Abstract
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.
Highlights
The gastrointestinal epithelium represents the direct contact surface between the body and external environment
The IPEC-J2 cells treated with 20 ng/mL for 48 h showed the highest degree of cell destruction and the most cellular fragments, which are typical characteristics of apoptosis
We found that the expression of key genes involved in cell cycle, such as PCNA, CCNE2, CDC23, ORC1 and MCM3 in tumor necrosis factor-a (TNF-a)-challenged intestinal epithelial cells (IECs) was up-regulated by the treatment of inactive A. muciniphila
Summary
The gastrointestinal epithelium represents the direct contact surface between the body and external environment. Normal intestinal functions are closely linked to the balance of proliferation and apoptosis of IECs. An obvious example for the dysfunction of IECs is the intestinal inflammation caused by social, environmental or dietary stress in young animals, which leads to a growth defect [3]. The increasing number of antibiotic-resistant bacterial strains in animal gut accelerates research to develop alternative methods for the prevention and therapy of intestinal inflammation in young animals. Amongst those alternatives, probiotics, could modulate inflammation, by regulating for instance the production of cytokines and IgA [5, 6]
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