Extracellular Vesicles Derived from Kefir Grain Lactobacillus Ameliorate Intestinal Inflammation via Regulation of Proinflammatory Pathway and Tight Junction Integrity

Abstract

The aim of this study was to demonstrate the anti-inflammatory effect of Lactobacillus kefirgranum PRCC-1301-derived extracellular vesicles (PRCC-1301 EVs) on intestinal inflammation and intestinal barrier function. Human intestinal epithelial cells (IECs) Caco-2 were treated with PRCC-1301 EVs and then stimulated with dextran sulfate sodium (DSS). Real-time RT-PCR revealed that PRCC-1301 EVs inhibited the expression of pro-inflammatory cytokines in Caco-2 cells. PRCC-1301 EVs enhanced intestinal barrier function by maintaining intestinal cell integrity and the tight junction. Loss of Zo-1, claudin-1, and occludin in Caco-2 cells and the colitis tissues was recovered after PRCC-1301 EVs treatment, as evidenced by immunofluorescence analysis. Acute murine colitis was induced using 4% DSS and chronic colitis was generated in piroxicam-treated IL-10-/- mice. PRCC-1301 EVs attenuated body weight loss, colon shortening, and histological damage in acute and chronic colitis models in mice. Immunohistochemistry revealed that phosphorylated NF-κB p65 and IκBα were reduced in the colon tissue sections treated with PRCC-1301 EVs. Our results suggest that PRCC-1301 EVs may have an anti-inflammatory effect on colitis by inhibiting the NF-κB pathway and improving intestinal barrier function.

Bioactive Compounds from Kefir and Their Potential Benefits on Health: A Systematic Review and Meta‐Analysis

“…The L. kefirgranum , L. kefir , L. kefiranofaciens , and L. paracasei species were responsible for producing these bioactive compounds. Therefore, the Lactobacillus genus seems relevant for making anti-inflammatory compounds in the kefir [ 13 , 50 , 53 ]. Galactose and glucose, and to a lesser extent, mannose, arabinose, and rhamnose, were the significant precursors of the polysaccharide component of the bioactive compounds [ 55 ].…”

“…Extracellular vesicles at 100 μ g/mL from L. kefirgranum reduced the gene expression of IL-2, IL-8, and TNF α proinflammatory cytokines by 58, 64, and 67%, respectively, in Caco-2 cells for DSS-induced acute colitis model [ 50 ]. Extracellular vesicles (1 × 10 9 particles/mL) also inhibited TNF α -induced colitis.…”

“…In contrast to acute colitis, ingestion of extracellular vesicles was ineffective in preventing weight loss in chronic colitis [ 50 ]. Therefore, due to the broader effects obtained for 3 mg/kg bw, the high dosage seemed more effective for chronic and acute colitis treatment.…”

“…The compounds displayed anti-inflammatory action mechanisms by inhibiting the NF- κ B pathway in the Caco-2 cells and the colon mucosa due to the expression of the I κ B α inhibitor [ 50 , 53 , 56 ]. In addition, bioactive agents promoted the integrity of the intestinal barrier, increasing the expression of occludin, ZO-1, and claudin-1 occlusion proteins [ 50 ].…”

Lactobacillus rhamnosus GG Derived Extracellular Vesicles Modulate Gut Microbiota and Attenuate Inflammatory in DSS-Induced Colitis Mice

“…A. muciniphila (ATCC BAA-835) derived EV was reported as a beneficial factor that ameliorated the production of pro-inflammatory IL-6 from colon epithelial cells [11]. EVs derived from Lactobacillus kefirgranum PRCC-1301 might have an anti-inflammatory effect on colitis by inhibiting the NF-κB pathway and improving intestinal barrier function [12]. However, many enigmatic puzzles regarding the underlying functions of Gram-positive EVs still remain unclear.…”