Our Microbiome –Little Bugs with Lots of Influence

Susan Linke, MBA MS RD LD CLT

Dallas, TX

www.susanlinke.com

info@susanlinke.com

Objectives

The goal of this presentation is to give an overview of the microbiome and create an understanding of the dual relationship between our microbes and us. Upon completion, you will be able to:

Define microbiome/microbiota and describe its significance in human health and disease

Describe how diet impacts the microbiome

Evaluate the role and need for prebiotics and probiotics in supporting a healthy microbiome

The Human Microbiome Project

U.S. National Institutes of Health

2008 – 2012

Identify and characterize the microorganisms which are found in association with both healthy individuals and those with diseases

2013 – current

Explore the relationship between disease and changes in the human microbiome

Characteristics of the Human Microbiome

The human microbiota consists of ~ 100 trillion symbiotic microbial cells

Symbiosis – mutually beneficial relationship

Dysbiosis – microbial imbalance on or inside the body

The human microbiome consists of the genes these cells harbor

Each contain its own DNA

Primary location is in the gut

10,000+ species

1014 organisms

Bacteria, fungi, viruses, protozoa, helminths

~ 3% of body weight

Source: http://www.amnh.org/explore/science-topics/health-and-our-microbiome/meet-your-microbiome

Characteristics of the Human Microbiome

Characteristics of the Human Microbiome

Microbial populations vary by geographic location

High level of interpersonal variability

Commensal (normal or indigenous) bacteria perform many beneficial functions

High diversity r/t healthy microbiomes

Low diversity r/t dysbiosis

Studies suggest direct relationship between dysbiosis & metabolic diseases such as IBD, obesity, cancer (Clemente et al., 2012, Sartor and Mazmanian, 2012, Brown et al., 2013)

Composition of microbiome at distinct anatomical sites

Sources:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418802/figure/F1/

Capt J.A. Jones MD MS FACS, FACPM, FAsMA, Center for Space Medicine - Baylor College of Medicine

http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0160-7

Four main Gut phyla Firmicutes (64%)

Bacteroidetes (23%)

Proteobacteria (8%)

Actinobacteria (3%)

Often classified as 3 enterotypes Prevotella (Bacteroidetes)

Bacteroides (Bacteroidetes)

Ruminococcus (Firmicutes)

Development of Gut Flora

At birth, the GI tract is sterile

Microbiome is shaped by multiple factors:

Route of delivery

Early nutrition

Antibiotics

Vaccination

Antimicrobials

Hygiene

Alterations of “normal” development could predispose to inflammatory disease later in life

. Source: Cho I, Blaser MJ. (2012).The human microbiome: at the interface of health and disease. Nat Rev Gen. 13(4), 260-270.

How infants acquire gut microbes

The microbiome of children vs adults“First 3 years is when the microbiome is the most dynamic. Children developing immunity, metabolism, cognition” Martin J. Blaser MD

Yatsunenko et al, Nature. 2012 Jun 14; 486(7402): 222–227.

Functions of the Gut Microbiome

Immune development

Educates immune system to recognize self from non-self (auto-immune implications)

Digestion and nutrient absorption

Production of SCFA Acetate, propionate, butyrate

Main energy source of colonocytes

Maintain intestinal homeostasis

Secretion of antimicrobial products Prevent pathogen adherence to gut wall

Functions of the Gut Microbiome

Epithelial renewal and gut integrity

Metabolism & organ functions of brain, CVS, liver and others

Production of neurotransmitters responsible for mood

Regulation of gut motility

Detoxification of xenobiotics (carcinogens)

Vitamin synthesis

Gene expression

Importance of the Gut Microbiome

Obesity & Weight Management

Immune System Development in Infants

Autoimmune Disease

Food Allergies & Food Sensitivities

Mood

Gut Integrity

And many other associations

Influences on Microbiome

Host genotype

Medications

PPI, NSAIDS

Excess Hygiene

Diet

Micronutrient status (i.e. vitamin D deficiency)

Age

Stress

Mode of birth – vaginal vs C-section

Influences on Microbiome

Antibiotics are the #1 disruptor

↓ beneficial flora, ↑ opportunistic organism

By age 18, most kids in US have had ~ 20 abx

Can take > 1 year for gut flora to rebound

Loss of beneficial microbes & their products

Production of microbial metabolites & proinflammatory mediators impact intestine & other organ systems (Sun et al)

Comparison between the geography of obesity and antibiotic use in 2010

From Foreign Invaders to Friendly Fire

New Immunologic Battlefield

Inverse relationship between the incidence of infectious disease (left) and immune disease (right) from 1950 to 2000. (Jean-Francois Bach/NEJM)

The Modern Plagues

Autoimmune conditions

At least 80

Crohn’s, Type 1 Diabetes

RA, Multiple Sclerosis

Neurological Conditions

ADHD, ASD, Alzheimer’s

Parkinson’s, anxiety

Depression

Metabolic disorders

Migraines

IBS, IBD

Food allergies & sensitivities

Childhood conditions

Eczema, Asthma

Cyclic vomiting syndrome

FPIES

Common ≠ Normal!

Increase in T2DM Decrease in T2 DM

Intestinal bacterial phyla

Firmicutes X

Bacteroidetes X

Intestinal bacterial species

Roseburia (Butyrate producing) X

Eubacterium halii X

Faecalibacterium prauznitzii –Butyrate producing

X

Lactobacillus gasseri X

Streptococcus mutans X

E. Coli X

Intestinal bacterial species associated with and/or predictive of insulin

resistance/T2DM development as future potential clinical diagnostic markers of T2DM

Obesity and the Microbiome

Transplanting gut microbes from obese mice to germ-free mice results in increased adiposity in the latter

Mice fed high calorie western diet had high firmicutes to bacteroidetes ratio. Similar findings in humans

High-fat diet can change relative abundance of microbial species in the gut & lower the overall diversity

Reversible with weight loss

Reinhardt, JPGN, 2009 ; Ferrer, Env Micro, 2012

Autoimmune Disease

Some combination of dysbiosis and increased intestinal permeability

Leads to loss of oral tolerance and reaction to commensal bacterial or common food antigens

In genetically susceptible individuals, this can cause autoimmunity, allergy, and inflammation

Vitamin D deficiency common

The Microbiome & AutoimmunityDifferences in genus-level microbiome content between children who develop type 1 diabetes and children who do not

NOTE: rRNA = ribosomal RNA SOURCE: Brown et al., 2011.

Gluten and Intestinal Permeability

Gliadin is a component of gluten that is poorly digested in the gut

Gliadin binds to the endothelial cell surface receptor CXCR3

Over-expressed in celiac patients

Gluten can cause release of zonulin

Gut bacteria can also cause release of zonulin

Zonulin causes opening of tight junctions

Source: Alessio Fasano Physiological Reviews 1 January 2011 Vol. 91 no. 1, 151-175

Gut Integrity

Genetics, gut microbiota, and uncontrolled immune response cause defects in epithelial barrier function by affecting barrier integrity, increasing tissue

destruction & mucosal inflammation.Source: http://journal.frontiersin.org/article/10.3389/fmed.2014.00024/full

Components of the mucosal barrier in healthy gut (left) and inflammatory bowel disease (right)

The basic structure of tight junctions and other junctional complexes are shown in the bottom-right box. JAM: junctional adhesion molecules

certain fatty acids ….. can reduce

inflammation and restore mucosal

permeability However, their therapeutic

efficacy, particularly in IBD, remains

debatable: butyrate, zinc, and probiotics

have the strongest evidence in this regard.

Microbes & Mood

“The gut and the bacteria in the gut are intricately and

inextricably interwoven with brain function.”

NeurologistAuthor:

Brain Maker

David Perlmutter MD

Microbes and Mood

Diet and the Microbiome

Diet is the most significant factor for health & diversity of the microbiomeAlessio Fasano MD

Professor, Harvard Medical School

Chief of Pediatric Gastroenterology & Nutrition

Massachusetts General Hospital

Source: Perlmutter, D., & Loberg, K. (2015). Brain maker: The power of gut microbes to heal and protect your brain--for life (1st ed). Little, Brown and Co.

Diet and the Microbiome

Most consistent and predictable way of reshaping the gut microbiome

Everything we consume will either enhance, maintain or undermine the health of our microbiome

Changes in microbiota composition can be quick (24 hrs)

Diet rapidly and reproducibly alters the human gut microbiome

LA David, et al (Harvard Univ), Nature 2014 Vol 505:559-563

10 participants divided into 2 groups x 5 days

milk, cheese and meat

grains, vegetables, legumes

Relative abundance of bacteria species shifted in 1 day

Increase in microbes used to produce cheeses and cure meats

Within 3 days saw changes in types of genes turned on in the microbes

Animal diet

↑ abundance of bile-tolerant species

(i.e. Bacteroidetes, bilophila wadsworthia – linked to colitis in animal studies)

↓Firmicutes that metabolize plant polysaccharides

Diet and the Microbiome

Overall Diet

Type of diet supports/determines type of microbial population that thrives

Variety is important

High fiber diets, healthy fats

Probiotic & prebiotic foods

Avoid pasteurized foods

Avoid chlorinated tap water

Avoid processed foods and added sugars

Glucose, salt, emulsifiers, organic solvents, gluten, microbial

transglutaminase, and nanoparticles are …… used by the

food industry, claim the manufacturers, to improve the

qualities of food. All of the aforementioned additives increase

intestinal permeability by breaching the integrity of tight

junction paracellular transfer.

Diet and the Microbiome

Probiotics in the Diet

Fermented Foods

Needs to reach the large intestine

fat has a protective effect

read labels for “live cultures”

Functional Foods

Foods with added pre and probiotics

Ex: yogurts, cereals, chocolate, granola bars

Probiotic (Fermented) Foods

Active-Culture Yogurt

Kefir

Kombucha Tea

Tempeh

Kimchi

Sauerkraut

Pickles

Pickled fruits and vegetables

Cultured condiments

Fermented meat, fish, and eggs

Benefits of Fermented Foods

Potent sources of probiotics

Increase bioavailability of certain vitamins & minerals

Rich in enzymes

Destroy or inhibit pathogenic bacteria

Improve digestion

Fermentation Basics

Wild fermentation – letting what’s on the food grow naturally Time consuming

Inoculating with starter culture speeds up process

Can use salt, salt and whey or a starter culture

Caution with vinegar in foods:

Not all fermented foods are pickled and not all pickles are fermented

Probiotic sprays for your home???

Prebiotics

Indigestible by human enzymes

Need to reach large intestine

Fermented by the intestinal microflora

Selectively stimulates the growth and/or activity of intestinal bacteria associated with health and well-being

Prebiotics

Established health benefits:

Improve calcium absorption

Modify glycemic index

Reduce gut transit time by enhancing colonic bacterial fermentation

Increase growth of lactobacilli, bifidobacteria, bacteroides, decrease pathogenic strains

Ongoing research

Benefits for IBD & IBS, obesity and others

Combo pre and probiotic supplements – more research needed to evaluate impact on probiotic and resident bacteria

Sources: Choosing a prebiotic product, ILSI Europe Concise Monograph, 2013

Slavin J. Fiber and Prebiotics: Mechanisms and Health Benefits. Nutrients. 2013;5(4):1417-1435

Prebiotics

Often labeled as:

Galacto-oligosaccharides (GOS)

Fructo-oligosaccharides (FOS)

Oligofructose (OF)

Chicory fiber

Inulin

Arabinogalactans

Prebiotic content of foods

http://jn.nutrition.org/content/129/7/1407S/T1.expansion.html

Prebiotics

Fiber and resistant starch (plant based, whole foods)

beans, nuts, seeds, roots, leaves, fibrous skins, stalks

All prebiotics are soluble fiber but not all soluble fiber are prebiotics

Foods: chicory root, Jerusalem artichoke, dandelion greens, garlic, leek, carrots, radishes, acacia fiber, wheat bran

Breast milk: increases bifidobacteria & discourages pathogens

Cooking can reduce prebiotic fiber 25 – 75%

Source: Verhasselt, V. (2010). Oral tolerance in neonates: from basics to potential prevention of allergic disease. Mucosal Immunology; 3(4):326-33. doi: 10.1038/mi.2010.25.

Probiotic Supplements

“Live microorganisms that, when administered in adequate amounts, confer a health benefit to the host” (Intl. Scientific Assoc. for Probiotics & Prebiotics)

Bacteria or yeasts

In supplements or foods (medicinal yogurts, juices, etc)

Fermented foods not defined as a true “probiotic”

Rationale: have undefined microbial content

Can’t be relied on for specific therapeutic effects in the same way as probiotic preparations that contain well defined strains, known clinical effects, precise doses

Nat Rev Gastroenterol Hepatol 2014. 11(8): p. 506-514

Probiotic Supplements

Note: novel uses based on research conducted the last 15 years. Source: Probiotic Advisor

Probiotic Supplements

Considerations when choosing probiotics

No “one strain fits all”

Choose by appropriate mode of action

3 key steps in choosing an effective probiotic:

1. Need to know genus, species and strain

2. Determine what research has shown strain to be effective for

3. Ensure the product contains viable amounts of organisms

Usually >109 CFU of each organism per dose

Probiotics for Eczema

Lactobacillus GG normalizes gut permeability in children with IBS & FAP

http://selfcarejournal.com/article/human-microbiota-in-health-and-disease/

Studies of probiotics in pediatric patients with IBS

http://selfcarejournal.com/article/human-microbiota-in-health-and-disease/

https://www.probioticadvisor.com/

Human Fecal Transplant Trial (FMT)

Microbiome monitored before and after transplant

Tyler Case Study- Severe EczemaDOB 8/2011

Uncomplicated vaginal delivery – no sedatives

Mom given IV antibiotics during labor due to GBS

Reduced or eliminated lactobacillus from birth canal

Breastfed for 14 months

Healthy first 4 months, no sickness or abx

Vaccine at 2 months for DTaP

Vaccine at 4 months for DTaP

Tyler Case Study- Severe EczemaDOB 8/2011

4 ½ months

Immune system went haywire,

developed eczema and looked like

burn victim within 24 hours. Became

allergic to almost everything he came

in contact with including soaps,

polyester & more

5 months

When he took off his mittens and

silently clawed his face in the

backseat…

Tyler Case Study- Severe EczemaDOB 8/2011

Dietary protocol – in addition to healthy diet

Remove gluten & dairy from Tyler & mom

Fermented foods

Testing

Environmental

Supplements

Tyler Case Study- Severe EczemaDOB 8/2011

Dietary protocol – in addition to healthy diet

Testing

For newly acquired food allergies & sensitivities

Peanut, egg, soy, wheat, dairy, fish, dog, cat

.0.35 considered “high,” peanut & egg are > 100

Multiple food sensitivities in addition to allergies

For micronutrient deficiencies

Genova stool test

Environmental

Supplements

Tyler Case Study- Severe EczemaDOB 8/2011

Overall, very inflamed with 17 yellows and 7 reds

Tyler’s Stool Test- Genova Labs- 2 ¾ yoNo lactobacillus- Remember, he’s never been on abx but main source of initial lactobacillus exposure is birth canal. Mom was put on abx pre-birth due to + GBS

Tyler Case Study- Severe EczemaDOB 8/2011

①Re②As③As

Spectracell Micronutrient Test Results:

Tyler Case Study- Severe EczemaDOB 8/2011

Dietary protocol – in addition to healthy diet

Testing

Environmental

Remove all fragrances, dyes, switch to natural cleaning products

Use only cotton clothing, bedding (allergy to polyester)

Supplements

Tyler Case Study- Severe EczemaDOB 8/2011

Dietary protocol – in addition to healthy diet

Testing

Environmental

Supplements

Diamine Oxidase (to dampen reaction to exogenous histamine)

Oral probiotics

Fermented foods

As needed to replete deficiencies, plus phosphatidylcholine (PC), EPO, omega-3 FA

Tyler at 10 months

Perhaps the mammalian immune system which appears designed to control microbes is, in fact, controlled by the microbes themselves.

We’re more microbe than human!

Final Thoughts

The human microbiome has a complex relationship between microbes & their hosts

The formation of our microbiome begins at birth and changes throughout our life

A broad range of diseases result from the disruption of our microbiome

Understanding the role of specific microbes will open the way to novel strategies for disease diagnosis, monitoring and therapy

Final Thoughts

Proactive steps can be taken to preserve the microbiome from birth

Avoid microbiome disruptors especially unnecessary antibiotic use

Diversity of healthy foods rich in pro and prebiotics

Probiotic supplements if needed

Questions?

Thank you!

Resources

NIH Human Microbiome Project http://hmpdacc.org/resources/tools_protocols.php

Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, by Martin Blaser MD

Caltech Sarkis Mazmanian Lab publications http://sarkis.caltech.edu/publications

Gut Microbiota for Health website (European Society for Neurogastroenterology & Motility (ESNM) http://www.gutmicrobiotaforhealth.com/en/home/

Brain Maker, by David Perlmutter MD

Dietaryfiber.org

Resources

Probiotic Advisor (membership required after free trial) https://www.probioticadvisor.com/

Fermented food recipes

http://nourishedkitchen.com/recipe-index/ferments-cultured-food/

Mastering Fermentation by Mary Karlin

http://masteringfermentation.com/mary.html

Stool testing

Genova GI Effects

Food sensitivities

MRT/LEAP www.nowleap.com

References

Breastfeeding and the use of human milk Pediatrics. 2005;115(2):496-506. doi: 10.1542/peds.2004-2491.

Microbial modulation of innate defense: Goblet cells and the intestinal mucus layer http://ajcn.nutrition.org/content/73/6/1131S.full. Accessed 4/22/2016, 2016.

The Body’s ecosystem | the scientist magazine® http://www.the-scientist.com/?articles.view/articleNo/40600/title/The-Body-s-Ecosystem/. Accessed 4/22/2016, 2016.

The human microbiome: At the interface of health and disease http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418802/. Accessed 4/22/2016, 2016.

Prebiotics | ISAPP http://isappscience.org/prebiotics/. Accessed 4/22/2016, 2016.

Pone.0078687 1..9 - low-incidence-of-spontaneous-type-1-diabetes-in-non-obese-diabetic-mice-raised-on-gluten-free-diets-is-associated-with-changes-in-the-intestinal-microbiome.pdf http://www.drperlmutter.com/wp-content/uploads/2014/03/Low-Incidence-of-Spontaneous-Type-1-Diabetes-in-Non-Obese-Diabetic-Mice-Raised-on-Gluten-Free-Diets-Is-Associated-with-Changes-in-the-Intestinal-Microbiome.pdf. Accessed 4/22/2016, 2016.

Biagi E, Nylund L, Candela M, et al. Correction: Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians PLoS ONE. 2010;5(6). doi: 10.1371/annotation/df45912f-d15c-44ab-8312-e7ec0607604d.

Blaser, M. J. & Falkow, S. What are the consequences of the disappearing human microbiota? Nature Rev. Microbiol. 7, 887–894 (2009)

Slavin J. Fiber and Prebiotics: Mechanisms and Health Benefits. Nutrients. 2013;5(4):1417-1435. doi:10.3390/nu5041417

References

Capt J.A. Jones MD MS FACS, FACPM, FAsMA, Center for Space Medicine - Baylor College of Medicine

Cho I, Blaser MJ. The human microbiome: At the interface of health and disease Nat Rev Genet. 2012;13(4):260-270. doi: 10.1038/nrg3182 [doi].

Clemente et al., 2012, Sartor and Mazmanian, 2012, Brown et al., 2013

Coskun M. Intestinal epithelium in inflammatory bowel disease Frontiers in Medicine. 2014;1. doi: 10.3389/fmed.2014.00024.

Cryan JF, O’Mahony SM. The microbiome-gut-brain axis: From bowel to behavior Neurogastroenterology & Motility. 2011; 2011;23(3):187-192. doi: 10.1111/j.1365-2982.2010.01664.x.

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De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from europeand rural africa Proc Natl Acad Sci U S A. 2010;107(33):14691-14696. doi: 10.1073/pnas.1005963107 [doi].

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Perlmutter, D., & Loberg, K. (2015). Brain maker: The power of gut microbes to heal and protect your brain--for life (First edition.). Little, Brown and Co.

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