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GOING WITH YOUR GUT:

Corrie Whisner, PhD

School of Nutrition and Health Promotion

Arizona State University

Building Healthy Lifestyles Conference

March 18-19, 2016

INSIGHTS ON PREBIOTICS, PROBIOTICS, SUPERBUGS AND HEALTH

WHAT IS THE HUMAN MICROBIOME?

WE ARE OUTNUMBERED!

Bacterial cells outnumber human cells 10 to 1

10% of total body volume is microbial cells

>

MICROBIOTA FUNCTIONS

Clarke et al. Molecular Endocrinology. 2014.

PROTECT

NOURISH

STRENGTHEN

WHAT INFLUENCES THE MICROBIOME?

Ottman N, et al. Front. Cell. Inf. Microbio. 2012.

WHAT INFLUENCES THE MICROBIOME?

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MICROBIOME AND IMMUNE FUNCTION DISEASE BURDEN HAS CHANGED

Nat Rev Microbiol. 2011;9[4]:281

Increased rates of:

• Inflammatory bowel diseases

• Allergies• Celiac disease• Obesity• Cardiovascular disease• Diabetes

“IF GUT BACTERIA ARE MAKING YOU ILL, CAN SWAPPING THEM MAKE YOU HEALTHY?”

Me, myself, us. The Economist. 2012; p69.

MICROBIOME AND OBESITY

Clarke et al. Molecular Endocrinology. 2014.

WHAT DO THESE ITEMS HAVE IN COMMON? DIY FECAL TRANSPLANTS

According to www.thepowerofpoop.com, a website devoted

to matching donors and recipients for fecal transplants, this

is all you need to perform a DIY fecal microbial transplant!

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SUPER BUGS AND FECAL TRANSPLANTS

MICROBIOME AND DISEASE

www.npr.org

“People infected with Clostridium difficile suffer debilitating diarrhea, but the bug often defies antibiotics.”

Welcome Trust Sanger Institute

MICROBIOME AND DISEASE

Alang N et al. Open Forum Infectious Diseases. 2015.

• Weight prior to treatment: 136 pounds; BMI=26

• Treated with feces from her 16 year-old daughter (140 pounds; BMI=26.4)

• 16 months after FMT – gained 34 pounds (BMI=33)

• 36 months after FMT – gained 41 pounds (BMI=34.5)

PROBIOTICS

WHAT ARE PROBIOTICS?

“Live microorganisms that when administered in adequate

amounts confer a health benefit on the host”

International Scientific Association for Probiotics and Prebiotics

COMMON PROBIOTICS

Bifidobacteria

adolescentis

animalis

bifidum

breve

longum

Lactobacillus

acidophilus

casei

fermentum

gasseri

johnsonii

paracasei

plantarum

rhamnosus

salivarius

Saccharomyces

boulardii

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PROBIOTICS - IRRITABLE BOWEL SYNDROME

• A total of 18 RCTs (n=1,650

patients)

• Irritable bowel syndrome

patients taking probiotics

• Lactobacillus

• Bifidobacterium

• Streptococcus

• Symptoms improved

significantly (RR of not

improving 0.71, 95% CI 0.57 to

0.88)

Moayyedi P, et al. Gut 2010; 59(3): 325-332.

PROBIOTICS–INFLAMMATORY BOWEL DISEASE

• A total of 18 RCTs (n=1,650

patients)

• Irritable bowel syndrome

patients taking probiotics

• Lactobacillus

• Bifidobacterium

• Streptococcus

• Symptoms improved

significantly (OR 1.6, 95% CI

1.2 to 2.2)

Moayyedi P, et al. Gut 2010; 59(3): 325-332.

UP-AND-COMING PROBIOTICS

Akkermansia muciniphila

Faecalibacterium

prausnitzii

Roseburia spp.

Eubacterium hallii

Human commensals

associated with healthy

intestines

PREBIOTICS

WHAT ARE PREBIOTICS?

Basic criteria for selection of prebiotics:

Resistance to digestion

Hydrolysis and fermentation by intestinal bacteria

Selective stimulation or growth of good bacteria

Beneficial health effects

Lactobacillus

Bifidobacteria

PREBIOTICS BOOST GOOD BACTERIA

Escherichia

Enterococcus

Good Microbes Bad Microbes

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• Found in fruits, vegetables and other plants

• Leeks

• Artichokes

• Chicory Root

• Wheat

• Asparagus

• Bananas

• Naturally occuring

• Inulin

• Fructooligosaccharides

• Can be synthetic

• Galactooligosaccharides

• Lactulose

WHAT ARE PREBIOTICS? WHEAT IS A GOOD SOURCE OF PREBIOTICS

71%

24%

2%2%

1%

Oligofructose

69%

23%

3%3%

2%

Inulin

Wheat Onion Banana Garlic Other

Moshfegh AJ, et al. J Nutr. 1999.

OSTEOPOROSIS IS COSTLY

• Low bone mass and deterioration of bone micro-

architecture

• 54 million Americans have osteoporosis and low bone

mass

www.nof.orgwww.webmd.com

OSTEOPOROSIS PREVENTION

Jasminka, et al. J Am Coll Nutr 2000; 19: 715.

CALCIUM REQUIREMENTS DON’T MATCH INTAKE

• Adolescent girls consume approximately 700-800 mg/d

• Adolescent boys consume approximately 800-900 mg/d

International Osteoporosis Foundation, www.iof.orgErvin RB, et al. Adv Data. 2004.

Calcium Requirements

STUDY DESIGN

• Double-blind, randomized controlled crossover

• Two, 3-week metabolic balance periods

• Controlled diets with 600 mg/d calcium

and 15 g/d fiber

• PROMITOR® Soluble Corn Fiber in fruit snacks

12 g/d delivered as

Soluble Corn Fiber

Control

12 g/d delivered as

Soluble Corn Fiber

Control

3 week

intervention

3 week

intervention

1 week

washout

Subject

Randomization

N = 24

Whisner et al. BJN. 2013.

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ENHANCED MINERAL SOLUBILITY

SCFAH

2+

Ca2+

Ca

2+

Ca

SCF + pH

Ca

2+

Ca

Blood

Lumen

SCF = Soluble Corn Fiber (prebiotic)SCFA = Short chain fatty acids

:)

H

HH

HH

SCF INFLUENCED LATE PHASE ABSORPTION

•Calcium absorption

increased by 12% with SCF

consumption compared to

Control

•Time effect consistent with

lower gut absorption

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0-24 h 24-48 h

Fra

cti

on

al

Calc

ium

A

bso

rpti

on

24 Hour Urine Pools

SCF Control

*P = 0.02

Whisner et al. BJN. 2013.

Ca ABSORPTION CORRELATED WITH FERMENTERS

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

Co

rre

lati

on

wit

h C

ha

nge

in C

a A

bso

rpti

on

***

**

* *

*

Bacteroidetes

Firmicutes

* P < 0.05

** P < 0.01

Change in Microbial Communities (Genus Level)

Whisner et al. BJN. 2013.

BENEFIT OF SCF DIFFERED BY PERSON

0

0.2

0.4

0.6

0.8

1

1.2

Control SCF

Fra

ctional

Calc

ium

Ab

sorp

tion

• Responder: • Increase in calcium

absorption by ≥ 3% with SCF compared to control

• Non-responder:• Change in calcium

absorption < 3% with SCF compared to control

Whisner et al. (unpublished data)

CHANGE IN Ca ABSORPTION DIFFERED BY GROUP

-15

-10

-5

0

5

10

15

20

25

30

35

Non-responder Responder

Chang

e i

n C

a A

bsorp

tion (

%)

P < 0.05

Whisner et al. (unpublished data)

HABITUAL DIET AND FUNCTIONAL FOODS

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DIET, THE MICROBIOME AND OBESITY GLOBAL INSIGHTS INTO DIETARY INTAKE

Schnorr SL et al. Nature Comm. 2014

WESTERN DIETS = MORE FIRMICUTES

De Fillipo C et al. Proced Natl Acad Sci. 2010

Burkina Faso Italy

MICROBIOME-CENTRIC VIEW OF FOOD INTAKE

REFINED GRAINS AND BUTYRATE

Lappi J, et al. J Nutr. 2013.

VS.

WG CEREAL INCREASES GOOD BACTERIA

9.3

9.4

9.5

9.6

9.7

9.8

9.9

Whole Grain Cereal Non-Whole Grain Cereal

Bif

ido

bac

teri

um

/ g

ram

of

fece

s

Pre-intervention Post-intervention

Carvalho-Wells et al. Brit J Nutr. 2010.

*P = 0.001

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WHEAT POLYPHENOLS IMPROVE OBESITY-RELATED

INFLAMMATION VIA GUT BUGS

Vitaglione P, et al. Am J Clin Nutr. 2015.

• Wheat polyphenols decreased inflammation over 8 weeks

• Increase in beneficial bacteria Bacteroides and Lactobacillus

• Decrease in inflammation correlated with increase in beneficial bacteria

INFLAMMATION

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GOING GLUTEN-FREE? THINK AGAIN

De Palma G, et al. Br J Nutr. 2009.: )

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De Palma G, et al. Br J Nutr. 2009.

Greater diversity

More pathogens

--~~

Opportunistic infections

GLUTEN-FREE AND THE HEALTHY GUT

1 month of gluten-free

De Palma G, et al. Br J Nutr. 2009.

Beneficial bacteria• Bifidobacteria• Lactobacillus• Faecalibacterium

prausnitzii• Clostridium lituseburense

Pathogenic bacteria• Enterobacteriaceae• Escherichia coli

FERMENTED FOODS TO BOOST GUT BUGS?

• Kombucha

• Miso

• Kimchi

• Tempeh

• Saurkraut

• Yogurt

• Kefir

• Etc…

TAKE-AWAY MESSAGES

• Eat more plants including grains

• Focus on fiber and polyphenol-rich foods

• Avoid DIY fecal transplants

• Make evidence-based decisions for probiotics…don’t flush away your money!

WE HAVE WORK TO DO

• Critical question: Can functional foods, prebiotics and

probiotics remodel disease or illness-prone microbiota

patterns?

• Age, gender and race / ethnicity

• Optimal strain and dose

• Using formulas appropriate for responsive populations

• Understanding how dietary components interact with

functional foods, pre- and pro-biotics

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THANKS!

XKCD Comic