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

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.

Lactobacillus plantarum supplementation alleviates liver and intestinal injury in parenteral nutrition‐fed piglets

“…Lactobacillus rhamnosus recovered the impaired autophagic flux to attenuate intestinal inflammation. 36 Surface-layer protein produced by Lactobacillus exerted its anti-inflammatory effects by activating autophagy. 37 Previous study found autophagy was suppressed in the PNALD model.…”

“…Consistently, this study found LP administration increased the abundance of Lactobacillus and reduced the abundance of Shigella . Lactobacillus rhamnosus recovered the impaired autophagic flux to attenuate intestinal inflammation 36 . Surface‐layer protein produced by Lactobacillus exerted its anti‐inflammatory effects by activating autophagy 37 .…”

Incomplete autophagy: Trouble is a friend

“…Meaningful, it is reported that the intestinal inflammation caused by F. nucleatum infection could be alleviated by Lactobacillus rhamnosus via restoring the autophagic flux 180 . Irinotecan induced hepatic steatosis via incomplete autophagy by Similarly, metformin, scoparone, and butyrate alleviated various inflammatory responses by restoring autophagy flux 181–183 …”

“…179 Meaningful, it is reported that the intestinal inflammation caused by F. nucleatum infection could be alleviated by Lactobacillus rhamnosus via restoring the autophagic flux. 180 Irinotecan induced hepatic steatosis via incomplete autophagy by Similarly, metformin, scoparone, and butyrate alleviated various inflammatory responses by restoring autophagy flux. [181][182][183] Altogether, these studies point to the major importance of the incomplete autophagy in the pathogenesis of inflammatory diseases and will aid in the development of novel strategies for the therapy of inflammatory diseases.…”

L. reuteri ZJ617 inhibits inflammatory and autophagy signaling pathways in gut-liver axis in piglet induced by lipopolysaccharide

“…A study has shown that LGG suppressed autophagy in Salmonella -challenged pigs [ 26 ]. L. rhamnosus effectively recovered autophagic flux and attenuated the inflammation in Caco-2 cells impaired by F. nucleatum [ 27 ]. L. reuteri 100–23, L. gasseri IPL A6.33, L. rhamnosus IPL A2.21, L. gasseri CMUL057 and L. acidophilus CMUL067 are able to induce autophagy activation to release the anti-inflammatory cytokine interleukin-10 and inhibit the secretion of the pro-inflammatory cytokine interleukin-1ß [ 28 ].…”