Integrated analysis of gut metabolome, microbiome, and brain function reveal the role of gut-brain axis in longevity

ABSTRACT

The role of microbiota-gut-brain axis in modulating longevity remains undetermined. Here, we performed a multiomics analysis of gut metagenomics, gut metabolomics, and brain functional near-infrared spectroscopy (fNIRS) in a cohort of 164 participants, including 83 nonagenarians (NAs) and 81 non-nonagenarians (NNAs) matched with their spouses and offspring. We found that 438 metabolites were significantly different between the two groups; among them, neuroactive compounds and anti-inflammatory substances were enriched in NAs. In addition, increased levels of neuroactive metabolites in NAs were significantly associated with NA-enriched species that had three corresponding biosynthetic potentials: Enterocloster asparagiformis, Hungatella hathewayi and Oxalobacter formigenes. Further analysis showed that the altered gut microbes and metabolites were linked to the enhanced brain connectivity in NAs, including the left dorsolateral prefrontal cortex (DLPFC)-left premotor cortex (PMC), left DLPFC-right primary motor area (M1), and right inferior frontal gyrus (IFG)-right M1. Finally, we found that neuroactive metabolites, altered microbe and enhanced brain connectivity contributed to the cognitive preservation in NAs. Our findings provide a comprehensive understanding of the microbiota-gut-brain axis in a long-lived population and insights into the establishment of a microbiome and metabolite homeostasis that can benefit human longevity and cognition by enhancing functional brain connectivity.

KEYWORDS:

• Gut metabolome
• gut microbiome
• brain function
• gut-brain axis
• longevity

Acknowledgments

Lu Shen and Zhixiang Zhao had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Lu Shen, Bin Jiao, Zhixiang Zhao and Beisha Tang designed the study. The cognitive assessment and fecal sample collection were completed by Qianqian Liu, Tianyan Xu, Meidan Wan, Lu Zhou, Guangrong Ma, Jifeng Guo, and Junling Wang. The acquisition of rs-fNIRS was finished by Ziyu Ouyang. The data was analyzed by Bin Jiao and Ziyu Ouyang. Bin Jiao and Ziyu Ouyang drafted the manuscript. Lu Shen supervised the completion of this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data will be available on request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2331434

Additional information

Funding

Details: This work was supported by the National Natural Science Foundation of China (No. U22A20300, 82071216); STI2030-Major Projects (No.2021ZD0201803); Science and Technology Innovation Program of Hunan Province (No. 2021RC3028); Science and Technology Major Project of Hunan Province (No. 2021SK1020); China Postdoctoral Science Foundation (No. 2022M723554); and Grant of National Clinical Research Center for Geriatric Disorders, Xiangya Hospital (No. 2022LNJJ16).