complex clinical study review - genova diagnostics · • acne or rosacea • undigested food in...

Complex Clinical Study ReviewAdvanced SIBO and GI Testing

Jill C. Carnahan, MD, ABIHM, ABoIM, IFMCPFlatiron Functional Medicine www.JillCarnahan.com

Lahnor Powell, ND, MPHMedical Education Specialist for Genova Diagnostics

Presenter

Jill Carnahan, MD. ABIHM, ABoIM, IFMCPwww.jillcarnahan.com

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• Could Irritable Bowel Syndrome (IBS) be an autoimmune disease?

• Explore the link between IBS and small intestinal bacterial overgrowth (SIBO)

• Present clinical cases and discuss treatment options for IBS/SIBO

• Review causes and treatment of small intestinal fungal overgrowth (SIFO)

Objectives for This Presentation

Case Study: 27 Year Old Female

• Fatigue and severe bloating after meals, frequent diarrhea and eczema

• In childhood treated for many ear infections, and strep throat up to 10X in 1 year

• Many environmental allergies and frequent migraines

• Diagnosed 2 years ago with Hashimoto’s thyroiditis

• Went on autoimmune paleo diet, lost 40 pounds

Bacterial Overgrowth of the Small Intestine

• Symptoms can resolve with balancing of the gut microflora

•Up to 37.5% of patients evaluated for IBS may also suffer from a quantitative increase in bacteria in the small bowel, especially following enteric infections

Pyleris E, et al. Dig Dis Sci. 2012;57(5):1321-29.

Bacterial and Fungal Dysbiosis

Lacy B, et al. Gastroenterol Hepatol (N Y). 2011;7(11):729-39.

Pathophysiology, Evaluation, and Treatment of Bloating: Hope, Hype, or Hot Air?

• Small Intestinal Bacterial Overgrowth (SIBO)

– Abnormally large numbers of bacteria (at least 100,000 bacteria per ml of fluid) present in the small intestine

• Signs & Symptoms

– Bloating, abdominal discomfort, diarrhea, abdominal pain, belching, gas

– Anemia, B12 deficiency, malnutrition, reduced bile acids, steatorrhea, weight loss, food allergies, brain fog, systemic inflammation, chronic fatigue, restless leg syndrome

– Also associated with micronutrient deficiencies (B12, A, D and E, iron, thiamine, nicotinamide)

What is SIBO?

• Defense mechanisms for preventing bacterial overgrowth– Gastric acid secretion

– Intestinal motility

– Intact ileocecal valve

– Immunoglobulins within intestinal secretion

– Bacteriostatic properties of pancreatic and biliary secretion

• Etiology of SIBO is usually complex– Achlorhydria

– Pancreatic exocrine insufficiency (PEI)

– Immunodeficiency syndromes

– Anatomical abnormalities

• Small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileocecal resections

– Motility disorders

• Scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction

Bures J, et al. World J Gastroenterol. 2010;16(24):2978-90.

Factors Contributing to SIBO

Chedid V, et al. Glob Adv Health Med. 2014;3(3):16–24.

• Post-infectious IBS

• Achlorhydria

• Pancreatic exocrine insufficiency

• Immune deficiency syndromes (selective IgA deficiency, CVID)

• Small intestinal obstruction/motility issues

• Celiac disease

• Crohn’s disease

• Short bowel syndrome

• NASH (nonalcoholic steatohepatitis)

• Scleroderma

• Autonomic neuropathy in diabetes

• Radiation enteropathy

Causes of SIBO

Celiac Patients Unresponsive to a Gluten-Free Diet

Ghoshal UC, et al. BMC Gastroenterol. 2004;4(10):1-6.

“In patients with celiac disease partially responsive or unresponsive to GFD, SIBO and

lactose intolerance should be suspected.”

Type 1 Diabetes

Ojetti V, et al. Eur Rev Med Pharmacol Sci. 2009;13(6):419-23.

“Conclusions: Patients with autonomic neuropathy have a significantly higher

prevalence of SIBO,…”

PPI-Induced SIBO

“Conclusions: Prolonged PPI treatment may produce bowel symptoms and SIBO.”

Compare D, et al. Eur J Clin Invest. 2011;41(4):380-86.

“Conclusions: Dysmotility and PPI

use were independent risk factors

for SIBO or SIFO and were present in

over 50% of subjects with

unexplained gastrointestinal

symptoms. Diagnosis of overgrowth

requires testing because symptoms

were poor predictors of overgrowth.”

Jacobs C, et al. Aliment Pharmacol Ther. 2013;37(11):1103-11.

Parodi A, et al. Clin Gastroenterol Hepatol. 2008;6(7):759-64.

• Rosacea patients have a significantly higher SIBO prevalence than controls

• Eradication of SIBO induced complete remission of cutaneous lesions

Weinstock LB, et al. Sleep Med. 2011;12(6):610-13.© JILL C CARNAHAN, MD

• Restless Leg Syndrome (RLS) patients are selectively predisposed to SIBO• SIBO leads to autoimmune changes, and subsequent auto-antibodies

attack on brain and/or peripheral nerves• SIBO inflammation leads to increased hepcidin and CNS iron deficiency

which, in turn, leads to RLS

“Escherichia coli, Enterococcus spp and Klebsiella pneumoniae were the most

common isolates within patients with SIBO.”

Pyleris E, et al. Dig Dis Sci. 2012;57(5):1321-29.

• May predominately be due to E. coli, klebsiella, enterococcus and streptococcus species

– Klebsiella produces neurotoxins

• Don’t forget Small Intestine Fungal Overgrowth (SIFO) can coexist!

• Problems may come from endotoxemia– Lipopolysaccharides (LPS)

• Impacts liver function and obesity

• Bile acids unable to conjugate toxins and get reabsorbed (water soluble)

https://commons.wikimedia.org/wiki/File:Diverse_e_Coli.png

SIBO Organisms

“Microbioma dysbiosis is present in metabolic syndrome, with lower prevalence of Bacteroidetes and increased prevalence of Firmicutes populations...Current evidence suggests that innate

immunity and intestinal microbiota may be the hidden link in the metabolic syndrome development mechanisms.”

Portela-Cidade J, et al. GE Port J Gastroenterol. 2015;22(6):240–58.

• Achlorhydria

• Hypochlorhydria

• Proton pump inhibitors

• Dysmotility

• Malnutrition

• Collagen vascular disease

• Immune deficiency

• Bowel Resection

• Bariatric surgery

• Advancing Age

• Chronic Pancreatitis

• Chronic ABX use

• IgA Deficiency

• Celiac Disease

• Crohn’s Disease

• Short Bowel Syndrome

• Non-alcoholic steatohepatitis

• Cirrhosis

• Fibromyalgia

• Rosacea/acne

Conditions Associated with SIBO

Hypochlorhydria

• Empiric testing with Betaine HCl

• Heidelberg testing

• Low serum zinc

• Low serum ferritin

• B12 deficiency

• Gluten sensitivity/celiac disease

https://upload.wikimedia.org/wikipedia/commons/a/a6/Hydrochloric_acid.jpg

Common Symptoms:

• Bloating or belching immediately after a meal

• Weak, peeling, or cracked fingernails

• Acne or Rosacea

• Undigested food in stool

• Iron or B12 deficiency

• Chronic intestinal infections

• Multiple food allergies

Potential Antecedents:

• Vegetarian lifestyle

• Aging

• Fasting

• Viral or bacterial infection

• Any debilitating chronic condition

• Chronic PPI, H2 blocker or anti-acid use

Hypochlorhydria

• Treatment:

– Betaine HCl with or without Pepsin

• Instructions

– Take 1 HCI capsule with your next large meal, ideal timing is 0-10min prior to meal

– At every meal after that of the same size take 1 more capsule/tablet

– Continue to increase the dose until you reach 7 capsules/tablets or when you feel a warmth in your stomach, whichever occurs first

https://www.maxpixel.net/Dinner-Meal-Beef-Meat-Delicious-Dish-Food-Plate-3101305

Hypochlorhydria

• Gold standard: Upper GI aspirate

• 3 hour Lactulose Breath test for hydrogen/methane

– H2 (Hydrogen) > 20 ppm

– CH4 (Methane) > 3

• 3-9 ppm Moderate; CH4 > 10 ppm Positive

• Combination H2 + CH4 >15 ppm

• Organic acids – not diagnostic

• Stool test – not diagnostic

• Commonly Associated Vitamin Deficiencies

– Low ferritin, B12, D3, K2, E, etc.

Diagnosis of SIBO

Small Intestinal Bacterial Overgrowth

Treatment of SIBO

https://commons.wikimedia.org/wiki/File:Diagram_showing_the_position_of_the_small_bowel_CRUK_360.svg

• Fermentable Carbohydrates/Saccharides:– Starch– Resistant Starch– Soluble Fiber– Sugar (in all it's forms)– Prebiotics (inulin, FOS, MOS, GOS, arabinogalactan)

• Sources of Fermentable Carbohydrates/Saccharides:– Starch: grains, beans, starchy vegetables– Resistant Starch: whole grains, seeds, legumes – Soluble Fiber: grains, beans, nuts/seeds, vegetables, fruit– Sugar: fruit, sweeteners

Low FODMAP: (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols)

https://en.wikipedia.org/wiki/Apple#/media/File:Honeycrisp.jpg

Low FODMAP DIET

High FODMAPs include:

– Most dairy products

– Certain fruits (apples, pears, cherries, raspberries, watermelons, stone fruit, mango, papaya)

– Certain vegetables (artichokes, asparagus, cabbage, garlic, mushrooms)

– Certain grains (wheat, rye, barley, spelt)

– Legumes (including soybeans)

– Sweeteners (including honey, agave nectar)

– Food additives (chicory root, inulin, xylitol)

https://www.lowfodmap.com/high-low-fodmap-foods/

LESS FERMENTABLE MORE FERMENTABLE

Artichoke Hearts* 1/8 c

Arugula

Bamboo Shoots

Beet 2 slices

Bok Choy 1 c/85g

Broccoli ½ c/1.6oz

Brussels Sprouts 2 ea

Cabbage 1 c/98g

Cabbage: Savoy ½ c

Carrot

Celery Root/Celeriac

Chives

Cucumber

Eggplant

Endive

Fennel bulb½c, leaves 1c

Green Beans 10ea/2.5oz

Greens: lettuce, collard,

chard, kale, spinach

Olives

Peas, green ¼ c

Peppers: Bell/ Sweet

Peppers: Chili 11cm/28g

Radicchio 12 leaves

Radish

Rutabaga

Scallion: green part

Snow Peas: 5 pods

Squash: Butternut ¼ c

Kobocha, Sunburst,

Yellow, Zucchini ¾ c

Tomato

Asparagus 1 spear

Artichoke Hearts* ¼ c

Butternut Squash

½ c/60g

Cabbage >1 c/98g

Cabbage: Savoy 3/4 c

Leek ½ ea/42g

Parsnip

Pepper: Chili 40g

Peas, green 1/3c

Spinach >15 leaves/

150g

Tomato: soup/juice

Tomato: Sun-dried

2 T/15g

Asparagus 4 spears

Artichoke

Avocado

Beet 4 slices

Bok Choy 1½ c/127g

Broccoli 1 c

Brussels Sprouts 6 ea/

114g

Cabbage: Savoy 1 c

Cauliflower

Celery

Fennel bulb >1 c,

leaves >3c

Garlic

Jerusalem artichoke

Leek 1 ea/84g

Mushrooms

Onions

Peas, green½ c/72g

Snow Peas 10 pods

Scallions: white part

Shallot

Sugar Snap Peas

Zucchini >¾ cup

Bean Sprouts

Corn

Okra

Potato: white/all colors

Potato: sweet

Starch powder: all

arrowroot, corn,

potato, rice, tapioca

Seaweeds

Turnip

Taro

Water Chestnuts

Yam

Yucca

Canned vegetables

SIBO Food Guide

Vegetables

SCD “LEGAL”LOW FODMAP

SCD “LEGAL”MODERATE FODMAP

SCD “LEGAL”HIGH FODMAP

SCD “ILLEGAL”

Dr. Siebecker 1/13/14

http://www.siboinfo.com

• Allowed: meat/fish/poultry, eggs, some beans, lactose-free dairy, non-starchy vegetables, ripe fruit, nuts/seeds, honey, and saccharine

• Not Allowed: grains, starchy vegetables, lactose, some beans and any sweeteners other than honey, saccharine and occasional stevia– Introduction Diet recommended to start

• Cooked vegetables, cooked ripe fruit, no beans and very little nuts are recommended

– Diet progresses as the intestines heal

– Personal tailoring of the diet within the allowed foods is recommended as individuals vary greatly as to what they can tolerate

– 75-84% success rate if followed strictly – originally used for children with celiac disease

– Must stay on diet to remain symptom-free

– Diet famous for explaining and including lactose-free dairy, especially intro diet or 24-hour homemade yogurt as well as introducing nut flours (almond) as a grain alternative

http://www.breakingtheviciouscycle.info/

Specific Carbohydrate Diet (SCD) (Elaine Gottschall)

• Elemental Diet– This approach seeks to starve the bacteria, but feed the person, by replacing meals for 2 weeks

with an Elemental Formula

– Elemental formulas are powdered nutrients in pre-digested, easily absorbed form

• Elemental Formulas– Many brands are available over the counter

– Studied formula: Vivonex Plus - which contains amino acids, maltodextrin, various oils and vitamins

• Advantages – 80-85% success rate eradicating SIBO, safe and tolerable 14 day course

• Disadvantages– Expensive

Elemental Diet

• Medications for 10-14 days– Rifaximin

– Add Metronidazole or Neomycin for methane producers

• Pro-Kinetic Agents– Low dose naltrexone (LDN)

– Low dose erythromycin

– Resolor (Canada) – serotonin agonist

– Iberogast

– Ginger

• Herbal Treatments 4-8 weeks– Berberine up to 5 grams daily (500mg-1500mg BID/TID)

– Oregano 200mg TID x 2-6 weeks

– Garlic: Allicin extract 450mg BID x 4-6 weeks

– Neem

SIBO Treatment

• May use Biofilm disruptors

• Probiotics may be contraindicated because SIBO often involves an overgrowth of D-lactate-producing species

• Address lifestyle modification for migrating motor complex (MMC)

– 4-5 hours between meals

– No eating 2 hours before bedtime

SIBO Treatment

“Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS

symptoms, bloating, abdominal pain, and loose or watery stools.”

Pimentel M, et al. N Engl J Med. 2011;364(1):22-32.

Rifaximin Plus Guar Gum

Fumari M, et al. Aliment Pharmacol Ther. 2010;32(8):1000-06.

The combination of rifaximin with partially hydrolysed guar gum seems to be more useful in eradicating SIBO compared with rifaximin alone Eradication rate with:

• Rifaximin alone = 61% • Rifaximin + Guar gum = 87%


• Fatigue, alternating constipation and diarrhea for one year

• Treated for a parasitic infection last year after spending a college semester abroad

• Stool testing negative for parasite

• Conventional lab workup revealed vitamin B12 deficiency

• Significant bloating and constipation for several years

• Hx of hypothyroidism and GERD

• Takes over the counter antacids daily and laxatives once a week


• History of bloating and diarrhea

Case Study: 70 Year Old Male

Case Study: 70 Year Old Male

• Complaints of Constipation


• TEST don’t GUESS– Use 3 hour lactulose breath test

• May need successive treatment rounds– If gas > 35-45 ppm

– Average decrease with antibiotics 25-35 ppm

• Methane and IBS-C are harder to treat– Double Antibiotics/Allicin needed for methane/constipation cases

• Re-test 2 weeks after completion of antibiotic treatment

• Must address motility with prokinetic if failure

• Must address diet or relapse will occur

Key Points

• Reasons why Rifaximin may not work

– SIBO too severe

– Methane needs dual treatmeni

– Bacteria not sensitive to Rifaximin

• Breath prep 48 hours no beans, 24 hours white rice/water, 12 hour fast

– Don’t do immediately upon waking; do 10 clearing breaths before

Key Points

Questions?

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We look forward to hearing from you!

• February 27, 2019 – Women, Menopause, Insulin Resistance, and Alzheimer’s: What is the Link?– Filomena Trindade, MD, MPH

• March 27, 2019 – Male Hormones: What You Need to Know– Pam W. Smith, MD, MPH

• April 24, 2019 – Hormone Testing: Selecting the Right Profile for Your Complex Patient – Stephen Goldman, DC

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complex clinical study review - genova diagnostics · • acne or rosacea • undigested food in...

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