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12 January 2024

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

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1
Department of Immunology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China
2
Basic Medical Research Center, School of Medicine, Nantong University, Nantong 226019, China
*
Authors to whom correspondence should be addressed.
Molecules2024, 29(2), 379;https://doi.org/10.3390/molecules29020379
This article belongs to the Special Issue Recent Advances in the Research of Natural Products: Isolation, Identification, Physicochemical Properties and Bioactivities
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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.

1. Introduction

Inflammatory bowel disease (IBD), mainly including Crohn’s disease (CD) and ulcerative colitis (UC), is a non-specific chronic gastrointestinal inflammatory disease with unclear etiology [1]. IBD is characterized by recurrent symptoms, including mucopurulent bloody stools, weight loss, abdominal spasm, fatigue, anemia, extraintestinal symptoms, and multiple complications such as joint pain and arthritis. At the same time, the body produces large amounts of cytokines, proteolytic enzymes, and free radicals, which eventually lead to inflammation and ulcers [1,2]. According to a study in the United States, IBD is listed as the fifth most expensive gastrointestinal disease, and its patients accumulate additional out-of-pocket costs of nearly $500 million per year in treatment [3]. The treatment of this disease is not ideal due to the lack of medicine with enough efficiency and efficacy, although recent studies have made significant progress in understanding the pathogenesis of IBD. Therefore, it is an urgent and challenging task to study the pathophysiological mechanisms of IBD under the complex interaction of various factors such as environmental changes, immune disorders, and intestinal flora [1].
The gut microbiota and their diverse metabolites have close interactions with the host and impact the susceptibility of the host to many diseases. The symbiotic gut bacteria produce a variety of metabolites, including short-chain fatty acids (SCFAs), tryptophan catabolites, essential vitamins such as B and K vitamins, phenolic acids, and bile acids. Among these metabolites, SCFAs are arousing increasing concerns of IBD researchers since the observations of various beneficial effects of these metabolites on multiple intestinal conditions and becoming the most well-studied microbial metabolites associated with IBD [4,5]. SCFAs usually contain less than six carbon atoms, mainly including formic acid, acetic acid, propionic acid, butyric acid, and valeric acid. They are the secondary metabolites produced by the fermentation of intestinal dietary fiber, such as peptides, proteins, resistant starch, and undigested fiber. This type of metabolite is an important part of the fecal samples of both healthy and diseased conditions. The production of SCFAs is regulated and affected by many factors, such as host nutrition, the presence/absence of specific symbiotic bacteria, and transgenic diversity in concentration [4]. Among the three major types of SCFAs, propionate and acetate are mainly produced by Bacteroidetes, while the production of butyrate is mainly mediated by Firmicutes [6]. Propionic acid can be produced through the lactic acid pathway of Firmicutes or the succinic acid pathway of Bacteroidetes [7].
The SCFAs play an important regulatory role in intestinal cell function and may also be associated with multiple intestinal pathophysiological processes such as inflammatory responses. The compositions, relative ratios, and activities of these SCFAs may be variable in different parts of the intestine and thus have various impacts on the physiological conditions of the intestine [8]. First of all, SCFAs contribute to nutritional balance and cellular integrity of the intestine by providing a molecular source for phospholipid synthesis [9]. In eukaryotic hosts, SCFAs can be used as energy sources by colon cells and can also be transported to blood circulation and other tissues and therefore act as important promoters and fuels of intestinal epithelial cells, which strengthen intestinal barrier function and prevent intestinal inflammation [10,11]. Furthermore, some of the SCFAs play a role in maintaining the structure of gut microbiota and the integrity of intestinal epithelium and may thus aid the function of the intestinal epithelial barrier. Studies have shown that SCFAs can reduce the pH value of the intestine while inhibiting the growth of destructive bacteria [12]. Of note, some studies have revealed that the ecological imbalance of IBD patients is related to the impaired SCFA fermentation pathway. By comparing the affected samples with healthy individuals, the researchers found that the bacteria that ferment fibers and produce SCFAs in the mucosa and feces of IBD patients usually showed a decrease [8]. More and more evidence suggests that gut microbiota disruption affects the key physiology of the host from metabolism to immune response, and the production of SCFAs is closely related to the risk of IBD [11].
According to some studies in recent years, many compounds and decoctions in traditional medicine show antioxidant and anti-inflammatory activities, thus exhibiting potential anti-IBD effects. Some of the medicines affect the production of SCFAs and thereby suppress inflammatory conditions in the colon by affecting multiple biological processes associated with gut homeostasis. Therefore, regulating SCFA content and composition might be an important approach to IBD treatment. Here, we first provide an overview of the major functions of SCFAs in colonic inflammation. On this basis, we summarize the effects of a variety of traditional medicines on the production of SCFAs. Meanwhile, we will discuss the potential mechanisms of action, the related regulatory factors, and signaling pathways employed by SCFAs to achieve their functions. In addition, we provide our understanding of the possible limitations of current research and propose prospects for future studies in evaluating the potential of SCFAs in developing new anti-IBD drugs.

2. SCFA-Mediated Immune Regulation Plays a Key Role in Maintaining Intestinal Homeostasis

Some SCFAs, especially acetate, propionate, and butyrate, have been shown to play a pivotal role in preventing intestinal inflammation via various mechanisms [13]. Here, we describe these advances mainly through three aspects. First of all, SCFAs may affect epithelial proliferation and differentiation to change the integrity and barrier function of the intestinal epithelium. Furthermore, the generated SCFAs in the gut can stimulate the epithelial cells to produce a variety of gut-protective molecules such as secretive IgA, mucin, and antimicrobial peptides (AMPs), to protect the epithelium against pathogenic microorganisms and virulent substances in the gut. Additionally, the immune regulatory role of some SCFAs may induce alterations of gut immune responses via various signaling pathways. All these effects of SCFAs may contribute to the quiescence of the gut inflammation and support an establishment of homeostasis of the gut. We will discuss the recent advances of SCFAs regarding multiple functions as follows (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).

2.1. Regulates the Functions of the Intestinal Epithelial Barrier

SCFAs have a role in promoting the healing of the intestinal epithelial barrier, mainly composed of cylindrical epithelial cells and other functional cell types such as goblet cells. Previous studies have shown that some of the SCFAs affect the functions of multiple IECs via various mechanisms to regulate the barrier function of epithelium [14]. For instance, Singh et al. showed that butyrate could promote intestinal epithelial cells to produce IL-18 [15], a cytokine that can enforce the barrier function of epithelium by promoting cell proliferation [16]. The researchers also showed that the effect of butyrate was mediated by G protein-coupled receptor GPR109a, a receptor for butyrate in the colon. Deficiency of GPR109a could induce an increase of colonic inflammation in mouse model and administration of the agonist of GPR109a, Niacin, could ameliorate colonic inflammation in a GPR109a dependent manner, further strengthened the effect of butyrate–GPR109a axis in regulating epithelial barrier function. Moreover, a study by Deleu et al. [17] evaluated the impact of acetate on intestinal barrier integrity, an SCFA that was considered to be less toxic to epithelial cells. Using organoid-based monolayer cultures obtained from UC patients, the researchers found that a high concentration of acetate could induce proliferation of epithelial cells indicated by enhanced level of cell proliferation marker, MKI67, in the cells. Meanwhile, acetate treatment also significantly enhanced the production of barrier genes such as MUC2 and CLDN1. Additionally, in a study by Peng et al., the researchers employed a cellular model of intestinal barrier established by Caco-2 cell monolayer and disclosed that butyrate could induce an increase of transepithelial electrical resistance and a decrease of inulin permeability, indicating an effect of butyrate in up-regulating intestinal barrier function [18].
Of note, the intercellular tight junction (TJ) proteins play an essential role in the integrity of the barrier [19] and act as a major component of the intestinal mucosal mechanical barrier [6]. These proteins distribute between adjacent intestinal epithelial cells and thus play a role in preventing harmful substances from entering the submucosa, which plays an extremely important role in maintaining intestinal health [20]. The major components of the TJ are transmembrane proteins, including occludin, claudins, junctional adhesion molecules (JAM), and auxiliary cytoplasmic proteins such as occlusive bands (ZOs) [21,22]. Studies have shown that SCFAs can maintain epithelial integrity and restore normal barrier function. SCFAs regulate the permeability between intestinal cells by regulating the expression of tight junction proteins. For instance, the study by Saleri et al. [23]. showed that different SCFAs regulated the production of specific TJ proteins. Using porcine intestinal epithelial cells, the researchers disclosed that butyrate could selectively up-regulate the production of ZO-1 and occludin, while it had minimal role on the level of claudin 4. Acetate significantly enhanced the levels of occludin, and claudin 4, but had no effect on ZO-1. In comparison, lactate could only affect the level of ZO-1. Only propionate could promote the production of the three TJ proteins. Some studies provided further evidence that SCFAs may affect the assembly of TJ proteins. As shown in Miao et al.’s study [24], sodium butyrate promoted the reassembly of TJ in Caco-2 monolayers via inhibiting MLCK/MLC2 pathway and phosphorylation of PKCβ2.

2.2. Regulates Barrier-Supporting Proteins

Besides the role of SCFAs in regulating epithelial barrier-forming genes, these molecules have a role in promoting the expression of multiple barrier-supporting proteins, including the mucus and some defense proteins such as immunoglobulin (Ig). In a study by Deleu et al., the researcher used a organoid-based epithelial monolayer culture to evaluate the potential role of acetate on the production of barrier-supporting proteins and showed that stimulation with acetate could enhance the production of MUC2 by the cells, demonstrating the impact of acetate on mucin production and barrier protection [17]. Another in vitro study using human cell models by Willemsen et al. revealed that butyrate and propionate could also stimulate the production of MUC2 by epithelial goblet cells and this process was mediated by prostaglandin E [25]. Although the exact signaling pathways employed by SCFAs in promoting mucin production have not been clearly elucidated, an early study by Poul et al. [26] pointed out that several SCFAs, including acetate, propionate, and butyrate, could act as ligands of G protein coupled receptors such as GPR41 and GPR43. The exact contribution of both receptors and their downstream signaling pathways in mucin production requires further clarification. Intestinal IgA plays an essential role in regulating gut homeostasis by binding and facilitating the removal of pathogenic bacteria and microbial factors and meanwhile restoring the commensal bacteria [27]. The study by Wu et al. [28] disclosed that acetate derived from microbiota can trigger IgA production in the intestine and the process is mediated by the receptor GPR43 [29]. Another study by Takeuchi et al. [30] disclosed that acetate not only enhances IgA production in the intestine but also modulates the binding specificity of IgA to certain commensal microorganisms such as Enterobacterales. However, if other common receptors of SCFAs such as GPR41 and GPR109a play a role in acetate-mediated IgA production and the anti-microbial activity of IgA need to be further determined. Moreover, the SCFAs may have a role in regulating IgA secretion in the saliva. In this line of evidence, Yamamoto et al. [31] found that the ingestion of polydextrose can promote SCFA absorption and thus lead to enhanced salivary IgA levels in rats. To date, no direct evidence demonstrates the effects of propionate and butyrate on IgA production, while, since propionate also binds to GPR43, it may induce the production of IgA, but the role needs to be further validated in future studies. Some other studies suggest that the impact of SCFAs on IgA production may differ in various tissues or different inflammatory conditions. An example of this notion is supported by the study of Chai et al. [32], which shows that reduced SCFA levels correlate with IgA builds up in the kidney of IgA nephropathy. Similarly, in a study by Tominaga et al. [33], the researcher showed that in division colitis the levels of SCFAs are also negatively correlated with IgA in the feces. Thus, the effect of SCFAs on IgA production may need to be further verified in more studies of different inflammatory environments. All these observations provided further evidence that SCFAs play an essential role in regulating the expression of barrier-supporting genes.

2.3. Regulates Gut Microbiota

The gut contains a large number of microbes with high complexity and heterogeneity, including bacteria, fungi, viruses, and other microbial populations [34]. The normal structure and composition of the microbiota may play an important role in maintaining intestinal homeostasis. Its dysregulation is associated with many human diseases, including IBD [9]. In normal conditions, the microorganisms in the gut may establish a symbiotic relationship with the host, and promote the fermentation of complex carbohydrates and the production of SCFAs to enhance the integrity of the intestinal barrier [35]. The SCFAs and SCFA-producing bacteria may in turn have a regulatory role in the composition and structure of the gut microbiota. For example, Wang et al. found that the loss of butyrate-producing Faecalibacterium prausnitzii was associated with the increased proportion of Bifidobacterium and the Lactobacillus in both fecal and biopsy specimens of IBD patients [36]. Moreover, the study of Kumari et al. [37] observed that the levels of butyrate-producing Clostridium coccoides and Clostridium leptum clusters were significantly reduced in fecal samples of UC patients. Additionally, SCFAs such as butyrate can induce the production of IL-18, which is involved in the synthesis of AMPs such as defensins, calprotectin, and lipocalin [38]. The AMPs play an essential role in suppressing the proliferation of some pathogenic bacteria such as staphylococcus. Both the composition of the microbiota and the levels of AMPs are important in the development of colonic inflammation [38]. Some of the AMPs are produced by epithelial cells during the inflammatory process and affect the progress of IBD [39]. Thus, gut microbiota and AMPs are important targets of SCFAs in regulating the development of IBD.

2.4. Regulates Immune Responses in the Gut

Precedent studies revealed the role of SCFAs in suppressing the inflammatory responses in the gut. It has been observed that some SCFAs can inhibit the recruitment of monocytes and macrophages, as well as neutrophils, by inhibiting the expression of chemokines and adhesion molecules, which can indicate its potential anti-inflammatory effect [40]. In a study using a mouse model, it was proved that propionate and butyrate can inhibit the maturation of DC, which is a bridge between the innate immune system and the adaptive immune system [41]. Furthermore, SCFAs can regulate the activity of mouse DCs, which can produce cytokines and interact with T cells. Under the stimulation of butyrate, DCs can inhibit the differentiation of IFN-γ-producing T cells [42]. Butyrate can also regulate the activity of mouse colon lamina propria macrophages, and inhibit the transcription of pro-inflammatory molecules such as Nos2, IL-6, and IL-12 [43], probably by suppressing the activation of NF-κB in the TLR ligand response [44]. Some other studies also support the role of butyrate in regulating the NF-κB pathway by inducing nuclear peroxisome proliferator-activated receptor (PPARγ) or by inhibiting histone deacetylase (HDAC) and proteasome activity [45,46].
Previous studies have demonstrated that the proportion of Tregs was increased in the intestine of IBD patients, especially in inflammatory lesions [47]. SCFAs can also play an immunomodulatory role in various T cells such as Th17, Th1, and Tregs in different cytokine environments [48]. As mentioned above, butyrate-mediated production of IL-18 can suppress Th17 differentiation in the gut and meanwhile enforce the function of Foxp3+ Treg cells [49]. This role of butyrate may be associated with its effect on regulating epigenetic modification, up-regulating histone H3 acetylation of Foxp3, and inducing Treg differentiation [50]. The HDAC inhibitory activity of butyrate also stimulates changes in gene expression in mouse DCs, including inhibition of IL-6 and IL-12, thereby affecting the polarization of Tregs [51].
Another function of SCFAs in immune regulation is manifested by its effect on regulating the production of immune regulatory molecules. A good example is its role in regulating the level of IL-22 in the intestine, an essential cytokine in regulating intestinal mucosal immunity. IL-22 may play pro-inflammatory and anti-inflammatory properties depending on the inflammatory microenvironment [52]. A study by Yang et al. reported that microbiota-derived SCFAs could promote the production of IL-22 by innate lymphoid cells (ILCs) and CD4+ T cells in the intestine [53].
As to the mechanisms of SCFAs in regulating immune responses, many studies have found the ability of SCFAs to bind to receptors such as GPR41, GPR43, and GPR109. The main GPCRs activated by SCFAs are GPR43 and GPR41, which lead to mitogen-activated protein kinase signaling and the production of chemokines and cytokines, and mediate protective immune response and tissue inflammation in mice [54]. SCFAs induce neutrophil chemotaxis and regulate phagocytosis and reactive oxygen species (ROS) production by activating GPR43 [54]. The production of IL-22 triggered by SCFAs was also mediated by the activation of GPR41 and inhibition of HDAC, which led to the up-regulation of aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α). The latter could bind to the Il-22 promoter and promote its transcription.

2.5. Regulates the Production of Reactive Oxygen Species (ROS)

ROS is a term to describe a series of oxygen-containing compounds with high oxidative properties produced during cell metabolism, mainly including hydroxyl radicals, superoxide anions, and hydrogen peroxide, which play a vital role in regulating many signaling pathways in maintaining the homeostasis of the intestine [55]. Some previous studies on the mechanism of SCFAs have focused on specific metabolites or genes involved in improving the therapeutic effect of colitis, such as reactive oxygen species (ROS) biosynthesis [56]. A previous study showed that SCFA induces apoptosis and activates autophagy in colitis [57]. This may be associated with the changes in ROS, which can be significantly induced in cells treated with high concentrations of SCFAs such as propionate [56]. Moreover, Maslowski et al. found that acetate can promote the release of ROS when added to mouse neutrophils by activating GPR43 [58]. The researchers believe that SCFAs may regulate inflammatory diseases by activating ROS to accelerate pathogen clearance [59]. In addition, SCFAs significantly altered the expression of genes involved in ROS production, such as PLIN5 [60], CDKN1A [61], UCP1 [61], COLIA1 [62], IMMP2L [63] and DUOXA2 [64]. These results suggest that SCFAs modulate the ROS signaling pathway by regulating metabolic and transcriptomic profiles and thus contribute to the regulation of colonic inflammation.

2.6. Regulates Colon Motility

Colon motility is a term to describe the peristaltic motion of the colon during the transportation of stool from small intestine to the rectum. Impaired colon motility is a frequently observed condition in patients with IBD [65] and may be an important factor that affects the development of IBD [66], possibly by regulating neuroplasticity in both active and quiescent IBD [67]. Using DSS-induced colitis model, Watanabe et al. [68] found that DSS treatment could induce neuroanatomical changes and damages to cholinergic neurons, which are closely related to impairment of colon motility. Thus, regulating colon motility may be a potential approach for treating IBD. Some studies have reported that SCFAs may have a role in modulating colon motility [69,70], although the effects are controversial. A good example for this line of evidence was provided by the study of Soret et al. [69], using ex vivo experiment the researchers investigated the effect of butyrate on the enteric nervous system (ENS) and colonic motility and found that butyrate could increase cholinergic-mediated colonic circular muscle contractile response. Regarding the mechanisms, they showed that butyrate could enhance the ratio of choline acetyltransferase (ChAT) but not neuronal nitric oxide synthase (nNOS)-immunoreactive myenteric neurons in an monocarboxylate transporter 2 (MCT2) dependent manner. While they also revealed that acetate and propionate did not have this effect. In comparison to this study, Cherbut et al. [70] found that intracolonic infusion of propionate or butyrate could significantly reduce colon motility and increase transit rate. About the mechanisms, the researchers revealed that local nerve fibers and polypeptide YY (PYY) were involved in the inhibitory role of the SCFAs since inhibition of intraluminal nerve activity using procaine infusion or neutralization of circulating PYY could block the effect of SCFAs on colon motility. Therefore, the exact role of SCFAs in colon motility may need to be further determined. The debatable effects of SCFAs in colon motility were also reported in studies of irritable bowel syndrome (IBS). As shown in Shaidullov et al.’s study [71], the researchers proposed that an imbalanced stimulatory and inhibitory effects of SCFAs on the regulation of colon contractility led to accelerated transit in IBS. Similar mechanisms in regulation of colonic motility by SCFAs may also apply to IBD and need to be validated in future.

4. Limitations and Solutions

An increasing number of studies have provided evidence that numerous decoctions or formulas in traditional medicine have promising therapeutic effects on colitis in animal models, at least in part, by regulating the production of various SCFAs. While further development and application of these medicines in clinical practice are still limited by several challenges: (1) The exact ingredients or compounds that play the role of promoting the production of SCFAs in a decoction/formula need to be identified since many unrelated ingredients may enhance the toxicity of the effective compounds. (2) The SCFAs induced by traditional medicine, or some compounds were generated by particular SCFA-producing bacteria, and thus it is important to evaluate the relative efficacy of the compounds, SCFA-producing bacteria, and the SCFAs, in in vivo studies, to determine the best approach for drug delivery. (3) Elucidating the multifaceted molecular processes behind the anti-inflammatory activity of SCFAs has been challenging because they may work with different signaling compounds. Since the role of SCFAs is sometimes combinatorial, diverse, and indirect, future research must explain its clinical treatment prospects. (4) After identification of the effective components for promoting SCFAs, their efficacy and cytotoxicity also need to be extensively evaluated in pre-clinical in vivo studies with multiple animal species. (5) The current research mainly focuses on the regulation of intestinal microbial diversity, structure, and abundance by traditional drugs, the potential mechanisms of action have not been elucidated. (6) The quality of the traditional medicines, especially some herbs, can be greatly affected by a variety of environmental factors, such as the temperature and humidity. Therefore, the examination of the chemical ingredients of the traditional medicines is necessary to guarantee the efficacy.
Given the beneficial effect of SCFAs described in numerous studies using many IBD mouse models [124], it should be noted that SCFAs may also have a pro-inflammatory effect [54]. Thus, it might be important to evaluate the status of the microenvironment before the application of SCFAs or SCFA-producing bacteria in treating UC-associated conditions. Future research must establish different standard animal models based on the relationship between the therapeutic efficacy of traditional medicine and the structure, composition, and action factors of SCFAs. In addition, it is important to further identify the composition of the decoction and its immune effect on SCFAs, which is an important issue in UC treatment research. The research work can provide a clinical basis for the applications of different traditional drugs to treat different types of UC, meanwhile largely improving the therapeutic efficacy of UC and achieving precision medicine. Additionally, integrated applications of various state-of-the-art technologies such as single-cell sequencing, multi-omics, computerized screening, microbiota interference, gene knockout techniques, and multicolor immunofluorescence in in vitro and in vivo experiments might be helpful for the identification of effective compounds in decoctions/formulas and the evaluation of the efficacy and cytotoxicity of the ingredients of traditional medicines, as well as the relative contributions of SCFAs. On this basis, a framework can be established for predicting and identifying IBD biomarkers and targets of host–microbial interactions, as well as improving the accuracy for clinical applications of the traditional medicines.

5. Conclusions

In this study, we summarized the major advances in the literature as to the roles of many decoctions, formulas, or compounds derived from traditional medicine and the medicines-triggered production of SCFAs in several animal models of colitis induced by various chemicals such as DSS, TNBS, DNBS, and acetic acid. In general, the traditional medicines described in this study commonly trigger the alterations of the gut microbiota of the animals, which show increased enrichment with SCFA-producing bacteria. The latter produces a variety of SCFAs in the intestine, such as acetate, propionate, butyrate, and valerate. These SCFAs in turn activate several receptors such as GPR41 and GPR43 to achieve their suppressive roles to many intracellular signaling pathways, including the NF-κB, AKT-STAT3, RORγT, NLRP3, and AhR signaling pathways. The altered activity of these signaling pathways then suppresses colon inflammation and enhances intestinal healing by regulating multiple biological processes, mainly including up-regulating the expression of barrier-supporting proteins such as the tight junction proteins, mucin, AMPs, and secretory IgAs to repair the intestinal mechanical barrier and the chemical barrier, promoting the proliferation of multiple intestinal epithelial cells, suppressing the production of ROS, inhibiting inflammatory responses in the colon, regulating colon motility, and balancing the gut microbiota and related metabolites. Overall, the SCFAs induced by various traditional medicines have provided an anti-colitis approach for the management of UC by various mechanisms.
Current studies have revealed the important role of SCFAs in body metabolism and the therapeutic potential for various related diseases. It is generally believed that SCFAs exerts beneficial effects on the host, but in certain cases, excessive SCFAs will harm the host, so the interaction between SCFAs and the host needs further research, which may promote our understanding of the specific mechanisms of action in related diseases and more effectively achieve personalized treatment. Moreover, the reduction of particular SCFA-producing bacteria in gut microbiota may be helpful to identify different subtypes of UC. The characteristic bacteria are likely to be used as diagnostic biomarkers for UC, suggesting that the usage of herbal medicine-based plant drugs may be a promising strategy for UC treatment via regulating intestinal microbiota [125]. Our study emphasizes the importance of SCFAs in maintaining intestinal health and encourages a further extensive study of traditional medicines that induce the production of SCFAs and regulate the enrichment of SCFA-producing microflora in the context of colonic inflammation, which may facilitate the development of new IBD therapies.

Author Contributions

Y.Y. and Y.L. searched the literature, planned and performed the studies, drew the figures, and wrote the first draft of the manuscript; Q.X. and L.M. designed the project and edited the final version of the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This study was partially supported by the National Natural Science Foundation of China (32070919 and 32270919), Jiangsu Specially Appointed Professorship, and Start-up funds for young scientists of Nantong University (03083051).

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Guan, Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J. Immunol. Res. 2019, 2019, 7247238. [Google Scholar] [CrossRef]
  2. Stokkers, P.C.; Hommes, D.W. New cytokine therapeutics for inflammatory bowel disease. Cytokine 2004, 28, 167–173. [Google Scholar] [CrossRef] [PubMed]
  3. Xie, F.; Xiong, Q.; Li, Y.; Yao, C.; Wu, R.; Wang, Q.; Luo, L.; Liu, H.; Feng, P. Traditional Chinese Medicine Regulates Th17/Treg Balance in Treating Inflammatory Bowel Disease. Evid. Based Complement. Altern. Med. 2022, 2022, 6275136. [Google Scholar] [CrossRef]
  4. Russo, E.; Giudici, F.; Fiorindi, C.; Ficari, F.; Scaringi, S.; Amedei, A. Immunomodulating Activity and Therapeutic Effects of Short Chain Fatty Acids and Tryptophan Post-biotics in Inflammatory Bowel Disease. Front. Immunol. 2019, 10, 2754. [Google Scholar] [CrossRef] [PubMed]
  5. Blaak, E.E.; Canfora, E.E.; Theis, S.; Frost, G.; Groen, A.K.; Mithieux, G.; Nauta, A.; Scott, K.; Stahl, B.; van Harsselaar, J.; et al. Short chain fatty acids in human gut and metabolic health. Benef. Microbes 2020, 11, 411–455. [Google Scholar] [CrossRef] [PubMed]
  6. Vogt, S.L.; Peña-Díaz, J.; Finlay, B.B. Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens. Anaerobe 2015, 34, 106–115. [Google Scholar] [CrossRef] [PubMed]
  7. Louis, P.; Hold, G.L.; Flint, H.J. The gut microbiota, bacterial metabolites and colorectal cancer. Nat. Rev. Microbiol. 2014, 12, 661–672. [Google Scholar] [CrossRef]
  8. Parada Venegas, D.; De la Fuente, M.K.; Landskron, G.; González, M.J.; Quera, R.; Dijkstra, G.; Harmsen, H.J.M.; Faber, K.N.; Hermoso, M.A. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front. Immunol. 2019, 10, 277. [Google Scholar] [CrossRef]
  9. Heimerl, S.; Moehle, C.; Zahn, A.; Boettcher, A.; Stremmel, W.; Langmann, T.; Schmitz, G. Alterations in intestinal fatty acid metabolism in inflammatory bowel disease. Biochim. Biophys. Acta 2006, 1762, 341–350. [Google Scholar] [CrossRef]
  10. Zhu, L.; Xu, L.Z.; Zhao, S.; Shen, Z.F.; Shen, H.; Zhan, L.B. Protective effect of baicalin on the regulation of Treg/Th17 balance, gut microbiota and short-chain fatty acids in rats with ulcerative colitis. Appl. Microbiol. Biotechnol. 2020, 104, 5449–5460. [Google Scholar] [CrossRef]
  11. Huda-Faujan, N.; Abdulamir, A.S.; Fatimah, A.B.; Anas, O.M.; Shuhaimi, M.; Yazid, A.M.; Loong, Y.Y. The impact of the level of the intestinal short chain Fatty acids in inflammatory bowel disease patients versus healthy subjects. Open Biochem. J. 2010, 4, 53–58. [Google Scholar] [CrossRef]
  12. Liu, P.; Wang, Y.; Yang, G.; Zhang, Q.; Meng, L.; Xin, Y.; Jiang, X. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol. Res. 2021, 165, 105420. [Google Scholar] [CrossRef]
  13. Wang, B.; Gong, Z.; Zhan, J.; Yang, L.; Zhou, Q.; Yuan, X. Xianglian Pill Suppresses Inflammation and Protects Intestinal Epithelial Barrier by Promoting Autophagy in DSS Induced Ulcerative Colitis Mice. Front. Pharmacol. 2020, 11, 594847. [Google Scholar] [CrossRef]
  14. Fukuda, S.; Toh, H.; Hase, K.; Oshima, K.; Nakanishi, Y.; Yoshimura, K.; Tobe, T.; Clarke, J.M.; Topping, D.L.; Suzuki, T.; et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 2011, 469, 543–547. [Google Scholar] [CrossRef]
  15. Singh, N.; Gurav, A.; Sivaprakasam, S.; Brady, E.; Padia, R.; Shi, H.; Thangaraju, M.; Prasad, P.D.; Manicassamy, S.; Munn, D.H.; et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 2014, 40, 128–139. [Google Scholar] [CrossRef] [PubMed]
  16. Chiang, H.Y.; Lu, H.H.; Sudhakar, J.N.; Chen, Y.W.; Shih, N.S.; Weng, Y.T.; Shui, J.W. IL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defence. Nat. Commun. 2022, 13, 874. [Google Scholar] [CrossRef] [PubMed]
  17. Deleu, S.; Arnauts, K.; Deprez, L.; Machiels, K.; Ferrante, M.; Huys, G.R.B.; Thevelein, J.M.; Raes, J.; Vermeire, S. High Acetate Concentration Protects Intestinal Barrier and Exerts Anti-Inflammatory Effects in Organoid-Derived Epithelial Monolayer Cultures from Patients with Ulcerative Colitis. Int. J. Mol. Sci. 2023, 24, 768. [Google Scholar] [CrossRef] [PubMed]
  18. Peng, L.; He, Z.; Chen, W.; Holzman, I.R.; Lin, J. Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier. Pediatr. Res. 2007, 61, 37–41. [Google Scholar] [CrossRef]
  19. Capaldo, C.T.; Powell, D.N.; Kalman, D. Layered defense: How mucus and tight junctions seal the intestinal barrier. J. Mol. Med. 2017, 95, 927–934. [Google Scholar] [CrossRef]
  20. Otani, T.; Furuse, M. Tight Junction Structure and Function Revisited. Trends Cell Biol. 2020, 30, 805–817. [Google Scholar] [CrossRef]
  21. Tsukita, S.; Tanaka, H.; Tamura, A. The Claudins: From Tight Junctions to Biological Systems. Trends Biochem. Sci. 2019, 44, 141–152. [Google Scholar] [CrossRef] [PubMed]
  22. Van Itallie, C.M.; Anderson, J.M. Phosphorylation of tight junction transmembrane proteins: Many sites, much to do. Tissue Barriers 2018, 6, e1382671. [Google Scholar] [CrossRef]
  23. Saleri, R.; Borghetti, P.; Ravanetti, F.; Cavalli, V.; Ferrari, L.; De Angelis, E.; Andrani, M.; Martelli, P. Effects of different short-chain fatty acids (SCFA) on gene expression of proteins involved in barrier function in IPEC-J2. Porc. Health Manag. 2022, 8, 21. [Google Scholar] [CrossRef] [PubMed]
  24. Miao, W.; Wu, X.; Wang, K.; Wang, W.; Wang, Y.; Li, Z.; Liu, J.; Li, L.; Peng, L. Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. Int. J. Mol. Sci. 2016, 17, 1696. [Google Scholar] [CrossRef] [PubMed]
  25. Willemsen, L.E.; Koetsier, M.A.; van Deventer, S.J.; van Tol, E.A. Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1) and E(2) production by intestinal myofibroblasts. Gut 2003, 52, 1442–1447. [Google Scholar] [CrossRef] [PubMed]
  26. Le Poul, E.; Loison, C.; Struyf, S.; Springael, J.Y.; Lannoy, V.; Decobecq, M.E.; Brezillon, S.; Dupriez, V.; Vassart, G.; Van Damme, J.; et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 2003, 278, 25481–25489. [Google Scholar] [CrossRef] [PubMed]
  27. Huus, K.E.; Bauer, K.C.; Brown, E.M.; Bozorgmehr, T.; Woodward, S.E.; Serapio-Palacios, A.; Boutin, R.C.T.; Petersen, C.; Finlay, B.B. Commensal Bacteria Modulate Immunoglobulin A Binding in Response to Host Nutrition. Cell Host Microbe 2020, 27, 909–921.e5. [Google Scholar] [CrossRef]
  28. Wu, W.; Sun, M.; Chen, F.; Cao, A.T.; Liu, H.; Zhao, Y.; Huang, X.; Xiao, Y.; Yao, S.; Zhao, Q.; et al. Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. Mucosal Immunol. 2017, 10, 946–956. [Google Scholar] [CrossRef]
  29. Brown, A.J.; Goldsworthy, S.M.; Barnes, A.A.; Eilert, M.M.; Tcheang, L.; Daniels, D.; Muir, A.I.; Wigglesworth, M.J.; Kinghorn, I.; Fraser, N.J.; et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 2003, 278, 11312–11319. [Google Scholar] [CrossRef]
  30. Takeuchi, T.; Miyauchi, E.; Kanaya, T.; Kato, T.; Nakanishi, Y.; Watanabe, T.; Kitami, T.; Taida, T.; Sasaki, T.; Negishi, H.; et al. Acetate differentially regulates IgA reactivity to commensal bacteria. Nature 2021, 595, 560–564. [Google Scholar] [CrossRef]
  31. Yamamoto, Y.; Morozumi, T.; Takahashi, T.; Saruta, J.; To, M.; Sakaguchi, W.; Shimizu, T.; Kubota, N.; Tsukinoki, K. Faster Short-Chain Fatty Acid Absorption from the Cecum Following Polydextrose Ingestion Increases the Salivary Immunoglobulin A Flow Rate in Rats. Nutrients 2020, 12, 1745. [Google Scholar] [CrossRef] [PubMed]
  32. Chai, L.; Luo, Q.; Cai, K.; Wang, K.; Xu, B. Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy. BMC Nephrol. 2021, 22, 209. [Google Scholar] [CrossRef]
  33. Tominaga, K.; Tsuchiya, A.; Mizusawa, T.; Matsumoto, A.; Minemura, A.; Oka, K.; Takahashi, M.; Yosida, T.; Kawata, Y.; Takahashi, K.; et al. Evaluation of intestinal microbiota, short-chain fatty acids, and immunoglobulin a in diversion colitis. Biochem. Biophys. Rep. 2021, 25, 100892. [Google Scholar] [CrossRef] [PubMed]
  34. Milani, C.; Duranti, S.; Bottacini, F.; Casey, E.; Turroni, F.; Mahony, J.; Belzer, C.; Delgado Palacio, S.; Arboleya Montes, S.; Mancabelli, L.; et al. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol. Mol. Biol. Rev. 2017, 81, 10–1128. [Google Scholar] [CrossRef] [PubMed]
  35. LeBlanc, J.G.; Milani, C.; de Giori, G.S.; Sesma, F.; van Sinderen, D.; Ventura, M. Bacteria as vitamin suppliers to their host: A gut microbiota perspective. Curr. Opin. Biotechnol. 2013, 24, 160–168. [Google Scholar] [CrossRef]
  36. Wang, W.; Chen, L.; Zhou, R.; Wang, X.; Song, L.; Huang, S.; Wang, G.; Xia, B. Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. J. Clin. Microbiol. 2014, 52, 398–406. [Google Scholar] [CrossRef] [PubMed]
  37. Kumari, R.; Ahuja, V.; Paul, J. Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India. World J. Gastroenterol. 2013, 19, 3404–3414. [Google Scholar] [CrossRef]
  38. Elinav, E.; Strowig, T.; Kau, A.L.; Henao-Mejia, J.; Thaiss, C.A.; Booth, C.J.; Peaper, D.R.; Bertin, J.; Eisenbarth, S.C.; Gordon, J.I.; et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 2011, 145, 745–757. [Google Scholar] [CrossRef]
  39. Ho, S.; Pothoulakis, C.; Koon, H.W. Antimicrobial peptides and colitis. Curr. Pharm. Des. 2013, 19, 40–47. [Google Scholar]
  40. Yan, Q.; Jia, S.; Li, D.; Yang, J. The role and mechanism of action of microbiota-derived short-chain fatty acids in neutrophils: From the activation to becoming potential biomarkers. Biomed. Pharmacother. 2023, 169, 115821. [Google Scholar] [CrossRef]
  41. Singh, N.; Thangaraju, M.; Prasad, P.D.; Martin, P.M.; Lambert, N.A.; Boettger, T.; Offermanns, S.; Ganapathy, V. Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J. Biol. Chem. 2010, 285, 27601–27608. [Google Scholar] [CrossRef] [PubMed]
  42. Gurav, A.; Sivaprakasam, S.; Bhutia, Y.D.; Boettger, T.; Singh, N.; Ganapathy, V. Slc5a8, a Na+-coupled high-affinity transporter for short-chain fatty acids, is a conditional tumour suppressor in colon that protects against colitis and colon cancer under low-fibre dietary conditions. Biochem. J. 2015, 469, 267–278. [Google Scholar] [CrossRef] [PubMed]
  43. Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 2014, 111, 2247–2252. [Google Scholar] [CrossRef]
  44. Lin, M.Y.; de Zoete, M.R.; van Putten, J.P.; Strijbis, K. Redirection of Epithelial Immune Responses by Short-Chain Fatty Acids through Inhibition of Histone Deacetylases. Front. Immunol. 2015, 6, 554. [Google Scholar] [CrossRef]
  45. Yin, L.; Laevsky, G.; Giardina, C. Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity. J. Biol. Chem. 2001, 276, 44641–44646. [Google Scholar] [CrossRef] [PubMed]
  46. Place, R.F.; Noonan, E.J.; Giardina, C. HDAC inhibition prevents NF-kappa B activation by suppressing proteasome activity: Down-regulation of proteasome subunit expression stabilizes I kappa B alpha. Biochem. Pharmacol. 2005, 70, 394–406. [Google Scholar] [CrossRef]
  47. Maul, J.; Loddenkemper, C.; Mundt, P.; Berg, E.; Giese, T.; Stallmach, A.; Zeitz, M.; Duchmann, R. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology 2005, 128, 1868–1878. [Google Scholar] [CrossRef]
  48. Park, J.; Kim, M.; Kang, S.G.; Jannasch, A.H.; Cooper, B.; Patterson, J.; Kim, C.H. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 2015, 8, 80–93. [Google Scholar] [CrossRef]
  49. Harrison, O.J.; Srinivasan, N.; Pott, J.; Schiering, C.; Krausgruber, T.; Ilott, N.E.; Maloy, K.J. Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3⁺ Treg cell function in the intestine. Mucosal Immunol. 2015, 8, 1226–1236. [Google Scholar] [CrossRef]
  50. Furusawa, Y.; Obata, Y.; Fukuda, S.; Endo, T.A.; Nakato, G.; Takahashi, D.; Nakanishi, Y.; Uetake, C.; Kato, K.; Kato, T.; et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013, 504, 446–450. [Google Scholar] [CrossRef]
  51. Ricote, M.; Li, A.C.; Willson, T.M.; Kelly, C.J.; Glass, C.K. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998, 391, 79–82. [Google Scholar] [CrossRef]
  52. Zhang, X.; Liu, S.; Wang, Y.; Hu, H.; Li, L.; Wu, Y.; Cao, D.; Cai, Y.; Zhang, J.; Zhang, X. Interleukin-22 regulates the homeostasis of the intestinal epithelium during inflammation. Int. J. Mol. Med. 2019, 43, 1657–1668. [Google Scholar] [CrossRef] [PubMed]
  53. Yang, W.; Yu, T.; Huang, X.; Bilotta, A.J.; Xu, L.; Lu, Y.; Sun, J.; Pan, F.; Zhou, J.; Zhang, W.; et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat. Commun. 2020, 11, 4457. [Google Scholar] [CrossRef]
  54. Vinolo, M.A.; Rodrigues, H.G.; Nachbar, R.T.; Curi, R. Regulation of inflammation by short chain fatty acids. Nutrients 2011, 3, 858–876. [Google Scholar] [CrossRef]
  55. Morris, O.; Jasper, H. Reactive Oxygen Species in intestinal stem cell metabolism, fate and function. Free Radic. Biol. Med. 2021, 166, 140–146. [Google Scholar] [CrossRef]
  56. Huang, C.; Deng, W.; Xu, H.Z.; Zhou, C.; Zhang, F.; Chen, J.; Bao, Q.; Zhou, X.; Liu, M.; Li, J.; et al. Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells. Comput. Struct. Biotechnol. J. 2023, 21, 1606–1620. [Google Scholar] [CrossRef]
  57. Tang, Y.; Chen, Y.; Jiang, H.; Nie, D. The role of short-chain fatty acids in orchestrating two types of programmed cell death in colon cancer. Autophagy 2011, 7, 235–237. [Google Scholar] [CrossRef] [PubMed]
  58. Maslowski, K.M.; Vieira, A.T.; Ng, A.; Kranich, J.; Sierro, F.; Yu, D.; Schilter, H.C.; Rolph, M.S.; Mackay, F.; Artis, D.; et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009, 461, 1282–1286. [Google Scholar] [CrossRef]
  59. Tan, J.; McKenzie, C.; Potamitis, M.; Thorburn, A.N.; Mackay, C.R.; Macia, L. The role of short-chain fatty acids in health and disease. Adv. Immunol. 2014, 121, 91–119. [Google Scholar] [PubMed]
  60. Tan, Y.; Jin, Y.; Wang, Q.; Huang, J.; Wu, X.; Ren, Z. Perilipin 5 Protects against Cellular Oxidative Stress by Enhancing Mitochondrial Function in HepG2 Cells. Cells 2019, 8, 1241. [Google Scholar] [CrossRef]
  61. Oelkrug, R.; Goetze, N.; Meyer, C.W.; Jastroch, M. Antioxidant properties of UCP1 are evolutionarily conserved in mammals and buffer mitochondrial reactive oxygen species. Free Radic. Biol. Med. 2014, 77, 210–216. [Google Scholar] [CrossRef] [PubMed]
  62. Fu, X.H.; Chen, C.Z.; Wang, Y.; Peng, Y.X.; Wang, W.H.; Yuan, B.; Gao, Y.; Jiang, H.; Zhang, J.B. COL1A1 affects apoptosis by regulating oxidative stress and autophagy in bovine cumulus cells. Theriogenology 2019, 139, 81–89. [Google Scholar] [CrossRef]
  63. He, Q.; Gu, L.; Lin, Q.; Ma, Y.; Liu, C.; Pei, X.; Li, P.A.; Yang, Y. The Immp2l Mutation Causes Ovarian Aging Through ROS-Wnt/β-Catenin-Estrogen Pathway: Preventive Effect of Melatonin. Endocrinology 2020, 161, bqaa119. [Google Scholar] [CrossRef] [PubMed]
  64. Hoste, C.; Dumont, J.E.; Miot, F.; De Deken, X. The type of DUOX-dependent ROS production is dictated by defined sequences in DUOXA. Exp. Cell Res. 2012, 318, 2353–2364. [Google Scholar] [CrossRef] [PubMed]
  65. Barros, L.L.; Farias, A.Q.; Rezaie, A. Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment. World J. Gastroenterol. 2019, 25, 4414–4426. [Google Scholar] [CrossRef]
  66. Bassotti, G.; Antonelli, E.; Villanacci, V.; Nascimbeni, R.; Dore, M.P.; Pes, G.M.; Maconi, G. Abnormal gut motility in inflammatory bowel disease: An update. Tech. Coloproctol. 2020, 24, 275–282. [Google Scholar] [CrossRef]
  67. Mawe, G.M. Colitis-induced neuroplasticity disrupts motility in the inflamed and post-inflamed colon. J. Clin. Investig. 2015, 125, 949–955. [Google Scholar] [CrossRef]
  68. da Silva Watanabe, P.; Cavichioli, A.M.; D’Arc de Lima Mendes, J.; Aktar, R.; Peiris, M.; Blackshaw, L.A.; de Almeida Araújo, E.J. Colonic motility adjustments in acute and chronic DSS-induced colitis. Life Sci. 2023, 321, 121642. [Google Scholar] [CrossRef]
  69. Soret, R.; Chevalier, J.; De Coppet, P.; Poupeau, G.; Derkinderen, P.; Segain, J.P.; Neunlist, M. Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology 2010, 138, 1772–1782. [Google Scholar] [CrossRef]
  70. Cherbut, C.; Ferrier, L.; Rozé, C.; Anini, Y.; Blottière, H.; Lecannu, G.; Galmiche, J.P. Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am. J. Physiol. 1998, 275, G1415–G1422. [Google Scholar] [CrossRef]
  71. Shaidullov, I.F.; Sorokina, D.M.; Sitdikov, F.G.; Hermann, A.; Abdulkhakov, S.R.; Sitdikova, G.F. Short chain fatty acids and colon motility in a mouse model of irritable bowel syndrome. BMC Gastroenterol. 2021, 21, 37. [Google Scholar] [CrossRef]
  72. Wang, X.; Liang, F.; Dai, Z.; Feng, X.; Qiu, F. Combination of Coptis chinensis polysaccharides and berberine ameliorates ulcerative colitis by regulating gut microbiota and activating AhR/IL-22 pathway. J. Ethnopharmacol. 2024, 318 Pt B, 117050. [Google Scholar] [CrossRef]
  73. Sun, X.; Zhang, Y.; Cheng, G.; Zhu, T.; Zhang, Z.; Xiong, L.; Hu, H.; Liu, H. Berberine improves DSS-induced colitis in mice by modulating the fecal-bacteria-related bile acid metabolism. Biomed. Pharmacother. 2023, 167, 115430. [Google Scholar] [CrossRef]
  74. Liu, C.S.; Liang, X.; Wei, X.H.; Jin, Z.; Chen, F.L.; Tang, Q.F.; Tan, X.M. Gegen Qinlian Decoction Treats Diarrhea in Piglets by Modulating Gut Microbiota and Short-Chain Fatty Acids. Front. Microbiol. 2019, 10, 825. [Google Scholar] [CrossRef]
  75. Hänninen, A.; Toivonen, R.; Pöysti, S.; Belzer, C.; Plovier, H.; Ouwerkerk, J.P.; Emani, R.; Cani, P.D.; De Vos, W.M. Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut 2018, 67, 1445–1453. [Google Scholar] [CrossRef] [PubMed]
  76. Xu, J.; Lian, F.; Zhao, L.; Zhao, Y.; Chen, X.; Zhang, X.; Guo, Y.; Zhang, C.; Zhou, Q.; Xue, Z.; et al. Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula. ISME J. 2015, 9, 552–562. [Google Scholar] [CrossRef]
  77. Wang, X.; Quan, J.; Xiu, C.; Wang, J.; Zhang, J. Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids. Chin. Med. 2023, 18, 110. [Google Scholar] [CrossRef]
  78. Wang, Z.; Shu, W.; Zhao, R.; Liu, Y.; Wang, H. Sodium butyrate induces ferroptosis in endometrial cancer cells via the RBM3/SLC7A11 axis. Apoptosis Int. J. Program. Cell Death 2023, 28, 1168–1183. [Google Scholar] [CrossRef] [PubMed]
  79. Bian, Z.; Sun, X.; Liu, L.; Qin, Y.; Zhang, Q.; Liu, H.; Mao, L.; Sun, S. Sodium Butyrate Induces CRC Cell Ferroptosis via the CD44/SLC7A11 Pathway and Exhibits a Synergistic Therapeutic Effect with Erastin. Cancers 2023, 15, 423. [Google Scholar] [CrossRef] [PubMed]
  80. Li, R.; Chen, Y.; Shi, M.; Xu, X.; Zhao, Y.; Wu, X.; Zhang, Y. Gegen Qinlian decoction alleviates experimental colitis via suppressing TLR4/NF-κB signaling and enhancing antioxidant effect. Phytomedicine 2016, 23, 1012–1020. [Google Scholar] [CrossRef]
  81. Hu, J.; Huang, H.; Che, Y.; Ding, C.; Zhang, L.; Wang, Y.; Hao, H.; Shen, H.; Cao, L. Qingchang Huashi Formula attenuates DSS-induced colitis in mice by restoring gut microbiota-metabolism homeostasis and goblet cell function. J. Ethnopharmacol. 2021, 266, 113394. [Google Scholar] [CrossRef]
  82. Yuan, X.; Wang, L.; Bhat, O.M.; Lohner, H.; Li, P.L. Differential effects of short chain fatty acids on endothelial Nlrp3 inflammasome activation and neointima formation: Antioxidant action of butyrate. Redox Biol. 2018, 16, 21–31. [Google Scholar] [CrossRef]
  83. Niu, C.; Hu, X.L.; Yuan, Z.W.; Xiao, Y.; Ji, P.; Wei, Y.M.; Hua, Y.L. Pulsatilla decoction improves DSS-induced colitis via modulation of fecal-bacteria-related short-chain fatty acids and intestinal barrier integrity. J. Ethnopharmacol. 2023, 300, 115741. [Google Scholar] [CrossRef] [PubMed]
  84. Wang, X.; Xu, L.; Wang, T.; Xu, J.; Fan, F.; Zhang, Y.; Wang, J.; Cao, Q. Pulsatilla decoction alleviates colitis by enhancing autophagy and regulating PI3K-Akt-mTORC1 signaling pathway. Mol. Med. Rep. 2022, 25, 108. [Google Scholar] [CrossRef] [PubMed]
  85. Li, Z.; Song, Y.; Xu, W.; Chen, J.; Zhou, R.; Yang, M.; Zhu, G.; Luo, X.; Ai, Z.; Liu, Y.; et al. Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis. J. Ethnopharmacol. 2023, 308, 116215. [Google Scholar] [CrossRef] [PubMed]
  86. Tang, S.; Liu, W.; Zhao, Q.; Li, K.; Zhu, J.; Yao, W.; Gao, X. Combination of polysaccharides from Astragalus membranaceus and Codonopsis pilosula ameliorated mice colitis and underlying mechanisms. J. Ethnopharmacol. 2021, 264, 113280. [Google Scholar] [CrossRef] [PubMed]
  87. Shao, S.; Wang, D.; Zheng, W.; Li, X.; Zhang, H.; Zhao, D.; Wang, M. A unique polysaccharide from Hericium erinaceus mycelium ameliorates acetic acid-induced ulcerative colitis rats by modulating the composition of the gut microbiota, short chain fatty acids levels and GPR41/43 respectors. Int. Immunopharmacol. 2019, 71, 411–422. [Google Scholar] [CrossRef]
  88. Ren, Y.; Geng, Y.; Du, Y.; Li, W.; Lu, Z.M.; Xu, H.Y.; Xu, G.H.; Shi, J.S.; Xu, Z.H. Polysaccharide of Hericium erinaceus attenuates colitis in C57BL/6 mice via regulation of oxidative stress, inflammation-related signaling pathways and modulating the composition of the gut microbiota. J. Nutr. Biochem. 2018, 57, 67–76. [Google Scholar] [CrossRef]
  89. Yu, Z.; Li, D.; Sun, H. Herba Origani alleviated DSS-induced ulcerative colitis in mice through remolding gut microbiota to regulate bile acid and short-chain fatty acid metabolisms. Biomed. Pharmacother. 2023, 161, 114409. [Google Scholar] [CrossRef]
  90. Zheng, J.; Li, H.; Zhang, P.; Yue, S.; Zhai, B.; Zou, J.; Cheng, J.; Zhao, C.; Guo, D.; Wang, J. Paeonol Ameliorates Ulcerative Colitis in Mice by Modulating the Gut Microbiota and Metabolites. Metabolites 2022, 12, 956. [Google Scholar] [CrossRef]
  91. Li, M.Y.; Luo, H.J.; Wu, X.; Liu, Y.H.; Gan, Y.X.; Xu, N.; Zhang, Y.M.; Zhang, S.H.; Zhou, C.L.; Su, Z.R.; et al. Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways. Front. Pharmacol. 2019, 10, 1552. [Google Scholar] [CrossRef] [PubMed]
  92. Zhu, J.J.; Liu, H.Y.; Yang, L.J.; Fang, Z.; Fu, R.; Chen, J.B.; Liu, S.; Fei, B.Y. Anti-tumour effect of Huangqin Decoction on colorectal cancer mice through microbial butyrate mediated PI3K/Akt pathway suppression. J. Med. Microbiol. 2023, 72, 001692. [Google Scholar] [CrossRef] [PubMed]
  93. Wang, Y.; Zhu, X.; Liang, Y.; Li, X.; Wang, Y.; Li, J. Sishen Wan Treats Ulcerative Colitis in Rats by Regulating Gut Microbiota and Restoring the Treg/Th17 Balance. Evid. Based Complement. Altern. Med. 2022, 2022, 1432816. [Google Scholar] [CrossRef]
  94. Chen, M.J.; Feng, Y.; Gao, L.; Lin, M.X.; Wang, S.D.; Tong, Z.Q. Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3. Chin. J. Integr. Med. 2023, 29, 424–433. [Google Scholar] [CrossRef] [PubMed]
  95. Fernández, J.; de la Fuente, V.G.; García, M.T.F.; Sánchez, J.G.; Redondo, B.I.; Villar, C.J.; Lombó, F. A diet based on cured acorn-fed ham with oleic acid content promotes anti-inflammatory gut microbiota and prevents ulcerative colitis in an animal model. Lipids Health Dis. 2020, 19, 28. [Google Scholar] [CrossRef] [PubMed]
  96. Li, J.; Ma, Y.; Li, X.; Wang, Y.; Huo, Z.; Lin, Y.; Li, J.; Yang, H.; Zhang, Z.; Yang, P.; et al. Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis. Front. Nutr. 2022, 9, 1035912. [Google Scholar] [CrossRef] [PubMed]
  97. Sun, Z.; Li, J.; Dai, Y.; Wang, W.; Shi, R.; Wang, Z.; Ding, P.; Lu, Q.; Jiang, H.; Pei, W.; et al. Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota. Front. Microbiol. 2020, 11, 731. [Google Scholar] [CrossRef]
  98. Su, L.; Mao, C.; Wang, X.; Li, L.; Tong, H.; Mao, J.; Ji, D.; Lu, T.; Hao, M.; Huang, Z.; et al. The Anti-colitis Effect of Schisandra chinensis Polysaccharide Is Associated With the Regulation of the Composition and Metabolism of Gut Microbiota. Front. Cell. Infect. Microbiol. 2020, 10, 519479. [Google Scholar] [CrossRef]
  99. Xuan, H.; Ou, A.; Hao, S.; Shi, J.; Jin, X. Galangin Protects against Symptoms of Dextran Sodium Sulfate-induced Acute Colitis by Activating Autophagy and Modulating the Gut Microbiota. Nutrients 2020, 12, 347. [Google Scholar] [CrossRef]
  100. Hu, L.; Wu, C.; Zhang, Z.; Liu, M.; Maruthi Prasad, E.; Chen, Y.; Wang, K. Pinocembrin Protects Against Dextran Sulfate Sodium-Induced Rats Colitis by Ameliorating Inflammation, Improving Barrier Function and Modulating Gut Microbiota. Front. Physiol. 2019, 10, 908. [Google Scholar] [CrossRef]
  101. Zimmerman, M.A.; Singh, N.; Martin, P.M.; Thangaraju, M.; Ganapathy, V.; Waller, J.L.; Shi, H.; Robertson, K.D.; Munn, D.H.; Liu, K. Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 302, G1405–G1415. [Google Scholar] [CrossRef]
  102. Segain, J.P.; Raingeard de la Blétière, D.; Bourreille, A.; Leray, V.; Gervois, N.; Rosales, C.; Ferrier, L.; Bonnet, C.; Blottière, H.M.; Galmiche, J.P. Butyrate inhibits inflammatory responses through NFkappaB inhibition: Implications for Crohn’s disease. Gut 2000, 47, 397–403. [Google Scholar] [CrossRef] [PubMed]
  103. Liu, T.; Li, J.; Liu, Y.; Xiao, N.; Suo, H.; Xie, K.; Yang, C.; Wu, C. Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-κB pathway in RAW264.7 cells. Inflammation 2012, 35, 1676–1684. [Google Scholar] [CrossRef] [PubMed]
  104. Lee, C.; Kim, B.G.; Kim, J.H.; Chun, J.; Im, J.P.; Kim, J.S. Sodium butyrate inhibits the NF-kappa B signaling pathway and histone deacetylation, and attenuates experimental colitis in an IL-10 independent manner. Int. Immunopharmacol. 2017, 51, 47–56. [Google Scholar] [CrossRef] [PubMed]
  105. Zhang, C.L.; Zhang, S.; He, W.X.; Lu, J.L.; Xu, Y.J.; Yang, J.Y.; Liu, D. Baicalin may alleviate inflammatory infiltration in dextran sodium sulfate-induced chronic ulcerative colitis via inhibiting IL-33 expression. Life Sci. 2017, 186, 125–132. [Google Scholar] [CrossRef] [PubMed]
  106. Yin, M.; Zhang, Y.; Li, H. Advances in Research on Immunoregulation of Macrophages by Plant Polysaccharides. Front. Immunol. 2019, 10, 145. [Google Scholar] [CrossRef] [PubMed]
  107. Fu, Y.P.; Feng, B.; Zhu, Z.K.; Feng, X.; Chen, S.F.; Li, L.X.; Yin, Z.Q.; Huang, C.; Chen, X.F.; Zhang, B.Z.; et al. The Polysaccharides from Codonopsis pilosula Modulates the Immunity and Intestinal Microbiota of Cyclophosphamide-Treated Immunosuppressed Mice. Molecules 2018, 23, 1801. [Google Scholar] [CrossRef] [PubMed]
  108. Liu, Y.J.; Tang, B.; Wang, F.C.; Tang, L.; Lei, Y.Y.; Luo, Y.; Huang, S.J.; Yang, M.; Wu, L.Y.; Wang, W.; et al. Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner. Theranostics 2020, 10, 5225–5241. [Google Scholar] [CrossRef]
  109. Sun, M.; Wu, W.; Liu, Z.; Cong, Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J. Gastroenterol. 2017, 52, 1–8. [Google Scholar] [CrossRef]
  110. Dalile, B.; Van Oudenhove, L.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 461–478. [Google Scholar] [CrossRef]
  111. Eastaff-Leung, N.; Mabarrack, N.; Barbour, A.; Cummins, A.; Barry, S. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J. Clin. Immunol. 2010, 30, 80–89. [Google Scholar] [CrossRef] [PubMed]
  112. Britton, G.J.; Contijoch, E.J.; Mogno, I.; Vennaro, O.H.; Llewellyn, S.R.; Ng, R.; Li, Z.; Mortha, A.; Merad, M.; Das, A.; et al. Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt(+) Regulatory T Cells and Exacerbate Colitis in Mice. Immunity 2019, 50, 212–224.e4. [Google Scholar] [CrossRef]
  113. Xu, X.; Wang, Y.; Wei, Z.; Wei, W.; Zhao, P.; Tong, B.; Xia, Y.; Dai, Y. Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathway. Cell Death Dis. 2017, 8, e2723. [Google Scholar] [CrossRef] [PubMed]
  114. Gálvez, J. Role of Th17 Cells in the Pathogenesis of Human IBD. ISRN Inflamm. 2014, 2014, 928461. [Google Scholar] [CrossRef]
  115. Venkataraman, B.; Ojha, S.; Belur, P.D.; Bhongade, B.; Raj, V.; Collin, P.D.; Adrian, T.E.; Subramanya, S.B. Phytochemical drug candidates for the modulation of peroxisome proliferator-activated receptor γ in inflammatory bowel diseases. Phytother. Res. 2020, 34, 1530–1549. [Google Scholar] [CrossRef]
  116. Peng, L.; Li, Z.R.; Green, R.S.; Holzman, I.R.; Lin, J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 2009, 139, 1619–1625. [Google Scholar] [CrossRef] [PubMed]
  117. Macia, L.; Tan, J.; Vieira, A.T.; Leach, K.; Stanley, D.; Luong, S.; Maruya, M.; Ian McKenzie, C.; Hijikata, A.; Wong, C.; et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 2015, 6, 6734. [Google Scholar] [CrossRef]
  118. Tourkochristou, E.; Aggeletopoulou, I.; Konstantakis, C.; Triantos, C. Role of NLRP3 inflammasome in inflammatory bowel diseases. World J. Gastroenterol. 2019, 25, 4796–4804. [Google Scholar] [CrossRef]
  119. Kim, M.H.; Kang, S.G.; Park, J.H.; Yanagisawa, M.; Kim, C.H. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology 2013, 145, 396–406.e10. [Google Scholar] [CrossRef]
  120. Bagalagel, A.; Diri, R.; Noor, A.; Almasri, D.; Bakhsh, H.T.; Kutbi, H.I.; Al-Gayyar, M.M.H. Curative effects of fucoidan on acetic acid induced ulcerative colitis in rats via modulating aryl hydrocarbon receptor and phosphodiesterase-4. BMC Complement. Med. Ther. 2022, 22, 196. [Google Scholar] [CrossRef]
  121. Qiu, J.; Zhou, L. Aryl hydrocarbon receptor promotes RORγt⁺ group 3 ILCs and controls intestinal immunity and inflammation. Semin. Immunopathol. 2013, 35, 657–670. [Google Scholar] [CrossRef]
  122. Hou, J.J.; Ma, A.H.; Qin, Y.H. Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: Insights from gut microbiota. Front. Cell. Infect. Microbiol. 2023, 13, 1279172. [Google Scholar] [CrossRef]
  123. Kawai, S.; Iijima, H.; Shinzaki, S.; Hiyama, S.; Yamaguchi, T.; Araki, M.; Iwatani, S.; Shiraishi, E.; Mukai, A.; Inoue, T.; et al. Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation. J. Gastroenterol. 2017, 52, 904–919. [Google Scholar] [CrossRef]
  124. Smith, P.M.; Howitt, M.R.; Panikov, N.; Michaud, M.; Gallini, C.A.; Bohlooly, Y.M.; Glickman, J.N.; Garrett, W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013, 341, 569–573. [Google Scholar] [CrossRef]
  125. Wang, M.; Fu, R.; Xu, D.; Chen, Y.; Yue, S.; Zhang, S.; Tang, Y. Traditional Chinese Medicine: A promising strategy to regulate the imbalance of bacterial flora, impaired intestinal barrier and immune function attributed to ulcerative colitis through intestinal microecology. J. Ethnopharmacol. 2024, 318 Pt A, 116879. [Google Scholar] [CrossRef]
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