Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 47, Issue 1, Pages 125-136Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2020.4780
Keywords
Fusobacterium nucleatum; Lactobacillus rhamnosus; autophagy; intestinal inflammation
Categories
Funding
- National Natural Science Foundation of China [81800467, 81330014, 81720108006, 81974062]
Ask authors/readers for more resources
The study reveals that L. rhamnosus can alleviate inflammation induced by F. nucleatum and restore impaired autophagic flux. Inhibition of autophagy weakens the effects of L. rhamnosus, with the PI3K/AKT/mTOR pathway being involved in this process.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available