PMID- 37968625 OWN - NLM STAT- MEDLINE DCOM- 20231117 LR - 20231119 IS - 1475-2859 (Electronic) IS - 1475-2859 (Linking) VI - 22 IP - 1 DP - 2023 Nov 15 TI - F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice. PG - 235 LID - 10.1186/s12934-023-02243-7 [doi] LID - 235 AB - BACKGROUND: Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice. RESULTS: Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1beta (IL-1beta), IL-2, IL-6, IL-12a, IL-17a, Interferon-gamma (IFN-gamma), tumor necrosis factor - alpha (TNF-alpha), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor beta (TGF-beta) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-kappaB (NF-kappaB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). CONCLUSION: Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile. CI - (c) 2023. The Author(s). FAU - Ye, Lin AU - Ye L AD - Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. FAU - Wang, Yizhong AU - Wang Y AD - Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. wangyz@shchildren.com.cn. AD - Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. wangyz@shchildren.com.cn. FAU - Xiao, Fangfei AU - Xiao F AD - Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. FAU - Wang, Xufei AU - Wang X AD - Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. AD - Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. FAU - Li, Xiaolu AU - Li X AD - Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. FAU - Cao, Rong AU - Cao R AD - Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. FAU - Zhang, Jiayue AU - Zhang J AD - Shanghai Jiao Tong University School of Nursing, Shanghai, 200025, China. FAU - Zhang, Ting AU - Zhang T AD - Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. zhangt@shchildren.com.cn. AD - Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 355 Luding Road, Shanghai, 200062, China. zhangt@shchildren.com.cn. LA - eng GR - 22ZR1451800/Natural Science Foundation of Shanghai Municipality/ GR - 19140904300/Science and Technology Commission of Shanghai Municipality/ GR - 81900472/National Natural Science Foundation of China/ GR - 81870373/National Natural Science Foundation of China/ GR - 202040481/Shanghai Municipal Health Commission/ PT - Journal Article DEP - 20231115 PL - England TA - Microb Cell Fact JT - Microbial cell factories JID - 101139812 RN - 0 (Cytokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Animals MH - Mice MH - *Colitis/chemically induced MH - Colon MH - Intestinal Mucosa/metabolism MH - Cytokines/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - *Extracellular Vesicles/metabolism MH - Dextran Sulfate/toxicity/metabolism MH - Mice, Inbred C57BL MH - Disease Models, Animal PMC - PMC10648384 OTO - NOTNLM OT - Colitis OT - Extracellular vesicles OT - F. Prausnitzii OT - IBD COIS- The authors declare no competing interests. EDAT- 2023/11/16 06:44 MHDA- 2023/11/17 15:25 PMCR- 2023/11/15 CRDT- 2023/11/16 00:16 PHST- 2023/09/10 00:00 [received] PHST- 2023/11/02 00:00 [accepted] PHST- 2023/11/17 15:25 [medline] PHST- 2023/11/16 06:44 [pubmed] PHST- 2023/11/16 00:16 [entrez] PHST- 2023/11/15 00:00 [pmc-release] AID - 10.1186/s12934-023-02243-7 [pii] AID - 2243 [pii] AID - 10.1186/s12934-023-02243-7 [doi] PST - epublish SO - Microb Cell Fact. 2023 Nov 15;22(1):235. doi: 10.1186/s12934-023-02243-7.