Moxidectin Effects on Gut Microbiota of Wistar-Kyoto Rats: Relevance to Depressive-Like Behavior

The prevalent comorbidity between neuropsychiatric and gastrointestinal (GI) disorders is believed to be significantly influenced by gut microbiota (GM). GM may also play a substantial role in comorbidity between substance abuse (e.g. Alcohol Use Disorder, AUD) and depression. The anti-parasitic drug Moxidectin (MOX) has been reported to reduce alcohol intake in male and female mice. This effect is purported to be centrally mediated with a significant contribution linked to purinergic, P2X4 purinergic receptors. However, MOX's effects on GM in animal models of depression is not known.

Adult male Wistar Kyoto (WKY) rats (5/group) were injected intraperitoneally (i.p.) once daily for 7 days with MOX (2.5mg/kg), or saline as control group. On day 8, approximately 20 h after the last MOX injection, animals were sacrificed, intestinal stools were collected and stored at -80°C DNA was extracted from the samples for 16S rRNA gene-based GM analysis using 16S Metagenomics application.

At taxa and species level, MOX affected a number of bacteria including a 30-fold increase in Bifidobacterium cholerium, a bacterium with a strong ability to degrade carbohydrates that resist digestion in the small intestine. There was a minimum of 2-fold increase in: five probiotic species of Lactobacillus, butyrate-forming Rosburia Facies and Butyrivibro proteovlasticus. In contrast, MOX depleted 11 species, including 2 species of Ruminoccus, which are positively associated with severity of irritable bowel syndrome, and 4 species of Provettela, which are closely associated with depressive-like behavior.

Thus, MOX enhanced probiotic species, and suppressed the opportunistic pathogens. Since overall effect of MOX appears to be promoting GM associated with mood enhancement (e.g. Bifidobacterium and Lactobacillus) and suppressing GM associated with inflammation (e.g. Ruminoccus), potential antidepressant and anti-inflammatory effects of MOX in suitable animal models should be investigated.