Infections by parasitic protozoans are largely neglected, despite threatening millions of people, particularly in developing countries. With descriptions of the microbiota in humans, a new frontier of investigation is developing to decipher the complexity of host–parasite–microbiota relationships, instead of the classic reductionist approach, which considers host–parasite in isolation. Here, we review with specific examples the potential roles that the resident microbiota can play at mucosal interfaces in the transmission of parasitic protozoans and in the progress of infection and disease. Although the mechanisms underlying these relationships remain poorly understood, some examples provide compelling evidence that specific components of the microbiota can potentially alter the outcomes of parasitic infections and diseases in humans. Most findings suggest a protective role of the microbiota, which might lead to exploratory research comprising microbiota-based interventions to prevent and treat protozoal infections in the future. However, these infections are often accompanied by an unbalanced microbiota and, in some specific cases, apparently, these bacteria may contribute synergistically to disease progression. Taken together, these findings provide a different perspective on the ecological nature of protozoal infections. This review focuses attention on the importance of considering polymicrobial associations, i.e., parasitic protozoans and the host microbiota, for understanding these human infections in their natural microbial context.

Lactobacilli can modulate adhesion of T vaginalis by significantly modifying the natural adhesive properties of various T vaginalis strains. This study highlights the importance of considering the role of the vaginal microbiota in the pathogenesis of trichomoniasis.

The human protozoan Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection, which is accompanied by a species-diversified vaginal microbiota named community state type IV (CST-IV). Coincidently, CST-IV includes species associated with bacterial vaginosis (e.g. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia). Both diseases are linked to the transmission of human immunodeficiency virus (HIV) and preterm birth, which complications are likely to result from the disruption of the cervicovaginal epithelial barrier. Here, we show that paracellular permeability of fluorescein isothiocyanate (FITC)-dextran through a monolayer of human ectocervical cells (hECs) is increased as a consequence of the activity of T. vaginalis and the aforementioned species of CST-IV bacteria cooperatively. T. vaginalis enhances paracellular permeability of hECs two times more than the individual bacterial species, by up to ∼10% versus ∼5%, respectively. However, any two or all three bacterial species are capable of synergizing this effect. T. vaginalis and the bacteria together increase the paracellular permeability of hECs by ∼50%, which is 5 to 10 times more than the results seen with the protozoan or bacteria alone. This effect is accompanied by enhancement of phosphatase activity, while phosphatase inhibition results in preservation of the integrity of the ectocervical cell monolayer. In addition, these microorganisms induce changes in the expression of tight junction proteins, particularly occludin, and of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Together, our findings establish that cooperative interactions between CST-IV bacteria and T. vaginalis enhance the paracellular permeability of the cervicovaginal epithelium by disturbing the integrity of the tight junction complex. Our study results highlight the importance of understanding the contribution of the vaginal microbiota to trichomoniasis.

Trichomoniasis, a prevalent sexually transmitted infection, is commonly symptomatic in women. The causative agent is , an extracellular protozoan parasite. The host-protective mechanisms and molecules of vaginal lactobacilli that counteract this pathogen are largely unknown. This study examines the inhibition promoted by against the adhesion of to host cells, a critical virulence aspect of this pathogen. We observed that the vaginal strain ATCC 9857 is highly inhibitory by various contact-dependent mechanisms and that surface proteins are largely responsible for this inhibitory phenotype. We found that the aggregation-promoting factor APF-2 from these bacteria significantly contributes to inhibition of the adhesion of to human vaginal ectocervical cells. Understanding the molecules and mechanisms used by lactobacilli to protect the host against might help in the development of novel and specific therapeutic strategies that take advantage of the natural microbiota.