Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay.

OBJECTIVE: To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. DESIGN: A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. RESULTS: Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. CONCLUSION: The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. TRIAL REGISTRATION NUMBER: NCT02099032 and NCT02146339; Results.

Milk Polar Lipids Affect In Vitro Digestive Lipolysis and Postprandial Lipid Metabolism in Mice.

BACKGROUND: Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism, but focused studies on postprandial lipemia are lacking. OBJECTIVE: We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro. METHODS: Female Swiss mice were gavaged with 150 µL of an oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. RESULTS: In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 µg/mL vs. 90 µg/mL; P = 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 µg/mL vs. 44 µg/mL; P < 0.05). The opposite was observed after 4 h with lower TGs (21 µg/mL vs. 35 µg/mL; P < 0.01) and NEFAs (20 µg/mL vs. 32 µg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B (Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B (Sar1b), in the duodenum of MPL mice compared with SPL mice (P < 0.05). In vitro, during the intestinal phase, TGs were hydrolyzed more in the MPL emulsion than in the SPL emulsion (decremental AUCs were 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipid absorption and sharper kinetics of lipemia. CONCLUSIONS: Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partly through differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism.

Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial.

Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant's quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.

The effects of Aronia berry (poly)phenol supplementation on arterial function and the gut microbiome in middle aged men and women: Results from a randomized controlled trial.

BACKGROUND AND AIMS: Berry (poly)phenol consumption has been associated with cardioprotective benefits, however little is known on the role the gut microbiome may play on such health benefits. Our objective was to investigate the effects of aronia berry (poly)phenol consumption on cardiometabolic health and gut microbiome richness and composition in prehypertensive middle-aged men and women. METHODS: A total of 102 prehypertensive participants were included in a parallel 12-week randomized double-blind placebo-controlled trial. Volunteers were randomly allocated to daily consume an encapsulated (poly)phenol-rich aronia berry extract (Aronia, n = 51) or a matched maltodextrin placebo (Control, n = 51). Blood pressure (BP) and arterial function (office and 24 h), endothelial function (measured as flow-mediated dilation), serum biochemistry (including blood lipids), plasma and urine (poly)phenol metabolites as well as gut microbiome composition through shotgun metagenomic sequencing were monitored over the study period. Relationships between vascular outcomes, (poly)phenol metabolites and gut microbiome were investigated using an integrated multi-levels approach. RESULTS: A significant improvement in arterial indices measured as augmentation index (AIx) and pulse wave velocity (PWV) was found in the Aronia compared to Control group (awake Δ PWV = -0.24 m/s; 95% CI: -0.79, -0.01 m/s, P < 0.05; 24 h peripheral Δ AIx = -6.8; -11.2, -2.3, %, P = 0.003; 24 h central Δ AIx = -3.3; -5.5, -1.0, %, P = 0.006). No changes in BP, endothelial function or blood lipids were found following the intervention. Consumption of aronia (poly)phenols led to a significant increase in gut microbiome gene richness and in the abundance of butyrate-producing species such as Lawsonibacter asaccharolyticus and Intestinimonas butyriciproducens species, compared to Control group. Results from an approach including metabolomic, metagenomic and clinical outcomes highlighted associations between aronia-derived phenolic metabolites, arterial stiffness, and gut microbiome. CONCLUSIONS: Aronia berry (poly)phenol consumption improved arterial function in prehypertensive middle-aged individuals, possibly via modulation of gut microbiome richness and composition based on the associations observed between these parameters. CLINICAL TRIAL REGISTRY: The National Institutes of Health (NIH)-randomized trial records held on the NIH ClinicalTrials.gov website (NCT03434574). Aronia Berry Consumption on Blood Pressure.

Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women.

BACKGROUNDHigh circulating levels of ceramides (Cer) and sphingomyelins (SM) are associated with cardiometabolic diseases. The consumption of whole fat dairy products, naturally containing such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown.METHODSIn a 4-week randomized controlled trial, 58 postmenopausal women daily consumed milk PL-enriched cream cheese (0, 3, or 5 g of milk PL). Postprandial metabolic explorations were performed before and after supplementation. Analyses included SM and Cer species in serum, chylomicrons, and feces. The ileal contents of 4 ileostomy patients were also explored after acute milk PL intake.RESULTSMilk PL decreased serum atherogenic C24:1 Cer, C16:1 SM, and C18:1 SM species (Pgroup < 0.05). Changes in serum C16+18 SM species were positively correlated with the reduction of cholesterol (r = 0.706), LDL-C (r = 0.666), and ApoB (r = 0.705) (P < 0.001). Milk PL decreased chylomicron content in total SM and C24:1 Cer (Pgroup < 0.001), parallel to a marked increase in total Cer in feces (Pgroup < 0.001). Milk PL modulated some specific SM and Cer species in both ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSIONMilk PL supplementation decreased atherogenic SM and Cer species associated with the improvement of cardiovascular risk markers. Our findings bring insights on sphingolipid metabolism in the gut, especially Cer, as signaling molecules potentially participating in the beneficial effects of milk PL.TRIAL REGISTRATIONClinicalTrials.gov, NCT02099032, NCT02146339.FUNDINGANR-11-ALID-007-01; PHRCI-2014: VALOBAB, no. 14-007; CNIEL; GLN 2018-11-07; HCL (sponsor).

Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets.

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.

Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice.

SCOPE: Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. METHODS AND RESULTS: Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p < 0.05), with larger adipocytes (p < 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p < 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p < 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p < 0.05), and more goblet cells in the colon (p < 0.05). CONCLUSIONS: Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak.