The Adverse Chemical Influences of Clostridia Bacterial Toxins and Chronic Health Problems –

Beyond Common GI Issues

Copyright© 2015, Kurt N. Woeller, D.O., Tracy Tranchitella, N.D., and Educational Resource Association. This material may not be reprinted,

distributed or used without permission.

Support Documents For Module #5

• Clostridia Antibiotic Protocol – examples (pdf)

• Clostridia Natural Remedy Protocol – examples (pdf)

• Clostridia Treatment Program – patient handout

• General Considerations for Organic Acids Testing for Clostridia Related Problems (pdf).

• Overview of Common Probiotics (pdf)

• Taking Probiotic Suggestions (pdf)

• Fecal Transplant Donor Test Recommendations (pdf)

• Lecture slides (pdf) + Lecture slides - note taking (pdf)

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Lecture Overview• Clostridia bacteria and various health problems, including

the pathogenicity of C. difficile.

• Clostridia bacteria toxins and how they negatively effect the brain and nervous system.

• HPHPA & 4-cresol (and potentially others) as the main culprits for dopamine converting enzyme inhibition.

• The toxic problems of excess dopamine

• A deeper understanding of probiotics – specific to clostridia bacteria (helpful against candida too).

• Various treatment options:• Antibiotic and botanical remedies

• Fecal Microbiota Transplant (FMT) information

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Clinical Usefulness of Clostridia Treatments

• Schizophrenia

• Psychosis

• Depression

• Chronic fatigue

• Tics, Tourette’s

• Autism, ADD/ADHD

• Autoimmune, i.e. RA

• Obsessive compulsive disorder.

• Seizure disorders

• Gastrointestinal disorders, diarrhea, constipation.

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Nutritional Neuroscience 2010 Vol 13 No 3: 1-10

Great Plains Laboratory – ‘Resource’ section, Articles

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Effect of anti-Clostridia therapy

on urine excretion of HPHPA* in

young woman with acute

psychosis-auditory

hallucinations

patient normals

During acute 7489 0-150

psychosis

After treatment 673 0-150

( depressed but no

psychosis)

*mmol/mol creatinine

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Clostridium difficile

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Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N

Engl J Med. 2015;372:825-834

• The Centers for Disease Control estimates that there were 453,000 documented cases of Clostridium difficile infection (CDI) in the United States in 2011 leading to 29,300 deaths.

• Between 10% and 30% of people who have an initial episode of CDI will develop at least one recurrence. NOTE: Approximately 20% recurrence rate.

• On the basis of the number of incident cases found in 2011, 45,300-135,900 people developed recurrent CDI.

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Prevalence of Clostridium difficile in the gastrointestinal tract of hospitalized children under two years of age. Med Dosw

Mikrobiol; 2010;62(1):77-84 (Poland)

• 178 fecal samples of children aged 2 months to 2 years, hospitalized in 2003-2006, were examined for the presence of toxin A/B of C. difficile.

• Toxigenicity of strains was confirmed using PCR

• Susceptibility to antimicrobials was determined

• The percentage of children infected with C. difficile was 68.6%.

• All strains were susceptible to Vancomycin and Metronidazole (Flagyl).

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Inflammatory Bowel Secondary to C. Difficile

• In 1977, it was established that Pseudomembranous colitis was caused by toxins produced from Clostridium difficile.

• Toxin A (enterotoxin) and toxin B (cytotoxin) are produced by C. difficile and are involved in the disease process.

• Pseudomembranous colitis is frequently nosocomial with an increased risk of spread among hospitalized patients.• The C. difficile spores contaminate the patient's immediate

environment and are spread to other patients on the hands of healthcare workers and medical equipment brought into the room.

• All groups of antibiotics like cephalosporin, penicillin, clindamycin and ampicillin are commonly associated with pseudomembranous colitis.

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Brush Border, Villi and Tight Junction Damage

Toxin A Toxin B

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Toxin A & Toxin B

• These two toxins are the main virulence factors related to mucosal damage from C. difficile.• There are other strains of Clostridia difficile that produce

4-cresol and not A and B toxin.

• Toxins A & B lead to digestive tract inflammation, i.e. Pseudomembranous colitis or clostridia difficile associated diarrhea (CDAD).

• Toxin A & Toxin B are both capable of causing mucosal damage (Kuehne SA, Cartman ST, Heap JT, Kelly ML,

Cockayne A, Minton NP; October 2010. "The role of toxin A and toxin B in Clostridium difficile infection". Nature 467 (7316): 711–3).

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Toxin A

• Categorized as an Enterotoxin:• Toxin released by microorganisms that target the

intestines.

• It functions by changing host cell metabolism disrupting actin and tight junction function.• This leads to cell death, mucosal damage, and fluid

secretions.

• Considered to be the main cause of CDAD as it damages intestinal villi and the brush border.

• Can also lead to the severe ulcerations seen in Pseudomembranous colitis.

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Toxin B• Categorized as an Cytotoxin:

• A chemical that is toxic to cells, i.e. certain immune cells, venom (i.e. snake, spider).

• Causes major cellular disruption by interfering with signaling pathways, tight junction formation, cytoskeleton of cell, and derangement of overall cell structure.

• It is a major virulence factor of C. difficile opening up tight junctions which leads to vascular swelling and hemorrhaging.

• Induces Tumor Necrosis Factor-α and other pro-inflammatory cytokines which can have local and systemic effects.

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Inflammatory membrane (Pseudomembrane) overlying site of mucosal injury

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What are Clostridium Bacteria?

• Obligate anaerobes:• microorganisms that are killed by

normal atmospheric oxygen (O2).

• Obligate = strictly, adhered to

• 5 main species known to cause disease: C. botulinum, C. difficile, C. perfringens, C. tetani, and C. sordellii.

• Clostridium spores – reproductive cell of clostridium. Has thick wall and can resist volatile environments. Helps with defense.

• About 100 species of Clostridia can inhabit GI tract.

Clostridium bacteria

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Spore formation – major factor for Clostridia bacteria recurrence

• Recurrences occur after use of Metronidazole and/or Vancomycin (vancocin).

• Forms spores that are highly resistant to heat and antibiotics.

• Spores not killed by common disinfectants like alcohol hand wipes - may actually help spores spread.

• Only bleach kills spores

• Carriers without symptoms may spread spores

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Other Toxins of Clostridia Bacteria

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Structure of 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA)

HO

CHOHCH2COOH123

1

23

4

5 6

Phenyl group

Hydroxyl group

Propionic acid

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HPHPA• Known producers of HPHPA: C. botulinum, C.

sporogenes (similar to C. botulinum, but doesn’t contain the neurotoxin), and C. caloritolerans.

• Severe botulinum infection:• Sudden onset weakness (arms, legs, chest), trouble

seeing and speaking, and eventual flaccid paralysis.

• Some cases of food borne C. botulinum can have mild symptoms with people seeking no medical attention.

• Autism-Spectrum Disorders (often seen with high HPHPA):• little to no speech

• low muscle tone

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Distribution of values for HPHPA Clostridia metabolite in urine samples of male infants,

control boys, and boys with autism.

Control

infants

Control

boys

2-13 years

Autistic

Boys

2-13

years

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Critical effect of intestinal bacteria on neurotransmitters

Organic acids test

Organic acids test

Organic acids test

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Structure of 4-cresol (methylphenol)

HOCH31

2

3

4

5 6

Phenyl group

Hydroxyl group

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4-Cresol

• Major producer is C. difficile

• No other species of clostridia are known to produce this chemical.

• High toxicity known to cause circulatory collapse and death.

• Known to have growth suppressing effects in animals.

• Signs of acute toxicity – hypoactivity, salivation, tremors, and convulsions.

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Critical effect of intestinal bacteria on neurotransmitters

Organic acids test

Organic acids test

Organic acids test

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• Clostridium difficile is an important nosocomial pathogen, resulting in antibiotic-associated disease ranging from mild diarrhea to the life-threatening pseudomembranous colitis. Upon antibiotic exposure, it is believed that the normal bowel microflora of patients is disrupted, allowing C. difficile to proliferate.

• C. difficile is among only a few bacteria able to ferment tyrosine to p-cresol, a phenolic compound that is toxic to other microbes via its ability to interfere with metabolism.

• Therefore, the ability of different C. difficile strains to produce and tolerate p-cresol may play an important role in the development and severity of C. difficile-associated disease. In this study, it was demonstrated that two C. difficile hypervirulent 027 strains (Stoke Mandeville and BI-16) are more tolerant to p-cresol than other C. difficile strains including 630, CF4 and CD196. Surprising, it was shown that Clostridium sordellii also has a high tolerance to p-cresol, suggesting an overlap in the tolerance pathways in these clostridia species.

Dawson LF, et.al. “Assessing the role of p-cresol tolerance in Clostridium difficile” J Med Microbiol. 2008 Jun

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Goodhart PJ, DeWolf WE Jr, Kruse LI. Mechanism-based inactivation of dopamine beta-hydroxylase by p-cresol and related

alkylphenols. Biochemistry. 1983 Jun 21; 22(13):3091-6.

• A wide range of phenols, including p-cresol, a major Clostridia metabolite, are strong inhibitors of dopamine-beta-hydroxylase which converts dopamine to norepinephrine.

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Goodhart PJ, DeWolf WE Jr, Kruse LI. Mechanism-based inactivation of dopamine beta-hydroxylase by p-cresol (4-cresol) and related

alkylphenols. Biochem. 1983 Jun 21; 22(13):3091-6.

• Most importantly, the reaction is irreversible and the p-cresol is incorporated into the enzyme active site so that further enzyme activity is destroyed.

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“Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders” - Elaine Y. Hsiao, et. al.

• Demonstrate GI barrier defects and microbiota alterations in the immune activation (MIA) mouse model that is known to display features of ASD.

• Oral treatment of MIA with the human commensal Bacteroides fragiliscorrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA display an altered serum metabolomic profile (4-ethylphenylsulphate), and B. fragilis modulates levels of several metabolites.

• Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior.

“Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a

potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.”

December 5, 2013

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The researchers further dissected what was going on by screening for chemicals in the blood that differed between autistic and wild-type mice. One compound, 4-ethylphenylsulphate (4EPS), stood out:

1. It was found at levels 46 times higher in autistic mice.

2. Injecting 4EPS into wild-type mice resulted in autism-like behaviors.

4EPS – Is similar in chemical structure to 4-Cresol which is known to inhibit Dopamine Beta-

Hydroxylase.

4-ethylphenylsulphate

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Elevated HPHPA and High HVA in 6 year Old Chinese ASD Child

HVA/VMA = 4.10

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Male - Before Treatment (depression)

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Male After Treatment (no depression)

HVA/VMA = 1.38

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3-indole-acetic acid

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3-Indoleacetic acid

• High 3-indoleacetic acid in urine is a byproduct of: C. stricklandii, C. lituseburense, C. subterminale, and C. putrefaciens.

• Very high amounts of this metabolite derived from tryptophan might indicate a depletion of tryptophan needed for other physiological functions.

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Phenyllactic Acid

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Phenyllactic Acid

• Very high amounts of phenyllactic acid are found in the rare genetic disease phenylketonuria (PKU).

• Moderate amounts of phenyllactic acid may be due to gastrointestinal overgrowth of the intestine of the following Clostridia bacteria: C. sordellii, C. stricklandii, C. mangenoti, C. ghoni, and C. bifermentans.

• C sordellii is usually considered a non-pathogen except in immunocompromised people, but has been implicated in catastrophic infectious gynecologic illnesses among women of childbearing age.

• The other species have rarely or never been reported to be pathogenic.

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4-Hydroxyphenylacetic acid

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4-Hydroxyphenylacetic acid • High 4-hydroxyphenylacetic acid is associated with small intestinal

bacteria overgrowth due to its production by the following Clostridia bacteria: C. difficile, C. stricklandii, C. lituseburense, C. subterminale, C. putrefaciens, and C. propionicum.

• It is likely that 4-hydroxyphenylacetic is also an inhibitor of dopamine-beta-hydroxylase.

• Elevated values are common in celiac disease and cystic fibrosis, and have also been reported in transient lactose intolerance, Giardia infection, ileal resection, septicemia, and projectile vomiting.

• The elevations of 4-hydroxyphenylacetic acid in celiac disease and cystic fibrosis are so prevalent that involvement of these Clostridia bacteria may play a role in these illnesses.

• In C. difficile infections, 4-hydroxyphenylacetic acid is utilized by this bacteria to produce 4-cresol.

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Structure of 2-hydroxyhippuric acid - metabolite of aspartame (Nutrasweet®), aspirin, foods, additives

HO

CONHCH2COOH1

2

3

4

5 6

Phenyl group

Hydroxyl groupglycine

salicylate

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Structure of aminophenol - major acetaminophen metabolite

HO1

2

3

4

5 6

Phenyl group

Hydroxyl group

NH2

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What About DHPPA?

• 3,4-dihydroxyphenylpropionic acid (DHPPA) is a marker for beneficial bacteria in the gastrointestinal tract such as Lactobacilli, Bifidobacteria, and E. coli – the exception is Clostridia orbiscindens which converts certain flavanoids (i.e., parsley, thyme, celery) into DHPPA.

• The quantity of C. orbiscindens in the gastrointestinal tract is negligible (approximately 0.1% of the total bacteria) compared to the predominant flora.

• DHPPA is an antioxidant that lowers cholesterol, reduces pro-inflammatory cytokines, and protects against pathogenic bacteria.

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16050–16055 | PNAS | September 20, 2011 | vol. 108 | no. 38

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“Gut Microbiome and Brain-Gut Axis in Autism — Aberrant Development of Gut-

Brain Communication and Reward Circuitry” Intech, 2013

Elizabeth M. Sajdel-Sulkowska1 and Romuald Zabielski2[1] Dept. Psychiatry Harvard Medical School and BWH, USA[2] DDept. Physiological Sciences, Warsaw University of Life Sciences, Poland

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• Animal studies have also shown that stress can change the composition of the microbiome, where the changes are associated with increased vulnerability to inflammatory stimuli in the gut.

• Stress is known to inhibit gut contraction, one of the crucial defense strategies against bacterial colonization of gut mucosa.

• Early psychological trauma of maternal separation resulted in persistent mucosal barrier dysfunction in neonatal rats, including host defense to luminal bacteria, by mechanisms involving peripheral CRH receptors.

Stress

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• Evidence indicates that the Vagus Nerve is involved in immunomodulation by attenuating the production of pro-inflammatory cytokines in experimental models of inflammation.

• The microbiome also plays an important role in anxiety-like and depressive behaviors as the effects are diminished in vagatomized animals.

• Suggests either the direct communication between the bacteria and the brain or through the brain-gut axis.

Vagus Nerve and Immune Function

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• Oral antibiotics disrupt the microbiome and favor environment for opportunistic bacteria.

• Clostridium tetani produces a potent neurotoxin, tetanus neurotoxin (TeNT), that is transported by the vagus nerve from the GI to the CNS.

• Inhibitory neurons that release the neurotransmitter GABA are a preferred target for tetanus neurotoxins - and the Purkinje cells of the cerebellum, which often appear highly abnormal in autistic individuals, are inhibitory neurons that release GABA.

Vagus Nerve Transport of Neurotoxins

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Detrimental Effects of Excess Dopamine

• Overstimulation of dopamine tracts

• Substitution of dopamine into norepinephrine tracts and sympathetic nervous system.

• Damage to neurons producing excess dopamine due to oxidative damage of abnormal dopamine metabolites.

• Depletion of glutathione in brain making it susceptible to other toxic chemicals.

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Linan Chen, et al(2008) Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative

stress in mice. J. Neurosci. 28, 425–433

• Dopamine is a very reactive molecule (particularly the cytosolic dopamine) compared with other neurotransmitters, and dopamine degradation naturally produces oxidative species.

• More than 90% of dopamine in dopamine neurons is stored in abundant terminal vesicles and is protected from degradation.

• However, a small fraction of dopamine is cytosolic, and it is the major source of dopamine metabolism and presumed toxicity – leading to glutathione depletion.

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Toxicity of excess dopamine

Homovanillic acid (HVA)Dihydroxyphenylacetic(DOPAC)

Cycled thousands of times

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Fig. 2. The tricarboxylic acid cycle during high levels of propionic acid. Propionic acid, presumably derived from Clostridia spp., is metabolized to propionyl-CoA using acetyl-CoA. Propionyl-CoA is further metabolized into methylmalonyl-CoA, which enters the tricarboxylic acid cycle as succinyl-CoA. Succinyl-CoA inhibits the first and fourth enzyme in the tricarboxylic acid cycle. In this manner, propionic acid may ‘short circuit’ the

tricarboxylic acid cycle, thereby reducing the production of nicotinamide adenine dinucleotide (NADH). This decrease in NADH is hypothesized to cause the decrease in complex I activity measured in the patients with

consistent elevations in short and long acyl-carnitines (CESLAC)

From: Gastrointestinal dysfunction in autism spectrum disorders: the role of the mitochondria and the enteric microbiome (2015).

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Treatment Options for Clostridia

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Flagyl, aka. metronidazole (pill or suspension) – 250mg to 750mg 3x/day for 10 to 14 days. Cyclical dosing is an option.

Vancomycin, aka. vancocin (oral) – 125mg to 750mg 3x/day for 10 to 14 days. Cyclical dosing is an option.

NOTE: Approximate dosing range for both is 20mg to 30mg/kg divided dosages three times daily. On average = 25mg/kg/day.

Cyclical Dosing Options:• One dose TID for 10 days, then every 3rd day – one

treatment day (one dose TID) for 3 weeks. OR• One dose TID every other day for 4 to 6 weeks

Clostridia – Antibiotic Treatment

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• Mostly used as an intravenous antibiotic against gram positive bacteria that have resistance to other antibiotics:• Methicillin-resistance Staph aureus.

• Early reports of high rate of kidney and hearing toxicity secondary to IV use seemed to be related to impurities.

• Vancocin is the oral antibiotic for Pseudomembranous colitis and C. difficile associated diarrhea.• Also, enterocolitis from Staph aureus.

Pediatric Dosing (less than 18 years of age): 30mg to 35mg mg/kg in 3 to 4 divided dosages for 7 to 10 day – not to exceed

2 grams (2000mg) in 24 hour period of time.

Vancomycin (Vancocin)

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• Effective against a number of intestinal pathogens such as: • Fusabacteria, Bacteroides, Clostridia, as well as

Giardia lamblia and Entamoeba histolytica.

• Available in both intravenous and oral route (capsules or oral suspension) Pediatric Dosing: 7.5mg/kg (23mg/kg/d)

every 8 hours (TID) either as capsule or oral suspension.

Flagyl (Metronidazole)

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Effect of metronidazole on urine HPHPA levels in autismWilliam Shaw Nutritional Neuroscience 2010 Vol 13 No 3: 1-10

-50

0

50

100

150

200

250

300

350

400

450

500

0 20 40 60 80 100 120

Days after start of treatment

Uri

ne

HP

HPA

m

mo

l/m

ol c

reat

inin

e Start metronidazole

Stopmetronidazole

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Alternative treatments for Clostridium difficile disease: what really works? Lynne V. McFarland Journal of Medical

Microbiology (2005), 54, 101–111

125 mg–500 mg every 3 days over a

meanof 27 days

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Using Botanicals Against Clostridia

Case Examples of Reduction and Elimination of Clostridia Toxins and One Apparent

Failure To Treatment

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1/9/13

8/5/2013

Vanco x 10 days + Diflucan x 30 days

Biocidin + Culturelle x 60 days

Ex: #1

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11/4/13

• Biocidin (2 capsules TID) x 14 days, then every 3rd day for additional 4 weeks did another treatment day of Biocidin (same dose).

• Culturelle – 4 capsules at bedtime

NOTE: discussed with parents if program didn’t work we would need re-implement a longer antibiotic program.

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12/19/2013

3/25/2014

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6/27/14

• Biocidin (8 drops TID) x 14 days, then every 3rd day for additional 4 weeks did another treatment day of Biocidin (same dose).

• Grapefruit Seed Extract (3 drops TID) every day• Culturelle – 4 capsules at bedtime

Ex: #2

4-cresol – very high

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10/21/14

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Additional OAT Results on Two Children (Before and After

Botanical Remedies)

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Example #1

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Program

• Biocidin – 8 drops TID for 14 days, then every 72 hours did another treatment day (of 8 drops TID) for additional 4 weeks.

• Culturelle – 4 capsules at night 90 minutes away from last dose of Biocidin.

• Retested Microbial Organic Acids Test during the last week of Biocidin program.

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Example #2 - History of strong negative reaction to Culturelle

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Child with history of negative reaction to Culturelle

• Biocidin – 5 drops TID every other day for 6 weeks.

• Ther-Biotic Complete – ¼ teaspoon nightly 90 minutes away from last dose of Biocidin.

• Repeat Organic Acids Test in 6 weeks during the last week of Biocidin use.

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Parent decided not to implement program

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USP Effectiveness Testing of Biocidin®

Demonstrates inhibitory activity of against both gram positive and gram negative bacteria, yeast and fungus.

Bilberry extract, Grape Seed extract, Milk

Thistle, Echinacea, Goldenseal, Shiitake,

White Willow, Garlic, Black Walnut (hull

and leaf), Raspberry, Fumitory, Gentian,

Noni, Tea Tree oil, Galbanum oil,

Lavender oil, Oregano oil

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Rheumatoid Arthritis and Clostridia

A Difficult Case of a Persistent Infection

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3/18/14

53 year old female with

diagnosis of Rheumatoid

Arthritis.

Test prior to intervention

4-cresol = 80

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In addition to pathogen intervention

• Patient on strict gluten-free and allergen-free diet

• Nutritional supplementation, i.e. antioxidants, probiotics.

• Low Dose Naltrexone (www.lowdosenaltrexone.org)

1. Clinical course overtime has been difficult with periods of partial remission followed by intense exacerbation of symptoms.

2. It was felt that clostridia and subsequent bowel toxicity where a contributing factor to ongoing health issues with RA.

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4/17/13

4-cresol – 0.15

3 Weeks after Flagyl

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5/31/13

Notice 4-cresol still

normal, but now

HPHPA high

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8/14/13

Implemented Flagyl

again, but this time

not successful.

Having intolerance

to antibiotics

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11/14/13

Biocidin implemented

for approximately

3 months.

4-cresol still

normal

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General OAT Recommendations

• Obtain initial Organic Acids Test or Microbial Organic Acids Test to obtain baseline of clostridia markers.

• Initiate antimicrobial therapy (botanical and/or medication) based on clinical presentation of patient.

• If doing just 10 days of antibiotics, retest OAT or mOAT 2 weeks after regimen completed, and again 1 to 2 months later.

• If doing extended cyclical program, retest OAT or mOAT during the last week of therapy, and then again 1 to 2 months later.

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Clostridia Treatment Suggestions• If using antibiotics (Vancocin or Flagyl) use

something daily for yeast too: • Nystatin

• Diflucan

• Botanical, i.e. Biocidin, GSE, Allicin, Yeast Control Packet

• If using botanical remedies as primary clostridia intervention, then consider additional antifungal medication based on severity of candida, i.e. mild/sensitive, moderate, severe.

• In many circumstances the botanicals used for clostridia will also treat the yeast.

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Clostridia Treatment Suggestions

• Recommend to use antibiotic (Vancocin or Flagyl) along with Nystatin or Diflucan:• Initiate one versus the other for at least 72 hours

• Minimally use antimicrobial botanical for yeast control.

• The higher the level of HPHPA or 4-cresol, or the combination of clostridia markers, should dictate intensity of program, i.e. antibiotics or combination of different botanicals – association with patients clinical presentation and history.

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Clostridia Treatment Suggestions

• The presence of high clostridia markers in association with elevated HVA indicates a more significant impact on Dopamine-Beta Hydroxylase.

• Child who is aggressive, self-injurious or with bowel issues (i.e. loose stools), and with high HPHPA and/or 4-cresol markers, consider antibiotic intervention if possible.

• Use some type of probiotic against clostridia even while using antibiotics.

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ProbioticsEmphasis on probiotics with known

specificity against clostridia bacteria (helpful against candida too)

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Lactobacillus rhamnosus

• Produces multiple peptidases which help to breakdown gluten and casein peptides.

• Wide-spread adherence within colon to suppress pathogenic E. coli.

• Antagonistic against rotavirus and Clostridium difficile.

• Ex: ProBio Premium, ProBiotic Support Formula, Ther-Biotic Complete, Therelac, Probiotic Infant Formula, Culturelle.

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Lactobacillus plantarum

• Helps with induction of interleukin-12 for central immune regulation.

• Decreases production of inflammatory mediators

• Supports intestinal barrier function

• Reduces translocation of gut bacteria

• Antagonizes C. difficile

• Ex: ProBio Premium, ProBiotic Support Formula, Ther-Biotic Complete, VSL#3.

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Lactobacillus paracasei

• Ferments inulin to produce high levels of lactic acid

• Contributes to a healthy vaginal microflora

• Has supportive benefit in conditions ranging from allergic rhinitis to non-rotavirus diarrhea in children.

• Antagonizes C. difficile, Staphylococcus aureus, and other pathogens.

• Ex: ProBio Premium, ProBiotic Support Formula, Ther-Biotic Complete, Therelac, VSL#3, Probiotic Infant Formula.

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Bifidobacterium bifidum

• Present in large numbers in a healthy colon

• Suppresses total and antigen-specific IgE production

• Enhances IgM and IgG responses to select antigens

• Activates B cell IgA secretion

• Enhances IgA response to C. difficile toxin A. Along with L. acidophilus, supports gut microflora during antibiotic therapy and reduces positive testing for C. difficile toxins.

• Ex: ProBio Premium, ProBiotic Support Formula, Ther-Biotic Complete, Probiotic Infant Formula.

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Bifidobacterium breve

• Stimulates Peyer’s patch B cell proliferation and antibody production.

• Eliminates stool Campylobacter jejuni in campylobacter enteritis helping to restore normal intestinal flora.

• Secretes various compounds favorable to modify intestinal microflora by reducing Bacteroides and Clostridium concentrations.

• Ex: Ther-Biotic Complete, VSL#3, Probiotic Infant Formula.

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Lactobacillus gasseri

• Native to the human gut and vaginal tracts of healthy women and normally present in human breast milk.

• Protects against intestinal mitogens and carcinogens.

• Produces hydrogen peroxide and bacteriocinsinhibitory to Clostridium, Listeria, and Enterococcus.

• Ex: Probiotic Infant Formula

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Bifidobacterium lactis

• Enhances leukocyte tumor cell-killing properties and phagocytic activity.

• Increases numbers of total, helper, and activated T cells.

• Significantly increases serum and mucosal IgA production to cholera toxin and Clostridium tetanus toxoid.

• Ex: ProBio Premium, ProBiotic Support Formula, Ther-Biotic Complete, Therelac, VSL#3, Probiotic Infant Formula.

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Saccharomyces boulardii

• Augments colon bifidobacterium populations and increases butyrate concentrations.

• Enhances brush border enzyme activities and improves gut barrier function.

• Antimicrobial yeast with activities against C. difficile, toxigenic E. coli, Candida, and other gastrointestinal pathogens.

• Ex: ProBiotic Support Formula, or individual S. boulardii supplement.

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Probiotic Infant Formula

¼ teaspoon = 10 billion CFU’s – Infant up to age 2

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High Dose Probiotics

2 capsules = 225 billion CFUs 1 packet = 225 billion CFUs

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Culturelle – Acidophilus GG, aka. L. Rhamnosus

1 capsule = 10 billion CFU

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Multi-Flora Probiotics

1 capsule equals approximately 25 billion CFUs

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Saccharomyces boulardii

1 capsule = 3 billion CFUs

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• Culturelle – anti-clostridia

• VSL#3 – anti-clostridia and high oxalates

• Pro-Bio Premium – re-establish gut flora, some activity against clostridia. High oxalates.

• ProBiotic Support Formula – re-establish gut flora, some activity against clostridia and yeast.

• Klaire Ther-Biotic Complete – re-establish gut flora, some activity against clostridia and yeast.

• Probiotic Infant Formula – positive activity against clostridia, re-establish flora for under and 2 years of age.

• Saccharomyces boulardii – anti-yeast and anti-clostridia

Treatment Specific Uses

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Fecal Microbiota Transplant (FMT)

• Defined as: Infusion of a fecal suspension from a healthy individual into the gastrointestinal tract of another person to cure a specific disease (Brandt LJ,

Aroniadis OC. An overview of fecal microbiota transplantation: techniques, indications, and outcomes. Gastrointest Endosc. 2013;78:240-249)

• FMT has an approximate 90% cure rate for patients with recurrent Clostridium difficile infection (CDI).

• Some researchers feel that it is the most effective treatment available for this CDI, far surpassing that of antibiotics.

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Fecal Microbiota Transplant

• The procedure can be done using fresh stool transplants, frozen stool transplants (capsules are a subtype), or biosynthetic combinations of organisms derived from normal fecal microbiota.

• CDI is defined in the American College of Gastroenterology (ACG) guidelines as "acute onset of diarrhea with documented toxigenic C. difficile or its toxin and no other documented cause for diarrhea.” (Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478-498.)

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ACG guidelines for C. difficile

For an initial case of CDI, the ACG recommends

1. Discontinue the contributing antimicrobial agent and treat mild to moderate cases with Metronidazole.

2. For severe CDI, or for patients not responding to Metronidazole, the ACG recommends Vancomycin.

3. Recommended treatment for a first recurrence of CDI is to repeat the regimen used for the initial episode unless the CDI is severe, in which case the patient should be switched to Vancomycin.

4. For a second recurrence, the ACG recommends a pulsed Vancomycin regimen.

5. For a third recurrence after this, the ACG recommends considering FMT.

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Infectious Diseases Society of America

See handout: Fecal Transplant Donor Test Recommendations

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Other Online Support Organizations

• The Power of Poop – www.powerofpoop.com

• Resource links for instructions on rectal fecal transplant and fecal transplant capsules, plus additional information.

• Fecal Microbiota Transplantation –www.fmt.gastro.org• Resource with information on testing, referral doctors,

research, etc.

• Open Biome - www.openbiome.org• Non-profit stool bank

• Assists doctors in obtaining prescreened fecal samples

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Topic

• “Small Intestine Bacterial Overgrowth (SIBO) –Clinical Issues, Diagnostic Testing and Treatment Options”• The role of Small Intestine Bacterial Overgrowth (SIBO) in

gastrointestinal problems.

• The pathogenicity of SIBO

• Common diagnostic tests for SIBO

• Using the Organic Acids Test in the assessment of SIBO

• Treatment options using antibiotic and natural remedies

Module #6

Thank YouKurt N. Woeller, D.O. & Tracy Tranchitella, N.D.

www.GIMasteryCourse.com

GIMasteryCourse@gmail.com