Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves’ Disease Patients by Propionic Acid

Su, Xinhuan; Yin, Xianlun; Liu, Yue; Yan, Xuefang; Zhang, Shucui; Wang, Xiaowei; Lin, Zongwei; Zhou, Xiaoming; Gao, Jing; Wang, Zhe; Zhang, Qunye

doi:10.1210/clinem/dgaa511

Cited by 92 publications

(114 citation statements)

References 49 publications

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“…In addition to gut flora, SCFAs, the metabolic products of bacterial dietary fibre, affects Treg and Th17 cell differentiation (15,37). Our studies demonstrated that stigmasterol increases the abundance of Clostridia.…”

Section: Discussionmentioning

confidence: 73%

Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis

Wen

Zhong

et al. 2021

Front. Immunol.

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Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance. Stigmasterol, a plant-derived sterol, has shown anti-inflammatory effects. Our study aimed to identify the effects of stigmasterol on experimental colitis and the related mechanisms. Stigmasterol treatment restored the Treg/Th17 balance and altered the gut microbiota in a dextran sodium sulfate (DSS)-induced colitis model. Transplantation of the faecal microbiota of stigmasterol-treated mice significantly alleviated inflammation. Additionally, stigmasterol treatment enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyrate. Next, human naïve CD4+ T cells sorted from IBD patients were cultured under Treg- or Th17-polarizing conditions; butyrate supplementation increased the differentiation of Tregs and decreased Th17 cell differentiation. Mechanistically, butyrate activated peroxisome proliferator-activated receptor gamma (PPARγ) and reprogrammed energy metabolism, thereby promoting Treg differentiation and inhibiting Th17 differentiation. Our results demonstrate that butyrate-mediated PPARγ activation restores the balance of Treg/Th17 cells, and this may be a possible mechanism, by which stigmasterol attenuates IBD.

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Section: Discussionmentioning

confidence: 73%

Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis

Wen

Zhong

et al. 2021

Front. Immunol.

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“…In this study, we found at the genus level, high red meat intake significantly increased the relative abundance of Bacteroides and Alistipes genera in colon, but reduced the abundance of Lachnospiraceae_NK4A136 group, Faecalibaculum, Blautia, and Dubosiella genera. Previous studies have shown that the genera of Bacteroides and Alistipes can affect amino acid transport, metabolism, energy production and transport, and inflammation (34)(35)(36). Bacteroides can secret metalloprotease toxin both in vivo and in vitro (37), which stimulate the cleavage of intercellular adhesion protein E-cadherin in colonic epithelial cells, resulting in increased colonic mucosal permeability and activating NF-kB pathway.…”

Section: Discussionmentioning

confidence: 99%

High Red Meat Intake Exacerbates Dextran Sulfate-Induced Colitis by Altering Gut Microbiota in Mice

Cui

Tan

et al. 2021

Front. Nutr.

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Inflammatory bowel disease (IBD) is a serious hazard to public health, but the precise etiology of the disease is unclear. High intake of red meat diet is closely related to the occurrence of IBD. In this study, we investigated whether the high intake of red meat can increase the sensitivity of colitis and the underlying mechanism. Mice were fed with different levels of red meat for 8 weeks and then the colonic contents were analyzed by 16S rRNA sequencing. Then 3% dextran sulfate sodium was used to induce colitis in mice. We observed the severity of colitis and inflammatory cytokines. We found that high-dose red meat caused intestinal microbiota disorder, reduced the relative abundance of Lachnospiraceae_NK4A136_group, Faecalibaculum, Blautia and Dubosiella, and increased the relative abundance of Bacteroides and Alistipes. This in turn leads to an increase in colitis and inflammatory cytokine secretion. Moreover, we found that high red meat intake impaired the colon barrier integrity and decreased the expression of ZO-1, claudin, and occludin. We also found high red meat intake induced the production of more inflammatory cytokines such as IL-1β, TNF-α, IL-17, and IL-6 and inflammatory inducible enzymes such as COX-2 and iNOS in dextran sulfate sodium-induced colitis. These results suggest that we should optimize the diet and reduce the intake of red meat to prevent the occurrence of IBD.

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“…T-cell maturation in the intestinal tract occurs in the gut associated lymphoid tissue (GALT) and from there cells migrate to the intraepithelial layer or lamina propria. These T-cells are (31,33,34,36), and in human studies (16,(37)(38)(39). Supplementation with propionate enhances the activity and numbers of the anti-inflammatory Treg FoxP3 + cells and reduces the activity and numbers of Th17 and to a lesser extent Th1 pro-inflammatory T-cells via histone deacetylase inhibition (25,34,(40)(41)(42).…”

Section: Immune Regulation By Scfasmentioning

confidence: 99%

“…Nutritional components and microbial metabolites such as acetate, propionate, butyrate, tryptophan and phytoestrogens, act as immune regulators. Numerous studies demonstrate the action of propionate in regulating T-cell activity in vitro ( 33 – 35 ), in animal in vivo studies ( 31 , 33 , 34 , 36 ), and in human studies ( 16 , 37 – 39 ). Supplementation with propionate enhances the activity and numbers of the anti-inflammatory Treg FoxP3 + cells and reduces the activity and numbers of Th17 and to a lesser extent Th1 pro-inflammatory T-cells via histone deacetylase inhibition ( 25 , 34 , 40 – 42 ).…”

Section: Immune Regulation By Scfasmentioning

confidence: 99%

Review: The Nutritional Management of Multiple Sclerosis With Propionate

Vige

Calder

2021

Front. Immunol.

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Over the last 15 years there has been an accumulation of data supporting the concept of a gut-brain axis whereby dysbiosis of the gut microbiota can impact neurological function. Such dysbiosis has been suggested as a possible environmental exposure triggering multiple sclerosis (MS). Dysbiosis has been consistently shown to result in a reduction in short-chain fatty acid (SCFA) producing bacteria and a reduction in stool and plasma levels of propionate has been shown for MS patients independent of disease stage and in different geographies. A wealth of evidence supports the action of propionate on T-cell activity, resulting in decreased T-helper cell 1 (Th1) and T-helper cell 17 (Th17) numbers/activity and increased regulatory T cell (Treg cell) numbers/activity and an overall anti-inflammatory profile. These different T-cell populations play various roles in the pathophysiology of MS. A recent clinical study in MS patients demonstrated that supplementation of propionate reduces the annual relapse rate and slows disease progression. This review discusses this data and the relevant mechanistic background and discusses whether taming of the overactive immune system in MS is likely to allow easier bacterial and viral infection.

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Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves’ Disease Patients by Propionic Acid

Cited by 92 publications

References 49 publications

Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis

Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis

High Red Meat Intake Exacerbates Dextran Sulfate-Induced Colitis by Altering Gut Microbiota in Mice

Review: The Nutritional Management of Multiple Sclerosis With Propionate

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