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Page 2 of 17 Sharma et al. Microbiome Res Rep 2024;3:3 https://dx.doi.org/10.20517/mrr.2023.51

The strains of the Bifidobacterium genus have gained a lot of attention mainly because of their beneficial
effects on the host by being the most efficient probiotic. The diversity of bifidobacteria keeps changing
throughout life, and it also gets affected by various other factors, including the type of delivery, formula
[3,4]
feeding, breastfeeding, etc. . Bifidobacteria play a significant role in maintaining gut homeostasis via
different mechanisms, such as immune system modulation, pathogen elimination, antimicrobial activities,
metabolite production, and the regulation of the intestinal epithelial barrier. Its role in gut homeostasis is
further discussed at length in this article.

The beneficial role of using bifidobacteria in anticancer therapy has been explored very extensively.
Interaction of Bifidobacterium with cell cycle regulatory proteins causes inhibition of the proliferating
cancer cells via successful activation of pro-caspases and up-regulation of the Bax proteins which are pro-
[5]
apoptotic in nature . The specifics pertaining to the beneficial role of Bifidobacterium resulting in the
generation of anticancer properties are due to their ability to fabricate short-chain fatty acids (SCFAs) that
impede the growth and maturation of cancer cells. These mass-produced SCFA, namely butyrate,
propionate, and acetate, also aid in alleviating inflammation, a major risk factor in the development of
[6]
cancer . Further, Bifidobacterium strains have showcased antitumor properties by conferring an increase in
CD8 T cells along with an increase in the CD8 /T Reg cells ratio .
[7,8]
+
+
The recent exploration of the role of bifidobacteria as an enhancer for checkpoint inhibitor immunotherapy
has revealed an increased efficacy of the treatment . When administrated orally, it has shown an improved
[9]
ability to control tumors, similar to PD-L1-specific antibody therapy, and when used in combinational
therapy, the tumor outgrowth was nearly eradicated. This was possibly due to dendritic cell accumulation in
the tumor microenvironment. Thus, cancer immunotherapy can certainly be modulated by
[10]
bifidobacteria . The exploration of using Bifidobacterium as a therapeutic agent for cancer treatment holds
a promising way ahead. Some studies indicated the efficacy and enhancement of cancer immunotherapy
due to the potential of bifidobacteria in the generation of antitumor responses. Researchers are also
investigating its role in targeted cancer therapy by using it as a drug delivery system . The area of
[11]
bifidobacteria and cancer research is still perplexing and evolving due to the varied nature of different
bifidobacterial strains influencing cancer prevention and development. Extensive research on the potential
use of these microorganisms as a drug delivery tool for cancer prevention and combination therapy is a
[12]
promising way ahead .
While the role of bifidobacteria in positive outcomes of anticancer therapy is very well understood, their
controversial negative role in cancer raises a lot of questions. Their relative abundance and additional
indirect effects are reported, from which we can hypothesize that dysbiosis in bifidobacteria present in the
gut can be an alarm linked with different malignant tumors. It is further explained in this article.

The review discusses the studies elucidating the role of bifidobacteria in maintaining gut homeostasis, the
effects of its altered diversity in several cancer types, and its potential use as a therapeutic and delivery agent
for therapeutic substances against cancer. The relationship described between bifidobacteria strains and
neoplastic growth does not indicate a causal relationship. We are only trying to highlight the dysbiotic
population, its various effects, and its relevance to cancer.

BIFIDOBACTERIUM : A STAR PLAYER OF GUT HOMEOSTASIS
A growing body of evidence illustrates the role of bifidobacteria in maintaining human health by regulating
intestinal homeostasis. The diversity analysis of bifidobacteria in various diseased conditions has been
reported, in turn speculating its role in balancing the healthy gut microbiota composition. Any major shift