Lactobacillus rhamnosus attenuates intestinal inflammation induced by Fusobacterium nucleatum infection by restoring the autophagic flux

Duan,Caihan; Tang,Xuelian; Wang,Weijun; Qian,Wei; Fu,Xiaochao; Deng,Xiaohua; Zhou,Shunchang; Han,Chaoqun; Hou,Xiaohua

doi:10.3892/ijmm.2020.4780

Lactobacillus rhamnosus attenuates intestinal inflammation induced by Fusobacterium nucleatum infection by restoring the autophagic flux

Authors:
- Caihan Duan
- Xuelian Tang
- Weijun Wang
- Wei Qian
- Xiaochao Fu
- Xiaohua Deng
- Shunchang Zhou
- Chaoqun Han
- Xiaohua Hou
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Affiliations: Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Hubei Center of Industrial Culture Collection and Research, Wuhan, Hubei 430020, P.R. China, Division of Experimental Animals, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: November 3, 2020 https://doi.org/10.3892/ijmm.2020.4780
Pages: 125-136
Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autophagy plays a dual role in the responses to the gut microflora. The present study aimed to examine the effects of Lactobacillus rhamnosus (L. rhamnosus) on Fusobacterium nucleatum (F. nucleatum)‑induced intestinal dysfunction and to elucidate the underlying mechanisms, with particular focus on autophagy. Inflammatory models were established by treatment with L. rhamnosus following F. nucleatum intervention using cells or a mouse model of dextran sulfate sodium (DSS)‑induced acute colitis. Autophagosomes were visualized by confocal microscopy following transfection with a tandem GFP‑mCherry‑LC3 construct and also by transmission electron microscopy. Autophagy‑associated protein levels were examined by western blot analysis and immunohistochemistry. It was observed that F. nucleatum induced the production of pro‑inflammatory cytokines in Caco‑2 cells and aggravated DSS‑induced acute colitis. The autophagic flux was impaired following infection with F. nucleatum. L. rhamnosus treatment attenuated the inflammation induced by F. nucleatum infection and effectively recovered the impaired autophagic flux. In addition, the production of pro‑inflammatory cytokines induced by F. nucleatum was enhanced with autophagy inhibitors or the RNA interference of autophagy‑related gene 16 like 1 (Atg16L1) in Caco‑2 cells. Notably, this inhibition of autophagy weakened the effects of L. rhamnosus. Finally, the PI3K/AKT/mTOR pathway was found to be involved in this process. On the whole, the present study demonstrates that the mediation of autophagy by L. rhamnosus may be involved in the protective effects against F. nucleatum‑related intestinal inflammation. Thus, L. rhamnosus treatment may prove to be a novel therapeutic strategy for F. nucleatum‑realated gut disorders.

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