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Sharma et al. Microbiome Res Rep 2024;3:3 https://dx.doi.org/10.20517/mrr.2023.51 Page 7 of 17

apart from other bacteria, bifidobacteria was also seen in significantly lower amounts. It was also negatively
correlated with the neutrophil-to-lymphocyte ratio (NLR). Previous studies have shown that NLR is
[55]
associated with a poor prognosis in the case of pancreatic cancer . Thus, a decrease in Bifidobacterium
levels, which is correlated with the NLR, plays a role in pancreatic malignancy. Additionally, lower levels of
Bifidobacterium will not be sufficient to inhibit tumor growth via the TNF-α-mediated pathway, and
[56]
therefore, they can participate in pancreatic cancer progression . Thus, we can postulate that a relatively
lower abundance of Bifidobacterium may be involved in pancreatic cancer progression and poor prognosis.

Bifidobacterium and colorectal cancer
The incidence of colorectal cancer ranks third and is the second most deadly cancer globally . A few
[57]
studies have addressed the profiling of fecal microflora in the case of colorectal cancer. A research paper
published in 2018 revealed the changes in the gut microbiota population in gastrointestinal neoplasm. In the
case of rectal cancer, there was a significantly lower abundance of the Bifidobacteriaceae family and
Bifidobacterium genus . One of the characteristic features of rectal cancer is elevated frequencies of
[58]
aneuploidy along with Tp53 gene mutation. Folic acid plays an important role in regulating the genomic
stability and thereby preventing the tumor growth. Folate deficiency can not only aggravate the genomic
damage and increase the genomic instability in normal cells but also aggravate the colorectal cancer
progression and make the normal colonic epithelial cells susceptible to malignant transformations [59,60] .
Folate is not naturally synthesized in the human body. However, it is most significantly synthesized in the
[61]
gut by Bifidobacterium . Decreased levels of Bifidobacterium will not be able to synthesize enough folate,
and thus, it will elevate the risk of aneuploidies related to rectal cancer, leading to severity in rectal cancer
cases.

One of the risk factors for colon cancer is β-glucuronidase, which plays a primary role in carcinogenesis.
β-glucuronidase hydrolyses the glucuronides, leading to formation of aglycone and glucuronic acid. It also
transfers glucuronides to alcohols, phenols, and carboxylic acids, in turn participating in the detoxification
process. However, increased activity of this enzyme leads to a reduction in glucuronides by forming the
conjugates of glucuronic acid with toxins, hormones, drugs, etc. This leads to an increased production of
carcinogens in the body, eventually elevating the risk of colon cancer .
[62]

In 2014, Molan et al. described the effect of two prebiotics, i.e., First Leaf (FL) and Cassis Anthomix 30
(CAM30), on fecal Bifidobacteria, Lactobacilli, Bacteroidetes spp., Clostridium spp. and β-glucuronidase. The
consumption of FL and CAM30 caused increased growth of probiotics like Bifidobacteria and Lactobacilli
while also reducing the number of harmful Bacteroidetes and Clostridia. The improved growth of
bifidobacteria reduces the β-glucuronidase activity, ultimately preventing the occurrence of colon cancer .
[63]
It is important to note that a reduced abundance of Bifidobacterium is reported in several colorectal cancer
cases, and these lower levels of bifidobacteria will be inadequate to regulate the β-glucuronidase activity and
further fail to prevent the risk of carcinogenesis. Nevertheless, the mechanism behind how bifidobacteria
controls the activity of β-glucuronidase remains an enigma.

Bifidobacterium and ovarian cancer treatment failure
Epithelial ovarian cancer is a rare type of ovarian cancer as well as one of the lethal malignancies found in
females . In August 2021, a study was published emphasizing the gut microbiota population in patients
[64]
[65]
receiving chemotherapy . Patients with platinum resistance showed a reduced diversity of gut microbiota
in comparison to healthy controls and had an overabundance of Coriobacteriaceae and Bifidobacterium. It
was observed that these microorganisms are lactate-producing and an increase in the lactate-producing
bacteria would also elevate lactate production. The Warburg effect is one of the important hallmarks of
cancer. In simple terms, it is the utilization of glucose by cancer cells under aerobic conditions with an