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Page 14 of 16 Ding et al. Microbiome Res Rep 2024;3:16 https://dx.doi.org/10.20517/mrr.2023.64

abundance of B. longum subsp. infantis and regulates Th1/Th2 balance by affecting the JAK/STAT signaling
pathway in both male and female mice. The other seven strains of B. longum subsp. infantis affected changes
in gut microbiota but did not regulate the JAK/STAT signaling pathway. This may indicate that changes in
microbial communities were not sufficient to affect the JAK/STAT signaling pathway and the difference in
metabolites among strains in vivo or in vitro may contribute to this result. Furthermore, it was found
significant differences in metabolites between B6MNI and seven other strains B. longum subsp. infantis in
vitro (data not shown). B6MNI affected the content of tryptophan metabolites through a mouse model ,
[44]
which may be the reason for its different effects compared to the other seven strains B. longum subsp.
infantis. Therefore, B. longum subsp. infantis has the potential to prevent allergies and asthma despite its
strain-specific. These regulatory effects are expected to improve the immune function of infants and young
children and prevent the occurrence of allergic diseases. Exploring the intricacies of gut microorganisms
and their responsible mechanisms is crucial for advancing the development of microbial formulations
tailored for infants at risk of microbiota imbalances. Such imbalances could compromise immune
Contributed to funding acquisition: Yang B, Zhao J, Chen W
maturation and increase susceptibility to disease. It is essential to understand these processes to enable the
supplementation of specific probiotics in infants as early as possible after birth, thereby promoting their
overall health. The limitations and gaps in this study were the need for further analysis of strain differences
at the genetic level.

In conclusion, The regulation of Th1/Th2 in 3-week-old mice by eight Bifidobacterium longum subsp.
infantis strains exhibited strain-specificity, mainly reflected in their effects on specific immune cells, Th1/
Th2 immune balance, and gut microbiota. Among these strains, B6MNI showed the most significant
regulatory ability, possibly by regulating colon Th1/Th2 differentiation biomarkers through the JAK-STAT
pathway, promoting serum Th1 cytokines and immunoglobulin levels, and regulating gut microbiota
composition, especially increasing the relative abundance of Bifidobacterium and B. longum subsp. infantis.

DECLARATIONS
Authors’ contributions
Performed conceptualization: Yang B, Ross RP, Chen W
Supplied the method: Ding M, Li B
Supplied software: Chen H
Validated the method and software: Chen H, Jiang S
Contributed to formal analysis, investigation, and original draft preparation: Ding M
Contributed to review and editing: Yang B, Ross RP, Stanton C
Contributed to supervision: Zhao J

All authors have read and agreed to the published version of the manuscript.

Availability of data and materials
Raw sequencing reads were accessible from the National Center for Biotechnology Information (NCBI)
Sequence Read Archive (SRA) database under the accession number PRJNA884502.

Financial support and sponsorship
This study was funded by the National Key R&D Program of China (2021YFD2100700), National Natural
Science Foundation of China (32021005), 111 project (BP0719028), Collaborative Innovation Center of
Food Safety and Quality Control in Jiangsu Province.