The DOHaD Theory Applies to Periapical Periodontitis

Objectives: We examined whether the Developmental Origins of Health and Disease (DOHaD) theory applies to oral inflammation. This theory states that the nutritional environment from embryonic to infancy is “epigenetically memorized” and determines disease susceptibility and severity in adulthood.
Methods: C57BL/6 mouse male offspring from mothers fed a high-fat diet (HFD-offspring) throughout the duration of pregnancy and lactation were transitioned to a normal diet upon weaning. At 10-weeks of age, these mice were subjected to experimental endodontic infection with common human endodontic pathogens (S. intermedius, P. micra, P. intermedia, F. nucleatum). The evaluation of periapical inflammation was conducted at 16-weeks of age using microCT and histology, compared to offspring from mothers adhering to a normal diet (ND-offspring). Circulating cytokine level was also determined by ELISA. Body weights were measured before infection and at the endpoint. Student’s t-test was used for statistical analysis.
Results: The rate of weight gained post-infection is significantly higher in HFD-offspring (12.7%) than in ND-offspring (8.8%; p=0.019). HFD-offspring exhibited significantly elevated periapical bone destruction compared to ND-offspring (approx. 1.4-fold; p=0.016); in addition, the HFD-offspring consistently showed apical root resorption, indicating that transient severe inflammation may have occurred during the development of the root apex lesion. The tendency of elevated inflammatory infiltration in HFD-offspring was also confirmed in histology. Circulating IL-6 levels were approximately 2-fold higher in HFD-offspring than in ND-offspring, but these values were not high (20 pg/ml on average), suggesting that a periapical inflammation induces a low-grade systemic inflammation-like state in HFD-offspring.
Conclusions: The findings of this exploratory study suggest that the Developmental Origins of Health and Disease (DOHaD) theory applies to the context of oral inflammation. The presence of maternal obesity during pregnancy and lactation might exert a substantial influence on the vulnerability of offspring to inflammatory conditions, thereby serving as a potential risk factor for oral inflammation.