Simin Lai1, Jing Wang1, Biao Wang1, Rui Wang2, Guodong Li3, Yuwei Jia4, Teng Chen2, Yanjiong Chen5. 1. Department of Immunology and Pathogenic Biology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, People's Republic of China. 2. Forensic Medicine College, Key Laboratory of the Health Ministry for Forensic Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China. 3. National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University College of Medicin, Xi'an, People's Republic of China. 4. Department of Laboratory Medicine, Baoji Maternal and Child Health Hospital, Baoji, People's Republic of China. 5. Department of Immunology and Pathogenic Biology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, People's Republic of China. chenyanjiong@126.com.
Abstract
RATIONALE AND OBJECTIVES: Methamphetamine (METH) is a highly addictive and widely abused drug that causes severe neuroinflammation in the human brain. The gut microbiota has a tremendous impact on the core symptoms of neuropsychiatric disorders via the microbiota-gut-brain (MGB) axis. However, it is not clear whether alterations in the gut microbiota are involved in METH exposure. METHODS: We established a mouse model with chronic, escalating doses of METH exposure. Intervene in gut microbiota with antibiotics to observe the changes of locomotor activity caused by METH exposure in mice. qPCR and 16S rRNA gene sequencing were used to analyze the gut microbiota profiles. In addition, we tested the levels of inflammatory factors in the nucleus accumbens (NAc), prefrontal cortex (mPFC), hippocampus (HIp), and spleen. Finally, short-chain fatty acids (SCFAs) were supplemented to determine the interaction between behavior changes and the structure of gut microbiota. RESULTS: In this research, METH increased the locomotor activity of mice, while antibiotics changed the effect. Antibiotics enhanced the expression of pro-inflammatory cytokines in mPFC, HIp, and spleen of METH-exposed mice. METH altered the gut microbiota of mice after antibiotic treatment, such as Butyricicoccus and Roseburia, which are related to butyrate metabolism. Supplementation with SCFAs changed the behavior of METH-exposed mice and decreased Parabacteroides and increased Lactobacillus in METH-exposed mice gut. CONCLUSIONS: This research showed that antibiotics affected the behavior of METH-exposed mice and promoted inflammation. Our findings suggest that SCFAs might regulate METH-induced gut microbiota changes and behavior.
RATIONALE AND OBJECTIVES: Methamphetamine (METH) is a highly addictive and widely abused drug that causes severe neuroinflammation in the human brain. The gut microbiota has a tremendous impact on the core symptoms of neuropsychiatric disorders via the microbiota-gut-brain (MGB) axis. However, it is not clear whether alterations in the gut microbiota are involved in METH exposure. METHODS: We established a mouse model with chronic, escalating doses of METH exposure. Intervene in gut microbiota with antibiotics to observe the changes of locomotor activity caused by METH exposure in mice. qPCR and 16S rRNA gene sequencing were used to analyze the gut microbiota profiles. In addition, we tested the levels of inflammatory factors in the nucleus accumbens (NAc), prefrontal cortex (mPFC), hippocampus (HIp), and spleen. Finally, short-chain fatty acids (SCFAs) were supplemented to determine the interaction between behavior changes and the structure of gut microbiota. RESULTS: In this research, METH increased the locomotor activity of mice, while antibiotics changed the effect. Antibiotics enhanced the expression of pro-inflammatory cytokines in mPFC, HIp, and spleen of METH-exposed mice. METH altered the gut microbiota of mice after antibiotic treatment, such as Butyricicoccus and Roseburia, which are related to butyrate metabolism. Supplementation with SCFAs changed the behavior of METH-exposed mice and decreased Parabacteroides and increased Lactobacillus in METH-exposed mice gut. CONCLUSIONS: This research showed that antibiotics affected the behavior of METH-exposed mice and promoted inflammation. Our findings suggest that SCFAs might regulate METH-induced gut microbiota changes and behavior.
Authors: Javier A Bravo; Paul Forsythe; Marianne V Chew; Emily Escaravage; Hélène M Savignac; Timothy G Dinan; John Bienenstock; John F Cryan Journal: Proc Natl Acad Sci U S A Date: 2011-08-29 Impact factor: 11.205