Natural approach to reestablish Th17/Treg balance to treat inflammatory bowel disease by activating the SCFA-PPARγ Axis in Colitis
Background: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract. The cause of IBD remains unknown, however, because of the disease’s higher prevalence in more developed countries, it is believed that food intake plays an important role. This is based on the interaction of the gut microbes, which also live off the host diet, and the host immune system. Because inflammation is driven by the immune system, at the cellular level, new research dives deeper into understanding the homeostatic balance of Th17/Tregs. Th17 cells are associated with the inflammatory symptoms of IBD, while Tregs are natural repressors of out-of-control immune response.
Objective: The goal of this study was to provide a natural approach to treating IBD patients using the SCFA-PPARγ axis as a potential target, since its mechanistic action has been shown in herbal and diet remedies because it allows Treg differentiation while inhibiting Th17 differentiation.
Methods: An online search in the PubMed database was conducted from 2019 to 2023 using the following keywords: “TH17/Treg balance”, ” Diets”, ” Herbs”, “immune system”.
Results: Stigmasterol, a plant-derived sterol, with previously shown anti-inflammatory effects.1 Using a dextran sodium sulfate (DSS)-induced colitis model, they found that stigmasterol alleviated inflammation and enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), specifically butyrate. They concluded butyrate activated peroxisome proliferator-activated receptor gamma (PPARy) and reprogrammed energy metabolism from glycolysis to OXPHOS; this allowed Treg differentiation while inhibiting Th17 differentiation.1 The second natural remedy is Gegen Qinlian decoction (GQD), a traditional Chinese herbal mixture.2 Again, using a DSS-induced colitis model, they found that GQD suppressed oxidative stress by maintaining the mitochondrial membrane potential. A new paper came out later to further add to the investigation.3 They found that Gegen Qinlian decoction significantly boosted the abundance of the intestinal microbiota producing SCFAs. It’s likely that the increased strength of the mitochondrial potential observed in the pervious study played a part in the differentiation, but under the mechanism of SCFA-PPARγ Axis as observed in this paper.3 Next, to better explore the link between diet and IBD, a different dose of sucrose consumption was studied.4 The results showed that low-dose sucrose restored microbial dysfunction and enhanced the production of short chain fatty acids (SCFAs). The study demonstrates how reducing sugar intake is another method to increase SCFA. At a personal level, this is a lifestyle change that IBD patients can make to better alleviate their symptoms. However, on a larger social scale, there is a clear need for further investigation of what should be allowed by the FDA in food products.
Conclusion: In summation, the SCFA-PPARγ axis provides a potential target for a natural approach to preventing or even systematically changing societies’ diet to prevent IBS in general, rather than making another drug to fight the immune system. Future research needs to focus on human trials to truly view the effectiveness and practicality of targeting the SCFA-PPARγ axis.
- Wen S, He L, Zhong Z, et al. Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis. Front Immunol. 2021;12:741934. Published 2021 Oct 6. doi:10.3389/fimmu.2021.741934
- Zhao Y, Luan H, Jiang H, et al. Gegen Qinlian decoction relieved DSS-induced ulcerative colitis in mice by modulating Th17/Treg cell homeostasis via suppressing IL-6/JAK2/STAT3 signaling. Phytomedicine. 2021;84:153519. doi:10.1016/j.phymed.2021.153519
- Wang Y, Zhang J, Xu L, et al. Modified Gegen Qinlian Decoction Regulates Treg/Th17 Balance to Ameliorate DSS-Induced Acute Experimental Colitis in Mice by Altering the Gut Microbiota. Front Pharmacol. 2021;12:756978. Published 2021 Nov 4. doi:10.3389/fphar.2021.756978
- Zhang X, Zhang B, Peng B, et al. Different Dose of Sucrose Consumption Divergently Influences Gut Microbiota and PPAR-γ/MAPK/NF-κB Pathway in DSS-Induced Colitis Mice. Nutrients. 2022;14(13):2765. Published 2022 Jul 4. doi:10.3390/nu14132765