Mediterranean diet component oleic acid increases protective lipid mediators and improves trabecular bone in a Porphyromonas gingivalis inoculation model

Abstract

Aim Therapeutic modulation of bacterial‐induced inflammatory host response is being investigated in gingival inflammation and periodontal disease pathology. Therefore, dietary intake of the monounsaturated fatty acid (FA) oleic acid (OA (C18:1)), which is the main component of Mediterranean‐style diets, and saturated FA palmitic acid (PA (C16:0)), which is a component of Western‐style diets, was investigated for their modifying potential in an oral inoculation model of Porphyromonas gingivalis. Materials and Methods Normal‐weight C57BL/6‐mice received OA‐ or PA‐enriched diets (PA‐ED, OA‐ED, PA/OA‐ED) or normal standard diet for 16 weeks and were inoculated with P. gingivalis/placebo (n = 12/group). Gingival inflammation, alveolar bone structure, circulating lipid mediators, and in vitro cellular response were determined. Results FA treatment of P. gingivalis‐lipopolysaccharide‐incubated gingival fibroblasts (GFbs) modified inflammatory activation, which only PA exacerbated with concomitant TNF‐α stimulation. Mice exhibited no signs of acute inflammation in gingiva or serum and no inoculation‐ or nutrition‐associated changes of the crestal alveolar bone. However, following P. gingivalis inoculation, OA‐ED improved oral trabecular bone micro‐architecture and enhanced circulating pro‐resolving mediators resolvin D4 (RvD4) and 4‐hydroxydocosahexaenoic acid (4‐HDHA), whereas PA‐ED did not. In vitro experiments demonstrated significantly improved differentiation in RvD4‐ and 4‐HDHA‐treated primary osteoblast cultures and reduced the expression of osteoclastogenic factors in GF. Further, P. gingivalis infection of OA‐ED animals led to a serum composition that suppressed osteoclastic differentiation in vitro. Conclusions Our results underline the preventive impact of Mediterranean‐style OA‐EDs by indicating their pro‐resolving nature beyond anti‐inflammatory properties.

Immunometabolic capacities of nutritional fatty acids in regulation of inflammatory bone cell interaction and systemic impact of periodontal infection

“…Recent findings have described OA-ED as pro-resolving by enhancing serological RvD4 and 4-HDHA levels. Besides being pro-resolving, these lipid mediators reduced Tnfα -expression in gingival fibroblasts (GFb), which, downstream, could impact the microenvironment and reduce osteoclastic differentiation in GFb-co-cultures ( 27 ). Decreased osteoclast numbers in P. gingivalis -infected animals on OA-ED suggested that OA-intake actively impacts cells and their surrounding by advancing resolution, thereby improving bone microarchitecture in the oral cavity ( 27 ) and modifying cellular response to oral P. gingivalis inoculation in systemic bone.…”

“…After one initial week of acclimatization, 4-week-old male C57BL/6 wildtype mice were randomly divided into groups (n=12/group) and put on either PA or OA-enriched diets (PA-ED, OA-ED) (21% calories from fat) (Ssniff, Soest, Germany) or a standard diet (ND) (11% calories from fat) for a total of 16 weeks as described before ( Table S1 ) ( 27 ). Animals were assigned blinded number codes, which were used throughout the experiment.…”

“…P. gingivalis W50 ( 33 ) (American Type Culture Collection (ATCC53978) (Manassas, VA)) was grown in defined medium as described before ( 33 ) and administered via oral gavage at week 10 of FA-enriched diet feeding (n=12/group). Oral inoculation was performed as described previously ( 27 ). Briefly, animals received 0.1 mg/ml enrofloxacin over their drinking water for 4 days and were infected with 109 cfu P. gingivalis in 50 µl of 2% methylcellulose in PBS three times a week over a period of 5 weeks then compared to the methylcellulose-treated placebo group (‘control’).…”

“…This underlines the clinical significance and role of systemic comorbidities as enhancers of immunometabolic pathways that determine tissue homeostasis and shape bone morphology ( 27 ). Dietary substitution of PA-ED with OA-ED increased circulating C18:1 levels and reduced the number of periodontal ligament (PdL)-surrounding alveolar bone lacunae, thereby improving alveolar bone morphology ( 27 ). Furthermore, substituted OA-ED increased bone levels of the stress-reducing phospholipid 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) (PI(18:1/18:1)), a lipokine that is derived from mono-unsaturated FAs via SCD-1-activity and is involved in cell homeostasis and stress response ( 28 ) in response to oral P. gingivalis infection.…”

Advances in the prevention and treatment of Alzheimer’s disease based on oral bacteria

“…It is characterized by a generous consumption of whole grains, fruits, vegetables, legumes, and olive oil while emphasizing moderation in dairy products and alcohol, and limiting meat intake ( 112 ). Animal studies have demonstrated that the primary component of the Mediterranean diet, oleic acid, exhibits remarkable anti-inflammatory properties, and also contributes to the resolution of inflammation, thereby ameliorating tissue damage resulting from the host response to oral bacterial ingestion in mice ( 113 ). Mild cognitive impairment (MCI) represents an early stage of AD pathology and necessitates non-pharmacological interventions, including dietary and nutritional modifications.…”