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