For decades, bacteria were primarily regarded as hostile invaders—culprits behind infectious diseases that threatened human health. Yet, modern science has revolutionized this perspective, unveiling the complex, and often beneficial, relationships between humans and the microorganisms inhabiting their bodies. Chief among these microbial communities is the gut microbiome, a bustling ecosystem of bacteria and other microbes residing in the gastrointestinal tract. The gut microbiome’s influence on overall health and disease has dominated recent research and public conversations alike, revealing its role in digestion, immunity, and even mental health. However, another microbial environment, nestled at the outset of the digestive tract, has remained considerably underexplored: the oral microbiome.
The human mouth harbors the second most diverse microbial community in the body, second only to the gut. This vast microbial ecosystem is unique because it exists at the doorstep to the external world, constantly exposed to foods, drinks, airborne particles, and fluctuating environmental conditions. Despite its pivotal position and complexity, oral microbial studies have lagged, overshadowed by the gut microbiome’s prominence. Yet, a team of researchers led by Modupe O. Coker from Penn Dental Medicine is challenging this imbalance. By investigating how HIV infection and exposure shape the oral microbiome in children, their groundbreaking work invites a reevaluation of how we view microbiome stability and health dynamics.
The study zeroes in on supragingival plaque—the bacterial communities residing above the gum line—collected from Nigerian children living with HIV, children perinatally exposed to HIV but uninfected, and children entirely unexposed and uninfected. Each group was sampled at three different time points, enabling the researchers to track how oral microbial communities evolved or shifted over time. Notably, children living with HIV were undergoing highly active antiretroviral therapy (HAART), a factor that intertwined viral control with microbiome alterations.
Traditionally, microbiome stability, or the degree to which the microbial community remains consistent over time, has been championed as vital for health, particularly in the gut. In gastrointestinal studies, low taxonomic turnover—a term describing the degree of change or divergence in microbial populations over time—is associated with resilience and balanced digestion. However, the findings emerging from this oral-focused study upend this notion. Here, children unexposed and uninfected by HIV exhibited higher taxonomic turnover in their supragingival microbiomes, implying a more dynamic and fluctuating microbial community. Conversely, those living with HIV or exposed to the virus demonstrated more stable, less changing microbiomes.
This counterintuitive observation suggests that in the oral cavity, stability does not equate to health. Rather, a healthy oral microbiome appears to require adaptability and fluctuation, features stifled in children affected by HIV. This diminished dynamism may compromise the oral microbiome’s capacity to respond to constant environmental perturbations—whether introduced by diet, hygiene, or immune challenges—potentially impairing its functional efficiency and ecosystem balance. Allison E. Mann, an anthropologist and lead author on the study, remarks that the mouth, unlike the relatively protected gut, has evolved its microbiome for constant flux, adapting rapidly to changing external stimuli.
The physiological context of the study participants illuminates these findings further. Adolescence is a critical time of biological transformation, involving developmental and hormonal shifts, as well as mixed dentition—the presence of both primary and permanent teeth. Such transitions naturally drive changes in the oral microbial communities. From this perspective, the lack of expected microbiome fluctuation in children living with HIV signals an impaired adaptability, highlighting how chronic viral infection and treatment may interfere with natural microbial succession and ecosystem health in the mouth.
Moreover, the study draws connections between microbial stability and increased prevalence of cariogenic bacteria—those species known to cause dental caries or cavities. Children with more stable, less volatile microbiomes had higher frequencies of these cavity-associated bacteria, raising their risk for dental caries. This finding adds a critical clinical layer to the microbial data, linking ecological dysfunction in the oral microbiome with tangible health outcomes, an area often overshadowed by systemic concerns in HIV-affected populations.
An additional fascinating aspect uncovered by the research is the spatial homogenization of bacterial communities in children exposed to or infected by HIV. Under normal conditions, the microbiome at the anterior (front) and posterior (back) regions of the mouth exhibits clear differentiation, reflecting localized environmental factors such as saliva flow, nutrient availability, and tissue types. However, this study demonstrated that in HIV-affected children, the distinction between front and back microbial clusters blurs, producing a more homogeneous community. Vincent P. Richards, co-senior author on the study, suggests this may indicate the virus and associated treatments impact the oral glands and ducts differently, potentially altering salivary composition and flow, which are critical for maintaining microbial niches.
The acidic nature of saliva in children living with HIV, coupled with decreased salivary flow reported in previous studies, aligns with this microbial homogenization. Saliva is a major determinant in oral homeostasis, not only by physically clearing microbes but also by buffering pH and delivering antimicrobial peptides. Disruptions in saliva caused by HIV or its treatment may create an environment that undermines the complex spatial and functional structuring of microbial communities, fostering conditions that favor disease-associated bacteria and reduced microbial diversity.
Importantly, the cyclical relationship between systemic and oral health emerges as a central theme throughout this study. As Coker underscores, systemic health shapes oral health just as much as oral microbes can influence systemic disease processes. Early-life disruptions, such as prenatal exposure to HIV, ripple through the microbiome, immune system, and bodily development, underscoring how intertwined our ecosystems truly are. Elucidating these bidirectional pathways holds promise not just for understanding disease progression but also for crafting novel preventative strategies and therapeutic interventions that consider the microbiome as a foundational player.
This research is a striking addition to the growing body of evidence that challenges traditional hypotheses about microbiome function, stability, and human health. The oral microbiome, far from being a static community waiting to be disturbed, is a dynamic arena requiring balance between stability and plasticity. HIV infection and perinatal exposure appear to tilts that balance, locking the microbiome into a less adaptable and potentially harmful state. These insights compel scientists and clinicians alike to rethink treatment and monitoring approaches in HIV-affected populations, particularly pediatric groups, with oral health and microbiome ecology in sharper focus.
Looking ahead, the implications of these findings stretch beyond oral health. They hint at broader systemic consequences given the microbiome’s influence on immunity, metabolism, and even neurological development. Future research integrating microbiology, immunology, epidemiology, and clinical practice could open pathways to tailored microbiome modulation therapies. Such strategies might include nutritional interventions, targeted probiotics, or even microbiome transplants aimed at restoring healthy ecological dynamics, thereby improving both oral and systemic outcomes for vulnerable pediatric populations worldwide.
Ultimately, this study by Coker, Mann, Richards, and their collaborators exemplifies how modern microbiome research transcends traditional boundaries. It reminds us that our microbial partners are not mere passengers but dynamic participants in health and disease, whose intricate ecosystems demand nuanced study. As researchers continue to unravel these complex relationships, the promise of microbiome-informed medicine becomes ever clearer—and more urgent.
Subject of Research: People
Article Title: HIV infection and exposure is associated with increased cariogenic taxa, reduced taxonomic turnover, and homogenized spatial differentiation for the supragingival microbiome
News Publication Date: 16-Jun-2025
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References:
Coker, M. O., Mann, A. E., Richards, V. P., et al. (2025). HIV infection and exposure is associated with increased cariogenic taxa, reduced taxonomic turnover, and homogenized spatial differentiation for the supragingival microbiome. Microbiome. https://doi.org/10.1186/s40168-025-02123-9
Keywords: Dental care, Microbiota, Human immunodeficiency virus, Immune disorders, Saliva, Bacterial populations, Children