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New research reveals that oleic acid, abundant in olive oil, protects aging mice from gum infection-induced bone loss and gut microbiome disruption, highlighting how what we eat may help prevent age-related disease.

Study: Mediterranean diet component oleic acid decreases systemic impact of periodontal Porphyromonas gingivalis-infection in age: addressing role of stress resistance and microbiome. Image Credit: Me dia / Shutterstock

In a recent study published in the journal npj Aging, researchers investigated whether dietary intervention alleviates the age-related systemic impact of oral infection with Porphyromonas gingivalis in a mouse model.

Periodontitis is an age-related disease characterized by a hyperinflammatory immune response, systemic inflammation, and shifts in the pathological oral microbiome. Severe periodontal diseases (PDs) affect about 19% of adults worldwide, i.e., over one billion people. PD is a disease of the tissues around the teeth, where plaque and bacterial pathogens accumulate, leading to a heightened inflammatory response and impaired resolution of inflammation.

Comorbidities, such as diabetes, cardiovascular disease, and osteoporosis, can compromise tissue homeostasis at the infection site and lead to increased systemic bone loss. Oleic acid (OA) is a monounsaturated fatty acid, the main component of olive oil and the Mediterranean diet. Serum levels of OA negatively correlate with periodontal tissue loss. In contrast, serum levels of saturated fats, especially palmitic acid (PA), a component of the Western diet, positively correlate with PD.

One study reported that an OA-enriched diet (OA-ED) in mice with periodontal infection improved femoral bone microarchitecture and reduced systemic inflammation and alveolar bone loss compared to mice on a PA-enriched diet (PA-ED). Further, a diet rich in saturated fats is associated with PD progression in older individuals. However, whether aged individuals could benefit from specific nutritional components is unknown.

The study and findings

In the present study, researchers investigated whether nutritional interventions with OA could modulate responses to periodontal infection and protect against systemic effects associated with aging. First, young (five-week-old) and old mice (at least 73 weeks old) were fed a PA-ED, OA-ED, or normal diet (ND) for 16 weeks. Following five weeks of oral P. gingivalis inoculation, alveolar bone crest height was unchanged in young mice.

In contrast, the distance between the alveolar bone crest and the cemento-enamel junction increased by 63% in infected, old mice fed PA-ED compared to their aged OA-ED counterparts. Infection increased bone loss around the periodontal ligament (PDL) in old and young mice on PA-ED compared to those on OA-ED or ND. Furthermore, bone loss in PDL was accompanied by increased osteoclasts in aged, infected mice on PA-ED relative to their aged, OA-ED counterparts.

Next, microbial composition was analyzed in fecal samples one week and eight weeks after diet initiation. After one week, a distinct microbial pattern was observed in PA-ED-fed mice, characterized by increased Lachnospiraceae subtypes and reduced relative abundances of Muribaculaceae and Akkermansia. In contrast, the microbial composition was comparable between old and young mice on ND and OA-ED during the first eight weeks.

Further, mice were treated with an oral antibiotic (enrofloxacin) to evaluate whether dietary intake could modulate microbiome resilience in both age groups. The microbiome of old and young PA-ED-fed animals showed marked changes in taxonomic composition with antibiotic treatment. On the other hand, OA-ED-fed mice, especially young animals, had minor changes in taxonomic composition after antibiotic exposure.

Notably, while the microbiome of animals on ND or OA-ED returned to their pre-antibiosis state during the six-week follow-up, PA-ED-fed mice failed to recover their microbiome from antibiotic-induced shifts. The article notes that P. gingivalis itself was not detected in the gut, indicating that the observed microbiome effects were indirect. Further, the team performed a systemic serum analysis of stress resilience phospholipid indicators to investigate whether OA-ED supports stress response and resilience associated with age and P. gingivalis infection.

PA-ED mice differed in their serum phosphatidylinositol (PI) composition compared to ND and OA-ED mice. Uninfected ND and OA-ED animals showed age-related differences in PI proportions. Conversely, the PI proportion in uninfected PA-ED animals was comparable between old and young animals. However, P. gingivalis infection of old PA-ED-fed mice induced the most pronounced changes in lipidomic composition.

In contrast, infection of old OA-ED or ND mice did not induce marked changes in PI composition relative to their younger counterparts. PA-ED resulted in lower serum levels of the stress-reducing lipokine, PI(18:1/18:1), in both age groups compared to ND or OA-ED. PI(18:1/18:1) is linked to stress resistance, autophagy, and ERK1/2 modulation; however, the precise mechanisms underlying these associations remain under investigation. Moreover, P. gingivalis infection further reduced PI(18:1/18:1) levels in old and young PA-ED-fed mice and young ND-fed mice. By contrast, OA-ED stabilized PI(18:1/18:1) levels in infected young and old mice.

Additional experiments indicated that PA-ED increased osteoclast differentiation and primed bone marrow cells to inflammation, while OA-ED alleviated these effects. Furthermore, osteoblasts showed baseline inflammation and reduced responsiveness to infection in aged mice, promoting a pro-inflammatory microenvironment. PA-ED also increased femoral bone loss in response to infection in old mice.

The study design used only male mice to control for hormonal influences on bone metabolism; this limitation is important for interpreting and translating the results to both sexes. The authors also note that, while the study reveals strong mechanistic associations, further research is required to confirm these findings in humans.

Conclusions

The findings reveal that PA-ED aggravated P. gingivalis-related oral bone loss, especially in aged mice. Systemically, PA-ED destabilized the gut microbiota, elevating susceptibility to disturbances and infection-driven microbial shifts. PA-ED also decreased stress resistance and promoted cellular priming, enhancing osteoclast differentiation in infected mice of both age groups.

Osteoblasts showed baseline age-associated inflammation and reduced responses to infectious stimuli, promoting a pro-inflammatory microenvironment. This was accompanied by increased infection-induced femoral bone loss in old mice on PA-ED. Overall, the results suggest OA-ED is protective by limiting PD-associated systemic and local tissue damage with age. These results are based on preclinical animal models, and their applicability to human disease requires further investigation.