Symbiotics and Obesity

1. Symbiotics and Obesity Becky C. Williamson May 30, 2014 SodexoDistance Dietetic Internship Professional Research Presentation

2. Warm Up!– What is Wellness? • What is wellness to you personally and how do you bring these values to work each day? • Think about the population we serve in this hospital community. What do you think wellness looks like for them?

3. Objectives • The connection between “Prebiotics and Probiotics” will be discussed. • Recent research on prebiotics and probiotics relating to obesity modulation will be highlighted. • Food sources and recommendations of prebiotics will be suggested. • Recent probiotic indications and recommendations will be provided.

4. The Problem with Obesity • Obesity & metabolic diseases that alter gut microbiota (1): • Poor diet, chronic lifestyle stress, lack of physical activity, smoking, excessive alcohol intake. • Acute setting : + antibiotics • Recent research highlights obese subjects have a smaller proportion of beneficial bacteria in the gut vs. lean subjects (2). • Mechanism: High fat diet reduction of gut-friendly bacteria (esp. Lactobacilli (intestine) & Bifidobacteria (colon) LPL production-endotoxemia/low grade inflammation obesity related metabolic disorders (3,4).

5. Obesity Management Strategies • Lifestyle management – reduce stress, increase PA, smoking cessation, reduced alcohol intake. • Recent research indicates the gut community is regarded as an important factor related to obesity and metabolic disorders (5,6,7,8,9,10). • We know gut-friendly bacteria supports immune function, intestinal integrity, healthy digestive function and discourage colonization of pathogens. Theory: Gut-friendly diet increased Lactobacilli & Bifidobacteria good gut integrity reduction obesity/metabolic disorders.

6. The Major Players: Prebiotics + Probiotics = Symbiotics • Prebiotics: Indigestible carbohydrates (oligosaccharides–(FOS), glucans, galactans, inulins, etc) that are fermented by gut bacteria; “Fuel for our flora” • Mechanism : Microflora use prebiotics to for fuel to ferment into SCFA’s (butyrate), B-vitamins and folic acid and Vitamin K. • Several are easily and widely fermented by Bifidobacteria (5), one probiotic species. • The potential to alter satiety, glucoregulatory hormones, reduce abdominal adiposity • Probiotics: “Live micro-organisms” when administered in adequate amounts provide health benefits by maintaining gut-microflora. • Highly strain specific – Genus, species, strain • Lactobacillus (L.) and Bifidobacteria (B.) are key genus • 1000 + Species, such as: L. gasseri, L acidophilus, B. longum. • Strain: LG SBT2055

7. Question How can prebiotics be used to attenuate obesity-related metabolic disorders? Theory Answer: Reduce opportunities for obesity

8. Prebiotic Research 1 Cani, P.D., Lecourt, E., Dewulf, E.M., Sohet, F.M., Pachikian, B.D., Naslain, et al. Gut microbiota fermentation of prebiotics increases satietogenicand incretingut peptide production with consequences for appetite sensation and glucose response after a meal. (2009). Am J ClinNutr. 90:1236–43 • Study examined effects of prebiotic supplementation on satiety and related hormones to measure plasma gut peptide concentrations. • Randomized, double-blind, parallel, placebo-controlledtrial. • A total of 10 healthy adults (5 men and 5 women) randomly assigned to groups that received either 16 g prebiotics/d or 16 g dextrin maltose/d for 2 wk. • Meal tolerance tests performed measuring the following: hydrogen breath test, satiety, glucose homeostasis, and related hormone response.

9. Results & Conclusion • Breath hydrogen excretion (a marker of gut microbiota fermentation) increased by 3-fold and lowered hunger rates. • Increased plasma glucagon-like peptide (GLP-1) and peptide YY concentrations, whereas postprandial plasma glucose responses decreased after the standardized meal. • Significant correlations for plasma GLP -1 and breath H+excretion measured after the meal and glucose response was inversely correlated with the breath H+excretion. • Conclusion: Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects.

10. Prebiotic Research 2 Parnell, J.A., and Reimer, R.A.. (2009). Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J ClinNutr. 89: 1751-9 Study designed to examine effects of FOS independent of any other diet or exercise intervention • Randomized, double blind, placebo-controlled trial • 48 (39 women/ 9 men) otherwise healthy adults w/BMI> 25 randomly assigned to receive 21 g FOS or placebo for 12 wks. • Measured body composition, meal tolerance (satiety hormone response, food intake, and subjective appetite ratings) • Lifestyle & food intake consistent with normal.

11. Results & Conclusions • Body composition: Significantly higher wt. loss (fat mass) w/oligofructosethan with placebo; the control group gained weight. • Satiety Hormones: Plasma concentrations ghrelin (% at baseline) were significantly lower in the oligofructose group at several time points during the meal tolerance test than in the control group • Leptinvalues for oligofructose were significantly lower than for the control at several time points postprandiallywhen expressed as change over time. • Food intake, satiety, hunger: Significant reduction (26%; P=0.002) in energy intake in the oligofructose group than in the control group by week 6 • Glucoregulationand serum lipids: Absolute glucose concentrations decreased in the oligofructose group at 6 hrs at the final test as compared with the placebo group (P=0.05), and postprandial insulin was significantly lower in the oligofructose group than in the control group at several time points (P< 0.05) • Conclusions: Research suggests potential to attenuate metabolic disorders with reduction of fat mass body weight and reduced food intake and improved insulin response.

12. Probiotic Research 1 Kadooka, Y., Sato, M., Imaizumi, K., Ogawa, A., Ikuyama, K., Akai, Y., …Tsuchida, T. (2010). Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. European Journal of Clinical Nutrition, 64, 636-643. • To determine the effects of probiotic Lactobacillus gasseri SBT2055 (LG2055) on abdominal adiposity, body weight and other body measures in adults with obese tendencies. • Double-blind, multi-center, randomized, placebo-controlled intervention trial. • 87 healthy adults aged 33-63 yo w/ BMI between 24.2 – 30.7 kg/m2 & abdominal visceral fat area between 81.2 and 178.5 cm2 • 12-weeks: Control group to receive two 100 g FM products w/o LG2055 cells per day+ intervention group received two 100 g FM products with added LG2055 cells per day. • Measured: body weight, waist-hip circumference, % body fat, serum adiponectin.

13. Results & Conclusions • Results: • Abdominal fat: Tx group by time and within groups W0 – W12 statistically significant changes. No sig. change in control group • Body wt., BMI, waist/hip circumference, waist to hip ratio: • Tx group: Sig. changes in all areas between W8 and W12; • No sig. changes in control group in any parameter • Serum Adiponectin: Total adiponectinlevel in creased significantly in both groups, indicating no specific influence of LG2055 on adiponectin, but instead the favorable effect of FM itself. • Conclusion: LG BT2055probiotic strain significantly reduced the abdominal adiposity, body weight and other measures suggesting its beneficial influence on metabolic disorders.

14. Probiotic Research 2 • Jung, S.P., Lee, K.M., Kang, J., Yun, S., Park, H., Moon Y., Kim, J. (2013). Effect of Lactobacillus gasseri BNR17 on overweight and obese adults: a randomized, double-blind clinical trial. Korean J Fam Med. 34:80-89. • This study investigated the effect of LG BNR17, a probiotic strain isolated from human breast milk, on obese/overweight adults. • Placebo controlled, randomized, and double-blind trial. • 62 obese subjects (BMI≥ 23 kg/m2), 19 to 60 y.o. w/FBG≥ 100 mg/dL • For 12 weeks, subjects were given either placebo or BNR17 and were tested by measuring body fat, body weight, various biochemical parameters, vital signs, weeks 0, 4, 8, and 12. The subjects assumed usual daily activities without having to make behavioral or dietary modifications during the course of the study.

15. Results & Conclusions • Results: At the 12th week, a slight reduction in body weight was noted in the BNR17 group, but there were no significant weight changes between groups. Decrease of waist and hip circumferences in the BNR17 group was more pronounced than those in the placebo group. • Conclusion: Despite there being no change in behavior or diet, administration of only the supplement of BNR17 reduced weight and waist and hip circumference. However, there were no significant differences between the two groups.

16. The Verdict? • Prebiotics, such as FOS are used as fuel for beneficial gut flora to proliferate and may have potential to promote increased satiety, reduce adiposity and modify glucose response. • The addition of probiotics may be beneficial to modulate obesity, however, additional research is needed to observe modulation of obesity and endotoxemia-related metabolic disorders for recommendation purposes. • Specific benefits of probiotics is highly strain specific.

17. Recommendations • Prebiotics • FOS: Considered as dietary fiber, and have a GRAS status (Generally Recognized As Safe) in the US. • Food sources: Bananas, garlic, onion, tomato, wheat, asparagus, artichoke, leek, honey, rye, brown sugar, barley, triticale, beer, lettuce, chicory, burdock, beetroot, apples, oats. • How much: 4 g -10 g per day for the promotion of colon microbiota balance. • Probiotics: • Food sources: fermented foods, such as, yogurt, kefir, aged cheese (have live cultures of bifidobacteria and lactobacilli), and non-dairy fermented food, including kimchi, sauerkraut, miso, tempeh and soy beverages. • How much: Usually 1x109 or 1 billion colony forming units (CFU’s) is a good daily dose for good gut health.

18. References • Cani, PD, Osto M, Geurts L, et al. (2012) Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 1; 3(4). • Cani PD & Delzenne NM (2011) The gut microbiome as therapeutic target. ParmacolTher 130,202-212 • Dewulf EM, Cani PD, Claus SP, et al (2012) Inulin-type fructans w/prebiotic properties lessen endtoxemia and modulate host metabolism by changing gut microbiota composition in obese women. Obes Facts Eur J Obes 5, 200. • Caselato de Sousa, V.M., Freitas dos Santos, and E., Sgarbieri, V. C. (2011). The importance of prebiotics in functional foods and clinical practice. Food and Nutrition Sciences. 2, 133-144. • Penwar, H., Rashmi, H.M., Batish, V.K., Grover, S. (2013). Probiotics as potential biotherapeutics in the management of type 2 diabetes – prospects and perspectives. Diabetes Metab Res Rev. 29, 103-112 • Cani, P.D., Neyrinck AM, Fava F, et al. (2007) Selective increase of bifidobacteria in gut microflora improve high-fat diet-induced diabetes in mice through a mechanism associated with endotoxmia. Diabetologia 50, 2374-2383.

19. References (continued) 7. Cani, P.D., Lecourt, E., Dewulf, E.M., Sohet, F.M., Pachikian, B.D., Naslain, et al. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. (2009). Am J ClinNutr. 90:1236–43 8. Parnell, J.A., and Reimer, R.A.. (2009). Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J ClinNutr. 89: 1751-9 9. Kadooka, Y., Sato, M., Imaizumi, K., Ogawa, A., Ikuyama, K., Akai, Y., …Tsuchida, T. (2010). Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. European Journal of Clinical Nutrition, 64, 636-643. 10. Jung, S.P., Lee, K.M., Kang, J., Yun, S., Park, H., Moon Y., Kim, J. (2013). Effect of Lactobacillus gasseri BNR17 on overweight and obese adults: a randomized, double-blind clinical trial. Korean J Fam Med. 34:80-89. 11. Probiotics for GI Health in 2012: Issues and Updates. (2012) Primary Issues.Retrieved May 12, 2014 at: http://www.primaryissues.org/2012/11/probiotics_pi161/

20. Questions? Question for you…. What do you think you can do to help your community strive toward wellness? Thank you!