The microbiota as a modulator of mucosal inflammation and HIV/HPV pathogenesis: From association to causation

Abstract

Although the microbiota has largely been associated with the pathogenesis of viral infections, most studies using omics techniques are correlational and hypothesis-generating. The mechanisms affecting the immune responses to viral infections are still being fully understood. Here we focus on the two most important sexually transmitted persistent viruses, HPV and HIV. Sophisticated omics techniques are boosting our ability to understand microbiota-pathogen-host interactions from a functional perspective by surveying the host and bacterial protein and metabolite production using systems biology approaches. However, while these strategies have allowed describing interaction networks to identify potential novel microbiota-associated biomarkers or therapeutic targets to prevent or treat infectious diseases, the analyses are typically based on highly dimensional datasets —thousands of features in small cohorts of patients—. As a result, we are far from getting to their clinical use. Here we provide a broad overview of how the microbiota influences the immune responses to HIV and HPV disease. Furthermore, we highlight experimental approaches to understand better the microbiota-host-virus interactions that might increase our potential to identify biomarkers and therapeutic agents with clinical applications.

The Vaginal Microbiome Changes During Various Fertility Treatments

“…The persons with a deteriorated microbiome during treatment were found to be more frequently smokers and/or tested positive for HPV (human papillomavirus). The correlation between HPV infections and abnormal microbiota has already been reported in literature before [ 14 ]. Healthier lifestyle might have a positive impact on the microbiome.…”

The microbiome as a biomarker of anal precancerous lesions in people with HIV

“…Dysbiosis promotes impaired immune regulation and reduced mucosal integrity, creating a permissive environment for HPV infection and progression. It can also cause an inhibition of the antiviral immune response through cytokine dysregulation (including IL-1β, IL-6, IL-10, and TGF-β), supporting HPV persistence [33–39,40 ▪ ]. Furthermore, changes in microbial metabolites such as short-chain fatty acids, polyamines, and other bioactive molecules can impact epithelial cell function and immunity, promoting HPV-induced carcinogenesis (Fig.…”

“…Compositional and functional changes of microbial communities induced by HIV infection are characterized by an increase of active microorganisms, and different associated pathways related to immune modification and intestinal and systemic inflammation have been described [51,52], including decreased amino acid catabolism, induction of indolamine-2,3-dioxygenase-1 (IDO1), decreased butyrate-producing bacteria, and accumulation of inflammatory molecules [40 ▪ ]. The correlation between different markers of intestinal damage and microbial-induced immune activation suggests that HIV-associated dysbiosis, even in treated individuals, is a relevant driver of systemic inflammation [53–55].…”

“…In conclusion, although significant advances are improving the knowledge of HPV-microbiome interactions, we still need a better understanding of the specific mechanisms by which the microbiota influences HPV pathogenesis and modulates cancer development [40 ▪ ].…”