Escalating dose-multiple binge methamphetamine treatment elicits neurotoxicity, altering gut microbiota and fecal metabolites in mice

Chen, Lijian; Zhi, Xu; Zhang, Kaikai; Wang, Libin; Li, Jiahao; Liu, Jiali; Xu, Lingling; Yoshida, Jamie Still; Xie, Xing; Wang, Qi

doi:10.1016/j.fct.2020.111946

Cited by 51 publications

(34 citation statements)

References 73 publications

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“…Recent reports have shown that antibiotics positively affect liver injury caused by intestinal bacteria overgrowth, confirming the relationship between intestinal microbiota and liver diseases ( Sajjad et al, 2005 ; Wu et al, 2008 ). Our previous studies have shown that, after METH treatment, intestinal probiotics were decreased and opportunistic pathogens were increased ( Chen et al, 2021 ). Notably, antibiotics used in this study have been proven to affect clearing intestinal flora ( Rakoff-Nahoum et al, 2004 ; Carvalho et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…Mice were randomly divided into four groups with eight per group: control, antibiotic, METH, and antibiotic pretreatment. Briefly, based on the METH model of escalating dose/multiple binge, the doses were as follows ( Chen et al, 2021 ): days 1–2, 1.5 mg/kg; days 3–4, 4.5 mg/kg; days 5–6, 7.5 mg/kg; and days 7–8, 10 mg/kg, four injections a day every 2 h. Mice received antibiotics (vancomycin, 100 mg/kg; neomycin sulfate, 200 mg/kg; metronidazole, 200 mg kg; and ampicillin, 200 mg/kg) and were gavaged once a day for 1 week ( Gregory et al, 2015 ; Hu et al, 2017 ), and the following week, they were simultaneously injected with METH as mentioned above. All mice were deeply anesthetized with pentobarbital (45 mg/kg i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…Intestinal microbiological disorders are crucial for developing liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), cirrhosis, non-alcoholic steatohepatitis (NASH), and viral hepatitis ( Milosevic et al, 2019 ; Albhaisi et al, 2020 ). Our previous studies have demonstrated that METH induces a decrease in the abundance of intestinal probiotics in the gut and increases the conditionally pathogenic bacteria with pro-inflammatory effects ( Chen et al, 2021 ). Using antibiotics in mice liver disease models clearly demonstrates that targeting intestinal flora can alleviate hepatic inflammation by reducing lipopolysaccharide transport to the liver ( Tripathi et al, 2018 ; Mu and Zhu, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Antibiotics Attenuate Methamphetamine-Induced Hepatotoxicity by Regulating Oxidative Stress and TLR4/MyD88/Traf6 Axis

Chen

Pan

et al. 2021

Front. Pharmacol.

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Methamphetamine (METH) is a major psychostimulant drug of abuse worldwide, and its neurotoxicity has been studied extensively. In addition to neurotoxicity, METH can also induce hepatotoxicity. The underlying mechanism of intestinal microorganisms in METH-induced hepatotoxicity remains unclear. In this study, mice have received antibiotics intragastrically or PBS once each day for 1 week, followed by METH or saline. The antibiotics attenuated METH-induced hepatotoxicity as evidenced by histopathological observation and biochemical analysis; furthermore, they alleviated METH-induced oxidative stress. The effect of antibiotics on METH-induced hepatotoxicity was investigated using RNA-sequencing (RNA-seq). The RNA-seq results demonstrated that antibiotics could regulate 580 differentially expressed genes (DEGs), of which 319 were upregulated after METH treatment and then downregulated with antibiotic pretreatment and 237 were first downregulated after METH administration and then upregulated after antibiotic pretreatment, in addition to 11 upregulated and 13 downregulated ones simultaneously in METH and antibiotic-pretreated groups. RNA-seq analyses revealed that TLR4 is one of the hub genes. Western blot analysis indicated that antibiotics inhibited the increase of TLR4, MyD88 and Traf6 induced by METH. This research suggests that antibiotics may play an important role in preventing METH-induced liver injury by regulating oxidative stress and TLR4/MyD88/Traf6 axis, though further investigation is required.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antibiotics Attenuate Methamphetamine-Induced Hepatotoxicity by Regulating Oxidative Stress and TLR4/MyD88/Traf6 Axis

Chen

Pan

et al. 2021

Front. Pharmacol.

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“…Among men who use METH and also have sex with men, the overall composition of the gastrointestinal microbiome was altered 29 . It was reported that METH increased microbial diversity 30 , elevated the pathogenic bacteria 31 and altered the composition of gut bacteria 32 and metabolites in animals 33 . However, the fecal microbiota composition in heterosexual or Asian METH users remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Altered fecal microbiota composition in individuals who abuse methamphetamine

Yang

Liu

et al. 2021

Sci Rep

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As a severe public health problem, methamphetamine (METH) abuse places a heavy burden on families and society. A growing amount of evidence has indicated communication between gut microbiota and the CNS in drug addiction, with associations to neural, endocrine and immune pathways. Thus, we searched for alterations in the gut microbiota and their potential effects in METH users through 16S rRNA gene sequencing. A decreased Shannon index indicated lower bacterial diversity in the METH users than in the age-matched control group. The gut microbial community composition in the METH users was also altered, including reductions in Deltaproteobacteria and Bacteroidaceae abundances and increases in Sphingomonadales, Xanthomonadales, Romboutsia and Lachnospiraceae abundances. Moreover, the Fusobacteria abundance was correlated with the duration of METH use. Enterobacteriaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium had statistically significant correlations with items related to the positive and negative symptoms of schizophrenia and to general psychopathology in the METH users, and all have previously been reported to be altered in individuals with psychotic syndromes, especially depression. Abstraction, one of the items of the cognitive assessment, was positively related to Blautia. These findings revealed alterations in the gut microbiota of METH users, and these alterations may play a role in psychotic syndrome and cognitive impairment. Although the mechanisms behind the links between these disorders and METH abuse are unknown, the relationships may indicate similarities in the pathogenesis of psychosis induced by METH abuse and other causes, providing a new paradigm for addiction and METH use disorder treatment.

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“…In addition, there were already significant differences in gut microbiota before CPP training, which suggested that gut microbiota may be the regulatory factor of METH-induced behavioral abnormalities and differences in sensitivity to METH (Yang et al, 2020). Another study showed that METH exposure increased pathogenic bacteria abundances but reduced the abundance of probiotics (Chen et al, 2021). Angoa found that METH and its analogs caused significant timedependent and structural-dependent changes in the composition of gut microbiota, with Firmicutes and Bacteriodetes having the most significant changes (Angoa-Pérez et al, 2020).…”

Section: Prenatal Meth Exposure and Gut Microbiotamentioning

confidence: 99%

The Adverse Effects of Prenatal METH Exposure on the Offspring: A Review

Liu

Zhang

et al. 2021

Front. Pharmacol.

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Abuse of methamphetamine (METH), an illicit psychostimulant, is a growing public health issue. METH abuse during pregnancy is on the rise due to its stimulant, anorectic, and hallucinogenic properties. METH can lead to multiple organ toxicity in adults, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity. It can also cross the placental barrier and have long-lasting effects on the fetus. This review summarizes neurotoxicity, cardiovascular toxicity, hepatotoxicity, toxicity in other organs, and biomonitoring of prenatal METH exposure, as well as the possible emergence of sensitization associated with METH. We proposed the importance of gut microbiota in studying prenatal METH exposure. There is rising evidence of the adverse effects of METH exposure during pregnancy, which are of significant concern.

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Escalating dose-multiple binge methamphetamine treatment elicits neurotoxicity, altering gut microbiota and fecal metabolites in mice

Cited by 51 publications

References 73 publications

Antibiotics Attenuate Methamphetamine-Induced Hepatotoxicity by Regulating Oxidative Stress and TLR4/MyD88/Traf6 Axis

Antibiotics Attenuate Methamphetamine-Induced Hepatotoxicity by Regulating Oxidative Stress and TLR4/MyD88/Traf6 Axis

Altered fecal microbiota composition in individuals who abuse methamphetamine

The Adverse Effects of Prenatal METH Exposure on the Offspring: A Review

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