Mitigation and mechanism of low dose linoleic acid on depression caused by disorder of gut microbiome

ABSTRACT

Objectives

Depression is a widely prevalent mental disorder, and nutritional interventions play an increasingly important role in its treatment. In this paper, effects of linoleic acid (LA) on depressive behavior in mice induced by gut microbiome disorders were investigated.

Methods

Fifty C57BL/6J male mice were randomly separated into five groups, control group (CK), ceftriaxone sodium group (CRO), low-dose linoleic acid group (LLA, 1 g/kg), medium-dose linoleic acid group (MLA, 2 g/kg), and high-dose linoleic acid group (HLA, 5 g/kg). In the LLA, MLA, and HLA groups, mice were treated with ceftriaxone sodium (CRO) to induce depressive behaviors, followed by LA administration. Behavioral tests were used to evaluate depressive behavior. High-throughput sequencing and Hematoxylin–eosin (H&E) staining in gut microenvironment were carried out. ELISA kits were used to measure brain inflammatory factors, and 5-hydroxy-tryptamine (5-HT). Gas chromatography and western blot were used to determine fatty acids compositions and the enzymes expression involved in lipid metabolism in brain respectively.

Results

The results showed that 10 weeks CRO treatment contribute to depressive behavior, gut microbiome disturbance, and serotonin system disturbance. LLA and MLA improved the depressive-like behavior, and significantly increased the levels of 5-HT1A, 5-HTT and 5-HT in the hippocampus. LLA was found to improve the diversity of gut microbiome and alleviate colon tissue damage. Meantime, LLA increased the content of linoleic acid, improved the expression of FADS2 and COX-2, increased IL-10 levels, and decreased IL-6 levels in the brain.

Discussion

LA alleviated depressive behavior in mice by improving the gut microenvironment, regulate fatty acid metabolism, and modulate inflammation.

GRAPHICAL ABSTRACT

KEYWORDS:

• Depression
• linoleic acid
• gut microbiome
• inflammation
• arachidonic acid metabolism
• ceftriaxone sodium
• lipid metabolism
• serotonin system

Acknowledgments

We would like to thank Natural Science Foundation of Zhejiang Province, China (No.LY19C200012).

Disclosure statement

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

Ethics approval statement

The experimental animal materials were reviewed by the Experimental Animals Ethical Committee of Zhejiang University of Technology on 30 August 2021, and it is considered that the project meet the requirement of animal ethics and agrees to declare. The approval number is 20210422028.

Author contributions

Haining Yu: conceptualization, project administration, resources, writing – original draft, writing – review and editing, and Funding acquisition. Yinan Song: formal analysis, validation, visualization, writing – original draft, and writing – review and editing. Maoshan Lou: formal analysis, investigation, methodology, project administration, and writing – original draft. Shengrong Shen: project administration, and resources. All authors have read and approved the final manuscript.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This work was supported by the Natural Science Foundation of Zhejiang Province, China under Grant LY19C200012.

Notes on contributors

Haining Yu

Haining Yu, graduated from Zhejiang University with a Ph.D. in July 2004; postdoctoral fellow at Zhejiang University from August 2004 to March 2006; from March 2006 to now, Associate professor at College of Pharmaceutical Science, Zhejiang University of Technology. Main research fields or directions: Natural products; Active Substances from Marine; Lipid Metabolism; Gut Microbiome and Health.

Yinan Song

Yinan Song, from September 2021 to present, a graduate student in the College of Pharmaceutical Science, Zhejiang University of Technology, majoring in lipid metabolism, gut microbiome and health.

Maoshan Lou

Maoshan Lou, from September 2020 to present, a graduate student in the College of Pharmaceutical Science, Zhejiang University of Technology, majoring in lipid metabolism, gut microbiome and depression.

Shengrong Shen

Shengrong Shen, graduated from department of Biophysics of Zhejiang University with Ph.D. of Biophysics. He is a professor of Zhejiang University from December 2000 to present. Main research fields or directions: Molecular Nutrition; Food Safety and Nutrition; Tea and Phytochemistry; Free Radical Biology.