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Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05 Page 21 of 35

Bifidobacterium is a well-studied genus within the Actinobacteria phylum and has been studied for its health
[206]
benefits in the treatment and prevention of several diseases, alongside Lactobacillus . Certain
Bifidobacterium strains have gained popularity recently, including B. bifidum, for amelioration of DSS-
[207]
induced colitis by improving the gut barrier and inhibiting NF-κB activity . When combined with
Lactobacillus, B. bifidum also demonstrates the potential to treat cardiovascular disease through
[208]
immunomodulatory properties . A recent study showed that supplementation with B. longum spp.
infantis NCIMB 702255 decreased body weight gain in diet-induced obese Drosophila and reduced total
[187]
triglyceride and total glucose levels, compared to control . This Bifidobacterium strain also reduced
elevations of fatty acid oxidation genes, including acetyl Co-A carboxylase, fatty acid synthase, and
phosphoenolpyruvate carboxykinase. In another study, a significant reduction in body weight gain and fat
accumulation, as well as an improved plasma lipid profile, were observed in HFD-induced obese mice
supplemented with B. bifidum DS0908 and B. longum DS0950, indicating the potential of Bifidobacterium to
alleviate obesity markers . In addition, B. pseudocatenulatum was recently proposed as a potential
[209]
beneficial bacterium for neural and immune function improvement, based on 16S rRNA sequencing and
metagenomics data from 32 longevity families of three generations (i.e., centenarians, elders, and young
persons) . The data revealed other species to have potential associations with aging, namely Desulfovibrio
[210]
piger, Gordonibacter pamelaeae, Odoribacter splanchnicus, and Ruminococcaceae bacterium D5. Future
studies can investigate these species for gerobiotic potential.

Investigation of anti-aging and obesogenic probiotics in human trials
The demonstrated efficacy of probiotics in experimental models has led to their investigation in humans.
Recent clinical trials have reported excellent patient outcomes for the treatment of obesity following
probiotic treatment [Table 5] [211-214] . The primary outcomes for these trials include improvement of various
obesity markers, such as reduction in body weight and BMI, as well as improved lipid profiles. Changes to
the gut microbiota are also assessed following the treatment period to identify treatment-induced shifts in
composition. Clinical trials have also reported the efficacy of probiotics in aged populations [Table 5] [215-220] ,
with many studies investigating elders with mild cognitive impairment (MCI). MCI is a common precursor
[221]
to AD, dementia, and other age-related diseases, such as frailty . Alongside analyzing gut microbiota
composition, many of the studies on aging evaluate cognition with validated assessment tools and measure
serum brain-derived neurotrophic factor (BDNF). BDNF is a neurotransmitter modulator that plays a key
role in neuroplasticity and protects against neuroinflammation and neuronal apoptosis; decreased levels of
[217]
BDNF are associated with AD and mild cognitive impairment . However, studies focused on improving
physical ailments of aging as well as longevity or lifespan with probiotics are lacking.

The therapeutic evidence of probiotics for obesity and aging is undeniable, with an evident trend of gut
modulation, regulated gut function, and improved systemic health (i.e., decreased inflammation and
improved metabolism) following probiotic supplementation. However, it is important to highlight that the
bioactivity and microbial modulatory properties of probiotics are often strain-specific. Thus, probiotics of
interest must be studied for their specific influence on gut composition prior to their translation as
therapeutics. Studies that evaluate the effect of probiotics on obesity and aging simultaneously, such as
within sarcopenic obese models, are lacking. Further investigation is therefore required to elucidate the anti-
obesity and pro-longevity potential of known and novel strains within the Lactobacillus and Bifidobacterium
genera and beyond.

Synbiotics
Prebiotics may also be combined with probiotics, in the form of a synbiotic, to exert a synergistic effect.
Synbiotics are defined as “a mixture comprising live microorganisms and substrate(s) selectively utilized by
host microorganisms that confers a health benefit on the host” . Recent literature has investigated specific
[222]