Studying ancient human oral microbiomes could yield insights into the evolutionary history of noncommunicable diseases

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TL;DR

This review proposes that ancient oral microbiomes, reconstructed from dental calculus, could serve as proxies for noncommunicable disease (NCD) risk in past populations, focusing on cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer's disease. The authors curate modern oral microbiome markers associated with these NCDs and argue that applying similar markers to ancient DNA could reveal previously hidden morbidity and mortality patterns. While significant methodological challenges remain, this approach offers a novel path for understanding how diet, lifestyle, and environmental changes have shaped human health across evolutionary time.

Full summary

4,236 CHARS

**Background:** Noncommunicable diseases (NCDs) are among the leading causes of death worldwide, with seven of the top ten causes of death in 2019 attributed to NCDs, accounting for 44% of all global deaths. Despite their impact, little is known about NCD prevalence in ancient populations because most NCDs leave no distinguishing skeletal traces and are not associated with unique pathogens. The oral microbiome, which can be reconstructed from ancient dental calculus, offers a potential proxy for NCD risk. Dental calculus forms during life as oral microbiota organize into biofilms that calcify, encapsulating microorganisms and other materials. The oral microbiome performs critical systemic functions including pathogen inhibition, immune system training, nutritional absorption, and metabolic uptake enhancement.

**Methods:** This is a narrative review that synthesizes modern literature on associations between the oral microbiome and four NCDs—cardiovascular disease (CVD), diabetes mellitus (DM), rheumatoid arthritis (RA), and Alzheimer's disease (AD)—and proposes a framework for applying these associations to ancient populations. The authors review studies using 16S rRNA sequencing, shotgun sequencing, RTq-PCR, and animal models to identify microbial taxa and functional markers linked to each NCD. They then outline steps for developing predictive risk models from modern populations and validating them against skeletal markers of health (e.g., age-at-death, nonspecific stress markers) in ancient groups.

**Key Results:** For CVD, periodontitis-associated bacteria including P. gingivalis, A. actinomycetemcomitans, T. forsythia, E. corrodens, F. nucleatum, and Campylobacter rectus have been found within atheromatous plaque. Streptococcus species are directly associated with CVD, with some capable of binding to cardiovascular tissues. A meta-analysis of five cohort studies and 86,092 patients found significantly increased prevalence and incidence of coronary heart disease in periodontitis patients. For DM, studies show T2D patients have low rates of Bifidobacterium, significantly less abundant Actinobacteria, and higher Streptococci and Lactobacilli in supragingival plaque. T1D patients show elevated Eubacterium nodatum, higher abundances of Actinobacteria and Firmicutes including Streptococcus, Actinomyces, and Rothia genera. For RA, microbial markers include elevated Veillonella, Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella, and Rothia dentocariosa in dental plaques, with Cryptobacterium curtum emerging as a robust discriminant. For AD, patients show lower microbial richness and diversity, with higher abundance of Moraxella, Leptotrichia, and Sphaerochaeta, and reduced Rothia. Elevated antibodies against periodontitis-associated oral microbes (A. actinomycetemcomitans, P. gingivalis, C. rectus, T. denticola, F. nucleatum, T. forsythia, P. intermedia) have been linked to AD onset and progression.

**Clinical Implications:** This review proposes that oral microbiome markers associated with NCDs in modern populations could be used to develop predictive risk models for ancient populations, enabling researchers to investigate how dietary, lifestyle, and environmental changes (e.g., agricultural revolution, industrialization, colonization) modulated NCD risk over human evolutionary history. The authors note that an analysis of over 127 Medieval and Post-medieval individuals from London found clear associations between systemic health-associated skeletal traits (nonspecific periostitis, joint porosity, osteophytic lipping) and oral microbiome community features. However, significant challenges remain: ancient DNA is highly fragmented and prone to contamination; oral microbiota change over time, so modern associations may not hold for ancient populations; many NCDs have low prevalence (e.g., RA affects approximately 0.41–0.54% of US adults), requiring large sample sizes; and improved age estimations and standardized paleopathological data are needed. The authors conclude that while individual NCD diagnosis in ancient individuals is unlikely, this approach could reveal cryptic elements of frailty associated with microbial mechanisms underlying NCDs.