COMPLEX CLINICAL STUDY REVIEW - ADVANCED SIBO AND GI TESTING JILL C. CARNAHAN, MD, ABIHM, ABOIM, IFMCP - GENOVA DIAGNOSTICS
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Complex Clinical Study Review Advanced SIBO and GI Testing Jill C. Carnahan, MD, ABIHM, ABoIM, IFMCP Flatiron Functional Medicine www.JillCarnahan.com
Lahnor Powell, ND, MPH Medical Education Specialist for Genova Diagnostics
Jill Carnahan, MD. ABIHM, ABoIM, IFMCP
www.jillcarnahan.com
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Complex Clinical Study Review Advanced SIBO and GI Testing Jill C. Carnahan, MD, ABIHM, ABoIM, IFMCP Flatiron Functional Medicine www.JillCarnahan.com
Objectives for This Presentation • 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)
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
Pathophysiology, Evaluation, and Treatment of
Bloating: Hope, Hype, or Hot Air?
Lacy B, et al. Gastroenterol Hepatol (N Y). 2011;7(11):729-39.What is SIBO?
• 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)Factors Contributing to 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.Chedid V, et al. Glob Adv Health Med. 2014;3(3):16–24.
Causes of SIBO
• Post-infectious IBS • NASH (nonalcoholic steatohepatitis)
• Achlorhydria • Scleroderma
• Pancreatic exocrine insufficiency • Autonomic neuropathy in diabetes
• Immune deficiency syndromes • Radiation enteropathy
(selective IgA deficiency, CVID)
• Small intestinal obstruction/motility
issues
• Celiac disease
• Crohn’s disease
• Short bowel syndromeCeliac Patients Unresponsive to a Gluten-Free Diet
“In patients with celiac disease partially
responsive or unresponsive to GFD, SIBO and
lactose intolerance should be suspected.”
Ghoshal UC, et al. BMC Gastroenterol. 2004;4(10):1-6.Type 1 Diabetes
“Conclusions: Patients with autonomic
neuropathy have a significantly higher
prevalence of SIBO,…”
Ojetti V, et al. Eur Rev Med Pharmacol Sci. 2009;13(6):419-23.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.• Rosacea patients have a significantly higher
SIBO prevalence than controls
• Eradication of SIBO induced complete
remission of cutaneous lesions
Parodi A, et al. Clin Gastroenterol Hepatol. 2008;6(7):759-64.• 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
© JILL C CARNAHAN, MD Weinstock LB, et al. Sleep Med. 2011;12(6):610-13.“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.SIBO Organisms
• 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“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.Conditions Associated with SIBO • Achlorhydria • Chronic Pancreatitis • Hypochlorhydria • Chronic ABX use • Proton pump inhibitors • IgA Deficiency • Dysmotility • Celiac Disease • Malnutrition • Crohn’s Disease • Collagen vascular disease • Short Bowel Syndrome • Immune deficiency • Non-alcoholic steatohepatitis • Bowel Resection • Cirrhosis • Bariatric surgery • Fibromyalgia • Advancing Age • Rosacea/acne
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.jpgHypochlorhydria Common Symptoms: Potential Antecedents: • Bloating or belching immediately • Vegetarian lifestyle after a meal • Aging • Weak, peeling, or cracked fingernails • Fasting • Acne or Rosacea • Viral or bacterial infection • Undigested food in stool • Any debilitating chronic condition • Iron or B12 deficiency • Chronic PPI, H2 blocker or • Chronic intestinal infections anti-acid use • Multiple food allergies
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-3101305Diagnosis of SIBO
• 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.Small Intestinal Bacterial Overgrowth
Treatment of SIBO
https://commons.wikimedia.org/wiki/File:Diagram_showing_the_position_of_the_small_bowel_CRUK_360.svgLow FODMAP: (Fermentable Oligosaccharides,
Disaccharides, Monosaccharides and Polyols)
• 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
https://en.wikipedia.org/wiki/Apple#/media/File:Honeycrisp.jpgLow 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/
https://www.lowfodmap.com/high-low-fodmap-foods/
SIBO Food Guide
Vegetables
LESS FERMENTABLE MORE FERMENTABLE
SCD “LEGAL” SCD “LEGAL” SCD “LEGAL”
SCD “ILLEGAL”
LOW FODMAP MODERATE FODMAP HIGH FODMAP
Artichoke Hearts* 1/8 c Asparagus 1 spear Asparagus 4 spears Bean Sprouts
Arugula Artichoke Hearts* ¼ c Artichoke Corn
Bamboo Shoots Butternut Squash Avocado Okra
Beet 2 slices ½ c/60g Beet 4 slices Potato: white/all colors
Bok Choy 1 c/85g Cabbage >1 c/98g Bok Choy 1½ c/127g Potato: sweet
Broccoli ½ c/1.6oz Cabbage: Savoy 3/4 c Broccoli 1 c Starch powder: all
Brussels Sprouts 2 ea Leek ½ ea/42g Brussels Sprouts 6 ea/ arrowroot, corn,
Cabbage 1 c/98g Parsnip 114g potato, rice, tapioca
Cabbage: Savoy ½ c Pepper: Chili 40g Cabbage: Savoy 1 c Seaweeds
Carrot Peas, green 1/3c Cauliflower Turnip
Celery Root/Celeriac Spinach >15 leaves/ Celery Taro
Chives 150g Fennel bulb >1 c, Water Chestnuts
Cucumber Tomato: soup/juice leaves >3c Yam
Eggplant Tomato: Sun-dried Garlic Yucca
Endive 2 T/15g Jerusalem artichoke
Canned vegetables
Fennel bulb ½c, leaves 1c Leek 1 ea/84g
Green Beans 10ea/2.5oz Mushrooms
Greens: lettuce, collard, Onions
chard, kale, spinach Peas, green ½ c/72g
Olives Snow Peas 10 pods
Peas, green ¼ c Scallions: white part
Peppers: Bell/ Sweet Shallot
Peppers: Chili 11cm/28g Sugar Snap Peas
Radicchio 12 leaves Zucchini >¾ cup
Radish
Rutabaga
Scallion: green part
Snow Peas: 5 pods
Squash: Butternut ¼ c
Kobocha, Sunburst,
Yellow, Zucchini ¾ c
Tomato
Dr. Siebecker 1/13/14
http://www.siboinfo.comSpecific Carbohydrate Diet (SCD) (Elaine Gottschall)
• 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/Elemental Diet
• 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
– ExpensiveSIBO Treatment • 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
“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
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%
Fumari M, et al. Aliment Pharmacol Ther. 2010;32(8):1000-06.Case Study: 22 Year Old Female • 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
Case Study: 22 Year Old Female
Case Study: 22 Year Old Female
Case Study: 55 Year Old Female • Significant bloating and constipation for several years • Hx of hypothyroidism and GERD • Takes over the counter antacids daily and laxatives once a week
Case Study: 55 Year Old Female
Case Study: 70 Year Old Male • History of bloating and diarrhea
Case Study: 70 Year Old Male
Case Study: 44 Year Old Female • Complaints of Constipation
Key Points • 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
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