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Xu et al. Microbiome Res Rep 2024;3:13 https://dx.doi.org/10.20517/mrr.2023.68 Page 7 of 11

[73]
production of intestinal spoilage substances . Recent studies have observed the proliferation of
A. muciniphila in the gut after consumption of oligosaccharides, which may also be one of the anti-aging
[74]
mechanisms of prebiotics . The processed probiotic metabolites, collectively known as postbiotics, contain
[75]
various active ingredients such as vitamins, proteins, and SCFAs . Studies have reported the superior
probiotic and anti-aging properties of postbiotics in the internal environment compared to living microbes;
thus, preliminary progress has been made in the application of postbiotic extracts in skin aging and certain
chronic diseases . The intake of prebiotics and postbiotics is undoubtedly safer compared to direct
[76]
supplementation with exogenous probiotics, but the extent to which their actual anti-aging efficacy can be
attributed to themselves is worth speculating.

Dietary intervention
Compared to supplements, interventions based on a holistic diet may better reset the gut microbiota and
thus achieve long-term health maintenance for the aging population. CR that does not induce malnutrition
is optimal for extending lifespan. A study concluded that a fasting strategy of cutting food intake by 30% for
two weeks shaped the Lactobacillus-dominant gut microbiota in mice, and the median lifespan of the
[77]
experimental group increased by 20.8% after further full-life-cycle dieting . As estimated, the standard CR
adopted in most studies could extend the lifespan by an average of 10%-20% [78,79] . The other is the
Mediterranean diet, which emphasizes the intake of fruits, vegetables, and grains, and limits the
consumption of red meat and saturated fats. The maintenance of health-related microbiome, including
enrichment of potential probiotics such as Enterococcus faecalis and Rhodobacter sphaeroides and depletion
of deleterious bacteria such as Rhodobacter torques and Collinsella, has been found in the elderly with
[80]
Mediterranean diet intervention . This contributes to lowering inflammatory levels, improving cognitive
function, and reducing frailty, implying a healthier aging condition. The accessibility and health benefits of
the Mediterranean diet make it a recommended preventive medicine therapy, but its relevance for
generalization in anti-aging practice still requires individualized assessment by clinicians.

CONCLUSION
Aging is the joint outcome of both genetic and environmental factors. Microorganisms have been observed
to be involved in multiple aging-related diseases, and their inter-individual variability renders them an
alternative as aging-related markers and intervention targets. In this review, underlying mechanisms of
microbiota on host aging were explored, including inflammatory immunity, nutrient metabolic regulation,
and neuroprotection. By summarizing the microbial features of aging populations, the value of various
bacteria such as A. muciniphila and derived metabolites as biomarkers in characterizing aging and
monitoring anti-aging interventions was identified. Additionally, given the active interactions between gut
microbiota and host, we generalized the current status and future prospects of microbiota-targeted anti-
aging interventions such as FMT and probiotic supplementation, attempting to satisfy the healthy aging of
the widest range of aging populations.

Setting gut microbiota as an entrance to explore aging characterization and anti-aging interventions is
certainly a revolutionary mindset, but problems exist as well. The field of gut microbiota as aging-related
biomarkers is still in its infancy, and the characterization of aging by microbiota remains only qualitative,
lacking specific quantitative indicators to describe the correlation between both, thus necessitating the
standardization of authoritative guidelines . Secondly, the detailed mechanism between gut microbiota
[81]
alterations and host aging is not yet clarified, and the actual microbial involvement in the aging process may
be exaggerated or obscured. Thus, microbiota intervention combined with other anti-aging therapies might
be a viable option. In addition, given the complexity of aging, model organisms such as nematodes,
[82]
Drosophila, and mice are often employed to simplify variable control and experimental manipulation.