Page 107 - Read Online

Page 2 of 12 Procaccianti et al. Microbiome Res Rep 2023;2:24 https://dx.doi.org/10.20517/mrr.2023.23

INTRODUCTION
Bifidobacterium are non-spore-forming Gram-positive bacteria with a bifurcated (“bifid”) shape, belonging
to the Actinomycetota phylum. Since 1900, when they were first isolated from the feces of breastfed
infants , about 118 species have been identified and included in the Bifidobacterium genus (lpsn.dsmz.de
[1]
[2]
). Over the years, species belonging to this genus have become of increasing relevance given their beneficial
effects on human health, so much so as to obtain the GRAS (Generally Recognized As Safe) status by the
Food and Drug Administration (FDA) and inclusion in the QPS (Qualified Presumption of Safety) list of
the European Food Safety Authority (EFSA), and be widely used in the food and pharmaceutical industry as
probiotics.

Bifidobacterium can be found in several ecological niches, including the gastrointestinal tract of humans and
other mammals, insects, and birds . Bifidobacterium spp. are the first colonizers of the gut microbiota
[3,4]
(GM) of infants, in particular of those breastfed, where they abound due to their ability to metabolize
human milk oligosaccharides (HMOs) . Later, with the cessation of breastfeeding and the introduction of
[5]
solid foods, the near monodominance of Bifidobacterium spp. comes to an end and the GM begins to be
colonized by other (more strictly anerobic) microorganisms, assuming a more adult-like composition . In
[6]
most adult-type GMs, Bifidobacterium still constitutes a relevant component, albeit in much lower
proportions (mean relative abundance, 2-14%) . Further decline of Bifidobacterium spp. can be observed
[7]
with aging, along with a decrease in species diversity, which has been correlated with
immunosenescence [8-10] . In contrast, a higher occurrence or prevalence of Bifidobacterium was found in
centenarians (and beyond) worldwide, suggesting an association with healthy aging and longevity [10-12] .

The ecological fitness of Bifidobacterium can be explained by its ability to metabolize dietary and host-
derived carbohydrates, leading to the production of short-chain fatty acids (SCFAs) with a key and
multifactorial role in human physiology [2,13,14] . The glycobiome of Bifidobacterium is indeed one of the
largest among other gut commensals, comprising several glycosyl hydrolases, glycosyltransferases, and
carbohydrate esterases . Additionally, certain Bifidobacterium spp. can synthesize folates and tryptophan-
[15]
derived indoles . The former are involved in cell metabolism, immune development, and epigenetic
[16]
modifications [17-19] , while the latter improve the integrity of the intestinal epithelium and regulate intestinal
mucosa immune responses as aryl hydrocarbon receptor ligands [20-22] . Bifidobacterium can also limit the
growth of pathogens by modulating the immune system and producing antibacterial peptides (i.e.,
[23]
bacteriocins) and organic acids (i.e., lactic and acetic acids) . In particular, the accumulation of organic
acids leads to acidification of the surrounding environment, thus inhibiting the growth of low pH-sensitive
bacteria [24,25] .

All these activities underlie the beneficial effects of Bifidobacterium spp. and their use as probiotics in
different healthcare settings [26,27] . Unsurprisingly, GM alterations (i.e., dysbiosis) often include, regardless of
age, an underrepresentation of Bifidobacterium [28-31] . Furthermore, various studies have reported that the
administration of Bifidobacterium spp., alone or in combination with other lactic acid bacteria (particularly
Lactobacillus), helps to relieve the symptoms of several intestinal and extraintestinal disorders, e.g.,
[34]
[33]
inflammatory bowel disease , irritable bowel syndrome , antibiotic-associated diarrhea and
[32]
[35]
[37]
[36]
Clostridioides difficile-associated diarrhea , necrotizing enterocolitis , allergy , systemic lupus
[39]
[38]
erythematosus , and atopic dermatitis .
While in the aforementioned pathological contexts, the benefits of Bifidobacterium spp. are well established,
their role in the cancer setting is still controversial, with some evidence suggesting they may improve
immune function and reduce postoperative complications, and more recent evidence suggesting an