Impact of Multi-metal Mixture Administration Through Drinking Water on the Gut Bacterial Microflora and Oxidative Stress Parameters in Male and Female Mice

Background: Heavy metal containing wastes reaches to the food chain either directly or indirectly. These ingested toxic elements manifest direct impact on the gut ecosystem and its overall functioning. The present study explores the alteration in mice gut bacteria on exposure to mixture of toxic heavy metals through drinking water.  Methods: Twelve experimental groups of Swiss albino male and female mice were exposed to the metal mixture of varying concentrations. Profiling of gut bacterial flora was done by periodical collection of fecal samples via culture-based technique. Redox status of all experimental animals was analyzed in blood samples collected on the day 30. Results: In comparison to the controls, nearly a 10-fold decline in colony forming units/ml was observed at higher modal concentrations (50× & 100×) at the end of 15 days, but 100-fold reduced bacterial count was recorded following 30 days of dosing. Sex specific significant alteration in the bacteria count and diversity was also observed. Overall experimental results showed a heavy metal dose-dependent decline in bacterial count and loss in diversity. Disturbance in the oxidative stress markers was recorded in response to high dose of metal mixture. In group receiving 100× dose, malondialdehyde levels were increased in the erythrocytes (P<0.05), and all of the other antioxidant parameters were decreased (P<0.05), except for reduced glutathione in both male and female mice.  Conclusion: The present work is the first report on the multiple heavy metals induced gut microbiota alterations and its correlation to oxidative stress.