The gut microbiome contributes to splenomegaly and tissue inflammation in a murine model of primary biliary cholangitis.
The gut microbiome contributes to splenomegaly and tissue inflammation in a murine model of primary biliary cholangitis.
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肠道微生物组导致原发性胆汁性胆管炎小鼠模型中的脾肿大和组织炎症
DOI：
10.21037/atm-21-5448
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发表时间：
2022-05
影响因子：
--
通讯作者：
Lian, Zhe-Xiong
中科院分区：
文献类型：
--
作者：
Wang, Cheng-Bo;Wang, Yan;Yao, Yuan;Wang, Jin-Jun;Tsuneyama, Koichi;Yang, Qiong;Liu, Bin;Selmi, Carlo;Gershwin, M. Eric;Yang, Shu-Han;Lian, Zhe-Xiong
脾肿大不仅是众多急慢性病症的一个后果，由于脾脏与肠道微生物群的相互作用，它还可能加重这些病症的严重程度。本研究旨在探究肠道微生物群对脾肿大的影响。
根据我们之前的研究，我们使用p40−/−IL - 2Rα−/−小鼠作为原发性胆汁性胆管炎（PBC）的小鼠模型。通过脾脏重量评估脾肿大情况。通过肝脏单个核细胞（MNCs）数量和病理评分来评估肝脏炎症的严重程度。利用流式细胞术检测脾脏和肝脏中免疫细胞的变化。通过对p40−/−IL - 2Rα−/−小鼠联合使用抗生素治疗，观察肠道微生物群对脾肿大和肝脏炎症的影响。
部分p40−/−IL - 2Rα−/−小鼠出现脾肿大。结果显示，肝脏单个核细胞浸润、肝脏炎症的组织学评分以及胆管损伤与脾肿大程度呈正相关。脾肿大小鼠肝脏中的CD4 + 和CD8 + T细胞数量显著增多，在活化的效应记忆CD4 + T细胞和CD8 + T细胞中尤其明显。在肿大的脾脏中，包括粒细胞、B细胞、自然杀伤（NK）细胞和CD8 + T效应记忆细胞在内的部分其他免疫细胞比例也发生了改变。更重要的是，给予四联抗生素以清除肠道微生物群，可缓解p40−/−IL - 2Rα−/−小鼠的脾肿大，显著减轻肝脏炎症，并使肝脏和脾脏中T细胞的积聚和活化显著减少；然而，单一抗生素并未引发这些变化。
在我们的PBC小鼠模型中，脾肿大与更严重的肝脏炎症相关，而这种影响可通过四联抗生素治疗得到逆转。
Background Splenomegaly is not just a consequence of numerous chronic and acute conditions but may also contribute to their severity, due to the interaction of the spleen with the gut microbiome. This study aimed to explore the effect of the gut microbiome on splenomegaly. Methods We used p40−/−IL-2Rα−/− mice as a murine model of primary biliary cholangitis (PBC) as per our previous study. Splenomegaly was evaluated by spleen weight. Severity of liver inflammation was evaluated by hepatic mononuclear cell (MNCs) number and pathological score. Changes of immune cells in the spleen and liver were detected by flow cytometry. The effects of the gut microbiome on splenomegaly and liver inflammation were observed by combined antibiotic treatment in p40−/−IL-2Rα−/− mice. Results A proportion of p40−/−IL-2Rα−/− mice developed splenomegaly. The results revealed that liver mononuclear cells infiltration, histological scores of hepatic inflammation, and bile duct damage were positively correlated with the degree of splenomegaly. Hepatic CD4+ and CD8+ T cells numbers were significantly higher in mice with splenomegaly, and this was particularly observed in activated effector memory CD4+ T and CD8+ T cells. A proportion of some other immune cells including granulocytes, B, natural killer (NK), and CD8+ T effector memory cells were also altered in the enlarged spleen. More importantly, administration of quadruple antibiotics to deplete gut microbiota relieved the splenomegaly of p40−/−IL-2Rα−/− mice, significantly alleviated liver inflammation, and caused a significant reduction of liver and spleen T cell accumulation and activation; however, single antibiotics did not induce these changes. Conclusions Splenomegaly was associated with more severe liver inflammation in our PBC murine model, and this effect was reversed by quadruple antibiotic treatment.
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