JZUS - Journal of Zhejiang University SCIENCE

ENGINEERING Information Technology & Electronic Engineering B

Accepted manuscript available online (unedited version)

Commensal bacteria play a fundamental role in maintaining gut immune homeostasis

Author(s): Shuyu TU, Yanan ZHANG, Li ZHANG, Shu Jeffrey ZHU
Affiliation(s): Department of Cardiology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China; more
Corresponding email(s): shuzhu@zju.edu.cn, Zhangli4029@126.com
Key Words: Intestinal bacteria; Inflammatory bowel disease; Virus-bacteria interaction; Immune modulation

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Shuyu TU, Yanan ZHANG, Li ZHANG, Shu Jeffrey ZHU. Commensal bacteria play a fundamental role in maintaining gut immune homeostasis[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2400431

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publisher="Zhejiang University Press & Springer",
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%A Shu Jeffrey ZHU
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doi="https://doi.org/10.1631/jzus.B2400431"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: The intestinal microbiome, which is a key factor in the maintenance of host gut homeostasis, enhances intestinal mucosal barrier function and immune tolerance (Rooks and Garrett, 2016; Skelly et al., 2019). However, the specific immunomodulatory functions of microbiota-derived metabolites in mucosal inflammatory responses remain largely unknown. The effects of microbial metabolites may vary across different immune cell types and host homeostasis (Hu et al., 2023; Zhao et al., 2023). Hence, it is fundamental to understand how specific intestinal microbes and their metabolic small molecules cause or mitigate gut-related diseases like inflammatory bowel disease (IBD). It has been uncovered that during the pathogenesis of IBD, excessive T helper 1 cell (Th1)/Th17 activation and impaired function of colonic regulatory T cells (Tregs) occur (Subramanian, 2020). Given that colonic Tregs play an important role in inhibiting IBD via secreting immunosuppressive cytokines, the molecular mechanisms linking certain intestinal microbes and their metabolites to Treg-mediated immune tolerance are yet to be fully understood.

肠道菌群在维系肠道免疫稳态中的重要作用

涂舒谕¹，张雅楠²，张莉¹，朱书²
¹广东药科大学附属第一医院心血管内科，中国广州市，510080
²浙江大学动物科学学院动物预防医学研究所，中国杭州市，310058
摘要：肠道中种类庞杂的微生物群落统称为肠道菌群，其与宿主间相互影响，形成了复杂的共生体系统。肠道菌群与动物健康关系密切，具有消化、合成维生素以及合成其他重要代谢物和神经递质的功能。多项研究表明，菌群相关代谢产物可通过直接或间接方式调节宿主的生理功能和免疫反应，以维持局部及全身的稳态平衡。我们利用葡聚糖硫酸钠诱导的结肠炎小鼠模型证实，肠道共生细菌纽约杜伯氏菌及其人类同源菌无害梭菌，可通过产生短链脂肪酸（特别是丙酸）和赖氨酸调节免疫耐受，从而缓解结肠炎。赖氨酸可通过芳烃受体激活树突状细胞中的吲哚胺2,3-双加氧酶1（IDO1），诱导调节性T淋巴细胞（Treg）产生免疫抑制的肠道微环境，该研究可为炎症性肠病提供一种潜在的治疗策略。

关键词组：肠道菌群；炎症性肠病；病毒-细菌互作；免疫调节

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Reference

[1]CoxLM, SohnJ, TyrrellKL, et al., 2017. Description of two novel members of the family Erysipelotrichaceae: Ileibacterium valens gen. nov., sp. nov. and Dubosiella newyorkensis, gen. nov., sp. nov., from the murine intestine, and emendation to the description of Faecalibacterium rodentium. Int J Syst Evol Microbiol, 67(5):1247-1254.

[2]DuHX, YueSY, NiuD, et al., 2022. Gut microflora modulates Th17/Treg cell differentiation in experimental autoimmune prostatitis via the short-chain fatty acid propionate. Front Immunol, 3:915218.

[3]HuJ, HouQL, ZhengWY, et al., 2023. Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation. J Zhejiang Univ Sci B (Biomed & Biotechnol), 24(8):734-748.

[4]RooksMG, GarrettWS, 2016. Gut microbiota, metabolites and host immunity. Nat Rev Immunol, 16:341-352.

[5]SkellyAN, SatoY, KearneyS, et al., 2019. Mining the microbiota for microbial and metabolite-based immunotherapies. Nat Rev Immunol, 19:305-323.

[6]SubramanianBC, 2020. Inflammatory bowel disease: DCs sense LTB₄ to drive T_H1 and T_H17 differentiation. Cell Mol Immunol, 17:307-309.

[7]WangG, LiuJTY, ZhangYN, et al., 2023. Ginsenoside Rg3 enriches SCFA-producing commensal bacteria to confer protection against enteric viral infection via the cGAS-STING-type I IFN axis. ISME J, 17(12):2426-2440.

[8]ZhangYN, TuSY, JiXW, et al., 2024. Dubosiella newyorkensis modulates immune tolerance in colitis via the l-lysine-activated AhR-IDO1-Kyn pathway. Nat Commun, 15:1333.

[9]ZhaoWX, DuanCC, LiuYL, et al., 2023. Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency. J Zhejiang Univ Sci B (Biomed & Biotechnol), 24(7):650-662.

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肠道菌群在维系肠道免疫稳态中的重要作用

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