Short-chain fatty acid production pathways in gut microbiota (SCFA production pathways)

Short-chain fatty acid (SCFA) production pathways in the gut microbiota represent the metabolic processes by which anaerobic bacteria ferment non-digestible carbohydrates into acetate, propionate, and butyrate (Koh et al., 2016). These metabolites are vital for host health, with butyrate serving as the primary energy source for colonocytes and a critical regulator of gut barrier integrity (Rios-Covian et al., 2016). SCFAs function as signaling molecules by activating G protein-coupled receptors, specifically FFAR2 (GPR43) and FFAR3 (GPR41), and by inhibiting histone deacetylases (HDACs), which leads to anti-inflammatory effects and epigenetic modulation (Tan et al., 2014). Deficiencies in SCFA production are associated with the pathogenesis of inflammatory bowel disease (IBD), obesity, type 2 diabetes, and certain cancers (Blaak et al., 2020). Therapeutic interventions targeting these pathways include prebiotics, probiotics, and postbiotics designed to increase SCFA concentrations and restore metabolic homeostasis (Canfora et al., 2015). These pathways are increasingly viewed as a modular target for microbiome-based drug development, focusing on the restoration of specific bacterial taxa or the direct delivery of metabolites. Furthermore, certain systemic drugs like metformin have been shown to exert their effects partially through the modulation of these microbial pathways (Sun et al., 2018). Monitoring fecal SCFA levels and the abundance of key producers like Faecalibacterium prausnitzii serves as a primary method for assessing pathway activity (Louis & Flint, 2017).

Other names

Microbial short-chain fatty acid synthesisGut microbial fermentation pathwaysAcetate, propionate, and butyrate production pathways

Modulation of gut microbiota composition and metabolic activity to increase the fermentation of dietary fibers into SCFAs, which then act as ligands for host GPCRs (FFAR2/FFAR3) and as HDAC inhibitors.