WEBINAR Microbial Metabolism Associated with Health. 12 April 2018; CET

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1 WEBINAR Microbial Metabolism Associated with Health 12 April 2018; CET

2 PROGRAMME Brief Introduction of Both Organisations and Scientific Background Dr Bettina Schelkle (ILSI Europe, BE) Dr Karen Scott (University of Aberdeen, UK) Effects of the Intestinal Microbiota on Selected Dietary Components a) Introduction and Background to the Activity Prof. Colette Shortt (Johnson & Johnson, UK) b) Impact of Intestinal Metabolism and Findings Prof. Ian Rowland (University of Reading, UK) Health Benefits of Fermented Foods: Microbiota and Beyond Prof. Robert Hutkins (University of Nebraska, US) Questions and Answers 12 April 2018; CET

3 WEBINAR Microbial Metabolism Associated with Health Health Benefits of Fermented Foods: Microbiota and Beyond Robert Hutkins, University of Nebraska, US 12 April 2018; CEST

4 Conflict of Interest Disclosure Board of Directors, International Scientific Association for Probiotics and Prebiotics (ISAPP) Research funding from companies that sell or use probiotics or prebiotics in their products (Mead Johnson Nutrition, Danone, and Prenexus) Owner/Partner of Synbiotics Solutions, LLC 4

5 Outline Primer on fermentation and fermented foods Diet, microbiota, and gut health Health properties of fermented foods Can fermented foods be considered as a source of probiotics? 5

6 Fermentation Defined Biochemical Definition: Process of deriving energy from oxidation of organic substrates where the electron acceptor is an organic compound Food-Friendly Definition: Conversion of raw foods into fermented foods by microbes raw food microbes fermented food 6

7 Why Fermented Foods Have Been Popular for 10,000 Years Enhanced preservation Increased economic value Enhanced organoleptic properties Enhanced functionality Unique Enhanced nutritional value Protein, minerals, fiber, vitamins Restoring a healthy gut microbiome 7

8 Why is the Gut Microbiota in Need of Repair? altered intestinal microbiota (dysbiosis) Chronic inflammation Metabolic dysfunction Adapted from Sommer and Bäckhed, 2013, Nature Reviews Microbiology 11,

9 The Consequences of a Dysbiotic Microbiota Scientific Reports (2018) 8:1466 Frontiers in Microbiology, March 2018 Volume 9

10 Redressing Dysbiosis altered intestinal microbiota (dysbiosis) Chronic inflammation Diets rich in fermented foods? Metabolic dysfunction Healthy microbiota Adapted from Sommer and Bäckhed, 2013, Nature Reviews Microbiology 11,

11 Fundamental Questions Q1. Do fermentation-derived microbes survive transit and reach the gut? Q2. Do fermentation-derived microbes influence the gut microbiota? Q3. Q4. Do fermentation-derived microbes have biological or functional activity in the gut? Do fermentation-derived microbes contribute to gut or systemic health?

12 Challenges Along the Way salivary enzymes: amylase, lipase, kallikrein, lysozyme mineral salts: calcium and phosphate ions ph Mouth gastric enzymes: pepsinogen, lipase mucin ph microbial products: SCFA, anaerobic environment competitive exclusion mucus ph 5-7 Colon Stomach Small intestine pancreatic enzymes: trypsinogen, lipase, carboxypeptidase, amylase mucus bile salts ph 4-7

13 Challenges in the Gut: Colonization Resistance Food associated microbes Attachment site restriction Nutrient limitation ph changes (SCFAs) Bacteriocins Antimicrobial peptides Commensal microbiota Mucus layer Intestinal epithelium Adapted from Sassone-Corsi & Raffatellu.

14 1. So do Fermentation-Derived Bacteria Make it to the Gut? 0 There is increasing evidence that food-borne bacteria contained in fermented products are biologically active in the colon such activities might be part of the mechanisms underlying beneficial effects. Our study supports the concept that [fermentation] bacteria.. can be leveraged to re-engineer the gut microbiome and improve dysbiosis-related diseases.

15 Sauerkraut and Sausage Bacteria Alive in the Colon Subject Bacteria Microbes associated with fermented foods F. Dal Bello, Walter, Hammes, and Hertel, Microbial Ecology

16 Organisms in Cheese Also Reach the Colon Blue (rind) Cheddar (rind) Caerphilly (rind) Camembert (rind) Blue (cheese) Cheddar (cheese) Caerphilly (cheese) Camembert (cheese) String cheese

17 Organisms Isolated From Korean Adults & From Kimchi Lactic Acid Bacteria in fecal samples Lactobacillus fermentum Lactobacillus fermentum PL9988 inhibits pathogens and has immune-enhancing activity and anti-inflammation activities Journal of Functional Foods, 2016, 20:79 87

18 Bifidobacterium Key result: Regular yogurt consumption maintains bifidobacteria in the GIT at high levels

19 Even in the absence of numerical changes, fermentation microbes can still affect microbiome function Science Translational Medicine, 2011 Fermented milk did not change microbiota composition Fermented milk consumption did change the transcriptome (expressed genes) Increased fiber-utilizing genes

20 Fundamental Questions Q1. Do fermentation-derived microbes survive transit and reach the gut? Q2. Do fermentation-derived microbes influence the gut microbiota? YES POSSIBLY Q3. Q4. Do fermentation-derived microbes have biological or functional activity in the gut? Do fermentation-derived microbes contribute to gut or systemic health? POSSIBLY

21 Health Benefits of Fermented Foods 1. Observational and epidemiological evidence Some diets are associated with enhanced health or longevity Some of those diets are rich in fermented foods and beverages Are fermented foods, therefore, at least partially responsible for longevity and other health benefits? Evidence exists for various types of diet, including diets containing yogurt and cultured dairy products

22 Examined nearly 2000 adults w/o MetS Dietary habits tracked for 3 years Conclusions: Higher consumption of yogurt was associated with reduced risk of MetS in individuals TOTAL YOGURT TOTAL YOGURT Abdominal obesity Hypertrigliceridimia Low HDL-cholesterol High blood pressure High fasting plasma glucose Metabolic syndrome LOW-FAT YOGURT LOW-FAT YOGURT Abdominal obesity Hypertrigliceridimia Low HDL-cholesterol High blood pressure High fasting plasma glucose Metabolic syndrome WHOLE-FAT YOGURT WHOLE-FAT YOGURT Abdominal obesity Hypertrigliceridimia Low HDL-cholesterol High blood pressure High fasting plasma glucose Metabolic syndrome Reduced risk Increased risk

23 cohort study of 120,000 U.S. adults tracked subjects for 20 years Conclusion: Yogurt consumption was associated with less weight gain in all cohorts. Yogurt Weight Change Associated with Each Increased Daily Serving, per 4- Year Period (lb)

24 Health Benefits of Fermented Foods 2. Clinical evidence exist, but fewer studies Blood pressure Infectious disease Bone health Mental well-being Lactose malabsorption

25 1. Blood Pressure Journal of Dairy Science, 7 February 2018 systolic Subjects consumed Lactococcus lactis fermented milk daily for 5 weeks Treatment group had lower systolic and diastolic blood pressure diastolic Nattokinase, an enzyme found in natto, a soybean fermented food Nattokinase has fibrinolytic activity Consumption of nattokinase extracts was associated with reduced systolic and diastolic BP in hypertensive adults

26 2. Infectious Disease Clinical Nutrition 36 (2017) upper respiratory tract infections acute gastroenteritis Children who consumed fermented rice or milk had fewer infectious diseases (upper respiratory tract infections and acute gastroenteritis) Fecal biomarkers of innate and acquired immunity were higher in treatment groups fermented milk fermented rice placebo

27 3. Bone Health Osteoporosis patients consumed kefir or milk daily for 6 Bone mineral density, parathyroid hormone, and other bone health markers were improved in the kefir group Serum calcium Parathyroid hormone

28 4. Gut-Brain GASTROENTEROLOGY 2013;144: Healthy women consumed fermented milk + probiotics or placebo twice daily for 4 weeks Treatment affected activity of brain regions that control processing of emotion and sensation No intervention Control milk Fermented milk + probiotics Midbrain reactivity

29 5. Lactose Maldigestion Breath hydrogen and lactose intolerance symptoms are reduced among lactose malabsorbers following ingestion of yogurt Product Lactose (g) Breath H 2 Symptoms score Milk Yogurt A * 1.6* Yogurt B * 1.3* Yogurt C * 1.5* Adapted from Rosado et al., Eur.J. Clin. Nutr. 46, Adapted from Pelletier et al., Eur.J. Clin. Nutr. 55,

30 Model for Lactose Digestion by Yogurt Microbes Tolerant Maldigestion Yogurt Lac Lac St Lac Lb stomach Lac Lac Lac small intestine E E Glu Gal Glu Gal colon Lac colonic bacteria acid + gas

31 Making the case for yogurt A cause and effect relationship has been established between consumption of live yogurt cultures and improved lactose digestion in individuals with lactose maldigestion. Live yoghurt cultures in yoghurt improve digestion of lactose in yoghurt in individuals with lactose maldigestion.

32 Probiotics: Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Fermented Foods Probiotics (but they may share similar properties)

33 Fundamental Questions Q1. Do fermentation-derived microbes survive transit and reach the gut? Q2. Do fermentation-derived microbes influence the gut microbiota? YES POSSIBLY Q3. Q4. Do fermentation-derived microbes have biological or functional activity in the gut? Do fermentation-derived microbes contribute to gut or systemic health? POSSIBLY YES FOR YOGURT, MAYBE FOR OTHERS

34 Thank You! M. Marco et al. Health Benefits Of Fermented Foods: Microbiota And Beyond. Current Opinion in Biotechnology 2017; 44: (with R. Hutkins as co-author amongst others)

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