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. 2024 Apr 18;10(8):e29791.
doi: 10.1016/j.heliyon.2024.e29791. eCollection 2024 Apr 30.

Chronically socially isolated mice exhibit depressive-like behavior regulated by the gut microbiota

Linwei Ding  1 , Jiaqi Liu  1   2 , Yunjia Yang  1   3 , Zeying Cui  1 , Guankui Du  1   2   4   5
Affiliations

Chronically socially isolated mice exhibit depressive-like behavior regulated by the gut microbiota

Linwei Ding et al. Heliyon. .

Abstract

Objectives: Chronic loneliness is a widespread issue, and the gut-brain axis is known to be crucial in facilitating communication between the gut and brain. However, the precise mechanism by which chronic loneliness affects the gut-brain axis remains uncertain.

Methods: Fourteen 55-week-old Balb/c mice were used in the experiment, with seven mice being randomly assigned to the chronic social isolation (CSI) group. The CSI group mice underwent 12 weeks of isolation to simulate the psychiatric state of a population in prolonged social isolation. The mental state of the CSI mice was assessed through animal behavior analysis, while plasma cytokines were measured using ELISA. Additionally, the composition of the gut microbiota was analyzed using 16S rRNA sequencing, and the metabolite composition of the intestinal contents was examined using nontargeted metabolomics. The Student-T test was used to determine significant mean differences.

Results: Mice that were exposed to the CSI exhibited increased immobility time lengths in forced swimming and hanging tail experiments, and decreased movement lengths and number of times traversing the intermediate region, compared to control mice. Additionally, CSI decreased the abundance of the probiotics Ruminococcaceae, Akkermansiaceae, and Christensenellaceae. Additionally, CSI reduced the production of the metabolites oleamide and tryptophan. Furthermore, IL-1β, IL-4, and IL-6 were significantly increased, while TNF-α was significantly decreased.

Conclusion: CSI induces a dysbiotic gut microbiota and the production of neurorelated metabolites, which in turn increase inflammatory responses and result in depressive behaviors in CSI mice. Therefore, these findings suggest that the gut microbiota may serve as a target for the treatment of long-term social isolation-induced mental disorders.

Keywords: Depression; Gut microbiota; Inflammatory responses; Metabolite; Social isolation.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Chronic social isolation leads to the development of depression. A. Mice underwent 12 weeks of single-cage housing. Mouse animal behavior was tested. B. FST and C. TST immobility time within 5 min, and D. percentage of time engaged in slow activity.
Fig. 2
Fig. 2
Changes in the composition of the gut microbiota due to chronic social isolation. A. Changes in the composition at the phylum level, especially a decrease in the Firmicutes/Bacteroidetes ratio. B. Changes in the composition at the family level. C. Bacteria with significant changes at the family level.
Fig. 3
Fig. 3
LEfSe analysis of the characteristic bacteria associated with chronic social isolation. A. LEFSe multilevel species hierarchical tree. B. LDA discriminant results.
Fig. 4
Fig. 4
Chronic social isolation leads to changes in the metabolites of the gut microbiota. Among the 30 metabolites, 8 had a higher abundance, and 22 had a lower abundance in the chronic social isolation group.
Fig. 5
Fig. 5
ROC analysis of the gut microbiota metabolites. A. [6]-Gingerdiol 3-acetate, b. DG (16:1n7/0:0/22:4n6), and c. His_Lys_Pro_Trp.
Fig. 6
Fig. 6
Chronic social isolation leads to changes in the levels of some inflammatory factors. A. IL-1, B. TNF-α, C. IL-4, D. IL-6.
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References

    1. Su Y., Rao W., Li M., Caron G., D'Arcy C., Meng X. Prevalence of loneliness and social isolation among older adults during the COVID-19 pandemic, A systematic review and meta-analysis. Int. Psychogeriatr. 2023;35:229–241. - PubMed
    1. Lu J., Zhang N., Wang Y. Quality of life among different types of Chinese lonely elderly: a social isolation based analysis. Psychol. Health Med. 2022;27:1357–1365. - PubMed
    1. Bound Alberti F. This “modern epidemic”: loneliness as an emotion cluster and a neglected subject in the history of emotions. Emot. Rev. 2018;10:242–254.
    1. Hedayati M.M., Khazaei M.M. An investigation of the relationship between depression, meaning in life and adult hope. Procedia-Soc. Behav. Sci. 2014;114:598–601.
    1. Heuser C., Howe J. The relation between social isolation and increasing suicide rates in the elderly. Qual. Ageing. 2019;20:2–9.

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