Diet & the Microbiome

William DePaolo, PhD Associate Professor | Medicine Director | CMiST, Center for Microbiome Sciences & Therapeutics UW Medicine

CMiST Inspire Discovery Microbiota • The actual “bugs” that reside within and on us

• Referred mostly to Definitions Microbiome Every bug, all of their genes, and everything they produce

• Fungus = mycobiome • Virus = virome

CMiST Inspire Discovery Our microbial self 1014 or 100 trillion Bacteria within our gastrointestinal tract

1:1 Ratio with our own human cells

100-300:1 Number of bacterial genes to our own human genes

CMiST Inspire Discovery CMiST Inspire Discovery Stomach 102 Proximal ileum 102 Streptococcus Candida Lactobacillus Streptococcus Heliobacter pylori Peptostreptococcus Distal ileum 108 Clostridium Streptococcus 2 Duodenum 10 Bacteroides Streptococcus Actinomycinae Lactobacillus Corneybacteria

Colon 1012 Jejunm 102 Bacteroides Streptococcus Clostridium Lactobacillus Enterobacteriacae

CMiST Inspire Discovery Your intestines have good & bad bacteria

Good Bad

CMiST Inspire Discovery What does all of this bacteria do?

Boosts immunity Increases energy levels • 90% of our immune system is Absorption of nutrients located within the gut • Produces factors that replace mucus and prevent infections Promotes cardiovascular health • Maintains an acidic pH Improves cholesterol levels Supports healthy weight Produce chemicals that promote satiety Regulates hormones Estrogen, B12, folic acid Improves mental health and vitamin D Synthesizes neurotranmitters

CMiST Inspire Discovery Your microbiome is given to you at birth

• Our microbiome is imprinted during birth

• Route of birth

• Bottle vs breast fed

Bäckhed et al./Cell Host & Microbe 2015 • As infant develops, they will receive Lactobacillus (“good bacteria”) from the food that they ingest

CMiST Inspire Discovery Diversity of the microbiome is acquired throughout youth

Ravinder Nagpala, Rabina Mainalia, Shokouh Ahmadia,b, Shaohua Wanga, Ria Singha, Kylie Kavanaghc, Dalane W. Kitzmand, Almagul Kushugulovae, Francesco Marottaf and Hariom Yadava,∗ / Nutrition and Healthy Aging CMiST Inspire Discovery We shape its composition

Stress Over use of Over-nutrition Living with Hygiene antibiotics pets

= shifts in the composition, location or the function of your Microbiome

CMiST Inspire Discovery What is dysbiosis?

“Healthy” microbiome

Composition Function (purpose) Location 16S rRNA Metagenomics Must sample sequencing Meta-transcriptomics different sites Metabolomics

CMiST Inspire Discovery The microbiome is stable & resilient

CMiST Inspire Discovery Evolution of food practices

Paleolithic era Agricultural Industrial revolution • Wild plants (Neolithic) • Processed foods • Animals • Refined grains & fatty • Nuts & seeds revolution domesticated meats • Grains, legumes, • Alcohol & vegetable oils • Domesticated plants • Fast foods • Fermented foods

CMiST Inspire Discovery A western diet has impacted our health 1985 1995

2005 2015

Ward ZJ, Long MW, Resch SC, Gortmaker SL, Cradock AL, Giles C, et al. (2016) Redrawing the UW Obesity Landscape: Bias-Corrected Estimates of State-Specific Adult Obesity Prevalence. PLoS ONE 11(3): e0150735. doi:10.1371/journal.pone.0150735 CMiST Inspire Discovery A western diet reduces bacterial diversity

CMiST Inspire Discovery Ultra-process food is a

chemical sh*t storm CMiST Inspire Discovery Common food additives

Preservatives Emulsifiers Coloring & thickeners & flavoring agents • Nitrates & Nitrites • Sulphur dioxide • Carboxymethylcellulose • Saccharin • Benzoic, propanoic, • Xantham gum • Esters sorbic acids • Pectins • Monosodium • Sorbates glutamate • Artificial flavors • Artificial colorings

CMiST Inspire Discovery Intestinal bacteria

Produce mucus

Produce Produce SCFA antimicrobial (butyrate) peptides

CMiST Inspire Discovery What food additives do?

Increase antimicrobial Decrease Mucus Layer peptides Carageneenan & Carboxymethylcellulose Emulsifiers Emulsifiers

Decrease butyrate Emulsifiers

CMiST Inspire Discovery Can we treat obesity with the microbiome?

CMiST Inspire Discovery A 3-day cleanse changes the microbiome but, it is transient

CMiST Knight Lab UCSD and American Gut Inspire Discovery Commensals known to commensals overpopulate

Streptococcus Clostridium Klebsiella Bifidobacteria Varicella Lactobacillus Spirochaetaceae Saccaromyces boulardi

CMiST Inspire Discovery What is a probiotic?

Live microorganisms which, when administered in adequate amounts, confer a health benefit on the host -World Health Organization, 2002

CMiST Inspire Discovery Probiotic Live microorganisms administered in adequate amounts, confer a health benefit Definitions Prebiotic Non-digestible products that promote the growth of “healthy” gut bacteria

Synbiotic Products containing both pre- and probiotics

CMiST Inspire Discovery A brief history of probiotics

CMiST Inspire Discovery 1907 Metchnikoff proposed 1857 Lactobacillus that the acid producing discovered at the bacteria in fermented if Pasteur Institute consumed regularly, lead to a longer, healthier life

1965 New York, In 76 BC the Roman Lilly & Stillwell early 1930’s, in historian Plinius The bible states coined the term Japan, Minoru recommended the “ Abraham Shirota developed a probiotic administration of owed his fermented milk fermented milk longevity to the product called products for treating consumption of Yakult gastroenteritis sour milk.”

CMiST Inspire Discovery Where do probiotics come from?

Probiotics are naturally occurring in some foods

CMiST Inspire Discovery • Probiotics are actually members of a group of Where do bacteria that reside probiotics within our intestines

come from? • This group of bacteria is called the microbiota

CMiST Inspire Discovery Should you be taking a probiotic?

The number of diseases that have been linked to bacterial imbalance including depression, 40 arthritis, IBS and cancer.

CMiST Inspire Discovery Diseases Infectious diarrhea Irritable bowel proven to syndrome Antibiotic- benefit associated diarrhea from Weak immune system

probiotics Ulcerative colitis

Eczema

Cholesterol Anxiety & depression

CMiST Inspire Discovery How probiotics work: preventing infection

CMiST Inspire Discovery How probiotics work: strengthening our barrier

Inhibit bacterial Secrete anti- adhesion microbial peptides Immunomodulation

Prevent intestinal Reduce pH barrier dysfunction

Enhance barrier function

CMiST Inspire Discovery How probiotics work: strengthening our barrier

Lactobacillus

Carcinogens Enzymes in our bodies Pre-carcinogens

CMiST Inspire Discovery Are probiotics safe?

Don't start taking probiotics without talking to your doctor especially if you have an immune deficiency or are being treated for cancer.

FDA does not monitor probiotics so a lot of variation and mis-marketing

Erzebet S Art Collections CMiST Inspire Discovery What to look for…

Genus, species and strain of the microorganisms

Lactobacillus reuteri ATCC55730

Genus Species Strain

CMiST Inspire Discovery What to look for…

• Number of organisms contained in a single dose

Remember more is not always better

• How often you should take it and when (should be taken shortly after eating)

* * Pick one that has at least 7 strains and 5 billion CFUs (colony forming units) * *

CMiST Inspire Discovery What to look for…

How should this specific probiotic be stored • refrigeration • dark cool space

*always keep away from moisture and heat

CMiST Inspire Discovery What to look for…

“Viable through end of shelf life” vs “Viable at time of manufacture”

Encapsulated pills or other delayed-rupture technology ensure the bacteria survive the acidity of stomach & reach your colon.

CMiST Inspire Discovery What to look for…

Certification by an independent third party The Food and Drug Administration (FDA) does not regulate most probiotics & therefore the amount of bacteria stated on the label might not be what’s actually in there.

CMiST Inspire Discovery Not all probiotics are created equal

Bifidobacterium Bifidum Lactobacillus acidophilus Bifidobacterium longum Lactobacillus rhmanosus Saccharomyces • Supports boulardii production of • Relieves gas, bloating • Supports liver vitamins function • Supports healthy skin • Yeast probiotic • Boosts immunity • Improves lactose • Reduces intolerance • Effective at treating inflammation • Fights UTIs • Prevents Crohn’s Disease • Lowers cholesterol pathogens • Removes toxins • Reduces stress hormones and • Anti-toxin • Reduces E. coli GABA neurotransmitter • Anti-microbial • Vitamin K which reduces anxiety

CMiST Inspire Discovery Probiotics The human and gut microbiome market health is a is expected to reach major market $658 million by Probiotics can be 2023 from $294 helpful in some cases but there are relatively million in 2019 few studies to tell us if and when they are growing at a CAGR effective in adults. of 22.3%

CMiST Inspire Discovery Problems with many probiotics

• NOT potent 50% of all products do not contain the type or numbers of bacteria they claim

• NOT effective Many probiotic supplements do not ensure that they get through the stomach acids and survive

• NOT natural Many products are processed and have too much added

CMiST Inspire Discovery kills probiotics

• : best when “made with live, active cultures”

• Avoid: “heat treated after culturing”

CMiST Inspire Discovery Alternatives Probiotic to probiotic supplements: Prebiotic

• Prebiotics • Synbiotics Synbiotic

CMiST Inspire Discovery Alternatives to probiotic supplements:

Natto Pickles Tempeh Kombucha Saurkraut

CMiST Inspire Discovery Alternatives to probiotic supplements: Fecal Microbiota Transplants (FMT)

CMiST Inspire Discovery Fecal Microbiota Transplants

• Have been used to treat C. difficile infections >90% efficacy compared to antibiotics (~50%)

• Currently a number of clinical trials evaluating FMT in Inflammatory Bowel Disease Results have been mixed so far

CMiST Inspire Discovery Still many unknowns with FMT

CMiST Inspire Discovery Future of probiotic supplements

• Lacto-ceuticals Using the fermentation process with different types of food, such as

• Genetically modified Lactobacillus

CMiST Inspire Discovery Let food be thy medicine and medicine be thy food. -Hippocrates

CMiST Inspire Discovery