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Bacteroides thetaiotaomicron and its inactivated bacteria ameliorate colitis by inhibiting macrophage activation - 07/02/24

Doi : 10.1016/j.clinre.2023.102276 
Sikong Yinhe a, b, Li Lixiang a, c, Li Yan b, Gu Xiang a, Li Yanqing a, b, c, d, e, Zuo Xiuli a, b, c, d, e,
a Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China 
b Department of Gastroenterology, Qilu Hospital of Shandong University Qingdao, Qingdao, Shandong, PR China 
c Shandong Provincial Clinical Research Center for digestive disease, Shandong, PR China 
d Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China 
e Robot engineering laboratory for precise diagnosis and therapy of GI tumor, Qilu Hospital of Shandong University, Jinan, Shandong, PR China 

Corresponding author at: Department of Gastroenterology, Shandong University of Qilu Hospital, 758 Hefei Road, Jinan, Shangdong, PR China.Department of GastroenterologyShandong University of Qilu Hospital758 Hefei RoadJinanPR China

Highlights

Bacteroides thetaiotaomicron has strong anti-inflammatory effect on colitis.
P38 MAPK signaling pathway in macrophages was strongly inhibited by BT.
Gut microbiota dysbiosis is ameliorated by BT.

Il testo completo di questo articolo è disponibile in PDF.

Abstract

Background

Studies have demonstrated that Bacteroides thetaiotaomicron (BT) has protective effect against colon inflammation in murine models. Macrophages play an important role in gut immunity. However, the specific mechanisms of BT on macrophage are still unelucidated. Thus, our study investigates the anti-inflammatory effect of BT and its heat-treated inactivated bacteria on experimental colitis and macrophages.

Methods

A dextran sulfate sodium (DSS)-induced acute colitis model with male C57BL/6 mice, BT (ATCC29148) strain, THP1 cell lines were used in this study. Live and heat-treated inactivated BT (IBT) solution (1 × 10^9cfu/ml) were intragastrically gavaged daily for 14 days. Colonic inflammation was determined by the disease activity index (DAI) score, colon length, histological score, and inflammatory factors. THP1 cells were induced towards M1, then treated with different concentrations of inactivated BT solution and p38 inhibitor. Western blotting, immunohistochemistry, immunofluorescence and qRT-PCR were performed to assess the levels of inflammatory cytokines and molecules of MAPK pathway including IL-6, TNF-α, IL-1β, IL-22, p38 and phosphor-p38 expressions. Moreover, 16S rRNA sequencing of colitis murine fecal samples was applied to investigate the influence of supplementation of BT to the gut microbiota homeostasis.

Results

Both live and heat-treated inactivated BT decreased the DAI and histological scores as well as levels of inflammatory factors, particularly IL-6 while increasing IL-22 of DSS-induced colitis murine models. The cell experiments showed that inactivated BT downregulates IL-6 expression in THP1 via inhibiting p38 phosphorylation and affecting M1 polarization. Moreover, the 16S rRNA sequencing results showed that BT and IBT gavage could increase beta-diversity of gut flora in DSS-induced colitis mice. Furthermore, the significance test for differences between the groups showed that BT could increase Faecalebaculum, Lactobacillus and Bacteroides, while decreasing Akkermansia.

Conclusion

In summary, our findings imply that BT and its heat-treated inactivated bacteria exert a protective effect by suppressing macrophage-induced IL-6 through the inhibition of p38 MAPK pathway and ameliorating intestinal gut dysbiosis in experimental colitis.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : Bacteroides thetaiotaomicron, Inflammatory bowel disease, Colitis, Gut microbiota, Macrophage


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© 2023  Pubblicato da Elsevier Masson SAS.
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