HIV-Associated Interactions Between Oral Microbiota and Mucosal Immune Cells: Knowledge Gaps and Future Directions

Abstract

Even with sustained use of antiretroviral therapy (ART), HIV-infected individuals have an increased risk of systemic comorbid conditions and oral pathologies, including opportunistic infections, oral mucosal inflammation, and gingival and periodontal diseases. The immune-mediated mechanisms that drive this increased risk, in the context of sustained viral suppression, are unclear. HIV infection, even when controlled, alters microbial communities contributing to a chronic low-grade inflammatory state that underlies these non-HIV co-morbidities. The higher prevalence of dental caries, and mucosal and periodontal inflammation reported in HIV-infected individuals on ART is often associated with differentially abundant oral microbial communities, possibly leading to a heightened susceptibility to inflammation. This mini-review highlights current gaps in knowledge regarding the microbe-mediated oral mucosal immunity with HIV infection while discussing opportunities for future research investigations and implementation of novel approaches to elucidate these gaps. Interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-infected individuals. More broadly, additional research is needed to bolster general models of microbiome-mediated chronic immune activation and aid the development of precise microbiota-targeted interventions to reverse or mitigate adverse outcomes.

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria

“…We and other researcher teams have reported observations of higher levels of ECC in HI compared to uninfected children [4,[13][14][15][16][17][18]]. These higher rates for caries may be due to the higher rates of hyposalivation and hypoplasia observed in PLWH [14] when compared to their uninfected counterparts; compounded by the sustained consumption of sucrose-based (antiretroviral therapy) ART syrups and suspensions, hypoplastic teeth due to the immunological impact of HIV infection [17,18], low salivary flow [19] and cariogenic oral microbiota, including bacterial-fungal components of dysbiosis [20][21][22][23]. In spite of this emerging evidence, there is no clear consensus on whether the impact of perinatal HIV infection on caries risk in the primary dentition persists, diminishes, or accentuates in the permanent dentition.…”

Microbiota in the oral cavity of school-age children living with HIV who started antiretroviral therapy at young ages in South Africa

“…Multiple studies have investigated associations between oral microbiota and HIV status [10]. Oral diseases are more common in persons with HIV, even those on ART, and oral sampling is a convenient and noninvasive method of assembling informative samples for microbiota characterization making this a feasible line of investigation.…”

“…Sampling from the oral cavity is a convenient and accessible method to describe the microbiota profile. Many studies have investigated associations between oral microbiota and HIV status, with most finding shifts in abundances of oral bacterial taxa in adults and children with HIV compared those without [3][4][5][6][7][8][9][10][11].…”

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

“…In the context of HIV infection, microbial-induced immune activation occurs and correlates with markers of intestinal damage, suggesting that the microbiota is a relevant driver of systemic inflammation ( 35 – 41 ). Even the changes appreciated in the oral microbiota of people living with HIV (PLWH), who exhibit an increased prevalence of dental caries and periodontal inflammation, seem to be connected to shifts in systemic immune responses (reviewed in ( 42 )). Specific Lactobacillus species-rich vaginal microbiota have been associated to protection from HIV infection (last reviewed in ( 43 )).…”