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

level of age-related biomarkers; it is possible that the combination of serum biomarkers such as
[20]
[19]
inflammatory bodies (indicating inflammatory aging), Sirtuins (associated with malnutrition risk and
[21]
frailty phenotype), and Clusterin (monitoring neurodegeneration) will be adopted in conjunction for the
quantification of aging. A common shortcoming, however, is the unsatisfactory efficacy of the above
indicators in characterizing inter-individual variabilities and environmental sensitivities.
Gut microbiota can be summarized as bacterial communities that colonize or temporarily reside in the
gastrointestinal cavity . The spatiotemporal variations in the abundance, composition, and vitality of
[22]
microbiota constitute a vast microecology, thus bridging the human body and the external environment,
and exerting a pivotal impact on health and disease. The key point lies in the role of the gut microbiome in
characterizing diseases such as gastrointestinal cancers, diabetes, and obesity. For instance, significant
correlations have been reported between Helicobacter pylori infection and the high risk of gastric
lymphoma , as well as the indication of Fusobacterium nucleatum abundance in the prognosis of colorectal
[23]
[12]
cancer . These years, with the inclusion of dysbiosis in aging signatures in 2023 and multiple researches
[24]
elucidating the function of microbiota interventions in aging-related diseases, here we reiterate the
possibility of using gut microbiota as biomarkers to predict aging and evaluate the efficacy of anti-aging
interventions.

Gut microbiota as biomarkers to diagnose and monitor aging
Gut microbiota as predictive biomarkers
Multiple large-sample, multi-center, and group-based studies have partially clarified the inter- and intra-
population differences in aging-related microorganisms. Metagenomic sequencing of gut microbes from 32
long-lived families across three generations (including centenarians, the elderly, and the younger) revealed
reduced gut microbiota diversity and functional deficits of associated essential amino acids in the elderly.
However, interestingly, a significant enrichment of anti-inflammatory bacteria such as Desulfovibrio piger,
Gordonibacter pamelaeae, and Ruminococcaceae bacterium D5 was observed in centenarians compared to
younger and older age groups, and short-chain fatty acid high-yielding bacteria like Akkermansia
muciniphila and other potential probiotic behave similarly, which may contribute to the health maintenance
of aging individuals . In addition, an observational study of four age groups, young, old, centenarians, and
[25]
[26]
semi-centenarians, proposed the concept of enterotype , which divides the gut microbiota into multiple
functional core microbiome clusters. One group of enterotypes containing Bacillariophyceae, Prevotella,
and Rumenococcaceae decreased in abundance in the advanced age groups, suggesting that the delineation
and definition of enterotypes may help describe the downgrading of overall functional levels in the aging
population and also serve as potential aging-related microbial biomarkers.

Further, healthy elderly individuals also exhibit an evident flora profile compared to the non-healthy ones.
Akkermansia spp. and Erysipelaceae UGG were the units with significantly increased abundance in the
[27]
microbial taxa of a healthy aging population . Monitoring data on immune function, blood pressure, and
body weight in both groups also illustrated the role of quantitative changes in taxa such as Ruminococcus,
[28]
Prevotella, Oscellobacter CAG, and Bacteroides in the gut microbiome in healthy aging . Notably, a study
has confirmed the feasibility of using altered Sartorius spp./Pasteurella ratios as an essential microbial
alteration for aging-associated sarcopenia; the role of gut bacteria-derived metabolites in characterizing
[29]
aging-induced neurodegeneration has also been highlighted in another study , which inspired us to
construct a subsystem of aging-related diseases with associated microbial factors for a more precise aging
representation.