GUT MICROBIOME WHAT IS IT? WHY IS IT IMPORTANT FOR HUMAN HEALTH? Corrie Whisner, PhD School of Nutrition and Health Promotion Arizona State University Center for Research on Ingredient Safety Annual Meeting October 5, 2017
OVERVIEW 1. Microbiome 1. Gut microbiome defined 2. Classification 3. Functional roles 4. Methods of altering the gut microbiome 5. Links to health 2. Dietary intake 1. Western diet and obesity 2. MyPlate for gut microbes 3. Probiotics and cognitive health 4. Prebiotics and bone health 5. Emulsifiers 6. Artificial sweeteners 3. Conclusions
THE GUT MICROBIOME The ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space. Joshua Lederberg 1925-2008
HOW MANY MICROBES DEEP ARE WE? 10 microbial cells:1 human cell We are more microbe than human not quite More like a 1:1 ratio Luckey T. Am J Clin Nutr. 1972;25:1292 1294. Sender R, et al. PLoS Biol. 2016;14(8):e1002533. http://www.amnh.org
WHO AND WHAT IS GOING ON? Zoetendal EG, et al. Gut. 2008;57:1605-1615.
MICROBIOTA IN THE INTESTINE > 10 different phyla > 2000 unique species Volume 1 pint Weight of 3-5 pounds Tongue large intestine duodenum ileum Stool jejunum colon Human Microbiome Project Consortium. Nature. 2012;486:207.
FECAL MICROBIAL COMMUNITY ANALYSIS Siqueira, et al. J Oral Microb. 2012;4:10743
PREVALENT MICROBIOTA GROUPS Phylum Class Characteristics Examples Firmicutes Bacilli Clostridia Gram + Diverse in morphology (rod, coccoid, spiral), physiology (anaerobic, aerobic) Include commensal and beneficial bacteria Bacteroidetes Bacteroidetes Gram Composed of 3 large classes Widely distributed in environment (soil, seawater, animal gut) Proteobacteria Gammaproteobacteria Betaproteobacteria Gram Include a variety of pathogens Actinobacteria Actinobacteria Gram + Diverse morphology Major antibiotic producers in pharmaceutical industry Lactobacillus Ruminococcus Staphylococcus Enterococcus Faecalibacterium Bacteroides Prevotella Escherichia Pseudomonas Bifidobacterium Streptomyces Nocardia Johnson, Pediatrics. 2012
MICROBIOTA FUNCTIONS Repress pathogenic microbe growth Displace pathogens Produce anti-microbial factors Metabolic function Carbohydrate fermentation Short chain fatty acid production Synthesize vitamins Aid with mineral absorption Improve structural barriers Maintain tight junctions Fortify intestinal barrier Clarke et al. Molecular Endocrinology. 2014.
DISEASE BURDEN HAS CHANGED Increased rates of: Inflammatory bowel diseases Allergies Celiac disease Obesity Cardiovascular disease Diabetes Nat Rev Microbiol. 2011;9[4]:281
MICROBIOME AND IMMUNE FUNCTION
WHAT INFLUENCES THE MICROBIOME?
DIETARY INTAKE
MICROBIOME AND OBESITY Clarke et al. Molecular Endocrinology. 2014.
MICROBIOME-CENTRIC VIEW OF FOOD INTAKE
WESTERN DIETS = MORE FIRMICUTES Burkina Faso Italy De Fillipo C et al. Proced Natl Acad Sci. 2010
SCFA COULD PREVENT PATHOGEN GROWTH SCFA in Feces (umol/g) Short Chain Fatty Acid Production 90 80 70 60 50 40 30 20 10 0 Number of microbial sequences 90 80 70 60 50 40 30 20 10 0 Pathogenic Bacteria Burkina Faso Italy Burkina Faso Italy De Fillipo C et al. Proced Natl Acad Sci. 2010
DIET PREDICTS INDIVIDUAL VARIATION Zhernakova A et al. Science. 2016. Diversity positively influenced by consumption of fruits, vegetables, alcohol and fermented dairy products Western-diet soda and grain products associated with lower diversity Some of these findings differ from previous literature, especially in relation to grains
DIETARY PATTERNS IMPACT GUT BUGS Veggie-based Omnivore Plant-based foods Animalbased foods Ruminococcus Streptococcus Prevotella Lachnospira Roseburia De Filippis F et al. Gut. 2015. Microbial genera
PROBIOTICS AND THE BRAIN Depression and anxiety Lactobacillus helveticus + Bifidobacterium longum reduced anxiety behavior in rats and decreased psychological distress and cortisol levels in humans 1 Lactobacillus rhamnosus altered GABA receptors in brain via the vagus nerve 2 Multispecies probiotics improve cognitive reactivity and sad mood among humans 3 1 Messaoudi M, et al. Br J Nutr. 2011 2 Bravo JA, et al. PNAS. 2011 3 Steenbergen L, et al. Brain Behav Immun. 2015. www.npr.org
FERMENTED MILK MODIFIES EMOTIONS Consumption of fermented milk for 4 weeks Lactococcus lactis, Lactobacillus bulgaricus, Bifidobacterium animalis and Streptococcus thermophiles reduced activity in regions of the brain related to emotion and sensation Tillisch K, et al. Gastroenterology. 2013.
PREBIOTICS AND BONE HEALTH Osteoporosis is a major public health problem affecting ~ 10 million Americans Prebiotic dietary fibers have been shown to improve calcium absorption and bone density PROMITOR Soluble Corn Fiber (SCF) Subject Randomization N = 24 12 g/d delivered as Soluble Corn Fiber Control 12 g/d delivered as Soluble Corn Fiber Control Whisner CM, et al. Brit J Nutr. 2014. 3 week intervention 1 week washout 3 week intervention
SCF IMPROVES CALCIUM ABSORPTION Calcium absorption increased by 12% with SCF Correlated with beneficial bacteria known to produce short chain fatty acids Dialister Parabacteroides Bacteroides Alistipes Whisner CM, et al. Brit J Nutr. 2014. * P < 0.05
EMULSIFIERS IMPACT GUT MICROBIOME Carboxymethylcellulose and polysorbate-80 fed to mice Low grade inflammation Obesity/metabolic syndrome Increased intestinal symptoms among mice with colitis Chassaing B, et al. Nature. 2015.
ARTIFICIAL SWEETENERS AND GLUCOSE Saccharine, sucralose and aspartame are widely used by both lean and obese individuals Artificial sweeteners are generally considered safe Mice consuming these sweeteners experience glucose intolerance Suez J, et al. Nature. 2014.
ARTIFICIAL SWEETENERS AND GLUCOSE Saccharin impairs glucose control in humans Differential responses were observed Mechanisms appear to be the result of gut microbiota dysbiosis Suez J, et al. Nature. 2014.
CONCLUSIONS Novel food additives have revolutionized our food environment Dietary intake alters the gut microbiome Additives may differentially influence our health Need to explore the etiology behind individual dietary components alone and in combination with other dietary constituents.
http://www.xkcd.com/1543/ QUESTIONS?