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Review
. 2024 Jan 12;29(2):379.
doi: 10.3390/molecules29020379.

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Affiliations
Review

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Yuan Yao et al. Molecules. .

Abstract

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

Keywords: mechanism of action; natural compounds; short-chain fatty acids; traditional drugs; ulcerative colitis (UC).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
SCFAs play a pivotal regulatory role in maintaining gut homeostasis. SCFAs potentially play an essential role in each stage of the inflammatory process and tissue healing, exerting regulatory effects on the functionality of nearly all types of immune cells, thereby demonstrating their immunomodulatory impact. SCFAs contribute to maintaining the integrity of the intestinal barrier by promoting the proliferation of various epithelial cells, upregulating the expression of tight junctions in intestinal epithelial cells, and facilitating the secretion of barrier-supporting proteins such as IgA, AMPs, and mucins, meanwhile regulating the composition and structure of gut microbiota and oxidative stress. Furthermore, SCFAs exhibit various immunomodulatory actions: modulating the differentiation and function of Th17, Th1, and Tregs; inhibiting intestinal macrophages from producing pro-inflammatory cytokines by suppressing histone deacetylase (HDAC); inducing chemotaxis of neutrophils to the inflammatory site and enhancing their phagocytic activity; and stimulating intestinal B cells to produce IgA. The decoctions/compounds were marked in green. Green arrows were used to indicate the effects of a decoction or a compound on the targets. Abbreviations: (1) Baicalein; (2) Polysaccharides (CCP) and berberine (BBR); (3) Berberine; (4) Gegen Qinlian Decoction (GQD); (5) Qingchang Huashi Formula (QHF); (6) Pulsatilla decoction (PD); (7) Pulsatilla chinensis saponin (PCS); (8) Polysaccharides from Astragalus membranaceus and Codonopsis pilosula (PAC); (9) Polysaccharide of Hericium erinaceus mycelium (HEM); (10) Herba Origani Extract Pulvis (HOEP); (11) Paeonol (Pae); (12) Huangqin Decoction (HQD); (13) Sishen Wan (SSW); (14) Composite Sophora colon-soluble Capsule (CSCC); (15) Acorn-fed ham; (16) Fermented astragalus (FA); (17) Indigo naturalis; (18) Schisandra chinensis polysaccharide (SCP); (19) Galangin; (20) Pinocembrin (PIN).
Figure 2
Figure 2
The signaling pathways triggered by traditional medicine-derived SCFAs. Some decoctions/compounds in traditional Chinese medicines alleviate colitis by inducing the production of various SCFAs such as acetate, butyrate, and valerate, which target several signaling pathways such as GPRs to trigger the production of various barrier-supporting proteins such as the tight junction proteins, mucins, and immunomodulatory cytokines such as IL-22, which play a critical role in maintaining gut homeostasis. SCFAs also suppress pro-inflammatory pathways such as the TLR-NF-κB pathway, the NLRP3 inflammasome, and IL-6 mediated AKT pathway to down-regulate the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-8, which may influence IBD by regulating the recruitment of multiple immune cells to the site of inflammation. SCFAs may promote PPARγ production via the NF-κB pathway, then suppress the level of RORγT to control Th17 cell differentiation and interfere with inflammation by regulating the balance of Th17/Treg cells. Regulation of the AKT/STAT3 signaling pathway through SCFA production is an important mechanism in the treatment of colon inflammation by some traditional drugs. Abbreviations: (1) Baicalein; (2) Polysaccharides (CCP) and berberine (BBR); (3) Berberine; (4) Gegen Qinlian Decoction (GQD); (5) Qingchang Huashi Formula (QHF); (6) Pulsatilla decoction (PD); (7) Pulsatilla chinensis saponin (PCS); (8) Polysaccharides from Astragalus membranaceus and Codonopsis pilosula (PAC); (9) Polysaccharide of Hericium erinaceus mycelium (HEM); (10) Herba Origani Extract Pulvis (HOEP); (11) Paeonol (Pae); (12) Huangqin Decoction (HQD); (13) Sishen Wan (SSW); (14) Composite Sophora colon-soluble Capsule (CSCC); (15) Acorn-fed ham; (16) Fermented astragalus (FA); (17) Indigo naturalis; (18) Schisandra chinensis polysaccharide (SCP); (19) Galangin; (20) Pinocembrin (PIN).

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