By Dr Nirala Jacobi, BHSc, ND (USA)CMO, SIBOtest.com
Advances in the Treatment and
Management of SIBO:2015
Exponential increase in SIBO interest over last
few years2015 SIBO SymposiumIncrease in online interest: Blogs, summits, podcasts, support groupsSIBO FB support group in Victoria has over 1300 membersYour IBS patients are actively researching SIBO!
SIBOtest Mission
• To provide highest quality Breath Testing• To educate practitioners• Practitioner resource Section
Handouts: Diet, protocols, referral brochure• “Find a SIBO treating practitioner” section• Individual Practitioner pages
Position yourself as a natural SIBO treating expert!
SIBO
2015 SIBO Symposium
Main Presenters
•Drs Allison Siebecker, Steven Sandberg-Lewis- SIBO Centre, Portland, Dr Melanie Keller
•Dr Mark Pimentel, Motility clinic Cedars-Sinai Dr Lenny Weinstock, Dr Gary Mullin, Johns Hopkins University School of Medicine
Topics covered in this Presentation
Underlying Causes of SIBOAdvances in TestingAdvances in Treatment• Antimicrobials• Elemental Diet• Prokinetics
Dr Jacobi’s Clinical tips
The Basics of SIBO• Bacterial overgrowth of normal colonic bacteria
into the small intestines• Cause damage to the brush border and
therefore absorptive pathways• Often a consequence of gastroenteritis (food
poisoning) • 60% of IBS is considered to be SIBO• A very specific condition which requires proper
assessment and treatment• Please refer to the 2014 webinar for more
information (available at www.sibotest.com)
SIBO/IBS• SIBO-D = diarrhoea dominant
• SIBO-M = mixed diarrhoea and constipation
• SIBO-C = constipation dominant (methane mostly)
•NOTE: if excessive watery stools (in excess of 6-7 daily) it is unlikely to be SIBO. Typically SIBO has some mixed bowel patterns
Underlying causes of SIBO
• SIBO does have a CAUSE and if this cause is not addressed, relapse after treatment is common • The main causes are either:
The impairment of the migrating motor complex (MMC) and the enteric nervous systemorAnatomical issues causing the normal loops of small intestines to be affected (kinks in a garden hose)
Underlying causes of SIBO
• Post infectious • Diabetic enteropathy• Adhesions: abdominal surgery- appendix,
endometriosis, cesarean, cholecystectomy• Blind loops (gastric bypass patients) • Pseudo-obstruction: mechanical obstruction
without evidence of anatomical obstruction •Medications: narcotics (morphine, codeine, illicit
drugs), proton pump inhibitors• Stress :
HCL output Motility of the SI
Underlying causes of SIBO
• Large and small intestinal diverticulosis•Alcoholism•Other diseases: celiac disease, NASH,
pancreatic exocrine insufficiency
Post Infectious SIBO•Military study looked at the likelihood of
developing IBS after stressful events or gastroenteritis• Stressful events included: shooting a gun
in combat, shooting another human, active combat, and being injured in combat•Only gastroenteritis was associated with the development of IBS
Porter CK, et al. Dig Dis Sci 2013
Risk of Post infectious IBS
•Risk of PI-IBS increases 7 fold after infectious gastroenteritis• 4 main infectious organisms causing acute
gastroenteritis (food poisoning): • Campylobacter jejuni • E.coli• Salmonella• Shigella
CdtB toxin• These 4 organisms secrete a similar toxin:
cytolethal distending toxin B (CdtB) •Anti-CdtB secreted as a response to the
infection.•Anti CdtB – similar to vinculin, an
important component of the MMC and enteric nervous system•Mistaken identity: anti-vinculin antibodies
made instead of anti-CdtB attack the enteric nervous system
Food poisoning
• C. Jejuni• E. Coli• Shigella• Salmonella
Bacterial toxin CdtB
• AUTOIMMUNITY
• Anti vinculin antibodies
• Anti CdtB AB
Gut nerve damage
• Reduced ICC• Reduced
migrating motor complex (MMC)
SIBO
Common IBS/SIBO pathophysiology
Ileal Interstitial cells of Cajal (ICC) in normal
controls
Ileal ICC in SIBO
Inflammation
•Nerve inflammation is driving the autoimmunity• Inflammation without autoimmunity: ICC
cells able to repair within 3 weeks of resolution of inflammation
In patients with history of food
poisoning and IBS• 5 times more likely to get another episode
of food poisoning due to the slowed MMC• Takes fewer and fewer bacteria in each
episode to cause food poisoning• Each episode increases the likelihood of
developing SIBO due to further decreased motility
The big Question
In SIBO cases caused by post infectious gastroenteritis:
should our main goal be the resetting and repair of the MMC rather than primarily focusing on antimicrobials?
Clinical Pearl
• Prevention of food poisoning is important in our SIBO patients to prevent further damage to the MMC
My travel recommendation:Herbal bitters/IberogastAntimicrobial containing berberineSaccharomyces boulardii
Adhesions•Another cause for the development of
SIBO besides post infectious causes. • Post surgical: adhesions are a healing
mechanism. Appendectomy, cholecystectomy, hysterectomy, Laparoscopy, bowel resections etc.•Can often be palpated in an abdominal
exam. Movability of organs, areas of restriction
Treatment of adhesions
• Clear Passage: US based PT centre specialising in the non-surgical tx of adhesions
www.clearpassage.com• 20 hours of Tx over 5 days
Other optionsVisceral release therapy?Acupuncture?I don’t think Castor oil packs are enough
Testing for SIBO
•New Blood test for IBS – does NOT replace the breath test
• Lactulose/ Glucose breath tests• Hydrogen • Methane- new spot test may be on the horizon
•Other tests to consider for your SIBO patient
New IBS Blood Test (just released)
•Measures anti CdtB and anti vinculin•>60% accurate to diagnose IBS• Intended to prevent extensive work up
(colonoscopies, endoscopies)•Best suited for GPs as an initial workup: IBS
vs IBD•Does NOT replace lactulose breath test for
SIBOEstablishes IBS as an autoimmune condition
Drawbacks of the blood test
if negative, can still have SIBO but means it is less likely to be caused by autoimmune reaction. Follow up with breath test to confirm
Not yet offered by labs in Australia. 48 hour turn-around time to get blood to the lab in the USA
Lactulose Breath Test (LBT)
• Still considered to be the primary test for SIBO• SIBOtest uses same testing guidelines and
reference ranges as the SIBO center in Portland.• 3 hour breath test- • first 2 hours are considered SI time• Last hour could be slow transit or LI
SIBOtest – only lab in Australia to offer LBT for SIBO
Why test?
• To understand the levels of hydrogen and methane•Gives you a guideline as to how many
cycles of antimicrobials you may need•Re-test to ensure bacteria are eradicated
First Test June 2014
2nd test Nov 2014
3rd Test May 2015
Methane•Methanobrevibacter smithii – methanogen•Unknown if beneficial benefit but assoc.
with higher calorie extraction•Highly associated with SIBO-C• Patients feel best when methane <3ppm• Poorly absorbed from LI•Not produced with substrate lactulose•New “spot re-test” is coming…stay tuned
So the LBT is negative….
•No test is perfect• If your patient has all the classic
symptoms of SIBO: consider Glucose breath testing as a back up
Other tests for the SIBO patient (not
diagnostic for SIBO)•Celiac/Gluten intolerance: sxs often same
as SIBO•CDSA – calprotectin, elastase, fat in stool• Food sensitivities•MTHFR and other methylation tests –
Histamine sensitivity, B12/FA • Lyme disease: similar GI sxs
Alarm s/sxs in IBS-- require more extensive evaluation (e.g., imaging
studies and/or colonoscopy
• Fever• weight loss• blood in stools• nocturnal symptoms• progressive abdominal pain • laboratory abnormalities• abnormal physical findings• family history of inflammatory bowel disease
(IBD) or colorectal cancer (CRC)
Advances in Treatment
Antimicrobialso Rifaximino Herbal antimicrobialso Elemental Diet
Prokineticso Conventional: low dose erythromycin, LDN,
and Resoloro Herbal: Iberogast, Motilpro, Ginger
Maintenance Prokinetics Maintenance
diet
Re-test 6-8 weeks(+)Repeat above
(-) move to below
Positive Breath testAntimicrobials SIBO diet
Antimicrobials
•Rifaximin and other antibiotics (great resource for proper dosing www.siboinfo.com)
•Herbal antimicrobials
• Elemental Diet
Rifaximin•Only just approved by the FDA for the
treatment of IBS•Rifaximin (Xifaxan) – high Hydrogen•Rifaximin and Neomycin – high methane •Does not cause dysbiosis as it is bile soluble
not water soluble•Does not cause antibiotic resistance•Other antibiotics taken with Rifaximin seem
to also be less likely to cause bacterial resistance
Rifaximin•Dose is 550mg 3x daily •Compounded Xifaxan. Uncertain from
where this is sourced. There is quite a bit of grumbling about Rifaximin sourced from outside the US– questions about efficacy and systemic absorption (vs just staying in the intestinal lumen) • I have had patients get Rx a handful of
times in tough cases
Herbal Antimicrobials
•Dr Mullin Research at Johns Hopkins University showed herbal antimicrobials as effective as Rifaximin•His research used herbal products from 1
US based company•None were specifically formulated for SIBO
Mullin et al Global Advances in Health and Medicine May, 2014
Tried and Proven Herbal AntimicrobialsHydrogen •Berberine•Neem•Oil of oreganoMethane•Allimax (Biomedica)•Oil of oregano•Neem
Potential new antimicrobials
•Manuka herb• Pomegranate seed•Horopito
Clinic based research coming in 2015/2016
SIFO- small intestinal fungal overgrowth
• Fungal overgrowth often accompanies SIBO• The diet and the antimicrobials usually treat
this as well but consider • Additional antifungals • Probiotics (immune regulation)• Biofilm disruptors – seem more successful
with fungal infections
Elemental Diet (ED)• Very effective in reducing bacteria•Can decrease severe gas levels in one
course (2 weeks) – reductions of 148ppm have been documented•Vivonex formula – Dr Pimentel. •Homemade ED – Dr Siebecker- not
formally testedPimentel, M. A 14 day elemental diet is highly effective in normalizing lactulose breath test. 2004
Elemental Diet (ED)
•Recipe: Siboinfo.com; Resources; Handouts • Protein= amino acids, CHO= honey
(fructose & glucose)/glucose (dextrose), Fat= oil, Micronutrients= multi-vitamin, salt (electrolytes)• 2versions: 1. Matches Vivonex (High CHO)
2. Low CHO/High Fat
Commercial vs Homemade Vivonex
Expensive StudiedContains corn, soy, maltodextrin, preservativesPremixed packetsHigher carb, lower fat
HomemadeLess expensiveNot studiedCleaner ingredientsSeparate ingredients which have to be mixed together
Elemental diet
•Both Vivonex and Homemade are excellent for hydrogen and methane•Challenges:
Bad tasteEmotionally difficultDie offWeight lossCan aggravate yeast
Ingredients•Amino Acid Blend - 24g protein per serve•Dextrose (glucose)- 106g CHO per serve.
This can be adjusted•Oil (coconut ,MCT, olive, Macadamia, cod
liver) – 4.6g fat per serve
Based on a 2000cal diet/day3 serves dailyAdd Mulivitamin, Salt
Elemental Diet: Clinical Notes (Dr
Siebecker) •Recommend family/friends give encouragement during • Expect bowel changes-odd colors, diarrhea, constipation•Often takes 1-2 weeks for stool to normalized after, or longer•Die off can be very bad and last the whole time• Flu-like feeling• Fatigue•Headache•Aggravation of existing or past symptoms•New GI symptoms
Important points about ED
• Standard commercial “detox” formulas and protein powders are NOT the Elemental formula and will NOT work for this purpose
•Wait about 10 days after completing the ED before re-testing
ProkineticsNew Guideline: Typically started AFTER completion of antimicrobials and re-test is clear
Aims to reset the MMC (vs just laxatives)
Failure to use effective prokinetic is most common cause of relapse
ProkineticsConventionalResolor (Prucalopride)Low dose Erythromycin (LDE)Low dose Naltrexone (LDN)
NaturalIberogastGingerMotilpro
Conventional Prokinetics
• Prucalopride: 5HT4 agonist, works on stomach, SI, and colon. Limited data, difficult to get in the US but Preferred prokinetic of Dr Pimentel. Dose: 0.5-2mg before bed• Low dose Erythromycin (LDE) – Motilin
agonist, works on stomach and SI, mild effect on colon. In vitro- no effects on microbiome. Dose: 50mg before bed• LDN- in limited use and practitioners
report mixed results
Herbal Prokinetics: Iberogast
• 9 Herb European Combo= Dyspepsia & IBS• Iberis Amara, Angelica, Chamomile, Caraway, St. Mary’s
Thistle, Lemon Balm, Peppermint, Celandine, Licorice • 40+ years clinical use: nausea, GERD, bloating,
cramping/pain, constipation, diarrhea• 47+ articles (5 Rev/4 MA/6 RC/5 Ret/1 NI –including pediatric) • Dyspepsia, IBS, GERD, Ulcer, Rebound Acidity, Gastroparesis,
Visceral Hypersensitivity, Colon Cancer, Colitis, Inflammation, Radiation, Sepsis • No SIBO Studies
Iberogast studies• Proven Prokinetic Effects• More effective for Dyspepsia than some conventional prokinetcs• MoA: 1.Partial 5HT4 agonist 2.5HT3 antagonist 3.selective M3 inhibition
(muscarinic) 4. Opioid inhibition • Adaptogenic: treats both constipation & diarrhea & upper & lower sx• IBS adults: 65-80% sx improvement, Good or Very Good results in 80% • IBS children: 76% sx improvement, Good or Very Good results in 89% • Based on 1 mo of use 3xd. Results were better with shorter IBS/sx
duration • Low side effects: 0.04%, Safe for long term use/Pregnancy/children. • Dose: 20 drops 3 x daily before meals and before bed
Note: nightly dose is standard for prokinetic SIBO preventionOttillinger ’13,Simmen’06, Raedsch’07, Rosch’02
Ginger (Zingiber officinale)
• Bioactive compounds within the rhizome of ginger, particularly Gingerol and Shogaol class of compounds• The major chemical constituents of ginger are [6]-
gingerol, [8]-gingerol,[10]-gingerol, and [6]-shogaol• Promotes gastric emptying rate and motility
(gastroduodenal)•Modulates serotonin signaling by 5-HTP4 stimulation• Binds Type 3 (5-HTP3) receptors in enteric nervous
system and brain stem• NOTE: Ginger may be contraindicated with blood
thinning medications.
Ginger and Motility•The effect of a ginger rhizome extract (2 x 100 mg) was studied on fasting and postprandial gastroduodenal motility with stationary manometry in 12 healthy volunteers.•The results showed that: the interdigestive antral motility was significantly increased by ginger during phase III of the migrating motor complex•Oral ginger improves gastroduodenal motility in the fasting state and after a standard test meal
Int J Clin Pharmacol Ther. 1999 Jul;37(7):341-6. Effects of ginger on gastroduodenal motility.Micklefield GH1, Redeker Y, Meister V, Jung O, Greving I, May B.
MotilPro• Pyridoxal 5 Phosphate 10mg- Cofactor to
decarboxylate 5-HTP to Serotonin•Ginger 1000mg•Acetyl L-carnitine 500mg- synthesis of
acetylcholine• 5HTP 50mg – serotonin production, 5-HTP
also stimulates enteric neurons through activation of 5HT4 receptors.•Ascorbyl Palmitate (Corn dextrose and
palm oil) 30mg
Prokinetics – thoughts
•Need to stay on it for a minimum of 6 months even if sxs have resolved• Suggested to re-test after stopping the
prokinetic to ensure MMC is working• In case of debilitating adhesions or more
severe disease, may have to stay on it indefinitely
*Dr Jacobi’s Clinical Tips
SIBO patients are often very sensitive!
Microvilli and Brush border disrupted.
•Histamine intolerance (low DAO)• Salycilates• Sulfites
Histamine intoleranceFlushingRapid heart rateProfuse sweatingHeadacheMigraineFood allergiesSeasonal allergiesPrickly heatSwollen mozzie bitesRunny noseBloody nose
Car sickSeasickMotion sickItchyIrritableNauseaVomitingHigher libidoAsthmaExercise induced asthmaStomach ache
Menstrual crampsChest tightnessLoose stoolsSkin rashes (eczema, psoriasis, etc)insomnia
Foods high in Histamine• any fermented food: e.g. sauerkraut, yogurt, vinegar, cheese
• tinned fish products and any fish that isn’t fresh• tinned foods in general• alcohol• Left overs in general• vegetables: spinach, eggplant, tomato, avocado• all legumes: beans and lentils, this includes soybean products like tofu,
tempeh• fruit: strawberries, banana, raspberries, pineapple, kiwi, pears, papaya• nuts: peanut, walnut, cashews, sunflower seeds• condiments: anything containing yeast extract or preservatives, stock
powders, sauces, • soy sauce, fish sauce, spices like chill, curry, mustard• sweets: chocolate, cacao
Products to consider for your sensitive
client• Generally:L-GlutamineDigestive enzymes including brush border enzymesProbiotics (no prebiotics)
• Histamine sensitivityDAO- HistDAOVit C- not containing sweetenersB6/copper
• Salycilate sensitivityGlycine 2-5g daily (Dr Vera’s)
• Sulfite sensitivityMolybdenum
Constipation
•Methanogens- successful treatment: <3ppm on test • SIBO diet is typically constipating as well• Long standing constipation can result in
large intestinal ‘inertia’•Constipation/Bowel retraining page at
SIBOtest.com•Gets patient involved
Retraining a sluggish colon
• Oral: Magnesium, Herbal laxative: Cascara/Kawakawa (OptimalRX)• NOTE: prune based laxatives contain Sorbitol• I usually adjust the diet to contain some insoluble
fibre (brown rice, rice bran, increase dark leafy)• Exercising/Breathing- stimulating diaphragmatic
movementWalkingNadya Andreeva’s belly exercises - TED talk- 5 minDr Datis Kharrazian’s Vagal nerve exercises (gargling, gagging) YouTube 59minsCoffee enemas
Retraining a sluggish colon
• Stress reductionBreathing exercisesHeartMath- Inner Balance DeviceMeditation- Examples: HeadSpace, Chopra
• Position – Squatting Stool
SIBOtest
• To educate practitioners• Practitioner resource Section
Handouts: Diet, protocols, referral brochure• “Find a SIBO treating practitioner” section• Individual Practitioner pages
Position yourself as a natural SIBO treating expert!
SIBO
SIBO MasterClass
•Web based- conference call via Go2Meeting•Case review and Management with Dr.
Jacobi•Meets fortnightly for 6 weeks• Small class size – 12 practitioners max• Sign up at SIBOtest.com
Thank you!
Coming up in 2015/2016
• Pimentel: study of new drug stopping the production of methane• SIBOtest trial of new antimicrobials• Anti-Methanogen diet?• Need more research of herbal prokinetics