Page 150 - Read Online

Page 10 of 17 Sharma et al. Microbiome Res Rep 2024;3:3 https://dx.doi.org/10.20517/mrr.2023.51

and strategies to enhance site-specific colonization, holds promise for improving the efficacy of cancer
[81]
treatment .
Bifidobacterium in immunotherapy
Gut microbiota composition can highly influence the type and intensity of immune responses generated by
[82]
our body during a variety of diseases, especially autoimmune diseases and cancer .

Bifidobacterium spp. modified the intestinal microbiota when administered orally, resulting in an alteration
of the immune response to PD-L1 blockade and a significant increase in intratumor and circulating CD8 T
+
cells which were tumor antigen-specific, thereby indicating a possible increase in surveillance by dendritic
cells throughout the body. Increased abundance of B. longum in the stools of healing cancer patients showed
[83]
increased infiltration of T-cells in the tumor microenvironment . Research also suggests that using
Bifidobacterium during the pembrolizumab treatment in lung cancer was beneficial by showcasing
+
[84]
proficient antitumor activity and induced change in the population of CD45 cells .
Studies have also shown that Bifido strains B. adolesentis, B. breve, and B. Longum were involved in the
enhancement of cancer immunotherapeutic drugs via oral administration. Bifidobacterial species have
increased the anti-melanoma activity effects of induction of innate immunity. Moreover, a cocktail of
bifidobacteria can potentially fight tumor growth and its further experimentation can be extended to other
forms of cancer . Strains of B. adolescentis not only stimulate the production of anti-inflammatory
[84]
cytokines but also contribute to the decrease in the ulceration area and intestinal wall thickening.
Furthermore, an in-vivo study has reported that the Bifidobacterium bifidum strain can potently induce the
formation of regulatory Foxp3C T cells due to the presence of a cell surface β-glucan/galactan (CSGG),
which showcases a powerful suppressive activity against experimental colitis. Certain components of
Bifidobacterium, such as sortase-dependent pili, are involved in the activation of various signals in
macrophages due to the induction of TNF-α locally while simultaneously reducing proinflammatory
cytokine expressions. B. bifidum strain produces two extracellular molecules, namely BopA and TagA.
BopA, as a surface-associated protein, can stimulate the production of IL-8 and increase bifidobacterial
adhesion to epithelial cells. TagA acts like a peptidoglycan lytic enzyme, causing induction of the IL-2 and
proliferation of dendritic cells . Bifidobacterium also promotes local anti-CD47 immunotherapy due to
[85]
their ability to accumulate within the tumor microenvironment and enhance the stimulation via STING
[86]
signaling, i.e., stimulation of interferon genes . B. pseudolongum-derived inosine showed modulation in
[87]
checkpoint inhibitor therapy . Bifidobacterium also enhanced the natural killer cells (NK cells) activation
at proliferation at the tumor site via showcasing antitumor immunity.

Therefore, we can say that bifidobacteria are involved in cancer treatment by promoting the apoptosis of
cancer cells, reducing immunotherapeutic toxicity, alleviating side effects such as RID, CID and mucositis,
maintaining gut microflora homeostasis, inhibiting cancer cell proliferation, and magnifying the
immunotherapy [Figure 3].

Bifidobacterium and disease onset
It is certain that Bifidobacterium residing in the gut plays an important role in alleviating the symptoms of
cancer. Moreover, the presence of Bifidobacterium in a higher ratio prevents harmful pathogens from
getting attached to the intestinal wall and reduces the chances of occurrence of diseases such as IBS. Even
though its beneficial role has been explored, further research still needs to be done to know how the
Bifidobacterium plays a role in diseases apart from cancer.