Du Haoming, Cai Yiran, Shen Lulu, Zheng Yuxing, Zhao Lingling, Hu Ruibiao, Jiang Shan, Yuan Jiajia, Hu Chengming, Deng Qi, Huang Jiaoyan, Hu Jingbo, Wang Yuexiang, Tan Jing, Chen Jiahui, Liu Feitong, Duan Yuanyuan, Niu Haitao
School of Medicine, Key Laboratory of Viral Pathogenesis & Infection Prevention and Control, Jinan University, Ministry of Education, School of Medicine, Guangzhou, China.
Guangzhou Key Laboratory for Germ-Free Animals and Microbiota Application, Institute of Laboratory Animal Sciences, Jinan University, Guangzhou, China.
Animal Model Exp Med. 2025 Jun;8(6):965-976. doi: 10.1002/ame2.70034. Epub 2025 May 28.
The maturation of the immune system is critical during early life, as it involves the differentiation, maturation, and establishment of immune tolerance of immune cells. This process is influenced not only by genetic factors but also by environmental factors, particularly the symbiotic microbiota. Bifidobacterium animalis subsp. lactis (BB-12), originally found in dairy products, is widely used in infant formula and dietary supplements. However, its role and mechanisms in immune development during early life remain unclear.
Using GF mice as the experimental model, B. animalis subsp. lactis BB-12 was administered via gavage during early life. In the juvenile stage, changes in T-cell subsets in the spleen, thymus, and gut intraepithelial lymphocytes (IEL) were assessed using spectral flow cytometry. Additionally, targeted metabolomics analysis of tryptophan metabolism and short-chain fatty acid pathways in colonic tissue was conducted to explore how B. animalis subsp. lactis BB-12 influences the immune system through gut microbiota metabolism.
BB-12 effectively modulates the gut immune microenvironment, leading to beneficial changes in T-cell subsets in key immune tissues such as the spleen, thymus, and gut IELs. Metabolomics analysis further supports these findings by showing that BB-12 intervention greatly increased the production of tryptophan derivatives and acetic acid in the colon of GF mice.
The findings provide theoretical evidence for the role of B. animalis subsp. lactis in immune system development and support its application in dietary supplements, suggesting potential as a component for infant immune health and in preventing immune-related diseases.
免疫系统的成熟在生命早期至关重要，因为它涉及免疫细胞的分化、成熟以及免疫耐受的建立。这一过程不仅受遗传因素影响，还受环境因素影响，尤其是共生微生物群。动物双歧杆菌乳亚种（BB-12）最初发现于乳制品中，广泛应用于婴儿配方奶粉和膳食补充剂。然而，其在生命早期免疫发育中的作用和机制仍不清楚。
以无菌小鼠为实验模型，在生命早期通过灌胃给予动物双歧杆菌乳亚种BB-12。在幼年阶段，使用光谱流式细胞术评估脾脏、胸腺和肠道上皮内淋巴细胞（IEL）中T细胞亚群的变化。此外，对结肠组织中的色氨酸代谢和短链脂肪酸途径进行靶向代谢组学分析，以探讨动物双歧杆菌乳亚种BB-12如何通过肠道微生物群代谢影响免疫系统。
BB-12有效调节肠道免疫微环境，导致脾脏、胸腺和肠道IEL等关键免疫组织中T细胞亚群发生有益变化。代谢组学分析进一步支持了这些发现，表明BB-12干预大大增加了无菌小鼠结肠中色氨酸衍生物和乙酸的产生。
这些发现为动物双歧杆菌乳亚种在免疫系统发育中的作用提供了理论证据，并支持其在膳食补充剂中的应用，表明其作为婴儿免疫健康成分和预防免疫相关疾病的潜力。
