Yogurt intake and prevention of cardiometabolic diseases: The role of fermentation products

André Marette

Yogurt in Nutrition Initiative (YINI) USA

Buenos Aires, Argentina

October 18, 2017

Obesity and type 2 diabetestake epidemic proportion

White and Marette 2008, Human Kinetics Publishers

Insulin

resistance

T2D

b-cells

CVD

Spreading of

inflammation

Vascular dysfunction

Atherosclerosis

NAFLD

What is the origin of

in obesity-linked cardiometabolic diseases ?

Metabolic

inflammation

LPSmetabolites

gut hormones

nutrients

Adapted from Cani: Nat Rev Endo 2011

Dysbiosis and metabolic endotoxemia

Chassaing B et al, 2015

Microbial encroachment

Thinner mucus layer

Mozaffarian D, et alN Engl J Med. 2011 364(25):2392-404.

Compilation of scientific literature on yogurt and its roles in nutrition and health

Yogurt consumption and healthy habits

Panahi et al. 2017

AdiposityType 2

diabetesHypertension

Cardiovasculardisease

Metabolic syndrome

Cross-sectionalstudies

√ √ √ √ √

Prospective cohort studies

√ √ √ √ √

Meta-analyses(prospective

cohorts)None > 3 None ≥ 1 ≥ 1

Clinical studies Few None None Few None

Level of evidence

Low Strong† Low Moderate Low

Conclusions+ + ? = ?

Level of evidence of the effects of yogurt on cardiometabolic diseases

Systematic review of the association between dairy product consumption and risk of cardiovascular-

related clinical outcomes (Drouin-Chartier et al. 2016)

Yogurt vs type 2 diabetes1. Strong consistent evidence from multiple meta-analyses of

an inverse association between yogurt consumption and type 2 diabetes risk

2. Daily yogurt consumption in the context of a healthy diet may help prevent type 2 diabetes

3. BUT, no RCT; therefore, cannot determine causal link

4. Mechanisms not identified, is it related to:

- specific nutrients (e.g. high protein, dairy fat, calcium…)

- fermentation products and bacteria

- something about the yogurt matrix, or

- only indirect (healthy lifestyle and dietary patterns)

Vitamins and minerals

(calcium and vitamin D)

Protein(whey and casein)

Fermented milk(lactic acid bacteria)

Lipids(bioactive fatty acids)

• Increase satiety and reduce short-term food intake

• Reduced appetite sensations• Increased gastric transit time

• Enhanced calcium transport• Insulintropic• Decrease plasma cholesterol,

triglycerides and fatty acids• ACE inhibitory bioactive peptides (blood

pressure control)

• Improved insulin sensitivity and blood glucose control

• PPAR agonist• Enhanced transport of fat soluble vitamins• Adipocyte cell differentiation inhibition• Anti-inflammatory• Plaque formation inhibition• Anti-obesogenic

• Decreased food intake and increased energy expenditure

• Increased fat-cell oxidation• Increased fat cell breakdown

• Anti-atherosclerotic• Anti-hyperlipidemic

• Normalize glucose tolerance and insulin secretion

• Reduced vascular smooth muscle intracellular calcium (lower blood pressure)

• Improved energy regulation and lipid storage

• Decreased fatty acid synthesis• Increased lipolysis

• Fecal fatty acid excretion• Induction of thermogenesis• Calcium-specific appetite control

• Improved lactose digestion• Improved nutrient bioavailability and

digestion• Increased pH (Bifidobacteria)• Increased concentration of CLA

• Release of bioactive peptides• Increase in lactate : immunomodulation• Maintenance of gut microbiota• Release of microbial-derived products

• B vitamins: folate, riboflavin, B12• Amino acids (eg g-aminobutyric

acid)• Polysaccharides (immune and

prebiotic activies

Yogurt matrix

Adapted from Fernandez et al. Adv Nutr 2017 (In press)

Marco et al. Current Opinion in Biotechnology 2017, 44:94–102

Yogurt and reduced cardiometabolic risk

High quality

protein growth

and maintenance

of muscle mass

Wide range of fatty

acids and lactose

wich provides energy

High quantity of Ca and P main

constituents of bone mineral and

contribute to bone health

Other nutrients (e.g. K, Mg, vit A, B, Zc

essential for health)

Probiotic

bacteria

What are the putative mechanisms of action underlying the beneficial of

fermented milk products on cardiometabolic health ?

small peptides from fermentation with metabolic and CVD effects

• Yogurt peptides could release gut hormones (GLPs) to augment insulin secretion from β-cellsand slow the absorption of nutrients (Jakubowicz and Froy, 2012; Nilsson et al. 2004).

• Some RCTs and meta-analyses showed that some tripeptides derived from dairy proteins can decrease blood pressure possibly through ACE inhibition (Cicero et al. Am J Hypertens 2013;26:442–9; Turpeinen et al. . Ann Med 2013;45:51–6.)

Casein and whey bioactive peptides

Intestinal transit and energy expenditureAmino acid/nutrient release and absorption

Microbiota interaction

Digestive system

Anti-hypertensive by ACE inhibition (angiotensine-converting enzyme)

Vasodilators releaseAnti-thrombotic

Vascular system

Sympathetic nervousactivity

Satiety signals

Nervous system

AnticholesterolemicInsulin sensitivity and

glucose tolerance

Metabolic system

Macrophages stimulationProliferation and maturation

of immune cells

Immune system

Cardiovascular diseasesDiabetesObesity

Fight against cadiometabolic diseases

Fernandez et al. Adv Nutr 2017 (In press)

CONCLUSIONS

▸ Different types of dairy products have specific effects on glucose and lipid metabolism

▸ Fermented dairy products generally exert greater metabolic and anti-inflammatory effects.

▸ These immunometabolic effects are associated with taxonomic changes in the gut microbiota.

▸ Peptides released during fermentation may explain some of the health benefits of yogurt consumption on cardiometabolic diseases.

Collaborators

Université LavalDenis Roy

Yves Pouliot

Sylvie Gauthier

Patrick Mathieu

Jose Luis M. Gonzalez

Agriculture/Agri-Food CanadaMartin Lessard

Mylène Blais

Michaël Bouchard

Université de Sherbrooke

Claude Asselin

TransBioTech

Yvan Boutin

Students/Res. Ass.

Noémie Daniel

Lais Rossi Perazza

Mélanie Le Barz

Geneviève Pilon

Marie-Julie Dubois

Thibault Varin

Philippe St-Pierre

Christine Dion

Christine Dallaire

Valérie Dumais

Joanie Dupont-Morissette

Partners