Efavirenz-Altered Gut-Microbiota, Tph1, and Systemic 5-HT Levels: Could They Affect Depression Mechanisms in Mice?

Area of Science:

• Microbiome research
• Neuroscience
• Pharmacology

Background:

• The gut microbiota influences brain function via metabolites like serotonin (5-HT).
• Efavirenz (EFV), an HIV medication, is linked to depression and altered Tryptophan hydroxylase type 2 (Tph2) expression.
• The impact of EFV-induced gut dysbiosis on intestinal Tryptophan hydroxylase type 1 (Tph1) and depression remains unclear.

Purpose of the Study:

• To investigate the role of gut microbiota in depression mechanisms.
• To elucidate the relationship between EFV, gut dysbiosis, intestinal Tph1 expression, and systemic 5-HT levels.

Main Methods:

• CD1 mice were treated orally with EFV (10 mg/kg) for 36 days.
• Gut microbiota composition, short-chain fatty acids (SCFAs), Tph1 expression, and serum 5-HT levels were analyzed.

Main Results:

• EFV treatment altered gut microbiota, decreasing Bacteroidota and Lactobacillus spp. while increasing Bacillota_A_368345, Dubosiella spp., Blautia_A_141780, and Anaerostipes.
• Intestinal Tph1 expression was dysregulated, and serum 5-HT levels decreased.
• Changes in specific bacteria impacted SCFA production, potentially counteracting protective effects of Lactobacillus.

Conclusions:

• EFV-induced gut dysbiosis disrupts the gut-brain axis by altering Tph1 expression and reducing peripheral 5-HT.
• This disruption affects the brain's serotonergic system, potentially contributing to depression.
• Gut microbiota modulation plays a significant role in EFV's depressive side effects.