Frontiers in Immunology (Dec 2021)

Active or Autoclaved Akkermansia muciniphila Relieves TNF-α-Induced Inflammation in Intestinal Epithelial Cells Through Distinct Pathways

  • Yuheng Luo,
  • Yuheng Luo,
  • Yuheng Luo,
  • Cong Lan,
  • Cong Lan,
  • Cong Lan,
  • Kunhong Xie,
  • Kunhong Xie,
  • Kunhong Xie,
  • Hua Li,
  • Hua Li,
  • Hua Li,
  • Estelle Devillard,
  • Jun He,
  • Jun He,
  • Jun He,
  • Li Liu,
  • Jingyi Cai,
  • Jingyi Cai,
  • Jingyi Cai,
  • Gang Tian,
  • Gang Tian,
  • Gang Tian,
  • Aimin Wu,
  • Aimin Wu,
  • Aimin Wu,
  • Zhihua Ren,
  • Daiwen Chen,
  • Daiwen Chen,
  • Daiwen Chen,
  • Bing Yu,
  • Bing Yu,
  • Bing Yu,
  • Zhiqing Huang,
  • Zhiqing Huang,
  • Zhiqing Huang,
  • Ping Zheng,
  • Ping Zheng,
  • Ping Zheng,
  • Xiangbing Mao,
  • Xiangbing Mao,
  • Xiangbing Mao,
  • Jie Yu,
  • Jie Yu,
  • Jie Yu,
  • Junqiu Luo,
  • Junqiu Luo,
  • Junqiu Luo,
  • Hui Yan,
  • Hui Yan,
  • Hui Yan,
  • Quyuan Wang,
  • Quyuan Wang,
  • Quyuan Wang,
  • Huifen Wang,
  • Huifen Wang,
  • Huifen Wang,
  • Jiayong Tang,
  • Jiayong Tang,
  • Jiayong Tang

DOI
https://doi.org/10.3389/fimmu.2021.788638
Journal volume & issue
Vol. 12

Abstract

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Intestinal inflammation is a major threat to the health and growth of young animals such as piglets. As a next-generation probiotics, limited studies have shown that Akkermansia muciniphila could alleviate inflammation of intestinal epithelial cells (IECs). In this study, a TNF-α-induced inflammatory model of IPEC-J2 cells, the intestinal porcine enterocytes, was built to evaluate the effects of active or inactive A. muciniphila on the inflammation of IECs. The viability of IPEC-J2 cells was the highest when treated with active (108 copies/mL) or inactive (109 copies/mL) A. muciniphila for 7.5 h (P < 0.01). Treated with 20 ng/mL of TNF-α and followed by a treatment of A. muciniphila, the mRNA level of proinflammatory cytokines (IL-8, IL-1β, IL-6 and TNF-α) was remarkably reduced (P < 0.05) along with the increased mRNA level of tight junction proteins (ZO-1 and Occludin, P < 0.05). Flow cytometry analysis showed that active or inactive A. muciniphila significantly suppressed the rate of the early and total apoptotic of the inflammatory IPEC-J2 cells (P < 0.05). According to results of transcriptome sequencing, active and inactive A. muciniphila may decline cell apoptosis by down-regulating the expression of key genes in calcium signaling pathway, or up-regulating the expression of key genes in cell cycle signaling pathway. And the bacterium may alleviate the inflammation of IECs by down-regulating the expression of PI3K upstream receptor genes. Our results indicate that A. muciniphila may be a promising NGP targeting intestinal inflammation.

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