1. Copyright HD Scientific 2014-2105 All Rights Reserved 1 When Is Intestinal Gas Dangerous? Dangerous?

2. 2 Chronic IBS-Like Symptoms Frequent cause of primary care visits Frequent cause of primary care visits May be primary reason for visit or co-morbid with other condition May be primary reason for visit or co-morbid with other condition Range of severity Range of severity From mild to severe From mild to severe Moderate-Severe cases affect QOL, high health care costs Moderate-Severe cases affect QOL, high health care costs Often refractory/challenging Often refractory/challenging Poor response to conventional therapies Poor response to conventional therapies May need referral to GI May need referral to GI Diarrhea Loose stools Pain/Discomfort Gas Bloating Constipation Urgency Copyright HD Scientific 2014-2105 All Rights Reserved

3. 3 Common Causes of IBS-Like Symptoms 1.Irritable Bowel Syndrome 2.Small Intestinal Bacterial Overgrowth (SIBO) 3.Fructose Malabsorption 4.Lactose Intolerance 5.Inflammatory Bowel Disease 6.Celiac Disease Copyright HD Scientific 2014-2105 All Rights Reserved

4. Problem: Accurate Diagnosis Cannot make a symptom-based diagnosis for 5/6 Cannot make a correct diagnosis of IBS without first ruling out 5/6 4 1.IBS 2.SIBO 3.Fructose Mal. 4.Lactose Intol. 5.IBD 6.Celiac Disease 1.IBS 2.SIBO 3.Fructose Mal. 4.Lactose Intol. 5.IBD 6.Celiac Disease Outcomes Depend on Accurate Diagnosis Copyright HD Scientific 2014-2105 All Rights Reserved

5. When is Intestinal Gas Dangerous? The Seemingly Least Important Symptom is in Fact the Most Important Clue Intestinal gas production is caused primarily by bacterial fermentation The site of gas production is critical Small Intestine = SIBO Large Intestine = carbohydrate malabsorption 5 Copyright HD Scientific 2014-2105 All Rights Reserved

6. Definition of SIBO 6 Small Intestinal Bacterial Overgrowth (SIBO) is a disorder of either excessive growth or alteration of the types of bacteria present in the small intestine. SIBO is one of the most common gastrointestinal diseases, affecting approximately 30 million Americans Small Intestinal Bacterial Overgrowth (SIBO) is a disorder of either excessive growth or alteration of the types of bacteria present in the small intestine. SIBO is one of the most common gastrointestinal diseases, affecting approximately 30 million Americans Copyright HD Scientific 2014-2105 All Rights Reserved

7. “It is mandatory to consider SIBO in all cases of complex non- specific dyspeptic complaints (bloating, abdominal discomfort, diarrhea, abdominal pain), in motility disorders, anatomical abnormalities of the small bowel and in all malassimilation syndromes (malabsorption, maldigestion).” Bures J, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterology 2010 June 28; 16(24): 2978-2990 “It is mandatory to consider SIBO in all cases of complex non- specific dyspeptic complaints (bloating, abdominal discomfort, diarrhea, abdominal pain), in motility disorders, anatomical abnormalities of the small bowel and in all malassimilation syndromes (malabsorption, maldigestion).” Bures J, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterology 2010 June 28; 16(24): 2978-2990 Why? Managing SIBO is Mandatory 7 Copyright HD Scientific 2014-2105 All Rights Reserved

8. SIBO Causes Enterocyte/Microvilli Damage “Biopsies of the small bowel in bacterial overgrowth can mimic those of celiac disease, making the diagnosis more challenging.” Blunting of microvilli Enterocyte damage Toskes P, Giannella R, Jervis H, Rout W, Takeuchi A (1975). "Small intestinal mucosal injury in the experimental blind loop syndrome. Light- and electron-microscopic and histochemical studies". Gastroenterology 68 (5 Pt 1): 1193–203. PMID 1126607PMID1126607 8 Copyright HD Scientific 2014-2105 All Rights Reserved

9. Wide Ranging Clinical Ramifications of Undiagnosed/Untreated SIBO Copyright HD Scientific Inc. 2014-2015 All Rights Reserved 9 SIBO Bacterial Macro & Micro Nutrient Consumption Bacterial Metabolic Byproducts Bacterial Endotoxins Inflammatory Response SIBO Bacterial Macro & Micro Nutrient Consumption Bacterial Metabolic Byproducts Bacterial Endotoxins Inflammatory Response GI Symptoms Diarrhea Loose stools Urgency Gas Production Pain/Discomfort Constipation GI Symptoms Diarrhea Loose stools Urgency Gas Production Pain/Discomfort Constipation Gut Damage Enterocyte damage Villous atrophy Gut Damage Enterocyte damage Villous atrophy Carbohydrate Malabsorption Fructose Lactose Carbohydrate Malabsorption Fructose Lactose Malnutrition Macronutrients – Carbs, Lipids, Proteins Fat soluble vitamins – Vitamin A, D, E B Vitamins, Iron – B-12, thiamine Minerals – Calcium, magnesium Malnutrition Macronutrients – Carbs, Lipids, Proteins Fat soluble vitamins – Vitamin A, D, E B Vitamins, Iron – B-12, thiamine Minerals – Calcium, magnesium Extra-Intestinal Symptoms & Disease Osteoporosis Rosacea Anemia Polyneuropathy Fatigue Brain fog Malaise Weight loss Etc. Extra-Intestinal Symptoms & Disease Osteoporosis Rosacea Anemia Polyneuropathy Fatigue Brain fog Malaise Weight loss Etc. Bacterial Translocation Leaky Gut

10. Rosacea: SIBO-Related Bacterial Translocation? Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Parodi A 1, Paolino S, Greco A, Drago F, Mansi C, Rebora A, Parodi A, Savarino V. Clinical Gastroenterology & Hepatology. 2008 Jul;6(7):759-64. doi: 10.1016/j.cgh.2008.02.054. Epub 2008 May 5. The prevalence of SIBO was higher in patients than controls (52/113 vs 3/60, P <.001). 10 day treatment with Rifaxamin – non-absorbable antibiotic After eradication, cutaneous lesions cleared in 20 of 28 and greatly improved in 6 of 28 patients, whereas patients treated with placebo remained unchanged (18/20) or worsened (2/20) Eradication of SIBO induced an almost complete regression of cutaneous lesions and maintained this excellent result for at least 9 months Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Parodi A 1, Paolino S, Greco A, Drago F, Mansi C, Rebora A, Parodi A, Savarino V. Clinical Gastroenterology & Hepatology. 2008 Jul;6(7):759-64. doi: 10.1016/j.cgh.2008.02.054. Epub 2008 May 5. The prevalence of SIBO was higher in patients than controls (52/113 vs 3/60, P <.001). 10 day treatment with Rifaxamin – non-absorbable antibiotic After eradication, cutaneous lesions cleared in 20 of 28 and greatly improved in 6 of 28 patients, whereas patients treated with placebo remained unchanged (18/20) or worsened (2/20) Eradication of SIBO induced an almost complete regression of cutaneous lesions and maintained this excellent result for at least 9 months 10 Copyright HD Scientific 2014-2105 All Rights Reserved

11. Achlorhydria Celiac disease Crohn’s Diabetes Fibromyalgia Gastroparesis IBS 11 SIBO Associated Conditions Immunodeficiency syndromes Liver cirrhosis Chronic pancreatitis Restless legs syndrome Rosacea Scleroderma Short bowel syndrome Range of Symptom Severity MildSevere Copyright HD Scientific 2014-2105 All Rights Reserved

12. Copyright HD Scientific 2014 All Rights Reserved 12 Carbohydrate Malabsorption Fructose Malabsorption – Poor absorption of fructose containing foods Colonic bacteria consume unabsorbed fructose  leads to H2 production, bloating, gas & various GI symptoms Lactose Intolerance – Poor absorption of lactose due to lactase deficiency Colonic bacteria consume unabsorbed lactose  leads to H2 production, bloating, gas & various GI symptoms

13. 13 Breath H2 Testing is Best Method to Diagnose SIBO & Carbohydrate Malabsorption 40+ year history with lactose intolerance 25+ years with fructose malabsorption Used in virtually all research to diagnose SIBO and carbohydrate malabsorption Non-invasive Highly accurate Covered by virtually all insurance Copyright HD Scientific 2014-2105 All Rights Reserved

14. HydroStat Gives Critical Diagnostic Information Assess target organ of bacterial metabolic activity Small Intestine: SIBO Large Intestine: Fructose Malabsorption Lactose Intolerance 14 Copyright HD Scientific 2014-2105 All Rights Reserved

15. HydroStat Improves Diagnostic Ability HydroStat accurately diagnoses 3 of 6 common causes of IBS- like symptoms leading to targeted treatment and significantly improved outcomes 15 1.SIBO 2.Fructose Malabsorption 3.Lactose Intolerance 1.SIBO 2.Fructose Malabsorption 3.Lactose Intolerance Copyright HD Scientific 2014-2105 All Rights Reserved

16. 16 Diagnostic Workup for Moderate to Severe IBS-Like Symptoms HydroStat SIBO Fructose Malabsorption Lactose Intolerance HydroStat SIBO Fructose Malabsorption Lactose Intolerance History IBD (0.5%) Celiac (0.75%) Colorectal Cancer Travel Abroad History IBD (0.5%) Celiac (0.75%) Colorectal Cancer Travel Abroad Blood Tests CBC Celiac Panel Thyroid Panel Blood Tests CBC Celiac Panel Thyroid Panel Stool Studies Occult Blood Parasites Pathogens Stool Studies Occult Blood Parasites Pathogens Alarm Signals Rectal Bleeding Nocturnal Diarrhea Weight Loss >50 Years Old Alarm Signals Rectal Bleeding Nocturnal Diarrhea Weight Loss >50 Years Old + = >70% Treatment Success >70% Treatment Success Targeted Diagnostics  Targeted Therapy  Better Outcomes Copyright HD Scientific 2014-2105 All Rights Reserved