Open Your Mouth & Say “Ah” Searching for Signs of Energy Balance in the Oral Microbiome Center for Energy Balance Journal Club Kristi Hoffman, PhD, MPH 12/17/2015

Journal Club Outline What is the microbiome? Energy balance and the gut microbiota Why focus on the mouth? Data with the Mexican-American cohort Future Directions Outline

Man and microbe have a symbiotic relationship Adapted from Turnbaugh et al, 2007

The gut microbiome influences energy balance Diet rapidly alters gut microbiota Tremaroli & Backhed, Nature 2012 Obese gut dysbiosis influences host physiology

Obese phenotype transmissable via gut microbiome Tremaroli et al, Cell Metabolism 2015 Walker & Parkhill, Science 2013

What about the oral microbiota?

Obesity increases risk for oral pathology Reduced salivary flow rate Dry mouth Halitosis Dry mouth, halitosis and obesity Decreased salivary flow rate Obese children at higher risk of dental caries Relationship in adults less clear Obese adults and children have higher odds of periodontal disease Dependent on oral hygiene

Post-prandial saliva of obese exhibits greater proteolysis, less lipolysis Falchi et al, Nature Genetics 2014 Pepino et al, Obesity 2014 Smoking in goodson In animals, reduced responsiveness to peripheral taste receptor cells Vors et al, Int Journal of Obesity 2015

Salivary proteins vary by obese state Falchi et al, Nature Genetics 2014 Falchi et al, Nature Genetics 2014 Pepino et al, Obesity 2014 Smoking in goodson In animals, reduced responsiveness to peripheral taste receptor cells Pepino et al, Obesity 2014

Early oral microbiome studies found links with obesity Falchi et al, Nature Genetics 2014 Pepino et al, Obesity 2014 Smoking in goodson; Selemonas In animals, reduced responsiveness to peripheral taste receptor cells

Early oral microbiome studies found links with obesity Zeigler et al, Pediatric Obesity 2012 In animals, reduced responsiveness to peripheral taste receptor cells

Early oral microbiome studies found links with obesity Tremaroli et al, Cell Metabolism 2015 (figure) Shillitoe et al, Journal of Oral Microbiology 2012 (referenced research) Zeigler et al, Pediatric Obesity 2012

Mano a Mano Mexican-American Cohort Prospective cohort >25,000 self-identified Mexican-Americans Living in greater Houston metropolitan area Demographic and health information gathered at baseline Blood, urine, buccal sample Followed annually for changes in health status, including weight gain/loss, diabetes and cancer dx Chow et al, Int Journal of Epidemiology 2015

Characteristics of the Mexican-American cohort ALL UNPUBLISHED DATA REMOVED FROM PRESENTATION Chow et al, Int Journal of Epidemiology 2015

Mano a Mano Mexican-American Cohort Prospective cohort >25,000 self-identified Mexican-Americans Living in greater Houston metropolitan area Demographic and health information gathered at baseline Blood, urine, buccal sample Followed annually for changes in health status, including weight gain/loss, diabetes and cancer dx Buccal sample DNA Swish & spit mouth wash 16S rRNA gene >16,000 sequencing reads per sample! Chow et al, Int Journal of Epidemiology 2015

To summarize… ALL UNPUBLISHED DATA REMOVED FROM SLIDE PRESENTATION

What does it all mean?

What does it all mean? Oral microbiome as a biomarker Biological mechanism or proxy for other factors Identify those most in need of intervention for weight gain prevention

Many prospective cohorts have buccal or saliva samples Adapted and updated from Nutritional Epidemiology (2013), W. Willet

Future Plans Evaluate prediction model with additional taxa Increase sample size to 400 ALL UNPUBLISHED DATA REMOVED FROM SLIDE PRESENTATION

Acknowledgements Carrie Daniel-MacDougall Jing Zhang Joe Petrosino UT MD Anderson Cancer Center Carrie Daniel-MacDougall Jing Zhang Alkek Center for Metagenomics & Microbiome Research Joe Petrosino Nadim Ajami Diane Hutchinson Dan Smith