Abstract
The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.
Highlights
As a chronic and relapsing brain disease [1, 2], heroin addiction is usually characterized by sensitization, dependence, and compulsive drug use [3, 4]
We show that heroin dependence causes substantial changes in the composition of the gut microbiota contributes to pathological changes of intestinal mucosal barrier function
Compared to healthy controls (HCs), heroin addicts have a higher level of diamine oxidase (DAO), ET, and D-lactic acid (DLA) (10.97 ± 3.24 U/L vs. 13.54 ± 3.27 p < 0.0001; 18.22 ± 3.41 U/L vs. 20.83 ± 5.36 U/L p < 0.05; 7.92 ± 4.21 mg/L vs. 10.36 ± 5.01 mg/L p < 0.05; respectively, Table 1)
Summary
As a chronic and relapsing brain disease [1, 2], heroin addiction is usually characterized by sensitization, dependence, and compulsive drug use [3, 4]. The role of gut dysbiosis is considered an essential factor in the development of drug addiction [10, 16]. Gastrointestinal disorders may be accompanied by gut microbiota dysbiosis [17]. The association between gut microbiota and intestinal mucosa barrier function in the context of substance use disorder remains largely unknown. Further investigation is urgently needed to uncover the roles of intestinal microbiota in gastrointestinal symptoms in heroin addicts
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