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VS. PLANT-BASED THE EFFECTS OF A LOW-FOMAP DIET FOR SIBO/IBS

PLANT-BASED HEALTH CONFERENCE 2019 BY: ANGIE SADEGHI, MD “IT’S ALL ABOUT THE BIOME“ • “Within one linear centimeter of your lower colon, there lives and works more bacteria (about 100 billion) than all humans who have ever been born. • Yet many people continue to assert that it is we who are in charge of the world.”

Neil deGrasse Tyson

GUT MICROBIOME:

Bacteria, Viruses, Fungi, Archaea, Protozoa

Collective genome contains at least 100x as many genes as our own eukaryote genome

Grenham S, Front Physiol, 2011 Topping DL, Clifton PM. Physiol Rev 2001 Jul;81(3):1031-64. SHORT CHAIN FATTY ACIDS

McNabney and Henagan. Nutrients 2017, 9, 1348 OMNIVOROUS VS. PLANT-BASED Whole Food Plant-based diet: Omnivorous Diet:

Fiber Rich: Low-moderate fiber -Average fiber intake 60-100 g/day -Average fiber intake 10-50 g/ day Fruits Fruits Vegetables Vegetables Grains Grains Nuts Nuts Seeds Seeds Meat *** Eggs *** Low in fat: Dairy *** No cholesterol Small amount of saturated fat Moderate to high levels of saturated fat and cholesterol OMNIVOROUS DIET VS. PLANT-BASED DIET • Non-evidence based recommendations • Fish and eggs • Less “gassy foods” to “starve the SIBO” • The paleo diet • The auto-immune diet • Food combining • Carnivore diet • Keto diet • Evidence-based recommendations for controlling SIBO/IBS symptoms • Low-FODMAP diet Filippo et al. Proc Natl Acad Sci USA. 2010 Aug 17; 107(33):14691-14696 • Compared 14 healthy Burkina Faso (BF) in rural Africa children to 15 European children • BF children consume the traditional rural African diet • Low in fat and animal protein • Rich in starch, fiber, and plant polysaccharides • Mainly cereals (millet grain, sorghum), legumes (black-eyed peas, called Niébé), and vegetables

Filippo et al. Proc Natl Acad Sci USA. 2010 Aug 17; 107(33):14691-14696 • The EU children eat a typical western diet • High in animal protein, animal fat, and low in fiber • The fiber average content in EU diet • 5.6 g/d (0.67%) in 1- to 2-y-old children • 8.4 g/d (0.9%) in 2- to 6-y-old children • The average amount of fiber in BF diet • 10.0 g/d (2.26%) in 1- to 2-y-old children • 14.2 g/d (3.19%) in 2- to 6-y-old children

Filippo et al. Proc Natl Acad Sci USA. 2010 Aug 17; 107(33):14691-14696 Deflippo et al. Proc Natl Acad Sci USA. 2010 Aug 17; 107(33):14691-14696 Filippo et al. Proc Natl Acad Sci USA. 2010 Aug 17; 107(33):14691-14696 • Collected bacterial data: • 326 individuals aged 0–17 years • 83 Malawian, 65 Amerindian, and 178 residents of the USA • 202 adults aged 18–70 years • 31 Malawian, 35 Amerindian, and 136 residents of the USA

Yatsunenko et al. Nature. 2010 May; 486(7402): 222–227. Yatsunenko et al. Nature. ; 486(7402): 222–227 MICROBIOME DIVERSITY

Yatsunenko et al. Nature. ; 486(7402): 222–227. Note: High-fat chow: -vegetable oil -lard

Hildebrandt et al. Physiol Rev. 2001 Jul;81(3):1031-64. -Both wild-type and KO mice stayed lean on the standard chow diet

-Upon switching to a high-fat diet Wild-type mice became obese KO mice remained lean

Hildebrandt et al. Physiol Rev. 2001 Jul;81(3):1031-64. HIGH FAT DIET (HFD)

• Large alterations upon switching mice to a high fat diet : • Increased Firmicutes and Proteobacteria • Decreased Bacteriodes

• Microbiota changes seen independent of

• Therefore a high-fat diet itself, and not the obese state, accounts for the changes in the

Hildebrandt et al. Physiol Rev. 2001 Jul;81(3):1031-64. Desai et all. Cell. 2016 Nov 17; 167 (5): 1139-1353 GUT MUCUS LAYER

• First line of defense against invading pathogens • Produced by Goblet cells • Tightly adherent to the epithelium • Poorly colonized • Nutritional aspect: • Composed of mucin-2 glycoprotein (MUC2) • Has a high polysaccharide content • Apart from , alternative energy source • Bacteroides • Evolved to shift from dietary polysaccharides to mucus glycan metabolism in the absence of fiber

Desai et all. Cell. 2016 Nov 17; 167 (5): 1139-1353 Desai et all. Cell. 2016 Nov 17; 167 (5): 1139-1353 A high-fat diet:

• Endotoxemia measured by plasma Lipopolysaccharides (LPS)

• LPS are a byproduct of intestinal bacteria

• Strongly increased

• Reduced the expression of genes coding for proteins of the tight junctions

Cani PD et al. Diabetes. 2008; 57(6):1470 Stenman et al. World J Gastroenterol. 2012 Mar 7; 18(9): 923–929 Stenman et al. World J Gastroenterol. 2012 Mar 7; 18(9): 923–929 PRIMARY AND SECONDARY BILE SALTS Adv Nutr 2019;00:1–15 Adv Nutr 2019;00:1–15 Lawrence et al. Nature. 2014 Jan 23;505(7484):559-63. Lawrence et al. Nature. 2014 Jan 23;505(7484):559-63. METABOLITES

High TMAO levels cause 2-3 fold increase in risk of heart disease

For every 10 micromlar increase in TMAO, there is a 7.6% increase in all cause mortality as shown in a study of over 25K participants

Zeneng, et. al. European Heart J., Vol 40, Issue 7, 14 February 2019, Pages 583–594 Sciattarella, et. al. European Heart J., Vol. 38, Issue 39, 14 October 2017, Pages 2948–2956 9/23/19 35 Suez et al. Cell 2018 Sep 6;174(6):1406-1423 Suez et al. Cell 2018 Sep 6;174(6):1406-1423 Suez et al. Cell 2018 Sep 6;174(6):1406-1423 Suez et al. Cell 2018 Sep 6;174(6):1406-1423 REMEMBER THE 4 FUNDAMENTALS

• High Fiber diet- good • Low fiber diet- bad • High fat diet- bad • Animal protein- bad SMALL INTESTINAL BACTERIAL OVERGROWTH SIBO

• Symptoms • Clinical manifestations • Diagnose • Etiologies • Treatment options *** • Reverse Elimination Diet • Challenges • Expected timeline for resolution when someone is fully compliant • What can a practitioner expect when they begin treatment SIBO

• A 2018 meta analysis found that 38% of IBS cases were caused by SIBO

• Not all IBS is SIBO

Chen, Et. Al. J Gastroenterol. 2018 Jul;53(7):807-818

IBS-DIARRHEA

Pimentel et al. N Engl J Med 2011; 364:22-32 SYMPTOMS ASSOCIATED WITH SIBO

• Abdominal pain/discomfort • • Abdominal distension • Diarrhea or constipation • Foul smelling • Reflux/burping

Weiss, et, al. Dermatol Pract Concept. 2017 Oct; 7(4): 31–37 Weinstock, et. al. J Amer. Acad. Dermotology. May 2013Volume 68, Issue 5, Pages 875–876 CLINICAL MANIFESTATIONS OF SIBO

• Steatorrhea • /mineral deficiency

• — Fat-soluble (A, D, E, K)

• — Vitamin B12 • Vitamin excess • — Folate

Lappinga P, et al. Arch Pathol Lab Med. 2010 Feb;134(2):264-70 Dukowicz, et. al. Gastroenterol Hepatol (N Y). 2007 Feb; 3(2): 112–122 CAUSES OF SIBO CAUSES OF SIBO • Structural/Anatomic • St•ruc—tuSmallral/A nintestineatomic diverticula • — SmallSmall intestineintestine stricturesdiverticul a(radiation, medications, Crohn's disease) • — SurgicallySmall inte screatedtine str iblindcture loopss (radiation, medications, Crohn's disease) • — ResectionSurgically cofre ileocecalated blin dvalve loops • — FistulasResectio betweenn of ileoc proximalecal valv eand distal bowel • — GastricFistulas resectionbetween proximal and distal bowel • Motility• — G aDisordersstric resection • M•ot—ilityGastroparesis Disorders • — SmallGastro bowelpares idysmotilitys • — CeliacSmall bdiseaseowel dysmotility • — ChronicCeliac d iconstipationsease • Irritable• — C hBowelronic cSyndromeonstipation • CAUSES OF SIBO CONT.

•Elderly •Metabolic Disorders — Diabetes — Hypochlorhydria — Obesity •Organ System Dysfunction • — Cirrhosis • — Renal failure • — Pancreatitis • — HIV • — Crohn's disease • — Celiac disease • — Malnutrition/eating disorders •Medications • — Recurrent antibiotics • — Gastric acid suppression • — Chronic narcotic use CAUSES OF SIBO CONT.

• Endocrine disorders — Hypothyroidism — In a 2007 study, 54% of patients with hypothyroidism have SIBO

• Alcoholism

• Neurological diseases — Parkinson’s disease

•

Lauritano, et. al. J of Clin Endocrinology & Metabolism, Volume 92, Issue 11, 1 November 2007, Pages 4180–4184 SMALL INTESTINAL BACTERIA OVERGROWTH: NOT CAUSES

• Vegan diet • High fiber diet • Whole food plant-based diet DIAGNOSIS OF SIBO

• Aspirate of small bowel • >100,000 CFU/ML of aspirate BREATH TEST: Substrates used: Glucose or Lactulose

Positive test:

Rise of Hydrogen >20 PPM over baseline in the first 90 minutes of testing

Peak levels >10 PPM at any point during the test is a positive result SIBO GASSES: • Hydrogen producing bacteria • Anaerobic bacteria • Cause diarrhea • Produce serotonin, which can further increase motility • Methane producing organisms • Anaerobic archaea organisms • Linked with Constipation • Hydrogen Sulfide producing bacteria • Only found in 1-2% of SIBO patients • Usually linked with diarrhea & sulfur smelling gas • Bacteria acquire large amounts of sulfur from proteins, mainly & and reduce sulfur to hydrogen sulfide • Hard to diagnose (no current commercially available testing available)

Triantafyllou, et. al. J Neurogastroenterol Motil 2014; 20(1): 31-40 GOALS OF TREATMENT

• PREVENT RELAPSE! • 44% of patients successfully treated with antibiotics relapse within 9 months • Goal of treatment: • Treat the underlying cause • Provide nutritional support • Improve gut microbiome diversity • Decrease inflammation • Improve gut mucosal integrity • Treat the overgrowth with antimicrobials

Bures, et. al. World J Gastroenterol. 2010 Jun 28; 16(24): 2978–2990 NUTRITION THERAPY

• FODMAP DIET (Fermentable , , , and ) • Developed by Monash University in Sidney Australia in 2005 • Only indicated in research to be utilized for 6-8 weeks

• Problems: • Eliminates a lot of the rich foods • Decrease microbiome diversity • Some people end of eating more animal products due to limited food options • It doesn’t cure SIBO “band-aid therapy” • Short-term solution • Reintroduction of foods can be difficult

• Utilize a “Reverse Elimination Diet” to re-challenge and re-feed the gut microbiome LOW FODMAP DIET REDUCES SCFA

Sloan, et. al. PLoS One. 2018; 13(7): e0201410. • There was a decrease of Bifidobacteria

• There was a 47% reduction of total bacterial load

Halmos, et. al. Gut. 2015 Jan;64(1):93-100. FIRST VISIT:

• AVOID ALL DAIRY x1 month • Read labels because EVERYTHING HAS DAIRY • RTC 1 month • In the meanwhile rule out celiac disease and sensitivity • Follow up visit: -About 50% report total resolution of symptoms -The other 50% - ½ report improvement - ½ no improvement -Find underlying cause and treat -Decide whether to proceed with SIBO testing, antimicrobial therapy, nutritional therapy YOUR GUT CONNECTION: WWW.YOURGUTCONNECTION.COM

Eliminate gut-compromising foods including: • Animal products (meat, dairy, eggs) • Alcohol • Refined Sugar • Refined Oil (Fried foods, heated oils, etc) • Environmental toxins (Pesticide residues, heavy metals)

www.YourGutConnection.com YOUR GUT CONNECTION- SIBO REVERSE ELIMINATION DIET • Phase 1 • Focus is on starchy fruits and vegetables (bananas, plantains, root veggies, squash) • cooked foods • frozen produce • blended produce (pre-frozen or pre-cooked) • Phase 2 • Focus is on re-introducing simple • Organic white rice, cassava flour, green banana flower) • Trace amounts of whole fats (only whole fats such as coconut and ground flax) • Phase 3 • Focus is on re-introducing soaked, sprouted, and well-cooked legumes

www.YourGutConnection.com

YOUR GUT CONNECTION- SIBO REVERSE ELIMINATION DIET

• Phase 4 • Focus is on re-introducing soaked, sprouted nuts and seeds • Phase 5 • Focus is on re-introducing whole grains • Millet, buckwheat, quinoa, amaranth, sorghum, oats • Phase 6 • Focus is on re-introducing fermented foods • , sauerkraut, coconut yogurt, miso soup • Maintenance • Continue reintroducing more raw foods • Work on re-challenging the gut to break down previously “problematic foods” • Foods include: , , tomatoes, )

www.YourGutConnection.com TREATMENT INTERVENTIONS

• Antibiotics • Common antibiotics used in the treatment of SIBO are Rifaxamine and Neomycin • Benefits • Rifaxamine is very effective only in the small bowel • Doesn’t destroy the colonic bacteria • There is no known bacteria resistance • Risks • Can be very costly for patients (between $600-$1,200 out of pocket per round) Not all patients respond to 1 round of treatment TREATMENT INTERVENTIONS CONT. • Herbal anti-microbials • Contain concentrated doses of anti bacterial herbs and plant extracts, including: • Berberine • Thyme • Oregano • Lemon Balm • Sage Leaf • Chinese Licorice Root • Benefits: • More cost-effective • The response rate for normalizing breath hydrogen testing in patients with SIBO is equally effective • 46% for herbal therapies vs 34% for Rifaximin • Risks: • Cost is completely out of pocket to patients • Can be purchased on third party sites • Many physicians have not established access to these nutraceuticals

Chedid, et. al. Glob Adv Health Med. 2014 May; 3(3): 16–24. CHALLENGES & WHAT TO EXPECT

• Challenges • Nutrition confusion • Compliance • It requires people to prepare all

• Time

• Families who may no be on-board • Need to avoid eating out • Stay with the program for at least 6-12 weeks

• What can a practitioner expect when they begin treatment • A lot of questions • Portion control, protein, calories, specific foods • Food fears from previous allergy/sensitivity testing • Questions about co-morbidities WHAT TO EXPECT

• Expected timelines for resolution when someone is fully compliant • Depends: • Patients on the SAD diet • Patients with malnutrition • Patients with idiopathic SIBO • Patients with frequent use of colonics • Patients who are coming from restrictive diets for many years - Low-FODMAP • Patients with eating disorders -Even the vegans with eating disorders -Water/juice fasting for prolonged periods of time for fun CONCLUSION

• High-fiber & low-fat diet • SIBO or IBS-D • AVOID ALL DAIRY • Rule out celiac disease and gluten sensitivity • If SIBO: • Investigate and treat the underlying cause • Consider SIBO breath testing • Consider antimicrobial therapies • Use a Reverse Elimination Diet YOUR GUT CONNECTION www.YourGutConnection.com

Dr. Angie Sadeghi, MD Board Certified Gastroenterology & Internist

James Marin, RD, EN Registered , Environmental Nutritionist

Dahlia Marin, RDN Registered Dietitian Nutritionist

SUPPLEMENTARY SLIDES Desai et all. Cell. 2016 Nov 17; 167 (5): 1139-1353 Desai et all. Cell. 2016 Nov 17; 167 (5): 1139-1353 Cani PD et al. Diabetes. 2008; 57(6):1470 FOOD AND RESULTING MICROBIAL METABOLITES (FARMM)

• Objective: • Determine the relationship between dietary composition, gut microbiome composition, and the metabolic products that ultimately are present in the gut lumen and the plasma of humans

Manuscript in preparation IMPORTANCE OF FIBER

• Fiber provides direct physical benefits • Increases fecal bulking and laxation • A more important feature of dietary fiber— • A nutrient category that are not digestible by human enzymes • Provides an important substrate to the community of microbes in the distal gut • Humans produce ~17 gastrointestinal enzymes to digest mostly starch • Gut microbiota produce thousands of complementary enzymes • Enables them to ferment dietary polysaccharides into short-chain fatty acids (SCFAs)

Desai et all. Cell. 2016 Nov 17; 167 (5): 1139-1353

Singh et al. J Transl Med (2017) 15:73