Short-chain fatty acids (SCFAs) in gut health: Implications for drug metabolism and therapeutics

Short-chain fatty acids (SCFAs) are the primary energy substrate for colonocytes, synthesized in the gut when gut microbiomes ferment the dietary fibers. SCFAs play crucial roles in maintaining gut homeostasis and exerting systemic effects beyond the gastrointestinal tract. Liver disorders, cardiovascular, diabetes, and obesity like metabolic syndromes are strongly associated with these metabolites’ imbalance. Determining the genetic variability, diet-gene interactions, and microbiome diversity in SCFA production is essential for creation of targeted interventions to optimize gut health and mitigate disease risk. The present review aims to elucidate the nutrigenomics and nitrogenic analysis to improve SCFAs to modulate intestinal barrier function, regulate immune responses, and influence host metabolism. This review summarizes deep insights into the multifaceted functions of SCFAs, therapeutic potential of SCFAs in promoting a thriving gut system and overall health and their involvement in neurological and metabolic disorders, highlighting the complex mechanism between gut microbiota and systemic health. A model was proposed to produce resistant starch as source of SCFAs production. The specific bacteria involved in SCFAs production and their functions also discussed. In addition to outlining the potential benefits of SCFAs for human health, it specified the factors influencing and obstacles to this field of study and offered suggestions for future research directions.