Morphine mediated neutrophil infiltration in intestinal tissue play essential role in histological damage and microbial dysbiosis.
Morphine mediated neutrophil infiltration in intestinal tissue play essential role in histological damage and microbial dysbiosis.
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DOI：
10.1080/19490976.2022.2143225
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发表时间：
2022-01
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
作者：
肠道微生物生态系统表现出与宿主的复杂的双向交流，是决定粘膜免疫稳态或炎症状态的关键因素之一。阿片类药物的使用已被证实可诱导肠道微生物失调，与肠道组织炎症增加相一致。在这项研究中，我们研究了渗透的免疫细胞在吗啡诱导的小鼠肠道组织损伤和肠道微生物失调中的作用。结果显示，在吗啡治疗后，肠道组织中趋化因子的表达显着增加，随后中性粒细胞渗透增加，这是微生物群失调的直接结果，因为在抗生素治疗的动物和无菌小鼠中，这种影响减弱。用抗Ly6G单抗中和中性粒细胞，组织损伤明显减少，紧密连接蛋白组织增多。对肠道样本的16S rRNA测序强调了渗透的中性粒细胞通过为肠球菌等病原菌提供生长有利条件，同时导致乳杆菌等共生菌的显著耗尽，在调节微生物群落结构方面的作用。综上所述，我们提供了第一个直接证据，证明中性粒细胞渗透有助于吗啡诱导的肠道组织损伤和肠道微生物失调。我们的发现暗示，抑制中性粒细胞的渗透可能对阿片类药物使用相关的胃肠功能障碍提供治疗益处。
The gut microbial ecosystem exhibits a complex bidirectional communication with the host and is one of the key contributing factors in determining mucosal immune homeostasis or an inflammatory state. Opioid use has been established to induce gut microbial dysbiosis consistent with increased intestinal tissue inflammation. In this study, we investigated the role of infiltrated immune cells in morphine-induced intestinal tissue damage and gut microbial dysbiosis in mice. Results reveal a significant increase in chemokine expression in intestinal tissues followed by increased neutrophil infiltration post morphine treatment which is direct consequence of a dysbiotic microbiome since the effect is attenuated in antibiotics treated animals and in germ-free mice. Neutrophil neutralization using anti-Ly6G monoclonal antibody showed a significant decrease in tissue damage and an increase in tight junction protein organization. 16S rRNA sequencing on intestinal samples highlighted the role of infiltrated neutrophils in modulating microbial community structure by providing a growth benefit for pathogenic bacteria, such as Enterococcus, and simultaneously causing a significant depletion of commensal bacteria, such as Lactobacillus. Taken together, we provide the first direct evidence that neutrophil infiltration contributes to morphine-induced intestinal tissue damage and gut microbial dysbiosis. Our findings implicate that inhibition of neutrophil infiltration may provide therapeutic benefits against gastrointestinal dysfunctions associated with opioid use.
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