Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysis

Abstract Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC–MS metabolomi...

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Main Authors: Jing Zhang, Hongmei Xin, Wuji Wang, Yanyi Li, Riga Wu, Lisi Wei, Si Su, Xiaohong Wang, Xiujuan Wang, Xiaojuan Wang, Li Li, Rilebagen Hu
Format: Article
Language:English
Published: Nature Portfolio 2024-09-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-72793-2
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author Jing Zhang
Hongmei Xin
Wuji Wang
Yanyi Li
Riga Wu
Lisi Wei
Si Su
Xiaohong Wang
Xiujuan Wang
Xiaojuan Wang
Li Li
Rilebagen Hu
author_facet Jing Zhang
Hongmei Xin
Wuji Wang
Yanyi Li
Riga Wu
Lisi Wei
Si Su
Xiaohong Wang
Xiujuan Wang
Xiaojuan Wang
Li Li
Rilebagen Hu
author_sort Jing Zhang
collection DOAJ
description Abstract Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC–MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague–Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.
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spelling doaj-art-97ec23b657a44c82bc94ec5d4a1089d82025-08-20T02:56:16ZengNature PortfolioScientific Reports2045-23222024-09-0114111810.1038/s41598-024-72793-2Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysisJing Zhang0Hongmei Xin1Wuji Wang2Yanyi Li3Riga Wu4Lisi Wei5Si Su6Xiaohong Wang7Xiujuan Wang8Xiaojuan Wang9Li Li10Rilebagen Hu11Basic Medical College, Inner Mongolia Medical UniversityCollege of Humanities Education , Inner Mongolia Medical UniversityWuhan Pulmonary Hospital/Wuhan Institute for Tuberculosis ControlSchool of Nursing,Inner Mongolia Medical UniversityMongolian Medicine College , Inner Mongolia Medical UniversityMongolian Medicine College , Inner Mongolia Medical UniversityMongolian Medicine College , Inner Mongolia Medical UniversityLaboratory Animal Center, Inner Mongolia Medical UniversityBasic Medical College, Inner Mongolia Medical UniversityBasic Medical College, Inner Mongolia Medical UniversityBasic Medical College, Inner Mongolia Medical UniversityMongolian Medicine College , Inner Mongolia Medical UniversityAbstract Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC–MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague–Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.https://doi.org/10.1038/s41598-024-72793-2LactoferrinDepressionGut microbiotaMetabolic disordersMicrobiota-gut-brain axis
spellingShingle Jing Zhang
Hongmei Xin
Wuji Wang
Yanyi Li
Riga Wu
Lisi Wei
Si Su
Xiaohong Wang
Xiujuan Wang
Xiaojuan Wang
Li Li
Rilebagen Hu
Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysis
Scientific Reports
Lactoferrin
Depression
Gut microbiota
Metabolic disorders
Microbiota-gut-brain axis
title Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysis
title_full Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysis
title_fullStr Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysis
title_full_unstemmed Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysis
title_short Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC–MS metabolomics analysis
title_sort investigating the modulatory effects of lactoferrin on depressed rats through 16s rdna gene sequencing and lc ms metabolomics analysis
topic Lactoferrin
Depression
Gut microbiota
Metabolic disorders
Microbiota-gut-brain axis
url https://doi.org/10.1038/s41598-024-72793-2
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