College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Front Immunol. 2022 Mar 7;13:865982. doi: 10.3389/fimmu.2022.865982. eCollection 2022.
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 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 for 7 days as pretreatment; or for 14 days starting 7 days before subjecting to the DSS. Peroral treatment with improved colitis severity clinically and morphologically and reduced the colonic levels of Tumor necrosis factor-α (TNF-α) (), Interleukin 1-β (), and nterferon-γ (), the crucial pro-inflammatory cytokines in colitis onset. It also prevented the CD11bLy6G neutrophil recruitment and the skewed immune responses in mesenteric lymph nodes (MLNs) of CD11bCD11c dendritic cell (DC) expansion and Foxp3CD4 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 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 treatment. A shift in expression pattern was also observed with HSP70 in response to the pretreatment and with HSP25 in response to -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 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.
肠道屏障功能缺陷与胃肠道（GI）疾病有关，如炎症性肠病（IBD），以及全身炎症。随着全球 IBD 的发病率不断上升，应该更加关注饮食干预和具有增强肠道上皮细胞天然防御机制潜力的治疗方法。本研究旨在研究 ATCC PTA 4659 在结肠炎小鼠模型中的保护作用，并阐明其背后的机制。将野生型小鼠分配到对照组；或给予饮用水中的 3%葡聚糖硫酸钠（DSS），持续 7 天以诱导结肠炎；或给予 预处理 7 天；或从开始用 DSS 前 7 天开始连续 14 天给药。口服 可改善结肠炎的严重程度和形态，并降低结肠中肿瘤坏死因子-α（TNF-α）（）、白细胞介素 1-β（）和干扰素-γ（）的水平，这些是结肠炎发病的关键促炎细胞因子。它还可以防止 CD11bLy6G 中性粒细胞募集以及肠系膜淋巴结（MLNs）中 CD11bCD11c 树突状细胞（DC）扩张和 Foxp3CD4 T 细胞减少的偏倚免疫反应。使用 16S rRNA 基因扩增子测序和 RT-qPCR，我们证明了结肠炎驱动的细菌易位到 MLNs 和肠道微生物组失调，这部分被 治疗部分抵消。此外，结肠炎导致紧密连接（TJ）蛋白和细胞保护热休克蛋白（HSP）70 和 HSP25 的表达减少，但 治疗可增强其表达。HSP70 对预处理的表达模式发生变化，HSP25 对 -DSS 的反应也发生变化。此外，HSP 的变化与细菌负荷和上皮细胞增殖有关。总之，我们的结果表明，源自人类的 4659 菌株在年轻小鼠的实验性结肠炎中提供保护，而肠道 HSP 可能通过为健康和结肠炎中的上皮细胞提供支持性蛋白质-蛋白质网络来介导益生菌作用。
