Gut bacteria patterns linked to longer life in different age groups in China

According to the National Bureau of Statistics, China entered an era of population aging in 2013. Over the following 6 years, the proportion of individuals aged ≥ 60 years increased by 3.2% (51 million individuals), while those aged ≥ 65 years increased by 2.9% (44 million individuals), indicating a progressively pronounced trend of population aging (Xiang and Wang 2021). Additionally, although per capita life expectancy in China is 76.4 years, the average healthy life expectancy is only 68.7 years, indicating that older individuals may spend approximately 8 years living with disease. This trend is further supported by the growing prevalence of chronic conditions and the increasing number of older adults with functional impairments (Wang 2019), placing a substantial burden on families, society, and the nation in terms of geriatric care. Therefore, identifying determinants of healthy longevity and developing targeted interventions and guidelines are urgently needed to promote healthy aging in China.

The gut microbiota is a key factor associated with healthy longevity (Ghosh et al. 2022). Compared with healthy individuals, older adults and those in poor health exhibit decreased microbial diversity and increased proportions of pathogenic microbes. The composition of the “aging microbiota” changes with age, which not only adversely impacts gastrointestinal digestion and absorption but is also associated with cardiovascular, immune, neurological, and respiratory disorders (Haran and McCormick 2021). After the age of 80, the gut microbiota of centenarians (long-lived population) has been shown to progressively evolve into a distinct composition (Wilmanski et al. 2021), characterized by a decreased abundance of Faecalibacterium and Prevotella and increased abundance of Escherichia, Akkermansia, Clostridium, and Collinsella, compared with the typical gut microbiota of older adults (Kim et al. 2019). Furthermore, this long-lived population reportedly exhibits greater microbial diversity and richness compared with the younger adult population (Kong et al. 2016), suggesting that a higher abundance of beneficial microbes and greater diversity and richness may be key contributors to human longevity and health (Kong et al. 2019).

Accumulated evidence suggests that the gut microbiota influences aging and longevity primarily by regulating inflammatory and metabolic pathways (Buford 2017; Haran and McCormick 2021). These microbes play a critical role in shaping the human immune system (Schluter et al. 2020), with their dysregulation accelerating inflammatory aging, leading to the development of age-related diseases. The gut microbiota of long-lived individuals has been reported to produce secondary bile acids that modulate immune cells and reduce the risk of pathogen infection, thereby contributing to the maintenance of intestinal homeostasis (Sato et al. 2021). Moreover, the gut microbiota of long-lived individuals is better adapted to xenobiotic degradation and can modulate metabolic pathways associated with carbohydrate, amino acid, and lipid metabolism (Rampelli et al. 2020). Notably, the potential of gut microbiota modulation in extending lifespan has been extensively reported (Barcena et al. 2019). Approaches such as probiotic or prebiotic supplementation and microbiota transplantation have been shown to promote the production of beneficial metabolites, enhance the intestinal microenvironment, increase microbial diversity, and decrease inflammation, thereby contributing to delayed aging (Westfall et al. 2018).

In the current study, we collected fecal samples from individuals across three age groups (e.g., ≥ 90 years, 60‒89 years, and 45‒59 years), all of whom were free of any major diseases. Microbial composition and relative abundance were assessed using 16S rRNA sequencing and quantitative PCR (qPCR) to characterize the microbiota profiles of these age groups in the region. By comparing results across age groups, we identified microbial species potentially associated with healthy longevity and constructed a classification model for distinguishing different age groups. Additionally, the mechanisms through which the gut microbiota influence longevity were investigated via functional analysis of 16S rRNA sequencing data.

In this study, we demonstrated that long-lived individuals have a more diverse gut microbiota than older individuals, with diversity levels comparable to those observed in younger adults, consistent with previous findings. Significant differences in the relative abundance and predicted functions of several bacterial phyla and genera were identified across three age groups. Finally, we developed a qPCR-based method to detect differentially abundant microbes and constructed a logistic regression classification model capable of distinguishing between age groups. This model may serve as a promising tool for predicting longevity or evaluating healthy aging.

Bacteroidota was the most abundant phylum in the gut microbiota, demonstrating significantly higher relative abundance in both the longevity and young groups compared with the older group, with no significant difference between the longevity and young groups. An increased abundance of Bacteroidota has been identified as a hallmark of longevity (Pang et al. 2023). At the genus level, the longevity group exhibited significantly higher abundances of Klebsiella and Akkermansia, and lower abundances of Prevotella_9 and Megamonas compared with the older group. Furthermore, Akkermansia may play a role in prolonging longevity (Ioannou et al. 2025; Zeng et al. 2023). Notably, Akkermansia spp. stimulate intestinal epithelial cells to secrete more mucus, thereby increasing the thickness of the mucus layer and protecting against the invasion of pathogens and harmful substances (Mo et al. 2024). Additionally, Akkermansia spp. help maintain intestinal barrier integrity by upregulating the expression of tight junction proteins such as ZO-1 and occludin (Bian et al. 2019). Akkermansia spp. have also been shown to modulate immune responses by influencing immune cell populations (e.g., CD8⁺ T cells) (Ansaldo et al. 2019) and reducing levels of proinflammatory mediators, thereby attenuating both local and systemic inflammation (Zhao et al. 2024). Short-chain fatty acids, such as acetic and propionic acids, produced by Akkermansia spp., not only serve as an energy source for intestinal epithelial cells but also ameliorate metabolic disorders by enhancing insulin sensitivity and regulating glucose metabolism (Rodrigues et al. 2022; Yoon et al. 2021). By exerting these synergistic effects, Akkermansia spp. play a key role in maintaining the integrity of the intestinal mucosal barrier, supporting a balanced gut microbiota, and promoting overall health (Cani et al. 2022). The association between Megamonas, a prominent genus in the gut microbiota of Asian populations, and human diseases remains poorly understood. Preliminary evidence suggests potential associations between inflammatory bowel disease, colorectal cancer, ankylosing spondylitis, obesity, and neurological disorders. However, specific causal relationships and underlying molecular mechanisms warrant further investigation. A reduced relative abundance of Megamonas has been reported in long-lived individuals (Ai et al. 2024). Consistently, our earlier study (Liu et al. 2024) and current findings demonstrate a lower abundance of Megamonas in the longevity group compared with that in the older group. These findings suggest that Megamonas may be detrimental to longevity, although further research is needed to elucidate its biological role. Likewise, Prevotella is reportedly less abundant in long-lived populations (Shi et al. 2022), warranting further investigation into its potential impact on healthy aging.

Regarding pathway enrichment, biosynthesis of unsaturated fatty acids, pyruvate metabolism, synthesis and degradation of ketone bodies, valine, leucine, and isoleucine degradation, and tryptophan metabolism were significantly enriched in the longevity group, whereas nicotinate and nicotinamide metabolism and epithelial cell signaling in H. pylori infection were less enriched, compared with the older group. Unsaturated fatty acids have been reported to extend lifespan (Aiello et al. 2024; Gao et al. 2024; Liu et al. 2025). Monounsaturated fats have been shown to facilitate weight management and glycemic control, while polyunsaturated fats are associated with a reduced risk of cardiovascular disease. Papsdorf et al. (2023) demonstrated that supplementation with cis-monounsaturated fatty acids, such as oleic acid from olive oil, increased the formation of lipid droplets and peroxisomes, which, in turn, contributed to synergistic anti-aging effects and extended lifespan. Lipid droplets store fatty acids and help reduce lipid peroxidation, whereas peroxisomes support metabolic homeostasis by scavenging free radicals (Papsdorf et al. 2023). Our results revealed that ketone body production and degradation were enhanced in the gut microbiota of long-lived individuals. More recently, the beneficial role of ketone bodies as health-promoting metabolites has received growing attention. Beyond serving as a key energy source under low-carbohydrate conditions, ketone bodies reportedly exert anti-aging effects by promoting mitophagy (Puchalska and Crawford 2017). Further research is needed to explore their specific applications across different age groups to facilitate the development of ketone body-based interventions to promote healthy longevity. Multiple amino acid metabolic pathways were upregulated in the longevity group, including tryptophan metabolism, suggesting a potential role in supporting longevity. For instance, the tryptophan-derived metabolite 5-methoxyindoleacetic acid, which is associated with the Christensenellaceae R-7 group, has been implicated in delaying aging, extending lifespan, and reducing inflammation (Qiu et al. 2025).

A major goal of longevity-related microbiome research is to develop reliable methods for predicting healthy aging. Early detection of microbial disturbances or dysbiosis in older adults may facilitate targeted interventions that support healthier aging trajectories. In this cross-sectional study, we identified five genera that effectively distinguish long-lived individuals from typical older adults. Accordingly, we developed a qPCR-based detection method and constructed a logistic regression classification model, which identified long-lived individuals with 82.0% sensitivity, 76.0% specificity, and an AUC of 0.853. Future cohort studies will be conducted to validate the predictive performance of this model through long-term follow-up to establish its clinical utility as a tool for predicting healthy aging.

A key limitation of this study is its cross-sectional design, which enables the identification of associations but does not permit causal inference. Although we observed a significantly reduced relative abundance of Megamonas in the longevity group compared with other age groups, it remains unclear whether this reduction contributes to longevity or if the physiological characteristics of long-lived individuals result in reduced Megamonas abundance.

In summary, we analyzed fecal samples across different age groups and identified a longevity-associated microbiota profile characterized by increased diversity and richness, a marked increase in the relative abundance of Bacteroidota and Akkermansia, along with significantly enhanced metabolism of unsaturated fatty acids, tryptophan, and so on. In addition, we developed a qPCR-based method to detect differentially abundant microbiota and established a classification model capable of distinguishing between longevity and older groups. However, further research is needed to elucidate the specific mechanisms and pathways through which these beneficial microbial genera contribute to longevity and delay aging.

The authors express their gratitude to Editage (https://www.editage.cn/↗) for the expert linguistic services provided.

**YXW**: Writing – original draft, Methodology, Conceptualization. **JL**: Writing – review & editing, Methodology, Conceptualization. **WJW**: Writing – review & editing, Methodology, Data curation. **GFX**: Writing – review & editing, Methodology. **YL**: Writing – review & editing, Methodology. **PXS**: Writing – review & editing, Methodology. **XCZ**: Writing – review & editing, Methodology. **KHZ**: Writing – review & editing, Supervision, Resources, Project administration, Funding acquisition, Conceptualization.

This work was supported by Quzhou Science and Technology Research Project (2023K200).

The raw 16S rRNA sequencing data have been submitted to the SRA database with BioProject ID PRJNA1320995.