Paired oral clinical specimens reveal the underlying ecology supporting the emergence of inflammophilic microbiome communities.

Across human mucosal sites, dysbiotic inflammatory diseases are characterized by compositional shifts in the resident microbiota, in which commensal-dominated communities give way to pathobiont-enriched communities where "inflammophilic" species often predominate. Effective treatments for these complex polymicrobial infections remain limited, in part, because the ecological mechanisms driving their emergence and persistence are still poorly understood. To address this gap, we analyzed a unique cohort of pediatric patient-matched, disease-free dental plaque and odontogenic abscess specimens, providing a clinically relevant model to examine microbiome transitions from commensal to inflammophilic states. Using complementary community ecology modeling approaches and inferred metagenomic analyses, we identified microbial taxa and functional programs associated with inflammatory selective pressure and dysbiotic community emergence. Dental plaque communities are characterized by anabolic metabolic processes and carbohydrate-derived ATP generation, whereas abscess microbiomes are highly biased for catabolic metabolism, amino acid-derived ATP generation, and antimicrobial resistance. The results suggest that abscess communities are much less reliant upon interspecies metabolic complementation compared to dental plaque communities, which would imply an obligate dependence upon host inflammatory responses to provide the key metabolites required for growth. These findings support a model in which an inflammophilic community ecology is largely the net result of a combination of enhanced resistance to innate immunity and compatibility with the inflammatory nutrient environment. By defining the metabolic requirements and selective pressures governing these dysbiotic transitions, it may be possible to suppress inflammatory dysbiotic diseases using ecologically focused therapeutic strategies that exploit the limited biosynthetic capacity of commensal depleted inflammophilic communities.IMPORTANCEDysbiotic inflammatory diseases are frequently sustained by complex microbial community interactions, but the ecological processes involved remain poorly understood. In this study, we leveraged pediatric patient-matched, disease-free dental plaque and odontogenic abscess clinical specimens to examine how oral microbial communities shift from health-associated to inflammation-associated states. We found that abscess microbiomes are enriched for features consistent with adaptation to inflammatory environments, including antimicrobial resistance, catabolic metabolism, and utilization of host-derived nutrients. These findings support a model in which host inflammation functions as a selective ecological pressure, favoring the establishment of metabolically specialized, inflammophilic microbial communities. By defining the ecological and functional features that distinguish abscess-associated communities from disease-free plaque microbiota, this work provides a framework for understanding inflammatory dysbiosis and for developing ecological strategies to disrupt pathobiont-enriched communities while promoting the restoration of stable, health-associated microbiota.