GUT MICROBIOME

Corrie Whisner, PhDSchool of Nutrition and Health PromotionArizona State University

Center for Research on Ingredient SafetyAnnual Meeting – October 5, 2017

WHAT IS IT? WHY IS IT IMPORTANT FOR HUMAN HEALTH?

OVERVIEW1. Microbiome

1. Gut microbiome defined2. Classification3. Functional roles4. Methods of altering the gut microbiome5. Links to health

2. Dietary intake 1. Western diet and obesity2. MyPlate for gut microbes3. Probiotics and cognitive health4. Prebiotics and bone health5. Emulsifiers6. Artificial sweeteners

3. Conclusions

THE GUT MICROBIOME

“Theecologicalcommunityofcommensal,symbiotic,andpathogenicmicroorganismsthatliterallyshareourbodyspace.”

JoshuaLederberg1925-2008

HOW MANY MICROBES DEEP ARE WE?

http://www.amnh.org

10 microbial cells:1 human cell

We are more microbe than human…

not quite

More like a 1:1 ratio

LuckeyT.AmJClinNutr.1972;25:1292–1294.SenderR,etal.PLoSBiol.2016;14(8):e1002533.

WHO AND WHAT IS GOING ON?

ZoetendalEG,etal.Gut.2008;57:1605-1615.

MICROBIOTA IN THE INTESTINE• > 10 different phyla• > 2000 unique species• Volume – 1 pint• Weight of 3-5 pounds

duodenumileum

jejunum

largeintestine

colon

HumanMicrobiomeProjectConsortium.Nature.2012;486:207.

Tongue

Stoo

l

FECAL MICROBIAL COMMUNITY ANALYSIS

Siqueira,etal.JOralMicrob.2012;4:10743

PREVALENT MICROBIOTA GROUPSPhylum Class Characteristics Examples

Firmicutes BacilliClostridia

• Gram+• Diverseinmorphology(rod,

coccoid,spiral), physiology(anaerobic,aerobic)

• Includecommensalandbeneficialbacteria

• Lactobacillus• Ruminococcus• Staphylococcus• Enterococcus• Faecalibacterium

Bacteroidetes Bacteroidetes • Gram–• Composedof3largeclasses• Widelydistributedin

environment(soil,seawater,animalgut)

• Bacteroides• Prevotella

Proteobacteria GammaproteobacteriaBetaproteobacteria

• Gram–• Includeavarietyof

pathogens

• Escherichia• Pseudomonas

Actinobacteria Actinobacteria • Gram+• Diversemorphology• Majorantibioticproducers

inpharmaceuticalindustry

• 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

Clarkeetal.MolecularEndocrinology.2014.

DISEASE BURDEN HAS CHANGED

NatRevMicrobiol.2011;9[4]:281

Increasedratesof:

• Inflammatoryboweldiseases

• Allergies• Celiacdisease• Obesity• Cardiovasculardisease• Diabetes

MICROBIOME AND IMMUNE FUNCTION

WHAT INFLUENCES THE MICROBIOME?

DIETARY INTAKE

MICROBIOME AND OBESITY

Clarkeetal.MolecularEndocrinology.2014.

MICROBIOME-CENTRIC VIEW OF FOOD INTAKE

WESTERN DIETS = MORE FIRMICUTES

DeFillipoCetal.ProcedNatlAcadSci.2010

BurkinaFaso Italy

SCFA COULD PREVENT PATHOGEN GROWTH

DeFillipoCetal.ProcedNatlAcadSci.2010

0102030405060708090

SCFAinFeces(u

mol/g)

ShortChainFattyAcidProduction

BurkinaFaso Italy

0102030405060708090

Num

bero

fmicrobialse

quen

ces

PathogenicBacteria

BurkinaFaso Italy

DIET PREDICTS INDIVIDUAL VARIATION

ZhernakovaAetal.Science.2016.

• Diversitypositivelyinfluencedbyconsumptionoffruits,vegetables,alcoholandfermenteddairyproducts

• Western-dietsodaandgrainproductsassociatedwithlowerdiversity

• Someofthesefindingsdifferfrompreviousliterature,especiallyinrelationtograins

DIETARY PATTERNS IMPACT GUT BUGS

DeFilippisFetal.Gut.2015.

Omnivore

Veggie-based

RuminococcusStreptococcus

PrevotellaRoseburia

Lachnospira

Anim

al-

basedfood

sPlant-b

ased

food

s

Microbialgenera

PROBIOTICS AND THE BRAIN

1MessaoudiM,etal.BrJNutr.20112BravoJA,etal.PNAS.20113SteenbergenL,etal.BrainBehavImmun.2015.

• Depressionandanxiety• Lactobacillushelveticus+Bifidobacteriumlongumreduced

anxietybehaviorinratsanddecreasedpsychologicaldistressandcortisollevelsinhumans1

• LactobacillusrhamnosusalteredGABAreceptorsinbrainviathevagus nerve2

• Multispeciesprobioticsimprovecognitivereactivityandsadmoodamonghumans3

www.npr.org

FERMENTED MILK MODIFIES EMOTIONS

TillischK,etal.Gastroenterology.2013.

• Consumptionoffermentedmilkfor4weeks• Lactococcus lactis,Lactobacillusbulgaricus,Bifidobacterium

animalisandStreptococcusthermophiles• reducedactivityinregionsofthebrainrelatedtoemotionand

sensation

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)

12 g/d delivered asSoluble Corn Fiber

Control

12 g/d delivered asSoluble Corn Fiber

Control

3 week intervention

3 week intervention

1 week washout

Subject Randomization

N = 24

WhisnerCM,etal.BritJNutr.2014.

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

* P < 0.05WhisnerCM,etal.BritJNutr.2014.

EMULSIFIERS IMPACT GUT MICROBIOME

ChassaingB,etal.Nature.2015.

• Carboxymethylcelluloseandpolysorbate-80fedtomice• Lowgradeinflammation• Obesity/metabolicsyndrome• Increasedintestinalsymptomsamongmicewithcolitis

ARTIFICIAL SWEETENERS AND GLUCOSE

SuezJ,etal.Nature.2014.

• Saccharine,sucraloseandaspartamearewidelyusedbybothleanandobeseindividuals

• Artificialsweetenersaregenerallyconsideredsafe• Miceconsumingthesesweetenersexperienceglucoseintolerance

ARTIFICIAL SWEETENERS AND GLUCOSE

SuezJ,etal.Nature.2014.

• Saccharinimpairsglucosecontrolinhumans• Differentialresponseswereobserved• Mechanismsappeartobetheresultofgutmicrobiotadysbiosis

CONCLUSIONS• Novelfoodadditiveshaverevolutionizedourfoodenvironment

• Dietaryintakealtersthegutmicrobiome

• Additivesmaydifferentiallyinfluenceourhealth

• Needtoexploretheetiologybehindindividualdietarycomponentsaloneandincombinationwithotherdietaryconstituents.

QUESTIONS?

http://www.xkcd.com/1543/