Role of microbiota-gut-brain axis in natural aging-related alterations in behavior

Yingli Jing; Qiuying Wang; Fan Bai; Zihan Li; Yan Li; Weijin Liu; Yitong Yan; Shuangyue Zhang; Chen Gao; Yan Yu

doi:10.3389/fnins.2024.1362239

Role of microbiota-gut-brain axis in natural aging-related alterations in behavior

Front Neurosci. 2024 Apr 18:18:1362239. doi: 10.3389/fnins.2024.1362239. eCollection 2024.

Authors

Yingli Jing^#^{1

2}, Qiuying Wang^#^{1

2}, Fan Bai^{1

2}, Zihan Li^{1

2}, Yan Li^{1

2}, Weijin Liu^{1

2}, Yitong Yan^{1

2}, Shuangyue Zhang^{1

2}, Chen Gao^{1

2}, Yan Yu^{1

2}

Affiliations

¹ China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China.
² Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.

^# Contributed equally.

Abstract

Introduction: Aging is a complex, time-dependent biological process that involves a decline of overall function. Over the past decade, the field of intestinal microbiota associated with aging has received considerable attention. However, there is limited information surrounding microbiota-gut-brain axis (MGBA) to further reveal the mechanism of aging.

Methods: In this study, locomotory function and sensory function were evaluated through a series of behavioral tests.Metabolic profiling were determined by using indirect calorimetry.16s rRNA sequence and targeted metabolomics analyses were performed to investigate alterations in the gut microbiota and fecal short-chain fatty acids (SCFAs). The serum cytokines were detected by a multiplex cytokine assay.The expression of proinflammatory factors were detected by western blotting.

Results: Decreased locomotor activity, decreased pain sensitivity, and reduced respiratory metabolic profiling were observed in aged mice. High-throughput sequencing revealed that the levels of genus Lactobacillus and Dubosiella were reduced, and the levels of genus Alistipes and Bacteroides were increased in aged mice. Certain bacterial genus were directly associated with the decline of physiological behaviors in aged mice. Furthermore, the amount of fecal SCFAs in aged mice was decreased, accompanied by an upregulation in the circulating pro-inflammatory cytokines and increased expression of inflammatory factors in the brain.

Discussion: Aging-induced microbial dysbiosis was closely related with the overall decline in behavior, which may attribute to the changes in metabolic products, e.g., SCFAs, caused by an alteration in the gut microbiota, leading to inflammaging and contributing to neurological deficits. Investigating the MGBA might provide a novel viewpoint to exploring the pathogenesis of aging and expanding appropriate therapeutic targets.

Keywords: aging; behaviors deficits; inflammation; microbiota; microbiota-gut-brain axis; short-chain fatty acids.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The present study was funded by the National Natural Science Foundation of China (grant no. 81901272) and the Special Fund for Basic Scientific Research of Central Public Research Institutes (grant no. 2022cz-5 and 2023cz-6).