Lincoln College of Postprofessional, Graduate and Continuing Education

Herbal Considerations to Effectively Treat

SIBO and SIFO
Instructor:
Nirala Jacobi, ND, LAc

Faculty and Instructors representing NUHS/Lincoln College of Postprofessional, Graduate and Continuing
Education are responsible for disclosing any financial interest, research grants, program support, or other
matters that create any suggestion of a conflict of interest.
Copyright © 2017 by National University of Health Sciences. All Rights reserved.
Material attached may not be reproduced in any form without written permission.
200 East Roosevelt Road  Lombard, Illinois 60148-4583
630/889-6622 Phone / 630/889-6482 Fax
www.nuhs.edu (Continuing Education)
 Disclaimer

Herbal Considerations  CMO at SIBOtest.com

to Effectively Treat SIBO  I hold no financial interest in any of the information presented today

and SIFO
Dr. Nirala Jacobi, ND – NSW, Australia

Pros and cons of herbal medicines Botanical Mechanisms of overcoming

Bacterial Resistance
 Bacterial efflux pumps actively remove antibiotics and other substances out
 Pros:
of the cell–
• Herbs often have multiple effects, ie antibacterial and antifungal, antiinflammatory and
antioxidant, etc • Examples of herbs which inhibit or down regulate these: Berberine containing
plants, Thyme, Juniper, Licorice, Green Tea
• Mostly cause less damage to the microbiome
• Have evolved with bacteria and thus have overcome many of their resistance strategies  Alterations in bacterial cell wall permeability – gram neg bacteria down
• Can be combined to address multiple issues
regulate porin expression which limits antibiotic entry into the cell.
 Cons • Examples of herbs which alter bacterial cell wall: Bearberry, Goldenseal, Usnea
• Can be more costly due to length of treatment ▶ Plasmids: strains of bacterial DNA that contain resistance information. Highly
• Patients self medicating with inferior herbal products can be cause for concern due to
mobile and passed on to other bacteria
contamination (heavy metals etc) • Examples of herbs that modulate bacterial DNA: Barberry, Golden Seal, Oregon
• Allergies, salycilates, oxalates Grape, Thyme
• Doses often vary depending on formulation (standardized extract vs whole plant)
• Limited research in SIBO and SIFO, more research in IBS in general

Molecular mechanisms of antibiotic resistance. Blair et al, Nat Rev Microbiol 2015 Jan;13(1):42-51
Antibiotics for SIBO– out of the frying The Culprits
pan and into the fire? Predominant SIBO bacteria isolated on duodenal aspirate (Pimentel, 2015):
 gram positive:

Long term damage to the microbiome with repeated antibiotic courses Enterococcus spp
other studies also identified Streptococcus and Staphylococcus
“The fecal microbiome was severely affected by most antibiotics: for
 gram negative:
months, health-associated butyrate-producing species became strongly
underrepresented. Additionally, there was an enrichment of genes Proteus mirabilis
associated with antibiotic resistance. Clearly, even a single antibiotic
treatment in healthy individuals contributes to the risk of resistance
E.coli
development and leads to long-lasting detrimental shifts in the gut Klebsiella pneumoniae
microbiome.”

 Methanobrevibacter smithii (methane)

Co-morbid SIFO
Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces
Egija Zaura,a Bernd W. Brandt,a M. et al. Mbio November/December 2015 Volume 6 Issue 6 e01693-15 candida spp and other fungal spp
The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Pyleris E, Giamerellos-Bourboulis EJ, Pimentel M, et
al. Dig Dis Sci 2012 May;57(5):1321-9. doi: 10.1007/s10620-012-2033-7. Epub 2012 Jan 20.

Herbal uses in SIBO and SIFO Anti-microbials

 Antimicrobials 1. Berberine containing herbs

• Antibacterial/antifungals/antimethanogen 2. Garlic
 Anti-inflammatories, antioxidants, Immune modulators: 3. Oregano
• curcumin, green tea 4. Clove
 Herbal Prokinetics 5. Pomegranate
 Anti-spasmodics/carminatives: chamomile, caraway seeds 6. Artemisia annua
7. Usnea
8. Horopito
Berberine containing herbs Berberine - MOA
Clinically well established for reducing hydrogen
Phellodendron amurense, Mahonia aquafolium (Oregon grape), Coptis
chinensis (Goldthread), Berberis vulgaris (Barberry) , Hydrastis 1. Efflux pump inhibition
canadensis (Golden Seal) 2. Bacterial cell membrane permeability modification
 Berberine: different berberine alkaloids have different actions 3. Inhibition of biofilm formation
 effective against: E.coli, Klebsiella p., P. aeruginosa, Staphyloccocus 4. Inhibition of bacterial replication
spp, Streptococcus spp and candida spp
5. Anti-virulence properties via quorum quenching
 interferes with the adhesion of LTA (lipoteidoic acid), a ligand
responsible for the adherence of Streptococci to epithelial cells

Buhner, S (2012) Herbal Antibiotics, USA; Storey Publishing

Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition.
Ettefagh, KH et al. Planta Med 2011 May;77(8):835-40

Quorum quenching and antimicrobial activity of goldenseal (Hydrastis canadensis) against methicillin-resistant Staphylococcus aureus (MRSA).
Cech NB, et al. Planta Med. 2012 Sep;78(14):1556-61

Berberine containing herbs Berberine and hydrogen reduction on

 poorly absorbed from GI thus ideal for local infections
LBT
 Mucous membrane “tonifying” effect
• Berberine is also
 Antiinflammatory
 Antioxidant
Ingredient in many “gut antimicrobial formulas” – ensure a daily dose of 2-
3grams of berberine if included with other strong antimicrobials. Most herbal
formulas only deliver around 500mg
Tincture: standard dose is 30-50ml a week, may have to go much higher than
that

Caution:
High berberine can have hypoglycemic effects and also inhibit MOA enzyme
 Allium sativum (Garlic) Garlic extract and methane reduction

 Allium sativum is antifungal, antibacterial, antiviral

 Allicin (diallyl thiosulphinate)– widely studied constituent of Garlic
• Highly volatile compound (unstable) -
▶ Main MOA –inhibition of thiol containing enzymes which maintain intracellular
redox state within bacterial cells.
▶ Disrupts electrochemical potential of yeast cells – causes apoptosis
 Do not use “aged garlic” or fresh garlic extracts– not as effective and contain
Fructans (high FODMAP)
• Allisure 360mg BID- TID
• clinically proven to lower methane

Syzygium aromaticum (Clove) Syzygium aromaticum (Clove)

 contain15-20% of clove is essential oil, primarily Eugenol.
 Gastroprotective:
 Anti-proliferative , antiinflammatory • stimulates gastric mucous production
 Active against a wide variety of gram (-) and (+) bacteria, including • Antibacterial against H.pylori
K.pneumoniae, E.coli, Proteus mirabilis, Streptoccoccus, Staphyloccocus,
 Motility
Bacillus cereus, and H.pylori
• Helpful in IBS-C
 Broad spectrum anti-fungal – candida spp, Aspergillus, Dermatophytes
• Increase gastrointestinal muscle propulsion similar to metoclopramide and
(trichophyton etc) carbachol- cholinergic activity
 Anti-histamine: inhibits mast cell degranulation and reduction of mesenteric ▶ Dose
Mast cell infiltration
• 10-15ml per week of a 1:2 extract
• Caution – excess doses can increase bleeding time, some evidence of CYP3A4
inhibition

Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models.
Sein SK et al. Naunyn Schmiedebergs Arch Pharmacol 2011 Feb;383(2):149-58.
Antimicrobial agents from plants: antibacterial activity of plant volatile oils. Doorman HJ. J Appl Microbiol 2000 Feb;88(2):308-16.
Gastrointestinal effects of Syzigium aromaticum (L) Merr. & Perry (Myrtaceae) in animal models. Agbaje EO. Nig Q J Med Hosp 2008 Jul-Sep;18(3):137-41.
Antimicrobial activity of five herbal extracts against multi drug resistant (MDR) strains of bacteria and fungus of clinical origin. Khan et al. Molecules. 2009 Feb 4;14(2):586-97
Antiproliferative and Molecular Mechanism of Eugenol-Induced Apoptosis in Cancer Cells. Jaganathan, SK et al. Molecules. 2012 May 25;17(6):6290-304.
Punica granatum (Pomegranate) Punica granatum (Pomegranate)

 Juice, rind and seed used  “Significantly enhances growth of Lactobacillus spp, Bifidobacterium
breve and Bifidobacterium infantis while inhibiting the growth of pathogenic
 Active constituents: ellagic acid glycosides and ellagitannins, other tannins,
flavonoids clostridia and Staphylococcus aureus”

 Gram –positive bacteria : Staphylococcus aureus, Streptococcus, spp, and  Therapeutic Dose: 40-80ml/week ( 10ml daily) of a 1:2 tincture
Bacillus spp
 Gram-negative bacteria: E.coli, Campylobacter jejuni, Salmonella spp, Evaluation of antimicrobial activity of Punica granatum peel against enteric pathogens: an in vitro study. Pai V, et al Asian Journal of
Shigella spp, Vibrio spp, Klebsiella pneumonia, Pseudomonas aeruginosa, Plant Science and Research 1(2), 57-62

Yersinia enterocolitica, H.pylori The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health. Howel A, D’Souza D. Evid Based Complement
Alternat Med. 2013; 2013: 606212.
 Fungal: candida spp The effect of pomegranate (Punica granatum L.) byproducts and ellagitannins on the growth of human gut bacteria. Bialonska D,
Kasimsetty SG, Schrader KK, Ferreira DJ Agric Food Chem. 2009 Sep 23; 57(18):8344-9.
 Parasitic infections: Giardia spp, Blastocystis spp, Entamoeba h.,
Cryptosporidium parvum, and more..

Artemisia annua (Qing Hao) Artemisia annua (Qing Hao)

 Active constituents: essential oils and sesquiterpenoids  Immunomodulation- inhibits NO, iNO and NF-kB
(artemisinins)
 Therapeutic Dose: 20-50ml/week 1:2 extract
 Classically used for parasites, malaria
 Antimicrobial activity against
Gram –positive bacteria : Staphylococcus aureus, Streptococcus, spp, and Bacillus spp
Gram-negative bacteria: E.coli,, Salmonella spp, Klebsiella pneumonia, Pseudomonas Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia
aeruginosa, Proteus spp Cells.Cansheng Zhu, et al. PLoS One. 2012; 7(4): e35125.Published online 2012 Ap13. doi:

 Antiparasitic against: Toxoplasma gondii, Schistosoma (blood fluke), Fasciola Essential Oil of Artemisia annua L.: An Extraordinary Component with Numerous Antimicrobial Properties. Bilia AR, et al. Evid Based
Complement Alternat Med. 2014; 2014: 159819.
hepatica (liver fluke), Plasmodium f. Antibacterial Activity of Essential Oils and Plant Extracts of Artemisia (Artemisia annua L.) In Vitro. Massiha A, et al. Zahedan Journal
of research in Medical Sciences, 15(6), 14-18
 Usnea spp (Old Man’s Beard) Usnea spp (Old Man’s Beard)

 Over 600 Usnea spp – found on every continent  Anti-inflammatory- in one study as or more effective as NSAID and
hydrocortisone
 Primary active constituent: usnic acid
 Anti-oxidant: activates superoxide dismutase (SOD) and glutathione s-
 Primarily active against gram positive bacteria:
transferase (GST) enzymes, protects against damage in mucosal cells
Bacillus spp, Clostridium spp, Enterococcus spp, Listeria monocytogenes,
Staphylococcus spp, Streptococcus spp, etc  Therapeutic Dose 10-15ml daily 1:2 extract

 Some gram negatives: H.pylori, E. coli, Yersinia enterocolitica, Proteus

mirabilis Buhner, SH (2012) Herbal Antibiotics: Natural Alternatives for treating Drug-Resistant Bacteria, 2nd ed, Massachusetts, USA : Storey
Publishing, p.197
 Antiparasitic Contributions to the complex study of some lichens-Usnea genus. Pharmacological studies on Usnea barbata and Usnea hirta species.
Dobrescu D, et al. Rom J Physiol. 1993 Jan-Jun;30(1-2):101-7
 Candida spp Effects of water extract of Usnea longissima on antioxidant enzyme activity and mucosal damage caused by indomethacin in rats.
Halici, M, et al. Phytomedicine 2005 Sep;12(9):656-62.

SIFO – small intestinal fungal overgrowth Antifungal herbs

 Large intestinal fungal overgrowth also very common

 Issues with candida spp:  Many of the herbs discussed also exhibit antifungal properties
• Often cause similar symptoms to SIBO  Classic antifungal herbs include Pau D’Arco, Uva Ursi, Berberine herbs
• Commonly forms biofilm  Essential oils of clove, oregano, and thyme are particularily useful
• Overgrowth easily evades detection  Oregano
Dr Rao study  Horopito
 SIFO co-morbid with SIBO in 20%
 SIFO found in 26% of patients with “unexplained GI symptoms”

Small intestinal fungal overgrowth. Erdogan A, Rao SS. Curr Gastroenterol Report. 2015 Apr;17(4):16
 Oreganum vulgare (Oregano) Pseudowintera colorata (Horopito)

 Traditionally used for digestive, urinary, and respiratory disorders.

 Carvacrol main active antimicrobial constituent (mainly antifungal)  Native to New Zealand
 Active against candida spp, but also S. aureus, Pseudomonas a., and  Active constituent: Polygodial
Blastocystis hominis
 strong antifungal activity against the yeast like fungi C. albicans, C. utilis, C.
 Clinically shown to be effective for SIFO and methanogens krusei, Cryptococcus neoformans, S. cerevisiae and also filamentous fungi
including T. mentagrophytes, T. ruburum and Penicillium marneffei
 Effective against candida biofilm
 moderate antibacterial activity against both gram positive bacteria (including
 antioxidant
Bacillus subtilis and Staphylococcus aureus) and gram negative bacteria
 Usually dosed as oil of oregano (50-100mg 2x daily) (including Escherichia coli and Salmonella)
 MOA: polygodioal is a nonionic surfactant that damages the permeability
barrier of yeast cells.

Mechanism of Antifungal Activity of Terpenoid Phenols Resembles Calcium Stress and Inhibition of the TOR Pathway. Rao A, et al. Antimicrob. Agents Chemother.December 2010 vol.
54 no. 125062-5069▿
Mode of Action of Polygodial, an Antifungal Sesquiterpene Dialdehyde. Taniguchi, M, et al. Agricultural and Biological Chemistry, 52(61),
1409–1414.

Polygodial Liquid antimicrobial formula

 SIBO formula- 7.5ml 2 x daily
• Oregon grape (or Coptis/Goldenseal)
• Pomegranate
• Artemisia
• Burr Marigold

 SIBO/SIFO formula – 7.5 ml 2 x daily

• Pomegranate
• Usnea
• Horopito
• Oregon grape (or Coptis/Goldenseal)

McCallion et al 1982. Planta Medica, vol 44, pp134-138

 Curcumin- anti inflammatory and Curcumin in IBS
antioxidant
 Curcumin is one of the active constituents of Turmeric  2004 study of 207 randomized patients received either 1.8g or 3.6g of dried
turmeric daily for 8 weeks
 Widely studied herb with multiple applications
 “IBS prevalence decreased significantly in both groups between screening and
 Anti-inflammatory effect very well established, both in research and clinically baseline (41% and 57%), with a further significant drop of 53% and 60% between
baseline and after treatment, in the one- and two-tablet groups respectively (p <
• Inhibits NFkb, COX2, LOX, MMP, TNFa, PGE2 0.001). A post-study analysis revealed abdominal pain/discomfort score reduced
▶ stimulates the gallbladder to produce bile. significantly by 22% and 25% in the one- and two-tablet group respectively, the
difference tending toward significance (p = 0.071). There were significant
▶ The German Commission E, which determines which herbs can be safely improvements in all bar one of the IBSQOL scales of between 5% and 36% in
prescribed in Germany, has approved turmeric for digestive problems. And both groups, approximately two thirds of all subjects reported an improvement
one double-blind, placebo-controlled study found that turmeric reduced in symptoms after treatment, and there was a favorable shift in self-reported
bowel pattern. There were no significant differences between groups”
symptoms of bloating and gas in people suffering from indigestion.

Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. J Alt Complement Med. Bundy R, et al. 2004 Dec;10(6):1015-8.

Herbal Prokinetics GI Antispasmodics and Carminatives

▶ Dr. J’s Herbal Bitters formula:
Oregon grape/Gentian/Baical Skullcap/Dandelion root: 2-3 whole droppers in water 15 min
before meals  Spasmolytics help with regulating motility and abdominal hypersensitivity
- Dandelion root: cholagogue
- Gentian, Oregon Grape: bitters stimulate HCL secretion, possibly motility
 Chamomile – also anxiolytic
- Baical skullcap: anti-inflammatory, antioxidant
• a- bisabolol reduce visceral nociception
• Apigenin - mild anxiolytic via benzodiazepine receptors, anti-inflammatory – inhibits
 Formula IG – Iberis amara, Angelica archangelicacarum carvi, Silybum marianum, IL-6 and TNF-a
Melissa officinalis, chelidonium majus, Mentha piperitae, Glycerrhiza
• Traditionally used for nervous diarrhea - binds to 5HT 4 receptors
 20 drops 3 x daily before meals and before bed. Or 60 drops at bed time
• 2-3 tsp of flowers per cup of tea to be taken TID ic
 Formula MP: Ginger, 5HTP, acetyl L carnitine, P5P, dose 3 caps morning and night
• Tincture- 1-2ml TID pc
 Clove extract?
Carminatives- gas removal from GI tract
Parting Thoughts
 Caraway seed – very effective carminative and spasmolytic
• Active constituents: Carvol and d-limonene (carvene)  Use herbs before microbiome-disrupting antibiotics.
Relaxant effect on smooth muscle response to acetyl choline
•
 Only use herbal medicines from reputable manufacturers
Used as tea or in tincture
•
who test batches frequently
▶ Fennel
• Fenchone and anethol  Herbs can be combined to make patient specific
medicines
Carminative Tea - In equal parts:  Prescribe from professional brands only
• Caraway seeds
• Fennel seeds
• Anise seeds Thank You
▶ 1 teaspoon, crush seeds and steep for 20 minutes in 1 cup of water
▶ Drink after each meal

Relaxant effect of ethanol extract of Carum carvi on dispersed intestinal smooth muscle cells of the guinea pig. Al-Essa, MK et al.Pharm Biol 2010 Jan;48(1):76-80.