Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice

Abstract Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota–gut–brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefit...

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Main Authors: Yujie Zhang, Huijing Liang, Yimie Wang, Ruyue Cheng, Fangfang Pu, Yang Yang, Jinxing Li, Simou Wu, Xi Shen, Fang He
Format: Article
Language:English
Published: BMC 2022-06-01
Series:BMC Neuroscience
Subjects:
Online Access:https://doi.org/10.1186/s12868-022-00724-w
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author Yujie Zhang
Huijing Liang
Yimie Wang
Ruyue Cheng
Fangfang Pu
Yang Yang
Jinxing Li
Simou Wu
Xi Shen
Fang He
author_facet Yujie Zhang
Huijing Liang
Yimie Wang
Ruyue Cheng
Fangfang Pu
Yang Yang
Jinxing Li
Simou Wu
Xi Shen
Fang He
author_sort Yujie Zhang
collection DOAJ
description Abstract Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota–gut–brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefits of heat-inactivated Lacticaseibacillus paracasei N1115 (N1115). Thirty neonatal male mice were randomly divided into three groups and treated with sterilized water (control), an antibiotic cocktail (Abx), or antibiotics plus heat-inactivated N1115 (Abx + N1115) for 84 days. We found that while the mRNA levels of GABAAα1, GABAb1, and glucocorticoid receptor (GR) in the hippocampus and brain-derived neurotrophic factor (BDNF), GABAAα1, GABAb1, and nerve growth factor (NGF) in the prefrontal cortex were higher, the mRNA levels of 5-HT1A were lower in the Abx group. The Abx + N1115 group had lower mRNA levels of GABAAα1, GABAb1, and GR in the hippocampus and BDNF, GABAb1, and NGF in the prefrontal cortex than the Abx group. The latency period was longer in the Morris water maze test while longer rest time was seen in tail suspension test in the Abx group than the control and Abx + N1115 groups. In the open field test, the moving time and distance of the Abx group were reduced. Further, the alpha-diversity indexes of the Abx and Abx + N1115 groups were significantly lower than the control. Further, long-term exposure to antibiotics disrupted the intestinal microbiota as evidenced by decreased Bacteroides, Firmicutes, and Lactobacillus, and increased Proteobacteria and Citrobacter. However, N1115 significantly decreased the abundance of Citrobacter when compared with those in the Abx group. These results indicate that antibiotics can substantially damage the intestinal microbiota and cognitive function, causing anxiety and depression, which can be alleviated by heat-inactivated N1115 via modulation of the microbiota–gut–brain axis.
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spelling doaj.art-9ecb6c01517a4cf2b4044d57d9fb2aad2022-12-22T02:38:18ZengBMCBMC Neuroscience1471-22022022-06-0123111410.1186/s12868-022-00724-wHeat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in miceYujie Zhang0Huijing Liang1Yimie Wang2Ruyue Cheng3Fangfang Pu4Yang Yang5Jinxing Li6Simou Wu7Xi Shen8Fang He9Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Clinical Nutrition, West China Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityAbstract Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota–gut–brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefits of heat-inactivated Lacticaseibacillus paracasei N1115 (N1115). Thirty neonatal male mice were randomly divided into three groups and treated with sterilized water (control), an antibiotic cocktail (Abx), or antibiotics plus heat-inactivated N1115 (Abx + N1115) for 84 days. We found that while the mRNA levels of GABAAα1, GABAb1, and glucocorticoid receptor (GR) in the hippocampus and brain-derived neurotrophic factor (BDNF), GABAAα1, GABAb1, and nerve growth factor (NGF) in the prefrontal cortex were higher, the mRNA levels of 5-HT1A were lower in the Abx group. The Abx + N1115 group had lower mRNA levels of GABAAα1, GABAb1, and GR in the hippocampus and BDNF, GABAb1, and NGF in the prefrontal cortex than the Abx group. The latency period was longer in the Morris water maze test while longer rest time was seen in tail suspension test in the Abx group than the control and Abx + N1115 groups. In the open field test, the moving time and distance of the Abx group were reduced. Further, the alpha-diversity indexes of the Abx and Abx + N1115 groups were significantly lower than the control. Further, long-term exposure to antibiotics disrupted the intestinal microbiota as evidenced by decreased Bacteroides, Firmicutes, and Lactobacillus, and increased Proteobacteria and Citrobacter. However, N1115 significantly decreased the abundance of Citrobacter when compared with those in the Abx group. These results indicate that antibiotics can substantially damage the intestinal microbiota and cognitive function, causing anxiety and depression, which can be alleviated by heat-inactivated N1115 via modulation of the microbiota–gut–brain axis.https://doi.org/10.1186/s12868-022-00724-wAntibioticCognitive functionMicrobiota–gut–brain axisParaprobiotic
spellingShingle Yujie Zhang
Huijing Liang
Yimie Wang
Ruyue Cheng
Fangfang Pu
Yang Yang
Jinxing Li
Simou Wu
Xi Shen
Fang He
Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice
BMC Neuroscience
Antibiotic
Cognitive function
Microbiota–gut–brain axis
Paraprobiotic
title Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice
title_full Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice
title_fullStr Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice
title_full_unstemmed Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice
title_short Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice
title_sort heat inactivated lacticaseibacillus paracasei n1115 alleviates the damage due to brain function caused by long term antibiotic cocktail exposure in mice
topic Antibiotic
Cognitive function
Microbiota–gut–brain axis
Paraprobiotic
url https://doi.org/10.1186/s12868-022-00724-w
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