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从高度抗结肠炎的猪中进行靶向筛选可缓解小鼠的溃疡性结肠炎。

Targeted Screening from Highly Colitis-Resistant Pigs Can Alleviate Ulcerative Colitis in Mice.

作者信息

Fang Xiuyu, Liu Haiyang, Du Yongqing, Jiang Lin, Gao Feng, Wang Zhengyi, Chi Zihan, Shi Baoming, Zhao Xuan

机构信息

College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People's Republic of China.

College of Animal Science and Technology, Southwest University, Chongqing 400715, People's Republic of China.

出版信息

Research (Wash D C). 2024 Jul 16;7:0415. doi: 10.34133/research.0415. eCollection 2024.

DOI:10.34133/research.0415
PMID:39015206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11249912/
Abstract

Ulcerative colitis (UC) is often accompanied by intestinal inflammation and disruption of intestinal epithelial structures, which are closely associated with changes in the intestinal microbiota. We previously revealed that Min pigs, a native Chinese breed, are more resistant to dextran sulfate sodium (DSS)-induced colitis than commercial Yorkshire pigs. Characterizing the microbiota in Min pigs would allow identification of the core microbes that confer colitis resistance. By analyzing the microbiota linked to the disease course in Min and Yorkshire pigs, we observed that spp. were enriched in Min pigs and positively correlated with pathogen resistance. Using targeted screening, we identified and validated MZ16 from Min pigs as a bacterial species with biofilm formation ability, superior salt and pH tolerance, and antimicrobial characteristics. Subsequently, we administered MZ16 to conventional or microbiota-deficient BALB/c mice with DSS-induced colitis to assess its efficacy in alleviating colitis. MZ16 partially counteracted DSS-induced colitis in conventional mice, but it did not mitigate DSS-induced colitis in microbiota-deficient mice. Further analysis revealed that MZ16 administration improved intestinal ecology and integrity and immunological barrier function in mice. Compared to the DSS-treated mice, mice preadministered MZ16 exhibited improved relative abundance of potentially beneficial microbes (, , , , , and ), reduced relative abundance of pathogenic microbes (), and maintained colonic OCLN and ZO-1 levels and IgA and SIgA levels. Furthermore, MZ16 reduced proinflammatory cytokine levels by reversing NF-κB and MAPK pathway activation in the DSS group. Overall, MZ16 from Min pigs had beneficial effects on a colitis mouse model by enhancing intestinal barrier functions and reducing inflammation in a gut microbiota-dependent manner.

摘要

溃疡性结肠炎(UC)常伴有肠道炎症和肠上皮结构破坏,这与肠道微生物群的变化密切相关。我们之前发现,中国本土品种的民猪比商业化的约克夏猪对葡聚糖硫酸钠(DSS)诱导的结肠炎更具抵抗力。对民猪的微生物群进行特征分析将有助于鉴定赋予结肠炎抗性的核心微生物。通过分析与民猪和约克夏猪疾病进程相关的微生物群,我们观察到 spp. 在民猪中富集且与病原体抗性呈正相关。通过靶向筛选,我们从民猪中鉴定并验证了 MZ16 为一种具有生物膜形成能力、优异的盐和pH耐受性以及抗菌特性的细菌物种。随后,我们将 MZ16 给予患有DSS诱导结肠炎的常规或微生物群缺陷型BALB/c小鼠,以评估其缓解结肠炎的功效。MZ16 部分抵消了常规小鼠中DSS诱导的结肠炎,但并未减轻微生物群缺陷型小鼠中DSS诱导的结肠炎。进一步分析表明,给予 MZ16 可改善小鼠的肠道生态和完整性以及免疫屏障功能。与DSS处理的小鼠相比,预先给予 MZ16 的小鼠表现出潜在有益微生物( 、 、 、 、 和 )的相对丰度提高,致病微生物( )的相对丰度降低,并维持结肠OCLN和ZO - 1水平以及IgA和SIgA水平。此外,MZ16 通过逆转DSS组中NF - κB和MAPK途径的激活来降低促炎细胞因子水平。总体而言,来自民猪的 MZ16 通过增强肠道屏障功能并以肠道微生物群依赖的方式减轻炎症,对结肠炎小鼠模型具有有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edc6/11249912/45ad7d7f172f/research.0415.fig.007.jpg
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