Dynamic balancing of intestinal short-chain fatty acids: The crucial role of bacterial metabolism

Background: Short-chain fatty acids (SCFAs) play important physiological roles in human health. Adverse effects on health are known with a low or excessive concentration of SCFAs although the optimal level of SCFAs in the body is unknown yet. The level of endogenous SCFAs is affected by many factors of which gut bacteria are the most important one. However, how gut bacteria and a dietary intervention affect SCFA balance in the gut still needs to be clarified. Scope and approach: In addition to addressing the importance of a dynamic balance of SCFAs for health, we discuss the factors affecting the dynamic balance of SCFAs, especially the gut SCFA-producing bacteria, including the classification of the bacteria, their response to diet, the SCFAs metabolic pathways and the catalytic mechanisms of the main rate-limiting enzymes. Key findings and conclusions: SCFAs levels can be regulated endogenously and exogenously. Exogenous regulation delivers SCFAs to gut by esterification with dietary fibres. Endogenous regulation like diet, directly or indirectly affect gut microbiota, including their abundance, fitness and SCFAs production. Until now, 74 bacterial species are reported to produce SCFAs, the metabolic pathways are classified into 4 categories, and the 4 rate-limiting enzymes in the metabolic pathways are summarized. We also propose methods for long-lasting endogenous SCFAs balancing, including identifying the minimum sets of SCFA-producing bacterial group, and possible dietary intervention to form a minimum group of gut microbiota for SCFAs synthesis. An integrated approach will help realize the rational regulation of balanced SCFAs levels to benefit human health.