Regulatory role of short-chain fatty acids in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders of the gastrointestinal tract. Accumulating evidence shows that the development of IBD is always accompanied by the dysbiosis of the gut microbiota (GM), causing a decrease in prebiotic levels and an increase in harmful metabolite levels. This leads to persistent immune response and inflammation in the intestine, greatly impairing the physiological function of the gastrointestinal tract. Short-chain fatty acids (SCFAs) are produced by probiotic gut bacteria from a fiber-rich diet that cannot be digested directly. SCFAs with significant anti-inflammatory functions regulate immune function and prevent an excessive immune response, thereby delaying the clinical progression of IBD. In this review, we summarize the generation of SCFAs and their potential therapeutic effects on IBD. Furthermore, we suggest that SCFAs may modulate innate immune recognition and cytokine production to intervene in the progression of IBD. Additional randomized controlled trials and prospective cohort studies should also investigate the clinical impact of SCFA. Video Abstract.

Keywords: Gut microbiota; Immunomodulating activity; Inflammatory bowel disease; Short-chain fatty acids; Therapeutic effects.

Fig. 1

Dietary fiber is digested by intestinal microorganisms to form short-chain fatty acids, which exert anti-inflammatory activities through the G protein-coupled receptor pathway and histone acetylase. The cytokines refer to interleukin 23, interleukin 17 and interleukin beta, etc. They are produced by activation of innate and adaptive immunity after the microbiota is recognized by the immune system and are important contributors to the development of IBD. The Figures in this review were created with BioRender.com

Fig. 2

Short-chain fatty acids (SCFAs) inhibit the progression of inflammatory bowel disease (IBD) by regulating innate immune sensors Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflam-masomes and play a role in inhibiting the progression of IBD. SCFAs not only inhibit TLR sig-naling but also inhibit TLR4 expression by suppressing the histone acetylation pathway. SCFAs also prevent the progression of IBD by regulating the assembly and attenuation of NLRP3 in-flammasomes. The Figures in this review were created with BioRender.com

Fig. 3

Short-chain fatty acids (SCFAs) are microbial products that can be applied as potential immunonutrition therapies for inflammatory bowel diseases. SCFAs can prevent the development of excessive immune responses by modulating the recognition function of innate immunity, and SCFAs can also play a role in protecting the intestinal barrier by promoting the production of interleukin (IL)10 and inhibiting that of IL17. In addition, SCFAs have excellent anticancer effects. The Figures in this review were created with BioRender.com