Abstract
Methamphetamine use disorder (MUD) is a major public health problem worldwide with limited effective treatment options. Previous studies have reported methamphetamine-associated alterations in gut microbiota. A potential role of gut microbiota in regulating methamphetamine-induced brain dysfunction through interactions with the host immune system has been proposed, but evidence for this hypothesis is limited. The present study aimed to investigate the alterations in the fecal microbiota and explore its relationship with systemic inflammation in MUD. Fecal samples were obtained from 26 male subjects with MUD and 17 sex- and age- matched healthy controls. Fecal microbial profiles were analyzed by 16S rRNA sequencing. Plasma inflammatory markers were measured using enzyme-linked immunosorbent assay. Associations between fecal microbiota, systemic inflammatory markers and clinical characteristics were examined by Spearman partial correlation analysis while controlling for possible confounders. Compared with healthy controls, individuals with MUD showed no difference in fecal microbial diversity, but exhibited differences in the relative abundance of several microbial taxa. At the genus level, a higher abundance of Collinsella, Odoribacter and Megasphaera and lower levels of Faecalibacterium, Blautia, Dorea and Streptococcus were detected in subjects with MUD. More importantly, altered fecal microbiota was found to be correlated with plasma levels of CRP, IL-2, IL-6 and IL-10. The order Lactobacillales, exhibiting lower abundance in participants with MUD, was positively related to the duration of methamphetamine abstinence and the plasma level of anti-inflammatory cytokine IL-10. This study is the first to provide evidence for a link between altered fecal microbiota and systemic inflammation in MUD. Further elucidation of interactions between gut microbiota and the host immune system may be beneficial for the development of novel therapeutic approaches for MUD.
Highlights
Methamphetamine (METH), an amphetamine-type stimulant, is the most commonly abused drug in China, with 1.18 million officially registered drug users reporting methamphetamine use, accounting for 55.5% of all drug users nationwide by the end of 2019 (Office of China National Narcotics Control Commission, 2020)
There were no significant differences between the Methamphetamine use disorder (MUD) and Healthy controls (HC) groups in terms of age, body mass index (BMI) and years of education
No difference was observed between the MUD and HC groups regarding the alpha diversity of fecal microbiota, which is in agreement with previously published literature (Cook et al, 2019)
Summary
Methamphetamine (METH), an amphetamine-type stimulant, is the most commonly abused drug in China, with 1.18 million officially registered drug users reporting methamphetamine use, accounting for 55.5% of all drug users nationwide by the end of 2019 (Office of China National Narcotics Control Commission, 2020). Despite of the adverse health consequences and economic burden ascribed to MUD (United Nations Office on Drugs and Crime, 2021), there are currently no FDA-approved pharmacological interventions available for treating MUD and limited evidence for the effectiveness of cognitive-behavioral therapy (Paulus and Stewart, 2020), highlighting the urgent need for more effective treatment options. The alteration of Akkermansia has been identified to be associated with the rat’s behavioral response to METH in a conditioned place preference (CPP) model (Yang C. et al, 2021), suggesting a possible role of gut microbiota in modulating METH-induced behavior and vulnerability to MUD. Another study involving 16 male methamphetamine abusers and 14 healthy subjects reported alterations in gut microbiota diversity and composition associated with MUD (Yang Y. et al, 2021). This study was limited by a relatively small sample size and inablility to adjust for possible confounders, highlighting the need for additional investigation
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