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Ding et al. Microbiome Res Rep 2024;3:16 https://dx.doi.org/10.20517/mrr.2023.64 Page 13 of 16

publication reported that administration of Lactobacillus paracasei in infants between 4 and 13 months of
age can effectively reduce the incidence of allergies and asthma at the age of 8-9 by 11% and 3%,
[17]
respectively . Therefore, supplementation with specific probiotics in infants after birth has the potential to
reduce the incidence of childhood diseases effectively.

JAK-STAT mediates the responses to cytokines and growth factors and is part of homeostasis and
[32]
developmental processes . T-bet and GATA3 are two important transcriptional factors for secreting IFN-γ
and IL-4, respectively . Deficiency of STAT1 and STAT6 leads to failure of releasing mature IFN-γ and
[33]
[34]
IL-4 . B. longum subsp. infantis can release IFN-γ and inhibit the production of IL-4 by activating the JAK/
STAT pathway but in a strain-specific manner. Interestingly, B. longum subsp. infantis I5TI increased the
gene levels of the JAK/STAT pathway but failed to influence the level of cytokines and immunoglobulin
related to Th1/Th2 in both male and female mice. The reason for this may be that its effect on these genes
did not reach the level of translation, which was confirmed by western blot analysis in this study. B. longum
[41]
subsp. infantis B6MNI not only significantly increased the gene expression level of the JAK/STAT pathway,
but also increased their protein level in the colon. Strain specificity is exhibited in regulating both Th1/Th2-
related gene proteins among B. longum subsp. infantis. The reason for the variability of those strains may be
the characteristics of the strains themselves, for instance, different carbohydrate utilization , and
[35]
[36]
extracellular polysaccharide biosynthesis . In addition, different metabolites of the strains in vivo or in
vitro may also contribute to the variability of the strains . Therefore, the reason for strain specificity needs
[37]
further exploration.

B. longum subsp. infantis influenced gut microbiota composition in the mice. In this study, the variety of
gut microbial composition was more pronounced in male mice compared to that in female mice. A previous
[38]
study reported female mice with a higher relative abundance of Bifidobacterium , which was inconsistent
with our study. This gender-specific difference in intestinal microbiota may be related to estrogen . The
[39]
effect of B. longum subsp. infantis on the gut microbiota is reflected not only in the relative abundance of
some genera but also in the presence or absence of a specific genus. For example, the relative abundance of
B. longum subsp. infantis in the mice intestine was significantly increased after B. longum subsp. infantis
intervention. The relative abundance of B. longum subsp. infantis in the infant gut is inversely associated
with immune-mediated disease incidence during growth, which suggests the critical role of B. longum
subsp. infantis during early-life immune system imprinting . Therefore, these results indicate that the
[40]
microbiota colonization that occurs in early life influences a pivotal window of immunological
development.

B. longum can enhance the immune response of Th1 cells by stimulating immune cells to produce IFN-γ to
promote the development and function of Th1 cells . B. longum can also inhibit the activation and
proliferation of Th2 cells, reduce allergic reactions and humoral immune responses, regulate cytokine
balance in immune responses, such as increasing IL-10 production, and inhibit the development and
[42]
function of Th2 cells . Research has shown that the B. longum subsp. infantis can treat allergic asthma by
regulating Th1/Th2 balance, including elevating the level of Th1 related cytokine and decreasing the level of
[21]
Th2 cytokine . Supplementing specific Bifidobacterium or Lactobacillus in the early stages of life to prevent
the occurrence and development of allergic diseases in infants and young children can contribute to their
healthy development. For example, Lactobacillus rhamnosus HN001 supplementation can reduce the
incidence of eczema in infants by 50% . Additionally, taking HN001 from birth to 2 years old can prolong
[43]
the preventive or relieving effect on eczema to 4 years old . This study found that 8 strains of B. longum
[43]
subsp. infantis have different regulatory abilities on Th1/Th2 immune balance through mice models.
Among them, B6MNI was more pronounced. B. longum subsp. infantis B6MNI increased relative