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Page 6 of 17 Sharma et al. Microbiome Res Rep 2024;3:3 https://dx.doi.org/10.20517/mrr.2023.51

ulcer. However, patients with H. pylori infection can remain asymptomatic, while some patients develop
severe aggressive forms of gastric diseases like gastric cancer or gastric ulcer. In February 2021, a similar
intestinal microflora analysis study was published, which mainly focused on the H. pylori infectious
[49]
virulence genes along with gut microflora diversity in the patients of Trivandrum, Southwestern India . It
was seen that in Trivandrum, the most dominant H. pylori strain was of the VacAs1i1m1CagA+ genotype. It
is important to note that among the patients with H. pylori infection, only a few developed severe gastric
abnormalities such as gastric ulcers and gastric cancer. This indicates that there should be some other factor
that plays a vital role in developing severe gastric diseases. For further analysis, they compared the gut
microflora diversity of H. pylori-infected patients with gastric cancer or gastric ulcer (CA/GU-Hp+) with
relatively milder gastric diseases like non-ulcer dyspepsia or gastritis with and without H. pylori infection
(NUD/GAS-Hp+ and NUD/GAS-Hp-) and gastroesophageal reflux disease without H. pylori infection
(GERD-Hp-). Among those four groups, the CA/GU-Hp+ group had the lowest gut microflora diversity.
The most important finding was that it had the significantly lowest abundance of the Bifidobacterium genus
with strains including B. adolescentis, B. longum, and B. bifidum. Further whole-genome metagenomic
sequencing analysis of CA/GU-Hp+ and NUD/GAS-Hp+ groups showed seven Bifidobacterium species,
which were present in very inadequate amounts in the CA/GU-Hp+ group than the other. Those species
included B. adolescentis, B. bifidum, B. breve, B. longum, B. moukalabense, B. pseudocatenulatum, and
B. reuteri. This study indicates that H. pylori infection alone is not sufficient to develop severe gastric
abnormalities such as gastric cancer and gastric ulcers. A lower abundance of gut resident Bifidobacterium
genus with specific strains plays a significant role in developing severe gastric malignancy.

Bifidobacteria are considered the earliest colonizers of the human gastrointestinal tract. The diversity of
Bifidobacterium decreases as individuals age. Numerous published studies have revealed the amount and
strain of Bifidobacterium in the early stages of life, adulthood, and older age. The most abundant
Bifidobacterium species seen in infants are B. infantis, B. breve, B. longum, and B. bifidum. During
adulthood, the levels of Bifidobacterium decrease significantly. The most abundant bifidobacterial species
found in adults are B. adolescentis, B. catenulatum, and B. longum. It has been observed that in later stages
of life, with an increase in age, levels of Bifidobacterium further decrease. However, there are no profiles of
old-age specific Bifidobacterium species because of a lack of particular understanding of an “elderly age”. It
[50]
can be said that aging affects the Bifidobacterium population . Age is also one of the most salient risk
factors for gastric cancer, along with the stage of the cancer. The correlation between gastric cancer and age
is reported. A study published in the year 2022 reveals that there was a significant decrease in the survival of
gastric cancer patients as age increased. They included three different age groups in the study: groups I, II,
and III, with ages of < 65 years, 60-74 years, and > 75 years, respectively. Groups II and III showed
significantly lower survival, indicating a vital role of age in gastric cancer . American Society of Clinical
[51]
Oncology also describes age as one of the risk factors for gastric cancer. Gastric cancer mostly occurs in
people with age > 55 . Now, as mentioned earlier, bifidobacterial abundance starts decreasing with age,
[52]
and thus, we can say that there might be an association between bifidobacteria, age, and gastric cancer. A
lower abundance of bifidobacteria in elderly individuals may act as a risk factor for gastric cancer.

Thus, from this data, we can observe a lower abundance of Bifidobacterium participating in gastric
malignancies and developing more aggressive gastric tumors. Nonetheless, more extensive research
including gut microflora profiling with an emphasis on bifidobacteria levels is required.

Bifidobacterium and pancreatic cancer
Pancreatic cancer is the most lethal malignancy of all, and by the time it is diagnosed, it has already reached
an advanced stage with metastasis, poor prognosis, and a more aggressive form . A study published in
[53]
2022 reported the gut microflora profiles in pancreatic cancer patients . In pancreatic cancer patients,
[54]