Mouse IgA modulates human gut microbiota with inflammatory bowel disease patients.

IF 6.9 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Journal of Gastroenterology Pub Date : 2024-09-01 Epub Date: 2024-06-14 DOI:10.1007/s00535-024-02121-y

Keishu Takahashi, Naoki Morita, Ryutaro Tamano, Peng Gao, Noriho Iida, Akira Andoh, Hirotsugu Imaeda, Ken Kurokawa, Mayo Tsuboi, Yoku Hayakawa, Mitsuhiro Fujishiro, Reiko Shinkura

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Abstract

Background: The imbalance of commensal bacteria is called dysbiosis in intestinal microflora. Secreted IgA in the intestinal lumen plays an important role in the regulation of microbiota. Although dysbiosis of gut bacteria is reported in IBD patients, it remains unclear what makes dysbiosis of their microflora. The intervention method for remedy of dysbiosis in IBD patients is not well established. In this study, we focused on the quality of human endogenous IgA and investigated whether mouse monoclonal IgA which binds to selectively colitogenic bacteria can modulate human gut microbiota with IBD patients.

Methods: IgA-bound and -unbound bacteria were sorted by MACS and cell sorter. Sorted bacteria were analyzed by 16S rRNA sequencing to investigate what kinds of bacteria endogenous IgA or mouse IgA recognized in human gut microbiota. To evaluate the effect of mouse IgA, gnotobiotic mice with IBD patient microbiota were orally administrated with mouse IgA and analyzed gut microbiota.

Results: We show that human endogenous IgA has abnormal binding activity to gut bacteria in IBD patients. Mouse IgA can bind to human microbiota and bind to selectively colitogenic bacteria. The rW27, especially, has a growth inhibitory activity to human colitogenic bacteria. Furthermore, oral administration of mouse IgA reduced an inflammation biomarker, fecal lipocalin 2, in mice colonized with IBD patient-derived microbiota, and improved dysbiosis of IBD patient sample.

Conclusion: Oral treatment of mouse IgA can treat gut dysbiosis in IBD patients by modulating gut microbiota.

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小鼠 IgA 可调节炎症性肠病患者的肠道微生物群。

背景：共生菌的失衡被称为肠道微生物菌群失调。肠腔中分泌的 IgA 在调节微生物群方面发挥着重要作用。虽然有报道称 IBD 患者的肠道菌群失调，但仍不清楚是什么导致了他们的微生态失调。治疗 IBD 患者肠道菌群失调的干预方法也尚未确立。在这项研究中，我们重点研究了人类内源性 IgA 的质量，并探讨了与选择性结肠致病菌结合的小鼠单克隆 IgA 能否调节 IBD 患者的肠道微生物群：方法：用MACS和细胞分拣机分拣与IgA结合和未结合的细菌。方法：用 MACS 和细胞分拣仪对 IgA 结合和未结合的细菌进行分拣，用 16S rRNA 测序分析分拣出的细菌，以研究人类肠道微生物群中内源性 IgA 或小鼠 IgA 识别的细菌种类。为了评估小鼠 IgA 的效果，给与 IBD 患者微生物群不一致的小鼠口服小鼠 IgA，并分析肠道微生物群：结果：我们发现人类内源性 IgA 与 IBD 患者肠道细菌的结合活性异常。结果：我们发现人类内源性 IgA 与 IBD 患者肠道细菌的结合活性异常。尤其是 rW27，对人类结肠致病菌具有生长抑制活性。此外，口服小鼠 IgA 还能降低定植了 IBD 患者微生物群的小鼠体内的炎症生物标志物粪脂钙蛋白 2，并改善 IBD 患者样本的菌群失调状况：结论：口服小鼠 IgA 可以通过调节肠道微生物群来治疗 IBD 患者的肠道菌群失调。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gastroenterology 医学-胃肠肝病学

CiteScore

12.20

自引率

1.60%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.