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Small Intestinal Bacterial Overgrowth
11/1/2015
Speaker:
Adam Rinde, ND
Naturopathic Physician
Sound Integrative Health, P...
Today’s Discussion
• 1:00-1:30 p.m.: Background,
pathophysiology, clinical findings,
differential diagnosis.
• 1:30 p.m.-2...
Why is todays talk relevant?
• Likely half of your IBS patients might be dealing
with SIBO.
• Many other patients are deal...
Quick Note Of Disclosure
• I have no affiliations with Designs For Health or any
other companies or institutions besides S...
Key Learning Outcomes
• Understanding of background and clinical
workup related to SIBO
• Understanding of pathophysiology...
Germ Theory Vs. Bio-Terrain
Treating a germ vs. Balancing the Terrain
Louis Pasteur Vs. Antione B’echamp
Small Intestinal Bowel Overgrowth
Defined:
• Non-native bacteria and/or native bacteria, or
archaea are present in increas...
Normal Flora
PMID: 15316000 Copyright © 2014 American
Medical Association. All rights reserved.
Introducing…the known SIBO gut
microbes.
Methanogens
(Archaea) Hydrogen Sulfide
producers
Hydrogen
Producers
Not detectabl...
Features Of SIBO Gut Microbes
Methanogens
• Methanobrevibacter smithii, and other spp.
• Certain Clostridia and Bacteroide...
Features Of SIBO Gut Microbes
Methanogens
Kingdom Archaea
Associated with depletion of gut serotonin
4 H2 molecules are us...
Duodenal Microbes in IBS
compared to Controls : N=258
Giamarellos-Bourboulis et al., 2015
Mark, P., Ruchi, M., & Christopher, C. (2013). Gas and the Microbiome. Current Gastroenterology
Reports, 15(12), 1-6.
Anatomic or pathologic risk
factors
• Surgery
• Tumor
• Trauma
• Volvulus
• Ischemia
• Congenital short bowel
• Strangulat...
Functional Digestive Disorders at
Risk of Developing SIBO
• Irritable Bowel Syndrome
• Post-infectious IBS
• Gastroparesis...
Neuroendocrine Disorders
Leading To SIBO
• Fibromyalgia
• Type II Diabetes
• Parkinson’s Disease
• End Stage Renal Disease...
Additional risk factors for SIB0
• Fodmap/Carbohydrate Malabsorption
• Low Secretory IgA
• Low Hydrochloric Acid
• PPI’s
•...
Other Associations with SIBO
SIBO as a
contributing
Factor
• NAFLD
• FM/CFS
• Restless Leg
Syndrome
• Prostatitis
• Inters...
Disease Associations
Disorder Prevalence of SIBO Source
Irritable Bowel
Syndrome 4-78%
Grace, 2013; Quigley,
2013, Park, 2...
Disorder
Prevalence of
SIBO Source
CFS 81% Grace, 2013
Cystic Fibrosis 37% Lisowska, 2009
chronic pancreatitis 34-92% Grac...
Neuromuscular Disease
Prevalence
of SIBO Source
Muscular Dystrophy 65% Grace, 2013
Parkinson's Disease 54% Grace, 2013
Sur...
N of 1. Proposed unified definition:
SIBO as a heterogeneous disorder resulting as a sequelae of an upstream dysfunction w...
What keeps the small intestine relatively sterile?
• Ante-grade
digestion
• Peristalsis
• Adequate serum
IgA
• Migrating M...
Normal Motility Process
Segmentation
• Segmented contractions
• Peristalsis
• Occurs when food
enters the digestive
tract....
Fasting Pattern of Migrating Motor
Complexes, every 1-2 hours of fasting.
Phase II.
Intermittent
smooth
muscle
contraction...
Migrating motor
complex Inhibitors of MMC
• Low Small Intestine
pH
• Pancreatic
polypeptide binding
(PPY)
• Eating/grazing...
Migrating Motor Complex Alterations
in Disease
(PMID: 22450306 )
Interstitial Cells of Cajal: A network
mediator of the MMC.
SIBO Hypothesis of IBS
• Pioneered by Mark
Pimentel, MD from Cedar
Sinai Hospital, Los
Angeles.
• States that the near
maj...
Pimentel,2014. Global Symposium on
IBS, Los Angeles, CA
New Autoimmune Theory of IBS
1.Acute
Gastroenteritis
2.Cytolethal
...
Synthesis/new hypothesis of how
SIBO may develop in IBS/dysmotility
Acute Gastroenteritis
Disruption of ICC Cells /MMR
lea...
Implications of SIBO and Intestinal Permeability
Implications of SIBO and Intestinal Permeability
Subjective Clinical Findings of SIBO
History
Post-prandial bloating and distention.
Feculent breath smell, fish body odor ...
Core SIBO Symptoms that may
drive an SIBO investigation
Objective Clinical Findings
• Malabsorption findings rarely observed in
outpatient setting
• Borgborygymus
• Polyneuropath...
Differential Diagnosis in SIBO
• Functional Constipation
• Functional Diarrhea
• Carbohydrate Intolerance (Fructose Intole...
Differential Diagnosis in SIBO
Autoimmune
• Hypothyroidism (can have decrease motility but
also includes other specific fi...
SIFO Is The new Enteric Candidiasis?
Gastroenterology . 2011. Volume 140, Issue 5, Supplement 1, Page S-810
Investigation ...
workup and testing overview
• Blood tests are not often valuable in
detecting or confirming SIBO.
• Stool testing is not o...
Screening flow
processScreening Process
If you were at Monash University.
Monash Process
SIBO Workup Process
Diagnostic Testing
• Standard: Lactulose
Hydrogen Breath Test
• CDSA or Stool Microbiology
DNA
• Alter...
Additional Tests That May Be
Useful
Lactulose/Mannitol test
Intestinal Permeability Screen (Cyrex
Array 2)
Secretory IgA
U...
Diagnostics: Small Bowel Jejunal Aspirate
Vs. Hydrogen Breath Testing
.
Saad and Chey. 2014
Lactulose Breath Test vs .
Glucose Breath Test.
Criteria for Positive Lactulose
Hydrogen Breath Test
Criteria for Positive Lactulose
Glucose Breath Test
• A fasting hydro...
Regions of Intestine Accessible by Various
Diagnostic Methods To Detect SIBO
Duod./Jejunum……………/ Lactulose Breath Test
Lac...
Breath Testing for SIBO
(CPT code-91065
Quintron Breathtracker
• Usually requires appointment
with Gastroenterologist.
• L...
Sensitivity vs. Specificity
Lactulose Hydrogen Breath Test
False
Negatives
False
Positives
Rana,et.al.2014
Classic Findings LHBT
Methane Positive Hydrogen Positive
Conundrums
Merged Peek Flat Liner : H2S?
PMID: 1860825
Tip Of the
Iceberg
METHANE is only detected on breath test when quantities
of Methanogens are 106 or Greater.
According to...
RCCEG: Recommendations for the
Preparation and Performance of
Breath Testing (Saad & Chey, 2014)
Test Preparation
• Avoida...
Consolidation (personal opinion)
• Using Glucose Hydrogen Breath Test (GHBT) may
lead to false negatives in diarrhea subty...
Breast Testing Algorithm
Report Of Findings To Patient
(IFDYR)
• Introduction: materials
and methods used
• Factual observations
and results
• Inte...
bo@soundintegrative.com
Treatment: Know Your Patient
Plot chart of currently available strategies for modifying gut microbiota aiming to demonstrate
the relationship between t...
Cedar Sinai Updated SIBO/IBS
Treatment Algorithm
Adapted Cedar Sinai IBS/SIBO Protocol
Cedar Sinai Protocol
adapted from: Pimentel. 2006. A New IBS Solution.Health Point
P...
Rifaximin: The Data
• Mechanism of action: Acts on gram positive and gram negative bacteria
transcription by binding to th...
0
PMID: 21397724
Antibiotics treatment of methane+constipation-
predominant irritable bowel syndrome.
• N=31 breath methane positive with R...
Antibiotic Choices in SIBO
7-14 day course
• Ciprofloxacin (250 mg twice a day)
• Norfloxacin (800 mg/day)
• Metronidazole...
SIBO reoccurrence
• The relapse rate of SIBO after successful treatment is
high.
• 44% (35/80) of patients relapsed within...
Secondary Prevention:
Prokinetics
• Preventing Reoccurrence by improving motility
thereby increasing Phase III Migrating M...
Other Pro-Kinetic Agents
• Cisapride: relieves constipation-like
symptoms by indirectly stimulating the release
of acetylc...
Other emerging medication
groups in the IBS World
• Secretagogues: Lubiprostone: for IBS-C
• Opioid Agonist: Eluxadoline f...
Emerging issues related to
Rifaximin
• How many times can it be used without patient
developing a resistance?
• Does it “k...
2015
Sound Integrative Health
SIBO Therapeutic Order
Treatment Stepwise Process
Assess And Stabilize Adrenal and Immune Function: 2
weeks to 1 month and ongoing.
• Clinical Evaluation.
• Metabolic Detox...
Assess And Stabilize Adrenal and
Immune Function
Treatment
• Appropriate HPA support based on stage
of dysfunction and fin...
Assess And Stabilize Adrenal and Immune Function
Morning Glory Treatment
Bedtime Fodmap Friendly Bulk, Moisten, Soften
Mix...
Other acceptable Fiber Sources
• Soluble Fiber
• Guar Gum 5-15 grams per day
• Ground Flax Seed
• Resistant Starches (RS2)...
Modify Dysbiotic Lifestyle Factors
Modify Dysbiotic: Lifestyle:
Treatment Ongoing
Pick The Most Relevant
• Meal Spacing (3-4 hours)
between meals.
• Masticat...
Abdominal Release inspired by
Katy Bowman:
Release the Gut Shame!
• Start on Hands and Knees
• Release the stomach all the...
Step 3: Implement Sustainable Microbiome
Balancing Diet.
Implement Microbiome Balancing Diet
Multiple Options.
• Most researched in
FGID is Low Fodmap
Diet
• Most Popularized in
N...
The Low Fodmap Diet, edition 3,
Reducing poorly absorbed sugars to control gastrointestinal symptoms. 2012
Monash Universi...
Low Fodmap Diet
• Originated largely from research done by Dr Peter
Gibson, Professor of Medicine and Victoria at Monash
U...
Comparison of FGID friendly diets:
• Compares Low
Fodmap to
• SCD
• Anti-candida diet
• Paleolithic Diet
• Fructose Free D...
What are Fodmap’s? What is the
Science
• Fermentable, Oligo-, Di-, Mono-saccharides and PolyolS
(FODMAPs) are short chain ...
FODMAPS
Lactose
Fructose
Galactans
Fructans
Polyols
High FODMAP Absorption is poor by default
• The absence of luminal
enzymes capable of
hydrolyzing the glycosidic
bonds con...
Theoretical Model of Carbohydrate
Malabsorption
Barret and Gibson, 2007
Fodmap Malabsorption Model
Shepard,S.et.al.2013. PMID:23588241
23588241
Carbohydrate: chain length/digestion
Sugars (DP1-2) Site of absorption
Sucrose proximal sm intestine*
Glucose proximal s...
Randomized Fodmap Trial
• N=30 with IBS and 8 controls
• Low Fodmap Group (<.5 grams Fodmap) vs. Austrailian Diet Group Vs...
Carbohydrate
Intolerance in SIBO-positive patients
• SIBO-positive patients further showed significantly
higher prevalence...
Applications for Low Fodmap Diet
• Functional Bowel Disorders
• Irritable bowel syndrome
• Functional bloating
• Functiona...
Implications of long term use of Low
Fodmap Diet requires elucidation
• Monash Study indicated
that a long term low
Fodmap...
Step 4: Stabilizing Microbiome Balance
Step 4: Stabilizing Microbiome
Balance: 4 weeks to 3 months
• We are reducing and
stabilizing not
removing/eradicating.
• ...
Antibacterial activity of essential oils in
disc diffusion assays.
Significance levels obtained from two-
tailed t tests a...
Researched Natural Antimicrobial
Treatments
• Enteric Coated Peppermint Oil reported
benefit and improved breath hydrogen
...
• Original Retrospective
Chart Review showed:
• 23/67 Patients who took
1200 mg of Rifaximin
Daily had a negative LBT
afte...
Group 1 (triple Antibiotics) Group 2 (Biotics Group) Group 3 (Metagenics Group)
Clindamycin: 300mg TID x 4
weeks
Metronida...
Findings
• It again proved that
botanicals are decent
antimicrobials
• Did not control for diet
• Study did not show any
m...
• Start slow and work up to the maximum tolerable
dose
• Approach should have one Berberine based formula +
one phenolic m...
Foundations of treatment:
 An foundational Berberine-based formula in
combination with 1 or more
Biofilm Eradicator (Int...
Target Doses of Single Herbs. Will be Less when used in Combination!
Most from : (Bone, The Ultimate Herbal Compendium, 20...
General Principles:
• Reinforce Dietary Hygiene principles of meal
spacing and mastication and MOVEMENT(10,000
steps)
• Ut...
MMC treatment guidelines:
 If antimicrobials need to exceed 1 round, you might want to
start this stage in conjunction wi...
Step Six: Replenish Immune and Digestive Factors
(1-2 months)
• General Guidelines:
• Most patients tried these treatments before coming into your
office but now is a time when they sh...
• Replenish Gut Flora Friendly Diet:
• Reinforce Dietary Hygiene and Exercise
• FODMAP Challenge: Slowly graduating from a...
Probiotics for SIBO
• Most studies have been done for IBS not specifically for SIBO
• Bidobacterium infantis seems to outp...
Step Seven: Restore Gut Barrier (Ongoing)
General Guidelines:
• At this stage patient should be relatively stable.
• At this stage a gut healthy lifestyle should be...
• Supplementation
• Continue on lower dose maintenance probiotic (5 billion per day)
• Take gut lining supplementation inc...
Prevention
GI stabilization Supplementation
Lifestyle Maintenance
Address other health issues (pain, mental health)
Specif...
When treatment fails to help
• If you refer them away , make sure you invite them
back to discuss what they learned!
• Con...
Items in Development and more
experimental to add to resistant
patients and improve outcomes
• Elemental Diet to Stabilize...
Case Studies
Recap
Case Studies
Lessons from the past
Multifactorial. Too much too soon
HPI: Diarrhea (10 bowel movements per day), Weight loss, abrupt onset 3 months ago,
abdo...
Too much too soon
Return Visit 1@7 days
Reports improvement
Bowel movements down to 3 per
day
Bloating reduced with low fo...
Too much too soon
Return Visit 5 @10 days later
Diarrhea stopped after starting
Budesonide and VSL#3.No
bloating /No gas.
...
Too much too soon
ROC 14 days later
Budesonide and VSL#3 did not control things
Has been feeling anxious and irritable and...
Case 2: multifactorial, IS SIBO a Symptom
or the Cause ?
Return Visit 4 @30 days
Reflares when veering for from the low fo...
Case:2 Multifactorial
0
2
4
6
8
10
12
14
16
18
20
0 20 40 60 80 100 120 140 160 180
Methane
Hydrogen
35 year old Fear of Travel and Eating Out
HPI: Gas, Bloating, alternating constipation/diarrhea, crampy
abdominal pain in ...
35 year old: Fear of Travel and Eating Out
Total Gas Production Hydrogen/Methane positive
]35 year old. Fear of Travel and Eating Out
Return Visit 1@30 days
Reports improvement
Only a few days of
constipation, bl...
35 year old Fear of Travel and Eating Out
Email @45 days
Still digestively stable
Challenged fructans with minimal symptom...
Two Tacks, Post Infectious-IBS
43 year old male with constipation,
abdominal pain, nausea, joint pain, and
weight loss tha...
Two Tacks, Post Infectious-IBS
Treatment phase 3
Bitters before each meal
IGG/IgA Colostrum supplementation
Bile Salts 1-2...
Two Tacks, Post Infectious-IBS
Two Tacks, Post Infectious-IBS
Two Tacks, Post Infectious-IBS
Treatment phase 1
Homemade Elemental Diet
+ plant based
antimicrobial's
Prescription based
...
Case 1a: Two tacks: Post Infectious IBS
• 8/1/2014
“I am doing well and having more vitality and ability to eat
more as we...
Two Tacks, Post Infectious-IBS
Treatment phase 1
Homemade Elemental Diet
+ plant based
antimicrobial's
Prescription based
...
Case 1a: Two tacks: Post Infectious IBS
“ This protocol seems to be working very well. I have had a marked increase in
ene...
Recap
• Understanding of background and clinical workup related to
SIBO
• Understanding of pathophysiology and pathosequel...
Thank you
Contact
• Adam Rinde, ND
• Clinic Office: 425-889-5894
• Kirkland, Washington
• Email: drrinde@soundintegrative.com
• Webs...
Small Intestinal Bacterial Overgrowth Update 2015
Small Intestinal Bacterial Overgrowth Update 2015
Small Intestinal Bacterial Overgrowth Update 2015
Small Intestinal Bacterial Overgrowth Update 2015
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Small Intestinal Bacterial Overgrowth Update 2015

Dr. Adam Rinde updates Integrative Medicine Providers on Small Intestinal Bacterial Overgrowth (SIBO) which is explored as a potential contributing factor in Irritable Bowel Syndrome as well as a com-morbidity of motility disorders and diseases with disrupted motility (ie. Parkinsons Disease, and Diabetes). Dr. Rinde is a Bastyr University trained Naturopathic Physician in General Practice in Kirkland, Washington. He has a special interesting in mind-gut-immune-endocrine underpinnings of health.

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Small Intestinal Bacterial Overgrowth Update 2015

  1. 1. Small Intestinal Bacterial Overgrowth 11/1/2015 Speaker: Adam Rinde, ND Naturopathic Physician Sound Integrative Health, PLLC Kirkland, Washington
  2. 2. Today’s Discussion • 1:00-1:30 p.m.: Background, pathophysiology, clinical findings, differential diagnosis. • 1:30 p.m.-2:00 pm.: diagnostic testing, clinical approach. • 2:00 p.m.-2:15 p.m.: Q and A. sibo@soundintegrative.com • 2:15 p.m.-3:15 p.m.: Treatment approaches/algorithms . • 3:15 p.m.-3:30 p.m.: Q and A. • 3:30-3:50: Case Studies. • 3:50: Concluding Remarks
  3. 3. Why is todays talk relevant? • Likely half of your IBS patients might be dealing with SIBO. • Many other patients are dealing with chronic disease that contains SIBO as a co-morbidity. • The standard of care for SIBO is lacking long term efficacy and the route of delivery is not available to most and not greatly effective. • Naturopathic Physicians and Functional Nutritionists are experts in system balancing. • A better model for care needs to be developed that is more focused on gut terrain balancing and recurrence prevention. • SIBO provides an important model to understand the gut microbiome.
  4. 4. Quick Note Of Disclosure • I have no affiliations with Designs For Health or any other companies or institutions besides Sound Integrative Health, PLLC. • Cost of ND therapies and alternative labs are usually out of pocket hence l recommendations will need to be scaled accordingly to best compliance and affordability. • Many other treatments likely exist for SIBO then mentioned in this presentation .This lecture does not account for AOM and Ayurveda approaches that may also be effective • Much of the treatment process module does not account for waxing and waning of response and shifting response from other co-morbidities • Resource from today talk: http://www.soundintegrative.com/blog/sibo
  5. 5. Key Learning Outcomes • Understanding of background and clinical workup related to SIBO • Understanding of pathophysiology and pathosequelae of SIBO. • An appreciation for terrain balancing approaches and the functional connections in SIBO. • Actionable lecture to bedside steps to evaluate dysmotile or malabsorptive patient or those at risk for SIBO • Actionable lecture to bedside steps to treat and recover patients with SIBO • Actionable lecture to Bedside Steps to approach the most sensitive and treatment refractory patients
  6. 6. Germ Theory Vs. Bio-Terrain Treating a germ vs. Balancing the Terrain Louis Pasteur Vs. Antione B’echamp
  7. 7. Small Intestinal Bowel Overgrowth Defined: • Non-native bacteria and/or native bacteria, or archaea are present in increased numbers in the small intestine • Classically defined as a bacterial population in the small intestine exceeding 105 to 106 organisms/mL upon duodenal aspirate. • Modernly characterized by a greater than 20 ppm rise in Hydrogen before 180 minutes or any 2ppm rise or more in Methane above baseline on LHBT in the setting of upper intestinal digestive symptoms. • Can lead to small intestinal inflammation, maldigestion, malabsorption, and other extra- intestinal symptoms. Quigley,2010;Sachev,2013;Dukowick,2007;Bures 2010;Speigel,2011; Ghosal, 2012)
  8. 8. Normal Flora
  9. 9. PMID: 15316000 Copyright © 2014 American Medical Association. All rights reserved.
  10. 10. Introducing…the known SIBO gut microbes. Methanogens (Archaea) Hydrogen Sulfide producers Hydrogen Producers Not detectable on breath testing Associated with constipation Associated with diarrhea Triantafyllou,2014; Sahakian ,2009
  11. 11. Features Of SIBO Gut Microbes Methanogens • Methanobrevibacter smithii, and other spp. • Certain Clostridia and Bacteroides • Odorless • Normally Produced in Left Colon • In a gut neutral environment will compete and win with Hydrogen Sulfide reducers Hydrogen • Made up of gram positive and gram negative bacteria • More likely pain during and after defecation • More likely large and foul smelling stool • More likely urgency and weakness after the defecation Associated with constipation Associated with Diarrhea
  12. 12. Features Of SIBO Gut Microbes Methanogens Kingdom Archaea Associated with depletion of gut serotonin 4 H2 molecules are used to make 1 CH4 molecule Associated with obesity Play a key role in butyrate production in large Intestine by reducing hydrogen. Hydrogen Producers Mainly produced by gram negative proteobacteria and gram positive colonic bacteria that have entered the colon several species involved of oral-colonic flora Generally sensitive to peptidoglycan layer acting agents In the presence of methanogens in large Intestine will help digest polysaccharides and produce Butyrate Associated with constipation Associated with Diarrhea
  13. 13. Duodenal Microbes in IBS compared to Controls : N=258 Giamarellos-Bourboulis et al., 2015
  14. 14. Mark, P., Ruchi, M., & Christopher, C. (2013). Gas and the Microbiome. Current Gastroenterology Reports, 15(12), 1-6.
  15. 15. Anatomic or pathologic risk factors • Surgery • Tumor • Trauma • Volvulus • Ischemia • Congenital short bowel • Strangulating hernias, functional short bowel, • Thrombosis/embolus of superior mesenteric artery • Refractory celiac disease, • Chronic intestinal pseudo-obstruction • Radiation enteritis
  16. 16. Functional Digestive Disorders at Risk of Developing SIBO • Irritable Bowel Syndrome • Post-infectious IBS • Gastroparesis • Functional Constipation • Functional Diarrhea
  17. 17. Neuroendocrine Disorders Leading To SIBO • Fibromyalgia • Type II Diabetes • Parkinson’s Disease • End Stage Renal Disease • Chronic Pancreatitis • Myotonic Muscular Dystrophy Gut/Immune Barrier Dysfunctions Leading To SIBO • Diverticulosis • Refractory Celiac Disease • Ulcerative Colitis • Crohn's Disease
  18. 18. Additional risk factors for SIB0 • Fodmap/Carbohydrate Malabsorption • Low Secretory IgA • Low Hydrochloric Acid • PPI’s • Opioids • Others
  19. 19. Other Associations with SIBO SIBO as a contributing Factor • NAFLD • FM/CFS • Restless Leg Syndrome • Prostatitis • Interstitial Cystitis • Lyme Disease • Rosacea • Endometriosis
  20. 20. Disease Associations Disorder Prevalence of SIBO Source Irritable Bowel Syndrome 4-78% Grace, 2013; Quigley, 2013, Park, 2009. Celiac Disease 9-67% Grace, 2013 Connective tissue disease (scleroderma) 43-55% Grace, 2013 Crohn's Disease 25-88% Grace, 2013, Quigley, 2013. Diabetes Mellitus 8-44% Grace, 2013 Hypothyroidism 54% Grace, 2013 Non-specific Dysmotility 76% Grace, 2013 Radiation Enteropathy 26% Grace, 2013 Ulcerative colitis Grace, 2013, Quigley,
  21. 21. Disorder Prevalence of SIBO Source CFS 81% Grace, 2013 Cystic Fibrosis 37% Lisowska, 2009 chronic pancreatitis 34-92% Grace, 2013 PPI USE 26-75% Grace, 2013 ESRD 36% Grace, 2013 Fibromyalgia 20 % Grace, 2013 Immunodefficiency disorders 30-50% Grace, 2013 Liver Cirrhosis 17-36% Grace, 2013 Obesity 17-41% Grace, 2013 Parental Nutrition 70% Grace, 2013 Rosacea 46% Grace, 2013 Disease Associations
  22. 22. Neuromuscular Disease Prevalence of SIBO Source Muscular Dystrophy 65% Grace, 2013 Parkinson's Disease 54% Grace, 2013 Surgical Interventions Prevalence of SIBO Source Abdominal Surgery 82% Grace, 2013 Bilateral truncal vagotomy 93% Grace, 2013 Gastrectomy 63-78% Grace, 2013 Illeocaceal Valve Resection 32% Grace, 2013 Roux-en-Y reconstruction 86% Grace, 2013 Disease Associations
  23. 23. N of 1. Proposed unified definition: SIBO as a heterogeneous disorder resulting as a sequelae of an upstream dysfunction which effects motility and/or innate gastrointestinal antimicrobial defense F u n cti N eu G ut SIBO Neuroendocrine Dysfunction Gut Immune Barrier Dysfunction Pathologic Functional Digestive Disorder Drugs
  24. 24. What keeps the small intestine relatively sterile? • Ante-grade digestion • Peristalsis • Adequate serum IgA • Migrating Motor Reflex • Adequate gastric acid • Proper stomach and intraluminal pH • Ileocecal valve patency
  25. 25. Normal Motility Process Segmentation • Segmented contractions • Peristalsis • Occurs when food enters the digestive tract. Inter-digestive period • occurring between meals every 1.5-2 hours • recurrent event moving from stomach to small intestine. • mediated by the Migrating motor complex • House cleaning of the lumen • Also called the “cleansing wave”
  26. 26. Fasting Pattern of Migrating Motor Complexes, every 1-2 hours of fasting. Phase II. Intermittent smooth muscle contractions Phase III continuous sweeping contractions up to 11/min in the duodenum A quiescent stage Phase I oscillations of smooth muscle without contractions Foxx-Orenstein.2015.
  27. 27. Migrating motor complex Inhibitors of MMC • Low Small Intestine pH • Pancreatic polypeptide binding (PPY) • Eating/grazing Promoters of MMC • PH • Bile Acids • Somatostatin • Erythromycin • 5-HT2 antagonist. • Serotonin and Somatostatin • Motilin receptor agonist • Ghrelin receptor agonist • Melatonin
  28. 28. Migrating Motor Complex Alterations in Disease (PMID: 22450306 )
  29. 29. Interstitial Cells of Cajal: A network mediator of the MMC.
  30. 30. SIBO Hypothesis of IBS • Pioneered by Mark Pimentel, MD from Cedar Sinai Hospital, Los Angeles. • States that the near majority of people with IBS have SIBO • N=320 SIBO was found in 37.5% of sufferers that met ROME III criteria confirmed by duodenal aspirate testing. (Pyleris, et. al, 2012. •Recently Reddymasu, et al. 2010. Showed that 36% of those with IBS- prominent symptom of bloating and flatulence had SIBO. •Pimentel has shown that when SIBO is eradicated in subjects their IBS symptoms are significantly reduced. (up to 70% reduction)
  31. 31. Pimentel,2014. Global Symposium on IBS, Los Angeles, CA New Autoimmune Theory of IBS 1.Acute Gastroenteritis 2.Cytolethal Distending Toxin (CDT) causes production of anti-vinculin antibodies 3.Damage of function of Interstitial Cells of Cajal and Migrating Motor Complex 4.IBS with SIBO Develops 5.IBS Persists This takes about 3 months to develop
  32. 32. Synthesis/new hypothesis of how SIBO may develop in IBS/dysmotility Acute Gastroenteritis Disruption of ICC Cells /MMR leading to dismotility Release of CDT Toxin Leading to anti-vinculin antibodies which damage ICC SIBO Develops dysmotility and highly fermentable environment in the small intestine PMID: 15316000; PMID: 22450306, IBS Global Symposium, 2014
  33. 33. Implications of SIBO and Intestinal Permeability
  34. 34. Implications of SIBO and Intestinal Permeability
  35. 35. Subjective Clinical Findings of SIBO History Post-prandial bloating and distention. Feculent breath smell, fish body odor smell. Generalized abdominal Discomfort that is usually low grade, non specific, and not described as “Pain”. May have diarrhea, constipation, or both. Usually Absence of Red Flags. Non-specific symptoms: fatigue, joint pain, brain fog, myalgia's that may mimic somatization.
  36. 36. Core SIBO Symptoms that may drive an SIBO investigation
  37. 37. Objective Clinical Findings • Malabsorption findings rarely observed in outpatient setting • Borgborygymus • Polyneuropathy due to vitamin B-12 deficiency • Tetany due to Hypocalcemia • Small intestinal succussion splash (PMID:23997926) • Generalized abdominal discomfort or light pain on light palpation • Dermatitis due to selenium deficiency • Rosacea sometimes • Cachexia due to malnutrition
  38. 38. Differential Diagnosis in SIBO • Functional Constipation • Functional Diarrhea • Carbohydrate Intolerance (Fructose Intolerance, Sorbitol Intolerance, Lactose Intolerance) • Gastroparesis • Celiac Disease • Inflammatory Bowel Disease • Chronic Mesenteric Ischemia (has postprandial abdominal pain) • Chronic pancreatitis • Parasitic infection (giardia, amebiasis) • Chronic C. Difficile • Enteric candidiasis/Small Intestinal Fungal Overgrowth (SIFO)
  39. 39. Differential Diagnosis in SIBO Autoimmune • Hypothyroidism (can have decrease motility but also includes other specific findings) Neoplastic • Ovarian Cancer (the bloating likely would not wax and wane) • Colon Cancer (the digestive symptoms would likely not wax and wane, and may include middle of the night symptoms) Medication/Iatrogenic
  40. 40. SIFO Is The new Enteric Candidiasis? Gastroenterology . 2011. Volume 140, Issue 5, Supplement 1, Page S-810 Investigation of Small Intestinal Fungal Overgrowth (SIFO) and/or Small Intestinal Bacterial Overgrowth (SIBO) in Chronic, Unexplained Gastrointestinal Symptoms Carolyn Jacobs, Jessica Valestin, Ashok Attaluri, Gideon K. Zamba, Satish S. Rao Results: 124 (M/F=38/86; ages 17-82) subjects were evaluated; 77/124 (62%) had a positive culture for overgrowth. Among these 23/124 (19%) had SIFO, 23/124 (19%) had mixed SIFO/SIBO and 31/124 (25%) had SIBO. All patients with SIFO grew candida • 36 subjects with SIBO had aerobic flora (enterococcus sp, streptococcus sp, etc.), and 3 had anaerobic flora (bacteroides sp). Prevalence of symptoms and its severity are detailed in table. Nausea was more prevalent and severe in SIFO whereas abdominal pain and gas were more common in SIBO. Symptoms do not predict presence/ • absence of infection. • Conclusion: SIFO and mixed SIFO/SIBO overgrowth is common an occurs in three of five individuals with chronic, persistent GI symptoms in tertiary care practice.
  41. 41. workup and testing overview • Blood tests are not often valuable in detecting or confirming SIBO. • Stool testing is not often useful for diagnosis but may be helpful for monitoring or co-morbidity screening. • There are no useful imaging tests. • Jejunal Aspirate is invasive and not practical. • Most practical tests is Hydrogen Breath Testing done in a lab or home setting.
  42. 42. Screening flow processScreening Process
  43. 43. If you were at Monash University.
  44. 44. Monash Process
  45. 45. SIBO Workup Process Diagnostic Testing • Standard: Lactulose Hydrogen Breath Test • CDSA or Stool Microbiology DNA • Alternatives: • Glucose Hydrogen breath test
  46. 46. Additional Tests That May Be Useful Lactulose/Mannitol test Intestinal Permeability Screen (Cyrex Array 2) Secretory IgA Urine Hippurate, Benzoate, Lactate.
  47. 47. Diagnostics: Small Bowel Jejunal Aspirate Vs. Hydrogen Breath Testing . Saad and Chey. 2014
  48. 48. Lactulose Breath Test vs . Glucose Breath Test.
  49. 49. Criteria for Positive Lactulose Hydrogen Breath Test Criteria for Positive Lactulose Glucose Breath Test • A fasting hydrogen level greater than 20 ppm in a compliant patient • The presences of a double peak hydrogen rise with an early increase (within 90 minutes) greater than 20 ppm OR a sustained increase greater than 10 ppm. • Mean methane 2 ppm rise or greater above baseline are considered methane positive. However methane production might mean functional constipation compared to SIBO.  Any 10 ppm> rise in hydrogen compared to baseline
  50. 50. Regions of Intestine Accessible by Various Diagnostic Methods To Detect SIBO Duod./Jejunum……………/ Lactulose Breath Test Lactulose Ileum………………………../ Colon Direct Aspiration and Culture Glucose Breath Test 10 X 0 Glucose Absorption complete 10x11 Absorption Complete
  51. 51. Breath Testing for SIBO (CPT code-91065 Quintron Breathtracker • Usually requires appointment with Gastroenterologist. • Likely more accurate then home test. • Better chance to be covered by insurance. Quintron Lac Check • Conveniently performed in office at home. • Higher margin for error. • Insurance coverage varies.
  52. 52. Sensitivity vs. Specificity Lactulose Hydrogen Breath Test False Negatives False Positives Rana,et.al.2014
  53. 53. Classic Findings LHBT Methane Positive Hydrogen Positive
  54. 54. Conundrums Merged Peek Flat Liner : H2S? PMID: 1860825
  55. 55. Tip Of the Iceberg METHANE is only detected on breath test when quantities of Methanogens are 106 or Greater. According to Pimental @ IBS Symposium 2014 the 104 to 106 group is likely “ below the tip of the iceberg” but still relevant.
  56. 56. RCCEG: Recommendations for the Preparation and Performance of Breath Testing (Saad & Chey, 2014) Test Preparation • Avoidance of antibiotics for 4 weeks before testing • Avoidance of bismuth for 2–4 weeks before testing Avoidance of probiotics for 2–4 weeks before testing • Avoidance of prokinetics for 3 half-lives before testing • Avoidance of colonic purging within 4 weeks of testing • Consumption of a diet free of non-absorbable carbohydrates (pasta, bread, fiber cereal, beans) the evening before testing . (Most start this 24 hours before the test) • Overnight fast before testing • Avoid cigarette smoking before and during testing • Consider mouthwash with chlorhexidine solution before substrate ingestion Test performance • All stationary gas chromatographs have proven accuracy • The Haldane–Priestly, Y-piece, or 2-bag system should be used for breath sample collection • Breath sample should be obtained after a maximal inspiration, 15-second period of apnea, and prolonged expiration • Breath sample analysis should be performed within 6 hours of collection unless stored at - 20C Avoidance of vigorous physical exertion during testing
  57. 57. Consolidation (personal opinion) • Using Glucose Hydrogen Breath Test (GHBT) may lead to false negatives in diarrhea subtypes • Negative hydrogen production and negative methane production in the context of constipation should taken in the context that the patient may have prolonged transit time. OR hydrogen sulfide production. But what to do for hydrogen sulfide production still in question? • Vice versa a patient with rapid transit time in lactulose hydrogen test may produce a false positive because it may be showing lactulose reaching the caecum in < 90 minutes.. • Baseline elevation in the context of good compliance; should be weighed for bacterial overgrowth, especially if its methane elevation due to constipation/impaction. • This is subject to change with more data and improved tests. PMID :21860825
  58. 58. Breast Testing Algorithm
  59. 59. Report Of Findings To Patient (IFDYR) • Introduction: materials and methods used • Factual observations and results • Interpretation • Discussion • Your impression • Recommendations
  60. 60. bo@soundintegrative.com
  61. 61. Treatment: Know Your Patient
  62. 62. Plot chart of currently available strategies for modifying gut microbiota aiming to demonstrate the relationship between the effectiveness and invasiveness/safety of the proposed approach. Simrén M et al. Gut doi:10.1136/gutjnl-2012-302167 Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.
  63. 63. Cedar Sinai Updated SIBO/IBS Treatment Algorithm
  64. 64. Adapted Cedar Sinai IBS/SIBO Protocol Cedar Sinai Protocol adapted from: Pimentel. 2006. A New IBS Solution.Health Point Press. Van Nuys,CA pg. 90
  65. 65. Rifaximin: The Data • Mechanism of action: Acts on gram positive and gram negative bacteria transcription by binding to the β-subunit of bacterial RNA polymerase. • No systemic absorption • Number Needed to Treat (IBS): 11 / Number Needed to Harm: 8,971 • Overall will normalize breath tests in 40-50% of patients. • Efficacy in improvement of global IBS Symptoms approximately 40% vs. 30% placebo. A 10% overall therapeutic gain by taking vs. not taking it. • FDA: approved for Hepatic Encephalopathy, IBS-D, Travelers Diarrhea* • Cost is $600+. • Mild Side Effects: Nausea, diarrhea, Headache, Mild, Upper Respiratory Infection, Abdominal Pain, Nasopharyngitis • Serious side effects that have been reported: Clostridium difficile, anaphylaxis, hives * Travelers Diarrhea approved for 200 mg TID X 3 days PMID:24004101,PMID 22024520, PMID:21780893, PMID,22298980, PMID:24004101, PMID:24891990 0
  66. 66. 0 PMID: 21397724
  67. 67. Antibiotics treatment of methane+constipation- predominant irritable bowel syndrome. • N=31 breath methane positive with ROME II criteria IBS • 16 with neomycin vs. 15 with Neomycin+ Rifaximin • Neomycin 500 mg BID X 14 days plus Rifaximin 550 mg TID for 12 days • Rifaximin/Neomycin group significantly better improvement in constipation, straining, and bloating. But not significantly better improvement in abdominal pain. • Subjects who achieved <3 ppm methane after treatment had less constipation then patients who had persistent methane elevation. (PMID: 24788320)
  68. 68. Antibiotic Choices in SIBO 7-14 day course • Ciprofloxacin (250 mg twice a day) • Norfloxacin (800 mg/day) • Metronidazole (250 mg 3 times a day) • Trimethoprim-sulfamethoxazole (1 double-strength twice a day) • Doxycycline (100 mg twice a day) • Amoxicillin-clavulanic acid (500 mg 3 times a day) • Tetracycline (250 mg 4 times a day) • Chloramphenicol (250 mg 4 times a day) • Neomycin (500 mg twice per day for 14 days) • Rifaximin (800–1200 mg/day) * standard is 1650 mg/per day
  69. 69. SIBO reoccurrence • The relapse rate of SIBO after successful treatment is high. • 44% (35/80) of patients relapsed within nine months after successful treatment with Rifaximin. • NOTE: these patients were treated with 1200 mg of Rifaximin for 7 days and retested negative for SIBO. • Higher risk of re-occurrence in older age, long term history of PPIs, and history of appendectomy. (PMID : 18802998)
  70. 70. Secondary Prevention: Prokinetics • Preventing Reoccurrence by improving motility thereby increasing Phase III Migrating Motor Complex using prokinetic agents. • For IBS-C Increase Motility Phase III migrating motor complex increasing bacterial clearance from the duodenum distally. • Erythromycin has been shown to increase Phase III MMC activity in the antrum of the duodenum: Some protocols use erythromycin at bedtime 50 mg for 3 months post eradication) Symptom reoccurrence reduced by to 138.5 +/- days 132.2 days with erythromycin as prevention strategy compared to 59.7 +/- 47.5 days with no prevention. • Low dose tegaserod has been used at 2-6 mg bedtime has been used as a 5-HT4 agonist however it has been blackboxed. (PMID:20574504) (PMID:20574504) (PMID: 22450306)
  71. 71. Other Pro-Kinetic Agents • Cisapride: relieves constipation-like symptoms by indirectly stimulating the release of acetylcholine in the muscarinic receptors. HOWEVER IT removed from the market because its effect on long QT syndrome, possibly contributing to arrhythmias. • Octreotide induces phase III of the migrating motor complex that causes a propagating peristaltic wave through the small intestine. • Prucalopride: activates 5-HT4 receptors as a prokinetic. Available in Canada, but not US. 1mg-2mg daily). Promising Data in women with idiopathic chronic constipation who failed laxatives. .(PMID:24732867)(PMID:24106924)
  72. 72. Other emerging medication groups in the IBS World • Secretagogues: Lubiprostone: for IBS-C • Opioid Agonist: Eluxadoline for IBS-D: • Others: Low Dose TCA’s
  73. 73. Emerging issues related to Rifaximin • How many times can it be used without patient developing a resistance? • Does it “kill-off” colon Flora? • If used with Neomycin, how does it change the pharmokinetics and resistance of Neomycin.
  74. 74. 2015 Sound Integrative Health SIBO Therapeutic Order
  75. 75. Treatment Stepwise Process
  76. 76. Assess And Stabilize Adrenal and Immune Function: 2 weeks to 1 month and ongoing. • Clinical Evaluation. • Metabolic Detoxification Questionnaire ™ . • Idenit-T™ Stress Assessment • Diagnostics Adrenal Stress Index, Or Bio health Laboratories Functional Adrenal Tests, others. • If relevant support for at least 2 weeks prior to treatment and reassess. Continue on support as needed throughout SIBO Treatment Reassess periodically
  77. 77. Assess And Stabilize Adrenal and Immune Function Treatment • Appropriate HPA support based on stage of dysfunction and findings • Buffered Vitamin C–mixed Ascorbates 1000mg-2000mg to support glutathione and to reduce Herxheimer reaction: Cost: $20/month • Adrenal Supportive Diet • Reduced Glutathione Supplementation as appropriate 1 gram daily in divided doses to reduce Herxheimer reaction. • Milk thistle 250mg twice per day to reduce Herxheimer reaction: Cost $20/month • If not stooling 1x per day give daily Morning Glory. Treatment beverage or appropriate over the counter medicine. slowly build. • Continue on this treatment ongoing as indicated throughout treatment
  78. 78. Assess And Stabilize Adrenal and Immune Function Morning Glory Treatment Bedtime Fodmap Friendly Bulk, Moisten, Soften Mix ¼ teaspoon-1 T green banana flour (RS2) + ½ -1 tablespoon of Acacia Powder (soluble fiber) + Vitamin C (2 grams) + Magnesium Citrate 350mg ¼ teaspoon maple syrup. Adjust dose accordingly Morning Stimulate Mix 2 grams Vitamin C with 350 mg of Magnesium citrate . Followed by a chaser of 6-oz of black coffee if allowed. Bowel movement should happen within 20 minutes of being awake. Warn patients that flatulence might increase at first but adjusts over. If this is unsuccessful consider OTC or Rx options
  79. 79. Other acceptable Fiber Sources • Soluble Fiber • Guar Gum 5-15 grams per day • Ground Flax Seed • Resistant Starches (RS2) • Potato Flour Starch • Resistant Starches (RS3) • Cooked and Cooled and reheated potatoes and Rice Response may vary . Start very low and build slowly!!!!
  80. 80. Modify Dysbiotic Lifestyle Factors
  81. 81. Modify Dysbiotic: Lifestyle: Treatment Ongoing Pick The Most Relevant • Meal Spacing (3-4 hours) between meals. • Mastication. • Dietary trigger awareness. • 10,000 steps per day • Control Stress Eating and Overeating. • Correct abdominal gut clenching and gas holding. • Correct constrictive clothing or accessories • Stool Squatting..
  82. 82. Abdominal Release inspired by Katy Bowman: Release the Gut Shame! • Start on Hands and Knees • Release the stomach all the way. Be proud of that thing! Give it a name! • As you are releasing un tuck your pelvis. If your pelvic stays stuck you are sucking in. • Your tailbone should rotate up as our pelvis rotates toward the floor. • Don’t push it out. Release it out. • Once at a good spot . Hang out and perform deep belly breaths • Notice thoughts of negative self talk like “I am fat “ or “ I look fat” or “ I hate my belly” or “my spine is weak”. Bowman, Katy (2014-09-25). Move Your DNA:
  83. 83. Step 3: Implement Sustainable Microbiome Balancing Diet.
  84. 84. Implement Microbiome Balancing Diet Multiple Options. • Most researched in FGID is Low Fodmap Diet • Most Popularized in ND world is SCD/Low Fodmap Combination • Other common approaches are: • Paleolithic Diet • Cedar Sinai Low Fermentation Diet
  85. 85. The Low Fodmap Diet, edition 3, Reducing poorly absorbed sugars to control gastrointestinal symptoms. 2012 Monash University
  86. 86. Low Fodmap Diet • Originated largely from research done by Dr Peter Gibson, Professor of Medicine and Victoria at Monash University, Sydney, Australia • Stands for Low Fermentable Oligosaccharide Disaccharide, Monosaccharide And Polyols • Additional Research coming out of Kings College in London
  87. 87. Comparison of FGID friendly diets: • Compares Low Fodmap to • SCD • Anti-candida diet • Paleolithic Diet • Fructose Free Diet • Lactose Free Diet • Low Carb Diet Shepard,S.et.al.2013. PMID:23588241
  88. 88. What are Fodmap’s? What is the Science • Fermentable, Oligo-, Di-, Mono-saccharides and PolyolS (FODMAPs) are short chain carbohydrates (e.g. fructans, galacto-oligosaccharides, polyols, fructose and lactose) that are poorly absorbed in the small intestine • FODMAPs: short chain sugars and water soluble fibers with low degree of polymerization (DP1-10) • Starch/polysaccharides: long chain carbs DP 10- 1,000+ • Small size makes FODMAPs • Osmotically active • Rapidly fermentable
  89. 89. FODMAPS Lactose Fructose Galactans Fructans Polyols
  90. 90. High FODMAP Absorption is poor by default • The absence of luminal enzymes capable of hydrolyzing the glycosidic bonds contained in carbohydrates • The absence or low activity of brush border enzymes (eg, lactase) • Or the presence of low- capacity epithelial trans- porters (fructose, glucose transporter 2 [GLUT-2], and glucose transporter 5 [GLUT-5])
  91. 91. Theoretical Model of Carbohydrate Malabsorption Barret and Gibson, 2007
  92. 92. Fodmap Malabsorption Model Shepard,S.et.al.2013. PMID:23588241 23588241
  93. 93. Carbohydrate: chain length/digestion Sugars (DP1-2) Site of absorption Sucrose proximal sm intestine* Glucose proximal sm intestine* Fructose along entire sm intestine Lactose along entire sm intestine Polyols along entire sm intestine • *Well absorbed
  94. 94. Randomized Fodmap Trial • N=30 with IBS and 8 controls • Low Fodmap Group (<.5 grams Fodmap) vs. Austrailian Diet Group Vs. Control on typical diet • Low Fodmap Group had lower overall gastrointestinal symptom scores (22.8; 95% confidence interval, 16.7-28.8 mm) while on a diet low in FODMAPs compared with the Australian diet (44.9; 95% confidence interval, 36.6-53.1 mm; P < .001) and the subjects' habitual diet. • Bloating, pain, and passage of wind also were reduced while IBS patients were on the low-FODMAP diet. • Symptoms were minimal and unaltered by either diet among controls. • Patients of all IBS subtypes had greater satisfaction with stool consistency while on the low-FODMAP diet • However, diarrhea-predominant IBS was the only subtype with altered fecal frequency and King's Stool Chart . (PMID: 24076059)
  95. 95. Carbohydrate Intolerance in SIBO-positive patients • SIBO-positive patients further showed significantly higher prevalence of malabsorption by lactose breath test (83% vs 64%), fructose breath test (70% vs 36%) and sorbitol breath test (70% vs 36%) when compared with the SIBO negative IBS patients. • Eradication of SIBO increased tolerance to fructose, Lactose, and Sorbitol. • Fructose, sorbitol and lactose breath tests could become a useful diagnostic approach in SIBO-negative patients with refractory symptoms. (PMID:24976698) PMID: 24976698
  96. 96. Applications for Low Fodmap Diet • Functional Bowel Disorders • Irritable bowel syndrome • Functional bloating • Functional constipation • Functional diarrhea • Other possibilities • IBD especially Crohn’s Disease • GERD/Dyspepsia
  97. 97. Implications of long term use of Low Fodmap Diet requires elucidation • Monash Study indicated that a long term low Fodmap diet may reduce butyrate production in the colon, thereby effecting protective factors of large Intestine. • Probably applies other low fiber diets PMID:25016597
  98. 98. Step 4: Stabilizing Microbiome Balance
  99. 99. Step 4: Stabilizing Microbiome Balance: 4 weeks to 3 months • We are reducing and stabilizing not removing/eradicating. • Plant antimicrobials vs. conventional antibiotics
  100. 100. Antibacterial activity of essential oils in disc diffusion assays. Significance levels obtained from two- tailed t tests are denoted by stars: * = significant (P < 0.05); ** = highly significant (P < 0.01); *** = very highly significant (P < 0.001). BMC Complementary and Alternative Medicine 2013, 13:338
  101. 101. Researched Natural Antimicrobial Treatments • Enteric Coated Peppermint Oil reported benefit and improved breath hydrogen breath test in a case report; of 0.2 mL three times daily for 20 days. (Logan & Beaulne, 2002). • Peppermint Oil has 5 RCTs that showed it was better then placebo for abdominal pain (Grade 2b evidence)
  102. 102. • Original Retrospective Chart Review showed: • 23/67 Patients who took 1200 mg of Rifaximin Daily had a negative LBT after therapy • 17/37 patients who took either 2 tabs BID of formula a+b or 2 tabs BID of formula c+d for 4 weeks had a negative LBT after therapy. ormula A Formula B Formula C Formula D Company A Company A Company B Company B inospora ordifolia dill seed Red Thyme Oil Coptis root and rhizome Equisetum arvense stemona sesilifolia Oregano Oiil Indian Barberry root exsract Pau D'Arco Artemesia absithinium Sage Leaf Extract Berberine Sulfate Thymus ulgaris Pulsatilla chinesis rhizome Lemon balm extract Chinese Skullcap Artemisia dracunculus Brucea Javanica Phillodendron bark ida ordifolia Pircrasma Excelsa bark Ginger rhizome Olea europaea Acacia Excelsa bark chinese licorice root Hedyotis diffusa chinese rhubarb root and rhizome Yarrow leaf and flower chinese rhubarb root and rhizome
  103. 103. Group 1 (triple Antibiotics) Group 2 (Biotics Group) Group 3 (Metagenics Group) Clindamycin: 300mg TID x 4 weeks Metronidazole 250 mg TID X 4 weeks Neomycin 500mg TID x 4 weeks FCcidal 2 cap BID X 4 weeks Dysbiocide 2 cap BID X 4 weeks. Candibactin-AR: 2 cap BID X 4 weeks Candibactin-BR:: 2 caps BID X 4 weeks. Rescue Protocol Group 1 (triple Antibiotics (n=10) Herbal Remedy (N=14) Negative LBT after therapy 6/10 (60%) 8/14 (57.1%) Controlled for : age, gender, SIBO risk status, IBS Status Rescue Protocol In Patients Who failed Rifaximin
  104. 104. Findings • It again proved that botanicals are decent antimicrobials • Did not control for diet • Study did not show any markers of patient improvement or lack of improvement other then breath results.
  105. 105. • Start slow and work up to the maximum tolerable dose • Approach should have one Berberine based formula + one phenolic monoterpenoid formula or 1 thiol reducing formula. • Should be taken with biofilm Eradicator • All supplements should be taken 30 minutes before a meal or 2-3 hours after a meal. • Review side effects and drug interactions of all herbs and disclose with patient. • Prepare patient for Herxhemier • Reassess after 4 weeks with Patient History/PE/maybe LHBT. • Use this with Digestive Wellness Questionnaire section 3-4 to Guide treatment and CDSA. • Retesting LHBT is reasonable but not always necessary • With no or moderate consider dosing and rotating herbal blends/antibiotics Basic Principles: Step Four: Stabilize Microbiome Balance. 2 weeks to 3 months
  106. 106. Foundations of treatment:  An foundational Berberine-based formula in combination with 1 or more Biofilm Eradicator (Interfase or Interfase plus, or NAC) Plus 1 Additional complementary herbs formula Phenolic monoterpenoid formulas (i.e. Oregano, Thyme (Carvacol/Thymol) And/or Thiol Reducing Agent formula: (i.e. Allicin) Other agents that might be helpful: Undecylenic acid and/or Caprylic Acid Cinnamomum stem bark oil (Cinnameldhyde) True/Purified Colloidal Silver/Silvercillin Artemesia (sesquiterpene lactones) Basic Principles: Step Four: Stabilize Microbiome Balance. 2 weeks to 3 months
  107. 107. Target Doses of Single Herbs. Will be Less when used in Combination! Most from : (Bone, The Ultimate Herbal Compendium, 2007)  Berberine: 1.4-1.8 grams per day.  Origanum Vulgare : 230-450 mg daily of 30% Carvacol  Thymus Vulguaris Oil: 40-50 mg per day  Allicin: 5 mg of enteric coated Allicin divided throughout the day. Biofilm Eradication  Interphase or Interfase plus* : 2 caps to 8 caps between meals Other agents that might be helpful:  Undecylenic acid :450mg-740mg in three divided doses daily  Cinnamomum stem Bark oil (Cinnameldhyde): 100mg of Cinnamon Stem Bark daily with (60% cinnameldhyde)  Purified Silver/Silvercillin 10-ppm silver nano-particle solution . NOTE make sure you are using correct form and only temporarily) .See PMID:15111684  Artemesia (sesquiterpene lactones): 300-600mg daily in divided doses. *Caution in highly sensitive and constipated patients due to metal mobilization All supplements taken 30 minutes before meals or 3 hours after meals Basic Principles: Step Four: Stabilize Microbiome Balance. 2 weeks to 3 months
  108. 108. General Principles: • Reinforce Dietary Hygiene principles of meal spacing and mastication and MOVEMENT(10,000 steps) • Utilize prokinetics to try and promote regular and restorative MMC’s that clear the gut of fermentable debris and bacteria • Therapeutic Targets: 5HT4, CCK, Motilin in attempt to create Phase III contractions of motility • Macrolide antibiotics erythromycin low dose but effect has been shown to wear off after 3 months. Safe on Biome however. Researched heavily in Gastroparesis. • Prucalopride (Resolor) has been used in chronic constipation. Only available mail order through Canada. • Naturopathic approaches include: • Herbal Bitters/Cholagogues/carminatives (Ginger, Bitter Blends/Iberogast) Step Five: Restore Digestive Clock
  109. 109. MMC treatment guidelines:  If antimicrobials need to exceed 1 round, you might want to start this stage in conjunction with antimicrobials. Reinforce meals spacing Choose 1 of the following  Herbal Pro-kinetic Blend (Iberogast or Liquid Ginger). Taken as directed before meals Plus 1 of the following night medication  Low Dose Naltrexone ( tapered up to 2.5 mg at bedtime for diarrhea and up to 5 mg at bedtime or split for constipation  Erythromycin 50mg-75 mg taken at bedtime Read up on side effects of LDN to prepare patient. Start slow. Uses Hx, PE, Digestive Wellness Questionnaire, and FGID diary to guide retreatment. , also consider retesting for LHBT to guide your treatment. If bloating and abdominal pain have reduced/stabilized then proceed to next step with caution. If Bloating, Abdominal, Pain, and digestive irregularity have all stabilized proceed to next step Step Five: Restore Digestive Clock
  110. 110. Step Six: Replenish Immune and Digestive Factors (1-2 months)
  111. 111. • General Guidelines: • Most patients tried these treatments before coming into your office but now is a time when they should likely help. • Goal is Balanced Upper intestinal PH, adequate digestion/absorption without bloating, stool regularity. • Use Hx P/E, Digestive Wellness Questionnaire (especially sections A,B, E), and FGID stool Diary to guide your decisions on how much or how little support is needed here • Might consider again CDSA or Heidelberg test at this stage • Slowly Graduating From a low Fodmap Diet to a Paleo Diet is likely better long term for flora of colon while still being gut friendly. • These treatments (digestive enzymes, Betaine-HCL, Immunoglobulins, and Pre/Probiotics) generally help with stabilizing gut flora, optimizing gut pH, mucin production, and protein, fat, carbohydrate digestion, as well as the multitude of benefits of probiotics • In these patients they will likely not need antimicrobials but may require a pulse dose with symptoms of re-flaring. • These patients should continue these treatment with Migrating Motor directed treatments as long as mild symptoms exists Step Six: Replenish Immune and Digestive Factors (1-2 months)
  112. 112. • Replenish Gut Flora Friendly Diet: • Reinforce Dietary Hygiene and Exercise • FODMAP Challenge: Slowly graduating from a low Fodmap Diet to a Paleolithic Diet. Establish personalized diet that is more flexible, more diverse, and sustainable. • Incorporate paleo friendly carbs: Plantain, Cassava, Taro Root, Sweet Potatoes, Parsnips, and Beets. • Replenish: Immune/Digestive: Core plan • Betaine HCL (650mg-1.3 mg) with 130-260 mg of Pepsin with each meal. • 306-623 mg of acid stable digestive enzymes including amylase, protease, lipase, phytase, cellulase, sucrase, maltase, and lactase with each meal • Probiotic formulation for current replenishment. Amount varies with each formula. Species such: L. Plantarum 299v h, L. Cassei, stretptococcus faecalis. Lactobacillus GG, Bifidobacterium brevis. • Replenish: Additional Supplements that are helpful • Spore Containing Probiotic for long term (Bacillus • Ox Bile extract 650mg-130 mg TID with meals. • Pancreatin 8X USP concentrate 650mg-1.3 mg TID with meals • IgG Immunoglobulins/Colostrum/Enteragam • If Diet remains low Fiber (<30 grams per day). You might consider adding a combination of soluble fiber (i.e. Psyllium) with RS2 starch like Banana Flour Starch (1/2 tsp to 1 tsp day). Step Six: Replenish Immune and Digestive Factors: 1-2 months
  113. 113. Probiotics for SIBO • Most studies have been done for IBS not specifically for SIBO • Bidobacterium infantis seems to outperform strains of Lactobacillus. • At present, the strongest evidence is for Bifidobacterium infantis 35624 at a dose of 13108 cfu/day taken for at least 4 weeks. However Lactobacillus GG has performed well in children • For SIBO specific studies of Probiotics • Lacotbacillus fermentum KLD 10 Billion BID no better then placebo (PMID: 9060066) • Lactobacillus plantarum 299V and Lactobacillus GG benefited children who had SIBO associated with short bowel syndrome in uncontrolled studies • Abstract of N of 25. Probiotics (lactobacilli casei, Lactobacillus plantarum, streptococcus faecalis, Bifidobacterim brevis) –Bioflora at 5 ml twice per day for 5 days outperformed Flagyl in symptomatic improvement 80% to 50%) Although full paper seems to be unavailable and the design questionable • . (PMID:21381407) ;(PMID:22730468)
  114. 114. Step Seven: Restore Gut Barrier (Ongoing)
  115. 115. General Guidelines: • At this stage patient should be relatively stable. • At this stage a gut healthy lifestyle should be in place. You can always keep re-enforcing this. • Use Section B,C and D on Digestive Wellness Questionnaire to Help Drive decisions • Might want to consider additional testing at this stage like Lactulose Mannitol testing .Cyrex testing for Zonulin/LPS , food allergy/sensitivity testing. • Treatments are directed at tightening gap junctions , reducing inflammation, restoring barrier, and limiting gut permeability • At this stage most patient will have graduated from most other supplementation except will likely stay on Stage 6 diet and supplementation. • In these patients they should notify you at first sign of a re- flare and come in for a visit. Step Seven: Restore Gut Barrier (Ongoing)
  116. 116. • Supplementation • Continue on lower dose maintenance probiotic (5 billion per day) • Take gut lining supplementation including daily and ongoing. Minimum criteria of formula • 750 mg to 1000 mg of L-Glutamine • N-acetyl D-glucosamine 375mg -1000 mg daily • Slippery elm (bark) powder: 200 mg to 400mg daily • Althea root powder: 120 mg to 250 mg Daily • DGL 400mg daily • Zinc Carnosine 75 mg daily • Some combination of astringing and ant-inflammatory herbs • Other helpful additions • Bone broths drinking frequently throughout the week • Beef Gelatin dissolved in food/drink frequently throughout the week. • Treat mild reoccurrences with symptoms lasting > 1 week with 2 round course of herbal antimicrobials Step Seven: Restore Gut Barrier (Ongoing)
  117. 117. Prevention GI stabilization Supplementation Lifestyle Maintenance Address other health issues (pain, mental health) Specific Dietary plan based on re-challenge Weed and Feed (pre/probiotic/plant-antimicrobials)(2 weeks cycles on 2 weeks off ) Fiber Goals!
  118. 118. When treatment fails to help • If you refer them away , make sure you invite them back to discuss what they learned! • Consider other modalities AOM , Ayurveda. • Consider psycho-emotional components if not improving. • Consider Mind/Body interventions including EMDR or Hypnosis. • Consider Pelvic Floor Dysfunction evaluation • Ongoing surveillance and sensitivity to eating disorders.
  119. 119. Items in Development and more experimental to add to resistant patients and improve outcomes • Elemental Diet to Stabilize the Gut proceeding Low Fodmap Diet • Quarom Sensing Inhibition • The use of bacteriophages. That target E.coli (highly involved in SIBO) • The use of biofilm eradicators in conjunction of treatment (NAC, Interfase) • Combination treatments of Naturopathic and Conventional Treatments • Pulse Dosing
  120. 120. Case Studies
  121. 121. Recap
  122. 122. Case Studies Lessons from the past
  123. 123. Multifactorial. Too much too soon HPI: Diarrhea (10 bowel movements per day), Weight loss, abrupt onset 3 months ago, abdominal pain, bloating, and gas. Can only control by strict dietary modification. She has a history of Hashimotos Thyroiditis otherwise no other pertinent health history. Denied treatment with steroids and instead treated with Ciprofloxacin which helped X 2 days. Mother is aging which is stressful. Was told by previous physician that she may have SIBO. Does not want to test but treat instead. Also has issues with insomnia that she treats with Ambien Labs: lab review from 3 months prior: ANA+ for Scleroderma/CREST, Celiac Panel negative, Lyme Panel Negative Stool testing: + for Lactoferrin Diagnostic Imaging: colonoscopy + for Microscopic Colitis. Lifestyle: continue exercise program Continue emphasis on sleep restoration Diet: low fodmap diet P/E: unremarkable, except for excessive bowel sounds and mild discomfort on abdominal exam Berberine 500 mg three times per day Activated Charcoal PRN with die-off reactions Discontinue FOS supplements
  124. 124. Too much too soon Return Visit 1@7 days Reports improvement Bowel movements down to 3 per day Bloating reduced with low fodmap Had 2 days of die-off controlled by Activated Charcoal THINKS WE HAVE EMPIRICALLY PROVEN SIBO, leaning towards a trial with Rifaximin if not completely resolved in 1 week Return visit 2@14 days Still at about 3 bowel movements per day on the looser side Still having some fatigue Stopping Ambien wants to switch to natural sleep alternative Start Rifaximin 550 mg Twice per day with food for 10 days (do note the recommended dose now is 550mg three times per day) Added Glychrrizza for for fatigue Return Visit 3 @ 10 days 2-3 formed bowel movements daily Staying on Low Fodmap Digestively stable
  125. 125. Too much too soon Return Visit 5 @10 days later Diarrhea stopped after starting Budesonide and VSL#3.No bloating /No gas. Diarrhea resumed after stopping Budesonide and VSL#3. But less severe 3-10 movements per day Plan: Resume High dose Probiotic . Adding on Budesonide again with no control after 1 week. Assuming this is a flare in the Colon.(colitis) Return visit 30 days Diarrhea Stabilized with Probiotic Alone. Digestively stable .Has built up to 3 Digestive Enzyme/HCL capsules per mea. Starting to go out to eat with friends again. Challenged Fodmaps and was positive for Glactan/Fructans Plan: Continue Probiotic –High Dose, Continue Fructan/Galactan Avoidance. Continue Digestive/Enzyme HCL Capsules Start: Gut repair: supplementation. Begin setting boundaries with family regarding caretaking roles.. Phone call 60 days later Added raw veggies and reflared. Is away on vacation. Not responding to our standard treatment Wants a prescription of Enterocort and High dose probiotics
  126. 126. Too much too soon ROC 14 days later Budesonide and VSL#3 did not control things Has been feeling anxious and irritable and overly stressed Added Loperamide to control diarrhea until further investigation Plan check thyroid: THYROID PANEL TSH 0.29 L mIU/L, T4/T3 normal Reduce thyroid dose from 60 mg to 45 mg. Monitor and repeat labs in 1 week Return visit 45 days later TSH stabilized to 2.4. Diarrhea stopped after changing thyroid dose. Following Body Ecology Diet, GI Repair Supplementation. Digestion is stable. Feels good about plan Has changed role as a care provider. Is looking at emotional causes to her health. Wants to focus on other concerns today such as BIO- HFRT
  127. 127. Case 2: multifactorial, IS SIBO a Symptom or the Cause ? Return Visit 4 @30 days Reflares when veering for from the low fodmap diet Has switched to Valerian Root and Kava Kava for sleep concerns it is helping Plan to have Lactulose Breath Test to see if residual overgrowth exists Breath test shows negative Hydrogen. A 19 PPM rise that happened around 140 to 160 minute mark of test . Return visit 45 days: Went on trip to and reflared 10-15 bowel movements per day Stools watery, abdomen, and crampy but not bloated. Plan: CBC, CMP, Electrolytes, (NML) Treat for microcolitis/scleroderma related malabsorption Budesonide 9mg 1-4 weeks HIGH DOSE prescription Probiotic She signed up for an online functional medicine specialist
  128. 128. Case:2 Multifactorial 0 2 4 6 8 10 12 14 16 18 20 0 20 40 60 80 100 120 140 160 180 Methane Hydrogen
  129. 129. 35 year old Fear of Travel and Eating Out HPI: Gas, Bloating, alternating constipation/diarrhea, crampy abdominal pain in supra-umbilical region associated with eating. Onset 17 years ago. Previous workup at GI ruled out IBD. Notable for anxiety related to travel and eating due to digestive concerns/ DWQ: A:10 B:9, C: 14, D:10 E: 15 Lab test/Testing: Methane and Hydrogen Positive. > 30 ppm rise in Hydrogen >3 ppm rise in Methane Lifestyle: Introduced mind/gut treatment concepts of meditation Diet Low fodmap Diet P/E: POSITIVE tenderness noted x 4 quadrants with light and deep palpation Berberine/Undelycinic Acid combination
  130. 130. 35 year old: Fear of Travel and Eating Out Total Gas Production Hydrogen/Methane positive
  131. 131. ]35 year old. Fear of Travel and Eating Out Return Visit 1@30 days Reports improvement Only a few days of constipation, bloating Increase Undecyn./Berberine dosage Continue on low fodmap Return visit 2@30 days Feels some occasional abdominal bloating Bowel movements 1-2 per day Anxiety around eating gone Start biogest 1-2 caps Start erythromycin 75 hs. Slowly begin challenging fodmaps Return Visit 3 @ 30 days Polyol challenge: negative Fructose challenge: + diarrhea Continue bio-gest Continue erythromycin Challenge fructans/lactose Maintain fructose avoidance
  132. 132. 35 year old Fear of Travel and Eating Out Email @45 days Still digestively stable Challenged fructans with minimal symptoms Challenged lactose with minimal symptoms Plan to avoid fructose Challenge galactans Continue digestive enzyme/HCL combo, stop erythromycin, Start Bifidobacterium/Lactobacilli Return visit 6 months later Has been doing well with plan Galactans challenged negative Wants to know what else he can do to prevent flare He continues on probiotic and avoiding fructose but has stopped most other supplements Started taking homeopathic remedy for anxiety flares Plan: Continue probiotic: add Gut Repair Formula Continue fructose Avoidance Return visit 30 days later, May 2014 Plan is holding Wants to discuss other concerns Will continue on current plan
  133. 133. Two Tacks, Post Infectious-IBS 43 year old male with constipation, abdominal pain, nausea, joint pain, and weight loss that has been flaring for 2 months. He has history of less severe symptoms following years of international travels remembers many traveling related infections. Has lost weight, cannot eat much. Only eating Ghee, bread, Coconut butter. Blood work was done and it was normal at PCP office. Has lost 10 lbs./ in 10 weeks and is worried he has cancer. Had a colonoscopy in 20’s and has advised to get another one. P/E: Abdominal exam: tenderness X 4 quadrants. Otherwise multi-system P/E was unremarkable Labs: at presentation: wbc: 3.5 (3.8-11.0), HCT 44.1% normal, Low absolute neutrophils 1.30(1.9-7.4), TSH 1.23 (.45-5.10), CMP-normal. Fecal immunochemistry: wnl Repeat CBC: wnl, CMP: WNL: Sed Rate: 22 (elevated) repeat 1 month later normalize RF/anti-ccp antibodies: negative Amylase: 48 Lipase:21 CRP: <.10 ANA screen: negative Lactulose breath Test: Methane positive and weakly hydrogen positive CDSA: positive to few Blastocystis Hominis, otherwise completely normal
  134. 134. Two Tacks, Post Infectious-IBS Treatment phase 3 Bitters before each meal IGG/IgA Colostrum supplementation Bile Salts 1-2 tabs with each meal for gallbladder support Betaine + Pepsin with each meals Continue with VSL #3 or transition on to ProbioMax Plus DF 30 by Xymogen Supporting liver detoxification processes. Oral glutathione with BCAA’s Increase proteins in diet to gradually 1.0 gram /kg daily 4-7 servings of phytonutrients daily
  135. 135. Two Tacks, Post Infectious-IBS
  136. 136. Two Tacks, Post Infectious-IBS
  137. 137. Two Tacks, Post Infectious-IBS Treatment phase 1 Homemade Elemental Diet + plant based antimicrobial's Prescription based probiotic at night-time Treatment Phase 2 Neomycin first (14 day course) and then phase in Metronidazole after 4 days on Neomycin (it’s a 10 day course) + Low Fodmap diet . Continuing probiotic at bedtime
  138. 138. Case 1a: Two tacks: Post Infectious IBS • 8/1/2014 “I am doing well and having more vitality and ability to eat more as well… There is still some rebuilding going on and I am happy with the progress”
  139. 139. Two Tacks, Post Infectious-IBS Treatment phase 1 Homemade Elemental Diet + plant based antimicrobial's Prescription based probiotic at night-time Treatment Phase 2 Neomycin first (14 day course) and then phase in Metronidazole after 4 days on Neomycin (it’s a 10 day course) + Low Fodmap diet . Continuing probiotic at bedtime
  140. 140. Case 1a: Two tacks: Post Infectious IBS “ This protocol seems to be working very well. I have had a marked increase in energy and appetite. It was shocking to me to realize that I was hungry for the first time in four months. I am still eating a very simple diet (that fully fits in the fodmap) and even have less nausea and often no cramping. My breath seems better as well. Another interesting change is my stool. It still is good but now it sinks in the toilet instead of floating. It simply seems more dense even as I am passing it. This has not been a problem area so I was surprised by this change” “I am writing to let you know that I am done with the antibiotic and feel a marked change in the SIBO symptoms. I have more energy and am feeling able to eat larger quantities of food. My instincts say that I am fairly complete with the SIBO symptomology and I'm now looking at more focus on the parasitic components. I am having far less and at times no cramping”
  141. 141. Recap • Understanding of background and clinical workup related to SIBO • Understanding of pathophysiology and pathosequelae of SIBO. • An appreciation for terrain balancing approaches and the functional connections in SIBO. • Actionable lecture to bedside steps to evaluate dysmotile or malabsorptive patient or those at risk for SIBO • Actionable lecture to bedside steps to treat and recover patients with SIBO • Actionable lecture to bedside steps to approach the most sensitive and treatment refractory patients
  142. 142. Thank you
  143. 143. Contact • Adam Rinde, ND • Clinic Office: 425-889-5894 • Kirkland, Washington • Email: drrinde@soundintegrative.com • Website and blog: www.soundintegrative.com
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Dr. Adam Rinde updates Integrative Medicine Providers on Small Intestinal Bacterial Overgrowth (SIBO) which is explored as a potential contributing factor in Irritable Bowel Syndrome as well as a com-morbidity of motility disorders and diseases with disrupted motility (ie. Parkinsons Disease, and Diabetes). Dr. Rinde is a Bastyr University trained Naturopathic Physician in General Practice in Kirkland, Washington. He has a special interesting in mind-gut-immune-endocrine underpinnings of health.

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