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Page 6 of 11 Xu et al. Microbiome Res Rep 2024;3:13 https://dx.doi.org/10.20517/mrr.2023.68

In addition, the advantage of FMT also lies in the capacity to treat various aging-related diseases through
the distal effects of axial networks such as the gut-brain axis, gut-skin axis, and gut-muscle axis.
Enterobacteria transplantation from young mice into premature aging mice revealed that the rejuvenated
microbiota could reverse aging-related dementia and cognitive decline to some extent via hippocampal
restoration . In a trial that involved 110 middle and old-aged women with dry, wrinkled skin, a 21.73%
[60]
improvement in skin elasticity and evident reduction in wrinkle depth were observed after consistently
administrating a specially formulated microbiota drug for 12 weeks . The senile osteoporosis cohort also
[61]
presented significantly better histologic indices, such as bone volume and trabecular bone thickness, than
the controls after receiving FMT . The above experimental findings could be considered compelling
[62]
arguments for FMT retarding aging and alleviating aging-related lesions. Remarkably, metabolomic analysis
showed a gradual resumption of the originally dysregulated bile acid profile after FMT, which elucidates the
contribution of gut microbiota to the endocrine metabolism of the organism .
[63]
Along with the benefits, we must also be alert to the shortcomings of FMT at this stage. The occurrence of
adverse events is a concern, since cases of death from resistant bacterial infections after FMT have been
[64]
reported, as well as ineffective transplantation, immune rejection, and gastrointestinal side effects . In
addition, FMT in unhealthy aging populations is intended to mitigate or even reverse the negative effects of
aging, but follow-up observational data on whether offsetting these effects on a large scale is feasible in the
long term is lacking. The specificity of the elderly also requires more rigorous process management for the
anti-aging application of FMT compared to current regulatory guidelines, including ethical approval,
metrics assessment, and adverse event monitoring.

Probiotics, prebiotics and postbiotics
WHO defines probiotic living microorganisms as those that benefit the health of the host when
supplemented adequately . Specific probiotics maintain health and exert aging-delaying effects in multiple
[65]
dimensions, such as dysbiosis regulation, anti-inflammation, and neuroprotection. In addition to the well-
known probiotics with anti-aging properties, such as Lactobacillus salivarius, Lactobacillus galacteri, and
Lactococcus lactis, other probiotics that have been observed to extend lifespan are emerging these years .
[66]
Recent studies have revealed that Lactobacillus plantarum JBC5 administration prolonged the average
longevity of Drosophila by 27.81%, mainly through the modulation of the serotonin signaling pathway .
[67]
Bifidobacterium adolescentis could raise superoxide dismutase values in serum and alleviate neuropathies by
[68]
combating oxidative stress . Lacticaseibacillus rhamnosus Probio-M9 significantly extended nematode
[69]
lifespan with a calorie-independent DAF-2 pathway and P38 signaling cascade . Moreover, Clostridium
pratense (the main producer of butyrate) and Bacillus spp. (production of glycosyl hydrolases) also deliver
superior anti-aging properties by regulating the balance of small molecules, such as short-chain fatty acids
in the gut . Probiotics from different phyla work through different biological pathways for anti-aging;
[70]
judging which is superior or inferior makes little sense. Currently, A. muciniphila is a well-deserved hotspot
with definite anti-glycemic and anti-aging performance . After oral administration of A. muciniphila, the
[71]
biosynthesis of secondary bile acids in premature aging mice was also enriched, thereby exerting the
[72]
protective effect on accelerated aging . Since the relevant research is just starting, the industrialization of
A. muciniphila in anti-aging still has a long way to go. The results of microbiota localization also remind us
that the action site of supplemented probiotics is rather limited and the species is relatively homogeneous,
making it difficult to achieve the holistic regulation of the gut microecology.

Except for probiotics themselves, prebiotics such as inulin, oligosaccharides, and polyphenols have been
repeatedly shown to selectively promote the growth of beneficial intestinal bacteria without being digested
and absorbed by the host, thus providing a certain anti-aging effect. In particular, oligosaccharides have
been proven in previous studies to regulate gut homeostasis by activating Bifidobacteria and inhibiting the