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Published on: May 2, 2018
Methamphetamine induces intestinal injury by altering gut microbiota and promoting inflammation in mice
Li-Bin Wang1, Ling-Ling Xu1, Li-Jian Chen2
1Department of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), No. 1838 North Guangzhou Road, 510515 Guangzhou, China.
Abstract:
Methamphetamine (METH) is a psychostimulant abused worldwide. Its abuse induces intestinal toxicity. Moreover, the gut microbiota is altered by drugs, which induces intestinal injury. Whether gut microbiota mediates METH-induced intestinal toxicity remains to be validated. In the present study, wild-type and TLR4-/- mice were treated with METH. Gut microbiota was determined using 16S rRNA gene sequencing. Transcriptomics of the intestinal mucosa was performed by RNA-Sequencing. Blood levels of pro-inflammatory cytokines and lipopolysaccharide (LPS), the intestinal barrier, and inflammation were also assessed. METH treatment weakened the intestinal barrier and increased pro-inflammatory cytokines and LPS levels in the blood. Moreover, METH treatment significantly decreased the diversity of probiotics but increased the abundance of pathogenic gut microbiota, contributing to the over-production of LPS and disruption of intestinal barrier. Inflammatory pathways were enriched in the intestinal mucosa of METH-treated mice by KEGG analysis. Consistently, activation of the TLR4 pathway was determined in METH-treated mice, which confirmed intestinal inflammation. However, pretreatment with antibiotics or Tlr4 silencing significantly alleviated METH-induced gut microbiota dysbiosis, LPS over-production, intestinal inflammation, and disruption of the intestinal barrier. These findings suggested that the gut microbiota and LPS-mediated inflammation took an important role in METH-induced intestinal injury. Taken together, these findings suggest that METH-induced intestinal injury is mediated by gut microbiota dysbiosis and LPS-associated inflammation.
Insights
Methamphetamine (METH) abuse harms the gut by altering microbiota and increasing inflammation. Gut bacteria and lipopolysaccharide (LPS) drive METH-induced intestinal injury.
Area of Science:
- Gastroenterology
- Microbiology
- Toxicology
Background:
- Methamphetamine (METH) abuse is a global issue with known intestinal toxicity.
- Drug-induced alterations in gut microbiota can lead to intestinal injury.
- The role of gut microbiota in mediating METH-induced intestinal toxicity requires further investigation.
Purpose of the Study:
- To investigate the role of gut microbiota and Toll-like receptor 4 (TLR4) signaling in METH-induced intestinal toxicity.
- To elucidate the mechanisms underlying METH-induced gut dysbiosis and inflammation.
Main Methods:
- Mice were treated with METH, and gut microbiota was analyzed using 16S rRNA gene sequencing.
- Intestinal mucosa transcriptomics was performed via RNA-Sequencing.
- Levels of pro-inflammatory cytokines, lipopolysaccharide (LPS), intestinal barrier integrity, and inflammation were assessed.
Main Results:
- METH treatment disrupted the intestinal barrier, increased pro-inflammatory cytokines and LPS, and altered gut microbiota composition.
- METH decreased beneficial probiotics while increasing pathogenic bacteria, leading to LPS over-production.
- Activation of the TLR4 pathway was observed in METH-treated mice, indicating intestinal inflammation.
Conclusions:
- Gut microbiota dysbiosis and LPS-mediated inflammation play a critical role in METH-induced intestinal injury.
- Antibiotic pretreatment or TLR4 silencing mitigated METH-induced gut dysbiosis, inflammation, and barrier disruption.
- Targeting gut microbiota and TLR4 signaling may offer therapeutic strategies for METH-induced intestinal damage.
