Metabolic cooperation supports mutual growth between the protozoan parasite Trichomonas vaginalis and dysbiotic vaginal bacteria.

The protozoan parasite Trichomonas vaginalis, the causative agent of trichomoniasis, is frequently associated with dysbiotic vaginal microbial communities characteristic of bacterial vaginosis (BV). While previous studies have shown that vaginal bacteria can modulate parasite pathogenicity, the metabolic basis underlying this ecological association remains unclear. Here, we investigated whether T. vaginalis and BV-associated bacteria (BVAB) engage in metabolic cooperation that could support their coexistence. Using in vitro co-culture systems, we examined microbial growth under defined nutrient conditions and integrated metabolomic profiling with targeted transcriptional analysis to characterize metabolic interactions between partners. In serum-free defined medium that does not support proliferation of either microorganism alone, T. vaginalis and BVAB exhibited mutualistic growth, indicating that they engage in cooperative metabolic interactions to overcome shared nutritional limitations. Gas chromatography-mass spectrometry revealed a coordinated metabolic shift toward amino acid catabolism during co-culture, with prominent accumulation of ornithine and putrescine linking the arginine dihydrolase (ADH) pathway to polyamine synthesis. Gene expression analyses showed strong upregulation of the parasite carbamate kinase gene during co-culture, implicating enhanced ADH pathway activity in this interaction. Inhibition of polyamine biosynthesis partially impaired the cooperative growth of both microorganisms, further supporting the importance of this metabolic axis. Together, these findings provide experimental evidence that cross-kingdom metabolic cooperation can reciprocally support infection and dysbiosis, highlighting how parasite-microbiome interactions can reshape metabolic networks to overcome environmental constraints and promote their persistence within host-associated microbial ecosystems.