BACKGROUND. High circulating levels of ceramides (Cer) and sphingomyelins (SM) have been associated with cardiometabolic diseases. The consumption of whole-fat dairy products, which naturally contain such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown. We investigated how milk PL supplementation impacts circulating and intestinal SM and Cer composition in association with improvement of cardiovascular markers. METHODS. In a 4 week-randomized double-blind controlled study, 58 postmenopausal women consumed daily a cream cheese containing 0, 3 or 5 g of milk PL. Postprandial metabolic explorations were performed before and after the supplementation. SM and Cer species were analyzed in serum, intestine-derived chylomicrons and feces. The ileal content of 4 ileostomy patients was also explored after milk PL intake in a crossover double-blind study. RESULTS. Milk PL consumption decreased serum atherogenic C24:1 Cer (Pgroup = 0.033), C16:1 (Pgroup = 0.007) and C18:1 (Pgroup = 0.003) SM species. Changes in serum C16+18 SM species were positively correlated with the reduction of total cholesterol (r = 0.706, P < 0.001), LDL-C (r = 0.666, P < 0.001) and ApoB (r = 0.705, P < 0.001). Milk PL decreased the concentration in chylomicrons of total SM (Pgroup < 0.0001) and of C24:1 Cer (Pgroup = 0.001). Saturated SM and Cer species, which are also the major species found in milk PL-enriched cheeses, increased in ileal efflux and feces. There was a marked increase in total fecal Cer after milk PL supplementation (Pgroup = 0.0002). Milk PL also modulated the abundance of some specific SM and Cer species in ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut. CONCLUSION. These data demonstrate that milk PL supplementation decreases atherogenic SM and Cer species associated with an improvement of cardiovascular risk markers. Our findings bring new insights on sphingolipid metabolism in the gastrointestinal tract, especially Cer as such signaling molecules potentially participating in the beneficial effect of milk PL. ClinicalTrials.gov, NCT02099032, NCT02146339. FUNDINGS. Agence Nationale de la Recherche, ANR-11-ALID-007-01; Regional Hospital Clinical Research Program (PHRCI-2014: VALOBAB, n°14-007); French Dairy Interbranch Organization (CNIEL); Groupe Lipides et Nutrition (GLN 2018-11-07), Hospices Civils de Lyon as sponsor.
Mélanie Le Barz, Cécile Vors, Emmanuel Combe, Laurie Joumard-Cubizolles, Manon Lecomte, Florent Joffre, Michèle Trauchessec, Sandra Pesenti, Emmanuelle Loizon, Anne-Esther Breyton, Emmanuelle Meugnier, Karène Bertrand, Jocelyne Drai, Chloé Robert, Annie Durand, Charlotte Cuerq, Patrice Gaborit, Nadine Leconte, Annick Bernalier-Donadille, Eddy Cotte, Martine Laville, Stéphanie Lambert-Porcheron, Lemlih Ouchchane, Hubert Vidal, Corinne Malpuech-Brugère, David Cheillan, Marie-Caroline Michalski