Probiotic Supplementation Reduces Inflammatory Profiles But Does Not Prevent Oral Immune Perturbations During SIV Infection

IV/SIV infections lead to a massive loss of mucosal CD4+ T cells and a breakdown of the integrity of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression can result in significant microbial and neoplastic co-morbidities, and can also contribute to and predict distal disease complications elsewhere. Innate lymphoid cells type 3 (ILC3) produce IL-17 and IL-22 and are vital for maintaining the integrity of the GI epithelium, mediating mucosal antimicrobial defense and stability of commensal microflora, but others and we have recently shown systemic alterations in ILC3 numbers and functions in the oral, reproductive and gastrointestinal mucosae. In this study we evaluated the effects of oral probiotic supplementation, which can stimulate and augment multiple inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4+ T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in the context of SIV infection, we also observed significant modulation among two genera, Porphyromonas and Actinobacillus, early after infection. Interestingly, although Pbx therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in the oral microbiome and CD4+ T cell populations, and also suggest that oral Pbx could be a simple therapy to improve anti-inflammtory states in the setting of more traditional antivirals.