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Page 2 of 16 Ding et al. Microbiome Res Rep 2024;3:16 https://dx.doi.org/10.20517/mrr.2023.64

Results: B. longum subsp. infantis I4MI and I8TI were shown to increase the ration of colonic IgG2a/IgE in male
mice (P < 0.05). B6MNI was demonstrated to significantly increase the levels of colonic IFN-γ and IgG2a, as well as
the ratio of IgG2a/IgE in female mice (P < 0.05). It was also shown to significantly increase the ratio of colonic
IgG2a/IgE (P < 0.05) and reduce the level of colonic IL-4 in male mice (P < 0.05). Furthermore, B6MNI was
demonstrated to regulate colonic JAK/STAT pathway in both male and female mice. I4MI, I5TI, and B6MNI were
shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in both male and female
mice, whereas I8TI was only shown to increase the relative abundance of Bifidobacterium and B. longum subsp.
infantis in male mice (P < 0.05).

Conclusion: These results indicated supplementation with B. longum subsp. infantis in early infancy may regulate
the Th1/Th2 immune balance, which may prevent the development of related diseases.

Keywords: Bifidobacterium longum subsp. infantis, Th1/Th2 balance, JAK/STAT pathway, gut microbiota,
bifidobacterial community
[14,15]

INTRODUCTION
With the rising incidence of various non-infectious diseases, there has been intense interest in discovering
potential causes with a focus on early-life immune development . During pregnancy, there is a bias towards
[1]
the production of T helper (Th) 2 cells at the maternal-fetal interface that induces maternal tolerance of the
[2,3]
fetus . Following birth, the development of the Th1 immune response in infants, believed to be mitigated
[4]
by exposure to environmental microbial components, resets the Th1/Th2 balance . However, low levels of
circulating Th1-associated cytokines and high levels of Th2-associated cytokines in infants have been linked
with sensitization and allergic diseases . Thus, early-life microbiota exposure may provide opportunities to
[5]
prevent allergy risks caused by the imbalance of Th1/Th2 .
[6]
B. longum subsp. infantis is an important bacterium in infant gut and is associated with several beneficial
[7]
effects such as the production of bioactive substances, immature immune system maturation, and
improvement of intestinal barrier integrity . One of the factors that helps B. longum subsp. infantis to
[8,9]
colonize the infant intestine is its capacity to digest the oligosaccharides found in human milk [7,10] . Studies
have reported that loss of Bifidobacterium in early life is related to a high risk of several immune diseases
and enteric inflammation, but the mechanism is unclear [11,12] . A recent publication has reported that
Lactobacillus casei NCU011054 could relieve intestinal immune dysfunction induced by cyclophosphamide
in immunosuppressive mice through the TLR/NF-κB pathway and then regulated Th1/Th2 immune
[13]
balance ; Lactobacillus plantarum NCU116 and Lactobacillus plantarum 19-2 may promote Th1 immune
response, thereby regulating intestinal immune in mice with cyclophosphamide-induced intestinal
injury ; Lactobacillus casei LCR35 inhibits the occurrence of atopic dermatitis by regulating Th1/Th2
balance and gut microbiota ; Supplementing probiotics during weaning also contributes to the immune
[16]
balance of infants. For example, feeding Lactobacillus paracasei F19 can reduce the cumulative incidence
[17]
rate of eczema , prevent the early manifestations of allergy, and enhance the immune response mediated
by T cells ; Lactobacillus rhamnosus reduces the incidence rate of eczema in children . Intestinal Th2 and
[19]
[18]
[20]
Th17 cytokines decreased in breastfed infants after being administered with B. longum subsp. infantis .
Administration of EVC001 to adult mice had a therapeutic effect on allergic asthma by accelerating Th1 and
[21]
silencing Th2 immune responses . Additionally, B. longum subsp. infantis EVC001 led to the maintenance
of the intestinal microenvironment by remodeling the intestinal microbiome in breastfed infants .
[11]
[22]
However, it is unclear if there are strain-specific variations among members of the B. longum subsp. infantis
taxon in terms of their ability to regulate the Th1/Th2 immune balance following infant supplementation.
Furthermore, gender differences impact the immune system in a microbiota-independent manner that