influenced by extracellular pH, butyrate-induced histone acetylation exhibited a pH dependence, underscoring the importance of considering extracellular pH when assessing the SCFA's functions.

Citations

• The Orphan G Protein-coupled Receptors GPR41 and GPR43 Are Activated by Propionate and Other Short Chain Carboxylic Acids
• THE METABOLISM OF TUMORS IN THE BODY
• The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

Discussions

• 🫧 In acidic environments, butyrate and other short-chain #fattyacids can accumulate in cells, causing cytosolic acidification. Van den Bogaart and colleagues explore how this impacts immune response [bsky, 0 points, 0 comments]