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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 (10 8  copies/mL) or inactive (10 9  copies/mL)  A. muciniphila  for 7.5 h ( P  &amp;lt; 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  &amp;lt; 0.05) along with the increased mRNA level of tight junction proteins ( ZO-1  and  Occludin ,  P  &amp;lt; 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  &amp;lt; 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.

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