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Polysaccharides from Paecilomyces hepiali Prevent Acute Colitis in Association with Modulating Gut Microbiota and Treg/Th17 Immune Balance in Mice.

ABSTRACT: Cordyceps exopolysaccharide (CEP) has shown emerging potential in adjustment of gut microbiota and immune cell function. In this study, a water-soluble CEP with a molecular weight of 58.14 kDa was extracted from the fermentation broth of Paecilomyces hepiali, an endophytic fungus of Cordyceps sinensis. Our results indicated that Paecilomyces hepiali polysaccharide (PHP) showed significantly preventive potential on dextran sulfate sodium (DSS)-induced colitis in mice, which can prevent colon shortening, reduce intestinal epithelial cell (IEC) destruction, suppress inflammatory cell infiltration, and regulate the balance between regulatory T (Treg) cells and T helper type 17 (Th17) cells. Meanwhile, the disturbed gut microbiota was partially restored after PHP treatment. Further Pearson correlation coefficient analyses exhibited that the alteration of the gut microbiota was significantly related to adjustment of the IEC barrier and Treg/Th17 balance. In conclusion, all findings proposed that purified PHP has the potential to develop into a promising agent for colitis prevention and adjuvant therapy via maintaining intestinal homeostasis of gut microbiota and immune system.

SUBMITTER: Cui L

PROVIDER: S-EPMC10343787 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Polysaccharides from Paecilomyces hepiali Prevent Acute Colitis in Association with Modulating Gut Microbiota and Treg/Th17 Immune Balance in Mice.

Cui Luwen L He Ningning N Yu Shengnan S Pang Hao H Zhang Zixuan Z Wang Jingyi J Hao Jianhua J Li Shangyong S

Molecules (Basel, Switzerland) 20230625 13

Cordyceps exopolysaccharide (CEP) has shown emerging potential in adjustment of gut microbiota and immune cell function. In this study, a water-soluble CEP with a molecular weight of 58.14 kDa was extracted from the fermentation broth of Paecilomyces hepiali, an endophytic fungus of Cordyceps sinensis. Our results indicated that Paecilomyces hepiali polysaccharide (PHP) showed significantly preventive potential on dextran sulfate sodium (DSS)-induced colitis in mice, which can prev ...[more]

PMID: 37446646

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Project description:Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. Rationale: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Methods: Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. Results: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. Conclusions: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.

Project description:BackgroundUlcerative colitis (UC) is a non-specific chronic intestinal inflammatory disease with unclear etiology. Previous studies have suggested that the imbalance of Treg/Thl7 cells may be involved in the development of UC. It was found that 6-gingerol can alleviate the intestinal inflammatory damage and improve the weight loss of colitis mice. However, whether 6-gingerol can regulate the balance of Th17/Treg cells and inhibit the intestinal inflammatory response remains to be clarified.MethodsIn this study, a dextran sulfate sodium (DSS)-induced colitis mouse model was established, and the effects of 6-gingerol on cytokines and the balance of Th17/Treg cells were observed usingserial assays, including enzyme-linked immunosorbent assay (ELISA), quantitative real time-polymerase chain reaction (qPCR), and Western blotting.ResultsDSS caused the damage of bowel tissue and a 100% weight loss rate in colitis mice. The treatment of 6-gingerol can significantly relieve bowel damage and reduce incidence of weight loss to 16.7% at a low or high dose (P<0.05), which was similar to the therapeutic effect of mesalazine. It was found that DSS can up-regulate the mRNA levels of IL-6 and IL-17 in serum (by qPCR), and the serum and bowel levels of IL-6 and IL-17 (by ELISA); these levels were significantly different from those of the blank group (P<0.05). Furthermore, 6-gingerol was found to inhibit the increase of mRNA levels and serum and bowel levels of IL-6 and IL-17 induced by DSS, which is similar with mesalazine. It was also found that DSS can down-regulate the mRNA level of IL-10 in serum, along with the serum and bowel level of IL-10, with this being significantly different from the levels of the blank group (P<0.05). 6-gingerol could also inhibit the decrease of mRNA levels and serum and bowel levels of IL-10 induced by DSS, which is also similar to mesalazine. In addition, DSS could increase Th17 cell count and decrease Treg cell count in blood, with significant difference from that of the blank group (P<0.05). 6-gingerol could significantly (P<0.05) inhibit the increase of Th17 cells and the decrease of Treg cells induced by DSS, which is similar to the effect of mesalazine. The detection of expression levels of transcription factors RORγT for Th17 and FOXP3 for Treg at both mRNA and protein levels showed that DSS can up-regulate the mRNA and protein levels of RORγT, and down-regulate the mRNA and protein levels of FOXP3. Furthermore, 6-gingerol could significantly (P<0.05) inhibit the up-regulation of RORγT mRNA and protein, and the down-regulation of FOXP3 mRNA and protein induced by DSS, which is similar to the effect of mesalazine.Conclusions6-gingerol showed efficacy in the treatment of DSS-induced UC in mice, by regulating the cell balance of Th17/Treg, and by relieving inflammatory responses both systematically and locally.

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Polysaccharides from Paecilomyces hepiali Prevent Acute Colitis in Association with Modulating Gut Microbiota and Treg/Th17 Immune Balance in Mice.

Publications

Polysaccharides from <i>Paecilomyces hepiali</i> Prevent Acute Colitis in Association with Modulating Gut Microbiota and Treg/Th17 Immune Balance in Mice.

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