Foodborne Carbon Dots-Induced Gut Microbiota Dysbiosis Lead to Reproductive Toxicity in Male Mice

Background: Increasing concerns have arisenabout the chronic ingestion of fluorescent carbon dots (CDs) in food and their impact on male fertility. This investigation focused on the effects of CDs on the gut-testis axis, particularly on dysbiosis of the gut microbiota and consequent reproductive health implications. Results: Carbon dots isolated from commercial cola were subjected to a 15-week study, revealing significant impairments in sperm function, including decreased sperm acrosome function and DNA integrity. Transcriptomic insights link the observed reproductive toxicity to alterations in the IL-17 signaling pathway and disruptions in fatty acid and tryptophan metabolism, suggesting a bacterial origin. Notably, metagenomic analyses revealed a shift in the gut microbiota composition, marked by an increase in the abundance oflipopolysaccharide-producing bacteria and a decrease in the abundance of beneficial, anti-inflammatory probiotics such as Bacteroides acidifaciens and Akkermansia muciniphila . This microbial imbalance prompts increased lipopolysaccharide (LPS) production, leading to intestinal barrier damage and systemic inflammation. Furthermore, disruptions in tryptophan metabolism, as evidenced by diminished levels of indole and kynurenine, were linked to an exacerbated inflammatory state and barrier dysfunction. Collectively, these findings elucidate a mechanism by which foodborne CDs trigger reproductive toxicity, beginning with gut microbiota dysbiosis, increasing systemic inflammation, and culminating in metabolic and reproductive disruption. Conclusions: Our study highlights the significant role of the gut microbiota in reproductive toxicity induced by chronic consumption of foodborne CDs, identifying the gut-testis axis as a critical mediator. These insights advocate for interventions targeting the gut microbiota balance to mitigate the reproductive health risks associated with foodborne nanoparticles.