Complex Clinical Study - PDF document

1 Complex Clinical Study Review Advanced
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 Presenter Jill Carnahan, MD. ABIHM, ABoIM

2 , IFMCP www.jillcarnahan.com Technical
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5 anced SIBO and GI Testing Jill C. Carn
anced SIBO and GI Testing Jill C. Carnahan, MD, ABIHM, ABoIM , IFMCP Flatiron Functional Medicine www.JillCarnahan.com • Could Irritable Bowel Syndrome (IBS) be an autoimmune disease? • Explore the link between IBS and small intestinal bacterial overgrowth (SIBO)

6 • Present clinical cases and discus
• 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 d

7 iarrhea and eczema • In childhood tre
iarrhea 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 :ashimoto’s thyroiditis • Went on autoimmune paleo diet, lost 40 pound

8 s Bacterial Overgrowth of the Small Inte
s 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 infecti

9 ons Pyleris E, et al. Dig Dis Sci. 201
ons 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

10 Overgrowth (SIBO) – Abnormally large
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

11 , reduced bile acids, steatorrhea, wei
, 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 me

12 chanisms for preventing bacterial overgr
chanisms for preventing bacterial overgrowth – G astric acid secretion – I ntestinal motility – I ntact ileocecal valve – I mmunoglobulins within intestinal secretion – B acteriostatic properties of pancreatic and biliary secretion • E tiology of SIBO is

13 usually complex – Achlorhydria – Pa
usually complex – Achlorhydria – Pancreatic exocrine insufficiency (PEI) – Immunodeficiency syndromes – Anatomical abnormalities • Small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileocecal resections – Motility disorders â€

14 ¢ Scleroderma , autonomic neuropathy in
¢ 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):1

15 6 – 24 . • Post - infectious IBS •
6 – 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

16 • NASH ( nonalcoholic steatohepatitis
• 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. “=n patients with cel

17 iac disease partially responsive or unr
iac disease partially responsive or unresponsive to GFD, SIBO and lactose intolerance should be suspected͘” 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

18 higher prevalence of S=BO,…” PPI -
higher prevalence of S=BO,…” PPI - Induced SIBO “Conclusions : Prolonged PPI treatment may produce bowel symptoms and S=BO͘” Compare D, et al. Eur J Clin Invest. 2011;41(4 ): 380 - 86 . “Conclusions : Dysmotility and PPI use were independent risk factors for

19 SIBO or SIFO and were present in over
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 overgrowth͘” Jacobs C, et al. Aliment Pharmacol Ther . 2013;37(11):1103 - 11. Parodi

20 A, et al. Clin Gastroenterol Hepatol .
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. S leep Med. 2011;12(6 ): 610 - 13. © JIL

21 L C CARNAHAN, MD • Restless Leg Syndr
L 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 defic

22 iency which, in turn, leads to RLS “
iency 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 , kl

23 ebsiella , enterococcus and streptococ
ebsiella , enterococcus and streptococcus species – Klebsiella produces neurotoxins • Do n’ t forget Small Intestine Fungal Overgrowth (SIFO) can coexist ! • Problems may come from endotoxemia – Lipopolysaccharides (LPS) • Impacts liver function and obesit

24 y • Bile acids unable to conjugate tox
y • 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 prevalen

25 ce of Firmicutes populations...Current
ce 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 . • Ac

26 hlorhydria • Hypochlorhydria • Proto
hlorhydria • Hypochlorhydria • Proton pump inhibitors • Dysmotility • Malnutrition • Collagen vascular disease • Immune deficiency • Bowel Resection • Bariatric surgery • Advancing Age • Chronic Pancreatitis • Chronic ABX use • IgA Deficiency • Celia

27 c Disease • Crohn’s Disease • Shor
c 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 • Lo

28 w serum ferritin • B12 deficiency •
w 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 R

29 osacea • Undigested food in stool •
osacea • 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 • Chr

30 onic PPI, H2 blocker or anti - acid us
onic 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

31 1 more capsule/tablet – Continue to
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

32 • Gold standard: Upper GI aspirate
• 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 –

33 not diagnostic • Stool test – not
not diagnostic • Stool test – not diagnostic • C ommonly 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_posi

34 tion_of_the_small_bowel_CRUK_360.svg •
tion_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 :

35 – Starch: grains , beans, starchy veg
– 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

36 and Polyols ) https://en.wikipedia.org
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 (arti

37 chokes, asparagus, cabbage, garlic, mus
chokes, 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 -

38 fodmap - foods/ https://www.lowfodmap.co
fodmap - foods/ https://www.lowfodmap.com/high - low - fodmap - foods/ 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 , star

39 chy vegetables, lactose, some beans and
chy 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 intesti

40 nes heal – Personal tailoring of the
nes 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

41 symptom - free – Diet famous for expl
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)

42 (Elaine Gottschall ) • Elemental Die
(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 Formu

43 las – Many brands are available over t
las – 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 â

44 €“ Expensive Elemental Diet • Medicati
€“ 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 – Gi

45 nger • Herbal Treatments 4 - 8 weeks â
nger • 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 contraindic

46 ated because SIBO often involves an over
ated 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

47 constipation, treatment with r ifaxim
constipation, treatment with r ifaximin 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 G uar G um Fumari M, et al. Aliment Ph

48 armacol Ther . 2010;32(8 ): 1000 - 06. T
armacol Ther . 2010;32(8 ): 1000 - 06. The combination of r ifaximin 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% Case Stu

49 dy: 22 Year Old Female • Fatigue , alt
dy: 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

50 deficiency Case Study: 22 Year Old Fema
deficiency Case Study: 22 Year Old Female Case Study: 22 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 Ca

51 se Study: 55 Year Old Female • History
se Study: 55 Year Old Female • History of bloating and diarrhea Case Study: 70 Year Old Male Case Study: 70 Year Old Male • Complaints of Constipation Case Study: 44 Year Old Female • TEST don’t GUESS – Use 3 hour lactulose breath test • May need successive trea

52 tment rounds – If g�as 35 - 4
tment rounds – If g�as 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 â

53 €¢ Must address motility with prokineti
€¢ 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 bean

54 s, 24 hours white rice/water, 12 hour fa
s, 24 hours white rice/water, 12 hour fast – Don’t do immediately upon waking͖ do 10 clearing breaths before Key Points Questions? US Client Services: 800 - 522 - 4762 UK Client Services: 020.8336.7750 We look forward to hearing from you! • February 27, 2019 – W

55 omen, Menopause, =nsulin Resistance, and
omen, Menopause, =nsulin Resistance, and Alzheimer’s͗ 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 Comp

56 lex Patient – Stephen Goldman, DC Upc
lex Patient – Stephen Goldman, DC Upcoming LIVE GDX Webinar Topics Register for upcoming LIVE GDX webinars and access archived webinars online at WWW . GDX . NET Complex Clinical Study Review Advanced SIBO and GI Testing Jill C. Carnahan, MD, ABIHM, ABoIM , IFMCP F