Pasteurized Akkermansia muciniphila Ameliorate the LPS-Induced Intestinal Barrier Dysfunction via Modulating AMPK and NF-κB through TLR2 in Caco-2 Cells.

Mengxuan Shi,Yunshuang Yue,Li Dong,Chen Ma,Fang Chen

doi:10.3390/nu14040764

Abstract

Akkermansia muciniphila is well known for the amelioration of inflammatory responses and restoration of intestinal barrier function. The beneficial effect of A. muciniphila occurred through contacting Toll-like receptor 2 (TLR2) on intestinal epithelial cells by wall components. In this case, the downstream mechanism of pasteurized A. muciniphila stimulating TLR2 for ameliorated intestinal barrier function is worth investigating. In this study, we evaluated the effect of live and pasteurized A. muciniphila on protecting the barrier dysfunction of Caco-2 intestinal epithelial cells induced by lipopolysaccharide (LPS). We discovered that both live and pasteurized A. muciniphila could attenuate an inflammatory response and improve intestinal barrier integrity in Caco-2 monolayers. We demonstrated that A. muciniphila enhances AMP-activated protein kinase (AMPK) activation and inhibits Nuclear Factor-Kappa B (NF-κB) activation through the stimulation of TLR2. Overall, we provided a specific mechanism for the probiotic effect of A. muciniphila on the intestinal barrier function of Caco-2 cells.

Highlights

Academic Editor: Dina BellizziAkkermansia muciniphila is an anaerobe and Gram-positive bacterium, representing approximately 1% to 3% of the total intestinal microbiota (109 cfu/g) [1]
As Toll-like receptor 2 (TLR2) is demonstrated to mediate the activation of AMPK, we investigated the effect of TLR2 and AMPK on the assembly of zonula occludens-1 (ZO-1) and claudin2 using Caco-2 cells treated with C29
Results suggested that stimulation of TLR2 is important for tight junction assembly through AMPK activation in cells treated with A. muciniphila. These results showed that the activation of the AMPK signaling pathway 10 of 1 through TLR2 was associated with increasing the level of ZO-1 and decreasing claudin2 by pretreatment with live or pasteurized A. muciniphila

Summary

Introduction

Akkermansia muciniphila is an anaerobe and Gram-positive bacterium, representing approximately 1% to 3% of the total intestinal microbiota (109 cfu/g) [1]. A. muciniphila generously distributes in the intestinal mucus layer and can contact epithelial cells at the villi tips more than other non-mucin-degrading bacteria [1,2]. A. muciniphila mainly uses intestinal mucins as its source of carbon and nitrogen and produces short-chain fatty acids, such as acetate and propionate [1]. Dietary supplementation enriches the abundance of A. muciniphila in mice, such as the dark sweet cherry [3], alpine bearberry, lingonberry, and cloudberry extracts [4], and inulin [5], fucoidan [6], polysaccharides from Gastrodia elata and Ophiopogon japonicas [7,8]. Recent studies indicate that supplementing with A. muciniphila can ameliorate metabolic syndrome, obesity, diabetes, and inflammatory bowel disease [10,11] in animals. A. muciniphila improved the dextran sulfate sodium (DSS)-induced colitis by reducing the production of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-2, IL-6, and IFN-γ, and chemokines

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