Alterations to the Gastrointestinal Microbiome Associated with Methamphetamine Use among Young Men who have Sex with Men

Abstract

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R2 = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes.

Association between CD4+ T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders

“…The gut microbiome of HIV-infected individuals is characterized by enrichment of pro-inflammatory bacterial taxa such as Erysipelotrichaceae , Enterobacteriaceae , Desulfovibrionaceae , and Fusobacteria and depletion of anti-inflammatory taxa such as Lachnospiraceae , Ruminococceae , Bacteroides , and Rikenellaceae [ 6 , 17 , 20 , 28 , 29 ]. Ruminococcaceae family members are the main producers of short-chain fatty acids, which induce the differentiation of anti-inflammatory regulatory T cells [ 20 , 29 ].…”

“…Conversely, the abundance of Veillonellaceae was increased in chronically ART-naïve individuals compared to those with HIV seronegative status [ 19 ]. Moreover, Veillonella abundance was correlated with elevated levels of pro-inflammatory cytokines [ 28 ]. This could explain our finding that CD4/CD8 ratio was negatively correlated with the relative abundance of Veillonellaceae and positively associated with that of Succinivibrionaceae .…”

“…Thirdly, we did not exclude the effects of HIV transmission routes on gut microbiota community composition. The use of methamphetamine and cannabis was found to affect the gut microbiota profile of HIV/AIDS patients [ 28 , 31 , 32 ]. In addition, drug use increased HIV infection and viral replication in immune cells, which accelerated the progression of AIDS [ 33 ].…”

Food insecurity partially mediates the association between drug use and depressive symptoms among men who have sex with men in Los Angeles, California

“…Emerging evidence suggests that substances (e.g. methamphetamine) alter the microbiome, promote inflammation and may even mediate behavioural responses to drugs (71)(72)(73) . Taken together, FI may partially explain the impact of drug use on depression, with a cumulative impact over the life course.…”

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

“…It remains to be determined if the changes in gut microbiota induced by METH have a time effect. A cohort study with 381 men found that the use of METH led to an abnormal increase in proinflammatory gut microbiota, including some bacteria that produce neuroactive substances and those associated with HIV (Cook et al, 2019). Another research conducted by Xu examined the composition and diversity of gut microbiota in 45 patients with substance use disorders, indicating that there seems to be a substance-related change in gut microbiota (Xu et al, 2017).…”