PMID- 35320932 OWN - NLM STAT- MEDLINE DCOM- 20220503 LR - 20221207 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Epithelial Heat Shock Proteins Mediate the Protective Effects of Limosilactobacillus reuteri in Dextran Sulfate Sodium-Induced Colitis. PG - 865982 LID - 10.3389/fimmu.2022.865982 [doi] LID - 865982 AB - Defects in gut barrier function are implicated in gastrointestinal (GI) disorders like inflammatory bowel disease (IBD), as well as in systemic inflammation. With the increasing incidence of IBD worldwide, more attention should be paid to dietary interventions and therapeutics with the potential to boost the natural defense mechanisms of gut epithelial cells. The current study aimed to investigate the protective effects of Limosilactobacillus reuteri ATCC PTA 4659 in a colitis mouse model and delineate the mechanisms behind it. Wild-type mice were allocated to the control group; or given 3% dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis; or administered L. reuteri for 7 days as pretreatment; or for 14 days starting 7 days before subjecting to the DSS. Peroral treatment with L. reuteri improved colitis severity clinically and morphologically and reduced the colonic levels of Tumor necrosis factor-alpha (TNF-alpha) (Tnf), Interleukin 1-beta (Il1beta), and nterferon-gamma (Ifng), the crucial pro-inflammatory cytokines in colitis onset. It also prevented the CD11b(+)Ly6G(+) neutrophil recruitment and the skewed immune responses in mesenteric lymph nodes (MLNs) of CD11b(+)CD11c(+) dendritic cell (DC) expansion and Foxp3(+)CD4(+) T-cell reduction. Using 16S rRNA gene amplicon sequencing and RT-qPCR, we demonstrated a colitis-driven bacterial translocation to MLNs and gut microbiota dysbiosis that were in part counterbalanced by L. reuteri treatment. Moreover, the expression of barrier-preserving tight junction (TJ) proteins and cytoprotective heat shock protein (HSP) 70 and HSP25 was reduced by colitis but boosted by L. reuteri treatment. A shift in expression pattern was also observed with HSP70 in response to the pretreatment and with HSP25 in response to L. reuteri-DSS. In addition, the changes of HSPs were found to be correlated to bacterial load and epithelial cell proliferation. In conclusion, our results demonstrate that the human-derived L. reuteri strain 4659 confers protection in experimental colitis in young mice, while intestinal HSPs may mediate the probiotic effects by providing a supportive protein-protein network for the epithelium in health and colitis. CI - Copyright (c) 2022 Liu, Gu, Zhu, Yuan, Zhu, Zhu, Yao, Hu, Zhang, Dicksved, Bao and Cai. FAU - Liu, Hao-Yu AU - Liu HY AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Gu, Fang AU - Gu F AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Zhu, Cuipeng AU - Zhu C AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Yuan, Long AU - Yuan L AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Zhu, Chuyang AU - Zhu C AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Zhu, Miaonan AU - Zhu M AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Yao, Jiacheng AU - Yao J AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Hu, Ping AU - Hu P AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Zhang, Yunzeng AU - Zhang Y AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China. FAU - Dicksved, Johan AU - Dicksved J AD - Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala, Sweden. FAU - Bao, Wenbin AU - Bao W AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. FAU - Cai, Demin AU - Cai D AD - College of Animal Science and Technology, Yangzhou University, Yangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220307 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Heat-Shock Proteins) RN - 0 (RNA, Ribosomal, 16S) RN - 0 (Tight Junction Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Animals MH - *Colitis/pathology MH - Dextran Sulfate/toxicity MH - Heat-Shock Proteins MH - *Inflammatory Bowel Diseases MH - *Limosilactobacillus reuteri/physiology MH - Mice MH - RNA, Ribosomal, 16S/genetics MH - Tight Junction Proteins MH - Tumor Necrosis Factor-alpha PMC - PMC8934773 OTO - NOTNLM OT - barrier function OT - gut microbiota OT - heat shock proteins OT - inflammatory bowel disease OT - probiotics COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/03/25 06:00 MHDA- 2022/05/04 06:00 PMCR- 2022/01/01 CRDT- 2022/03/24 05:04 PHST- 2022/01/30 00:00 [received] PHST- 2022/02/11 00:00 [accepted] PHST- 2022/03/24 05:04 [entrez] PHST- 2022/03/25 06:00 [pubmed] PHST- 2022/05/04 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.865982 [doi] PST - epublish SO - Front Immunol. 2022 Mar 7;13:865982. doi: 10.3389/fimmu.2022.865982. eCollection 2022.