HP Master Class - Rupa.pdf Helicobacter pylori diseases and infection slides
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Apr 25, 2024
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About This Presentation
Ppt on helicobacter pylori diseases and infections in developing countries
Slide Content
H. PyloriMasterclass
Dr. Amy Rolfsen, ND
Medical Consultant at DSL
Dr. Amy Rolfsen, ND
Medical Consultant at DSL
Manifestations
of H. pylori
of H. pylori
Classic GI Manifestations
●Reflux
●Upper GI pain
●Nausea
●Loss of appetite
●Vomiting
●Feeling of fullness
●Gastric ulcers
●Gastric cancer
●Reflux
●Upper GI pain
●Nausea
●Loss of appetite
●Vomiting
●Feeling of fullness
●Gastric ulcers
●Gastric cancer
Non-Classic GI Manifestations
●Gas & bloating
●Histamine symptoms
●Diarrhea
●Constipation
●Halitosis
●Persistent dysbiosis
●Hyperemesis gravidarum
●Gas & bloating
●Histamine symptoms
●Diarrhea
●Constipation
●Halitosis
●Persistent dysbiosis
●Hyperemesis gravidarum
Extraintestinal Manifestation
●Fatigue
●Depression and Anxiety
●Nutrient deficiency, especially iron deficiency
●Insomnia
●Skin conditions, including chronic urticaria
●Idiopathic thrombocytopenic purpura
●Insulin & blood sugar dysregulation
●Sinus/ENT issues
●Autoimmunity
●Neurodegenerative conditions
●Infertility
●Much more!
Franceschiet al. 2015, Nakagawa et al. 2018, Figuraet al. 2002
●Fatigue
●Depression and Anxiety
●Nutrient deficiency, especially iron deficiency
●Insomnia
●Skin conditions, including chronic urticaria
●Idiopathic thrombocytopenic purpura
●Insulin & blood sugar dysregulation
●Sinus/ENT issues
●Autoimmunity
●Neurodegenerative conditions
●Infertility
●Much more!
Franceschiet al. 2015, Nakagawa et al. 2018, Figuraet al. 2002
What do
we know
about
HP?
we know
about
HP?
H. Pylori Basics
●Co-evolving for 58,000+ years
●Gram negative –double cell membrane
●Helical rod w/ sheathed flagellae
●Huge amount of genetic variation
●Very resistant to treatment
●High recurrence rate –50-80%
Momeniet al., 2014, Krzyzek& Grande, 2020
●Co-evolving for 58,000+ years
●Gram negative –double cell membrane
●Helical rod w/ sheathed flagellae
●Huge amount of genetic variation
●Very resistant to treatment
●High recurrence rate –50-80%
Momeniet al., 2014, Krzyzek& Grande, 2020
(Testerman & Morris, 2014)
“Although further research may show that
human beings are better off without their
long-time companions H. pylori, I maintain
that we are at present too ignorant of the
diversity of H pylori strains and their
interactions with human beingsto
advocate their total elimination”
Dr. Martin Blaser
human beings are better off without their
long-time companions H. pylori, I maintain
that we are at present too ignorant of the
diversity of H pylori strains and their
interactions with human beingsto
advocate their total elimination”
Dr. Martin Blaser
Favourite conditions
●Chemotaxis towards
○Proteins
○Bicarbonate
○Cholesterol
●Chemotaxis away from
○Acid
●Found in:
○Juxtamucosalmucosa, gastric pits
○Human epithelial cells
○Yeast cells
Testerman& Morris, 2014, Sánchez-Alonzo et al. 2020, Siavoshi& Saniee, 2014, Chu et al.
2020, Garner & Cover 2021, Peterson & Krogfelt, 2003, Terebizniket al. 2020, Amievaet al.
2002, Bückeret al. 2012
●Chemotaxis towards
○Proteins
○Bicarbonate
○Cholesterol
●Chemotaxis away from
○Acid
●Found in:
○Juxtamucosalmucosa, gastric pits
○Human epithelial cells
○Yeast cells
Testerman& Morris, 2014, Sánchez-Alonzo et al. 2020, Siavoshi& Saniee, 2014, Chu et al.
2020, Garner & Cover 2021, Peterson & Krogfelt, 2003, Terebizniket al. 2020, Amievaet al.
2002, Bückeret al. 2012
What promotes H. pylori growth?
●Iron, nickel, copper,cobalt & other minerals
●Glucose
●Hydrogen
●Cholesterol
●Ammonia & amino acids
●Catecholamines
●High pH
●Biofilm
Benoit et al. 2020, Testerman& Morris, 2014, Backert& Clyne, 2011, Olson & Maier, 2002
●Iron, nickel, copper,cobalt & other minerals
●Glucose
●Hydrogen
●Cholesterol
●Ammonia & amino acids
●Catecholamines
●High pH
●Biofilm
Benoit et al. 2020, Testerman& Morris, 2014, Backert& Clyne, 2011, Olson & Maier, 2002
What does H. pylori produce?
●Enzymes: urease, catalase, oxidase, hydrogenase
●Lipopolysaccharide–low inflammatory
●Peptidoglycans
●Virulence factors
●Hydrogen sulfide
●Biofilm
●Gamma Glutamyl Transpeptidase (GGT)
●Outer membrane vesicles
●Outer membrane proteins
Backert& Clyne, 2011, Salama et al., 2013 Testerman& Morris, 2014, DiLodovico et al. 2019,
Hathroubiet al. 2018, Kidd et al. 1997, Stark et al. 2002, Lee et al. 2006, Kawahara et al.
2020
●Enzymes: urease, catalase, oxidase, hydrogenase
●Lipopolysaccharide–low inflammatory
●Peptidoglycans
●Virulence factors
●Hydrogen sulfide
●Biofilm
●Gamma Glutamyl Transpeptidase (GGT)
●Outer membrane vesicles
●Outer membrane proteins
Backert& Clyne, 2011, Salama et al., 2013 Testerman& Morris, 2014, DiLodovico et al. 2019,
Hathroubiet al. 2018, Kidd et al. 1997, Stark et al. 2002, Lee et al. 2006, Kawahara et al.
2020
Immune changes with HP
●Promotes Th1 polarization
●IL-1ß -promotes inflammation
●Activates inflammosomes
●IL-18,IL-10–promotes immune tolerance --> persistent infxn
●GGT –inhibits T cell proliferation --> persistent infxn
●Blocks IL-2 –downregulate NK & B cells
●PAMPs –evade detection by pro-inflammatory TLRs
●Inhibition of phagocytosis by macrophages
●Stimulates histamine release
●HP can reduce diversity of normal flora
Backert& Clyne, 2011; Salama et al., 2013; Kusters et al. 2020, Kidd et al. 1998, Tsai et al.
2015, Masiniet al., 1994, Chen et al. 2021
●Promotes Th1 polarization
●IL-1ß -promotes inflammation
●Activates inflammosomes
●IL-18,IL-10–promotes immune tolerance --> persistent infxn
●GGT –inhibits T cell proliferation --> persistent infxn
●Blocks IL-2 –downregulate NK & B cells
●PAMPs –evade detection by pro-inflammatory TLRs
●Inhibition of phagocytosis by macrophages
●Stimulates histamine release
●HP can reduce diversity of normal flora
Backert& Clyne, 2011; Salama et al., 2013; Kusters et al. 2020, Kidd et al. 1998, Tsai et al.
2015, Masiniet al., 1994, Chen et al. 2021
Coccoid H. pylori
●Morphological variation
●VBNC State, ABX resistant
●Driven by antibiotics, botanicals, PPIs,
●Low urease production, VFs still produced
●Potential solutions:
○More acid inhibition
○Linolenic acid
○NAC
Krzyzek& Grande, 2020, Ierardiet al. 2020, Kadkhodaeiet al. 2020
●Morphological variation
●VBNC State, ABX resistant
●Driven by antibiotics, botanicals, PPIs,
●Low urease production, VFs still produced
●Potential solutions:
○More acid inhibition
○Linolenic acid
○NAC
Krzyzek& Grande, 2020, Ierardiet al. 2020, Kadkhodaeiet al. 2020
Common Co-Infections
●Yeast
●E. coli
●Hydrogen-producing bacteria
●Blastocystis hominis & other protozoa
Karczewskaet al. 2009, Benoit et al. 2020, Palencia et al. 2016, Sánchez-Alonzo et al. 2021
Sánchez-Alonzo et al. 2020, Siavoshi& Saniee, 2014
●Yeast
●E. coli
●Hydrogen-producing bacteria
●Blastocystis hominis & other protozoa
Karczewskaet al. 2009, Benoit et al. 2020, Palencia et al. 2016, Sánchez-Alonzo et al. 2021
Sánchez-Alonzo et al. 2020, Siavoshi& Saniee, 2014
Friend or
Foe?
Foe?
H. pylori is a Pathogen
●Invades tissue & disrupts cell membrane
●Gastric & duodenal ulcer
●Group 1 carcinogen
●Gastric carcinoma
●Increased risk of
○CRC, esophageal/pharyngeal CA,MALT lymphoma
Backert& Clyne, 2011; Waskitoet al., 2007; Testerman& Morris, 2014; De Falco et al., 2015
●Invades tissue & disrupts cell membrane
●Gastric & duodenal ulcer
●Group 1 carcinogen
●Gastric carcinoma
●Increased risk of
○CRC, esophageal/pharyngeal CA,MALT lymphoma
Backert& Clyne, 2011; Waskitoet al., 2007; Testerman& Morris, 2014; De Falco et al., 2015
H. pylori is Beneficial/Commensal
●Populates majority of humans
●Protective against allergies
●May be protective against IBD
●More likely to be beneficial in childhood
●May be protective against celiac disease
Testerman& Morris,2014
●Populates majority of humans
●Protective against allergies
●May be protective against IBD
●More likely to be beneficial in childhood
●May be protective against celiac disease
Testerman& Morris,2014
H. Pylori on
GI-MAP
GI-MAP
"PCR sensitivity nearing 100% and
specificity of 100% can be obtained"
Testerman& Morris, 2014
specificity of 100% can be obtained"
Testerman& Morris, 2014
H pylorion GI-MAP
●Quantitative PCR Technology
●Extremely sensitive & specific
●Reference range set @ 95th %ile
●Clinically significant level will vary
●Quantitative PCR Technology
●Extremely sensitive & specific
●Reference range set @ 95th %ile
●Clinically significant level will vary
Virulence
Factors
Factors
Do Virulence Factors Change Tx?
Generally, treat until eradicated
●BabA–txmore aggressively, adhesion inhibition, consider cranberry
●CagA-inflammatory support, promote T-cell activity, consider curcumin,
resveratrol/red wine, ginger, black cumin seed, low salt diet
●DupA-demulcents
●IceA-inflammatory support, adhesion inhibitors
●OipA-inflammatory support
●VacA-mitochondrial support, INTRA-cellular antimicrobials,consider black cumin
seed, green tea, red wine/resveratrol, baicalskullcap
Generally, treat until eradicated
●BabA–txmore aggressively, adhesion inhibition, consider cranberry
●CagA-inflammatory support, promote T-cell activity, consider curcumin,
resveratrol/red wine, ginger, black cumin seed, low salt diet
●DupA-demulcents
●IceA-inflammatory support, adhesion inhibitors
●OipA-inflammatory support
●VacA-mitochondrial support, INTRA-cellular antimicrobials,consider black cumin
seed, green tea, red wine/resveratrol, baicalskullcap
Antibiotic
Resistance
Resistance
"...treatment should be
personalized based on drug
susceptibility testing."
Liu et al. 2021
personalized based on drug
susceptibility testing."
Liu et al. 2021
Interpreting
H. pylori on
GI-MAP
H. pylori on
GI-MAP
Questions?
Case
Management
Management
"...complete eradication is not
needed to prevent disease:
either reduction of the amount of
bacteria or altering of the
immune response might result in
a significant decrease in
inflammation..."
Kusters et al. 2020
needed to prevent disease:
either reduction of the amount of
bacteria or altering of the
immune response might result in
a significant decrease in
inflammation..."
Kusters et al. 2020
Establish Goals of Treatment
●Symptom relief
●Eradication vs Decimation
●Select biomarkers for success
●Retest& adjust protocol as needed
●Symptom relief
●Eradication vs Decimation
●Select biomarkers for success
●Retest& adjust protocol as needed
Always include
●Antimicrobials
●Gastroprotective & demulcents
●Mitochondrial support
●Acid modulator
●Anti-coccoid agents (linolenic acid, NAC, acid inhibition)
●Urease inhibitor
●Biofilm disruption
●Adhesion inhibitor
●Immune modulator
●Quorum sensing inhibitor
●Antimicrobials
●Gastroprotective & demulcents
●Mitochondrial support
●Acid modulator
●Anti-coccoid agents (linolenic acid, NAC, acid inhibition)
●Urease inhibitor
●Biofilm disruption
●Adhesion inhibitor
●Immune modulator
●Quorum sensing inhibitor
Treatments
That WORK
-Antibiotics
That WORK
-Antibiotics
Antibiotics Used
●Amoxicillin
●Clarithromycin ~ 20-30% resistance
●Metronidazole ~ 20-30% resistance
●Tetra/Mino/Doxycycline
●Fluoroquinolones ~ 31% resistance
●Nitazoxanide
●Rifabutin
●Amoxicillin
●Clarithromycin ~ 20-30% resistance
●Metronidazole ~ 20-30% resistance
●Tetra/Mino/Doxycycline
●Fluoroquinolones ~ 31% resistance
●Nitazoxanide
●Rifabutin
Triple Therapies
●PPI, Amoxicillin, Clarithromycin ~ 75%
●PPI, Amox, Metronidazole -95.5%
●Levofloxacin triple –49-96%
●Rifabutin, Amox, PPI –83.8%
●Rifaximin-based –10-60%
Liu et al. 2021, Rokkaset al., 2021, Nyssen et al., 2020, Hu et al., 2017
●PPI, Amoxicillin, Clarithromycin ~ 75%
●PPI, Amox, Metronidazole -95.5%
●Levofloxacin triple –49-96%
●Rifabutin, Amox, PPI –83.8%
●Rifaximin-based –10-60%
Liu et al. 2021, Rokkaset al., 2021, Nyssen et al., 2020, Hu et al., 2017
Acid Inhibition
●Degree of acid inhibition correlated with HP cure rate
●↑HP growth @ higher pH àmore sensitive to ABX therapies
●Concentrations of mucosal antibiotics increase at higher pH
●Amoxicillin active @ pH 5.5
●Clarithromycin active @ pH 7.4
●Metronidazole not acid sensitive
Sugimoto et al., 2019
●Degree of acid inhibition correlated with HP cure rate
●↑HP growth @ higher pH àmore sensitive to ABX therapies
●Concentrations of mucosal antibiotics increase at higher pH
●Amoxicillin active @ pH 5.5
●Clarithromycin active @ pH 7.4
●Metronidazole not acid sensitive
Sugimoto et al., 2019
Proton Pump Inhibitors
●May promote production àgastritis
●May promote corpus colonization àhypochlorhydria
●Comparative efficacy (Triple therapy):
○Esomeprazole –71-85%
○Omeprazole –77%
○Rabeprazole –62.9%
○Lansoprazole –57.3%
Meuwissenet al. 2001, McColl et al. 1998, Boltinet al. 2020, Gao et al. 2021
●May promote production àgastritis
●May promote corpus colonization àhypochlorhydria
●Comparative efficacy (Triple therapy):
○Esomeprazole –71-85%
○Omeprazole –77%
○Rabeprazole –62.9%
○Lansoprazole –57.3%
Meuwissenet al. 2001, McColl et al. 1998, Boltinet al. 2020, Gao et al. 2021
Vonoprazan–Not yet approved
●Potassium Channel Acid Blocker (PCAB)
●Maintains low gastric acidity longer than PPI (>24 hours)
●Increases efficacy of PAC from 74.8% to 91.4%
●Dual therapy with amox80-90%, clarith85-90%
●Excellent eradication rate with multiple combo of ABX
●Lower rate of HP recurrence compared with PPI
●Safe with bismuth
●Most marked effect in younger people
Liu et al. 2021, Suzuki et al. 2021, O’Connor et al., 2020, Rokkaset al., 2021, Ozaki et al. 2018,
Nabetaet al., 2020, Huh et al., 2021, Gunaratneet al., 2021, Hu et al., 2017, Tanabe et al., 2017,
Graham & Dore, 2018
●Potassium Channel Acid Blocker (PCAB)
●Maintains low gastric acidity longer than PPI (>24 hours)
●Increases efficacy of PAC from 74.8% to 91.4%
●Dual therapy with amox80-90%, clarith85-90%
●Excellent eradication rate with multiple combo of ABX
●Lower rate of HP recurrence compared with PPI
●Safe with bismuth
●Most marked effect in younger people
Liu et al. 2021, Suzuki et al. 2021, O’Connor et al., 2020, Rokkaset al., 2021, Ozaki et al. 2018,
Nabetaet al., 2020, Huh et al., 2021, Gunaratneet al., 2021, Hu et al., 2017, Tanabe et al., 2017,
Graham & Dore, 2018
Bismuth
●Direct antimicrobial against HP
●Disrupts HP enzymes, ATP synthesis, adhesion
●Suppresses HP’s ability to withstand stressors
●Synergy with antibiotics
○Could add 30-40% to eradication rates in resistant infections
○Added to PAC triple therapy –increases from ~75% to 85-90%
○Reasonable to add bismuth to any first line therapy
McNichollet al., 2020, Dore et al., 2016, Kim & Chung, 2021, Ge et al., 2012, Alkimet al., 2017,
Hu et al., 2017
●Direct antimicrobial against HP
●Disrupts HP enzymes, ATP synthesis, adhesion
●Suppresses HP’s ability to withstand stressors
●Synergy with antibiotics
○Could add 30-40% to eradication rates in resistant infections
○Added to PAC triple therapy –increases from ~75% to 85-90%
○Reasonable to add bismuth to any first line therapy
McNichollet al., 2020, Dore et al., 2016, Kim & Chung, 2021, Ge et al., 2012, Alkimet al., 2017,
Hu et al., 2017
Bismuth Quadruple
●Bismuth, PPI, Metronidazole, Tetracycline ~ 90%
●Lower adverse reactions than with Non-bismuth quad
●More effective than non-bismuthquad in areas of high resistance
●Available in prepared capsules for compliance -Pylera
●Modified
○Bismuth, PPI, Metro, Amox–85.4%
○Bismuth, PPI, Minocycline, AmoxOR Metro –Mino/amox89.5%, mino/metro76.8%
○Levofloxacin, Clarith, PPI, Bismuth –94%
○Pylera, PPI, Amoxx 10 days –100%
Liu et al. 2021, Hu et al., 2017
●Bismuth, PPI, Metronidazole, Tetracycline ~ 90%
●Lower adverse reactions than with Non-bismuth quad
●More effective than non-bismuthquad in areas of high resistance
●Available in prepared capsules for compliance -Pylera
●Modified
○Bismuth, PPI, Metro, Amox–85.4%
○Bismuth, PPI, Minocycline, AmoxOR Metro –Mino/amox89.5%, mino/metro76.8%
○Levofloxacin, Clarith, PPI, Bismuth –94%
○Pylera, PPI, Amoxx 10 days –100%
Liu et al. 2021, Hu et al., 2017
Non-Bismuth Quadruple
●Combination of Amox, Clarith, Metro & PPI
●Concomitant CT –all @ same time -77.1-93.3%
●Sequential ST–Amox/PPI, followed by Clarith/Metro –up to 96.7%
●Hybrid HT–Amox/PPI, add in Clarith/Metro @ day 8 –85.8%
●Reverse Hybrid RHT–CT for 7 days, then 7 days Amox/PPI >90%
Liu et al. 2021, Gisbert& Calvet, 2012
●Combination of Amox, Clarith, Metro & PPI
●Concomitant CT –all @ same time -77.1-93.3%
●Sequential ST–Amox/PPI, followed by Clarith/Metro –up to 96.7%
●Hybrid HT–Amox/PPI, add in Clarith/Metro @ day 8 –85.8%
●Reverse Hybrid RHT–CT for 7 days, then 7 days Amox/PPI >90%
Liu et al. 2021, Gisbert& Calvet, 2012
High Dose Dual Therapies
●Can decrease excess use of ABX
●Amoxicillin with PPI –83.2-95.3%
○Low side effects 12.9%
○Currently used as rescue protocol
●Nitazoxanide with PPI –83%
Liu et al. 2021, Mégraud2020, Hu et al., 2017, Yang et al., 2019, Suzuki et al., 2019
●Can decrease excess use of ABX
●Amoxicillin with PPI –83.2-95.3%
○Low side effects 12.9%
○Currently used as rescue protocol
●Nitazoxanide with PPI –83%
Liu et al. 2021, Mégraud2020, Hu et al., 2017, Yang et al., 2019, Suzuki et al., 2019
Nitazoxanide/Alinia
●Pro-drug activated by redox
●Only active against organism w/ specific enzymes
●Resistance up for debate
●May accelerate resistance to other abx
●Acceptable eradication rates in dual therapy with PPI
Mégraud2020, Lee et al., 2019, Sisson et al., 2020
●Pro-drug activated by redox
●Only active against organism w/ specific enzymes
●Resistance up for debate
●May accelerate resistance to other abx
●Acceptable eradication rates in dual therapy with PPI
Mégraud2020, Lee et al., 2019, Sisson et al., 2020
Summary
●Aim for >90% eradication
●Most common: PAC triple & Concomitant
●Highest eradication: Vonaprazantriple & reverse hybrid
●Other promising regimens:
○Pylera+ PPI + Amoxicillin
○High Dose Dual -Amoxicillin & PPI
●Better eradication with:
○More acid suppression
○Longer duration of treatment
Liu et al. 2021, Suzuki et al. 2021, Graham 2009, Nyssen et al., 2020, McNichollet al. 2020
●Aim for >90% eradication
●Most common: PAC triple & Concomitant
●Highest eradication: Vonaprazantriple & reverse hybrid
●Other promising regimens:
○Pylera+ PPI + Amoxicillin
○High Dose Dual -Amoxicillin & PPI
●Better eradication with:
○More acid suppression
○Longer duration of treatment
Liu et al. 2021, Suzuki et al. 2021, Graham 2009, Nyssen et al., 2020, McNichollet al. 2020
Natural Adjuncts to Antibiotics
●WenweishuTCM Patent –added to Clarith, Metro, PPI
●Probiotics –generally increase eradication by 12-14%
○Lactobacillus–↓ side effects & dysbiosis, ↑ diversity
○S. boulardii-↑ efficacy of PAC triple, ↓ side effects
○Bifidobacteria–resistant to metronidazole
○Bacillus–↓ side effects
●Linolenic acid
●Lactoferrin
●Berberine 120-500mg -↑ efficacy of PAC triple, ↓ side effects
●Black cumin seed 2g daily -↑ efficacy of bismuth quad
●Cranberry -↑ efficacy of clarithromycin & metronidazole
●Vit C –500mg & Vit E –200 IU -controversial
Testerman& Morris,2014, Holubiuk& Imiela, 2016, Yang et al. 2021, Jung & Lee, 2015, Cárdenas et al., 2020,
Dore et al. 2019, Zhou et al., 2019, Colladoet al. 2005, Wang et al. 2013, Hu et al. 2017, Lee et al. 2008, Hussain
et al. 2018, El Shahawyet al. 2020
●WenweishuTCM Patent –added to Clarith, Metro, PPI
●Probiotics –generally increase eradication by 12-14%
○Lactobacillus–↓ side effects & dysbiosis, ↑ diversity
○S. boulardii-↑ efficacy of PAC triple, ↓ side effects
○Bifidobacteria–resistant to metronidazole
○Bacillus–↓ side effects
●Linolenic acid
●Lactoferrin
●Berberine 120-500mg -↑ efficacy of PAC triple, ↓ side effects
●Black cumin seed 2g daily -↑ efficacy of bismuth quad
●Cranberry -↑ efficacy of clarithromycin & metronidazole
●Vit C –500mg & Vit E –200 IU -controversial
Testerman& Morris,2014, Holubiuk& Imiela, 2016, Yang et al. 2021, Jung & Lee, 2015, Cárdenas et al., 2020,
Dore et al. 2019, Zhou et al., 2019, Colladoet al. 2005, Wang et al. 2013, Hu et al. 2017, Lee et al. 2008, Hussain
et al. 2018, El Shahawyet al. 2020
Treatments
That WORK
-Natural
That WORK
-Natural
Mastic Gum
●Used for 2500 years –stomach pain, ulcer, dyspepsia
●Safe up to 2g/kg
●In vitro:
○Strong anti-HP activity
○Strong anti-biofilm activity
●In vivo:
○Relief of stomach pain in 80%
○Relief of ulcers & gastric tissue damage in 70%
○~ 50% eradication rate as monotherapy, less with PPI
Afrasiabianet al. 2016, Di Lodovico et al. 2019, Huwezet al. 1998, Maroneet al., 2001, Meriemet al. 2015, Pachiet al. 2020,
Ramezaniet al. 2009, Bebbet al. 2003, Daboset al. 2010, Zemarianiet al. 2017, Kottakiset al. 2008, Triantafyllouet al. 2007,
Landau et al., 2014, Paraschoset al. 2020, Al Habbalet al. 1984, Xynoset al. 2018, Memarianiet al. 2017, Shmuelyet al., 2016
●Used for 2500 years –stomach pain, ulcer, dyspepsia
●Safe up to 2g/kg
●In vitro:
○Strong anti-HP activity
○Strong anti-biofilm activity
●In vivo:
○Relief of stomach pain in 80%
○Relief of ulcers & gastric tissue damage in 70%
○~ 50% eradication rate as monotherapy, less with PPI
Afrasiabianet al. 2016, Di Lodovico et al. 2019, Huwezet al. 1998, Maroneet al., 2001, Meriemet al. 2015, Pachiet al. 2020,
Ramezaniet al. 2009, Bebbet al. 2003, Daboset al. 2010, Zemarianiet al. 2017, Kottakiset al. 2008, Triantafyllouet al. 2007,
Landau et al., 2014, Paraschoset al. 2020, Al Habbalet al. 1984, Xynoset al. 2018, Memarianiet al. 2017, Shmuelyet al., 2016
Black Cumin Seed
●Actions: anti-inflammatory, analgesic, antibacterial, antifungal, antiparasitic
●In vivo:
○2g daily with PPI x 2 weeks -66.7% (Stool antigen)
○6g daily with honey x 2 weeks –57% (UBT) with minimal s/e, significant ↓ in dyspepsia
○5g daily –significantly decreased HP levels and dyspepsia
○2g daily added to bismuth quad -↑ eradication and quality of life markers
●Potential anti-VacA& CagAactivity
●Safe up to 28g/kg in rabbits
Alizadeh-Nainiet al. 2020, Mohtashamiet al. 2015,
Hashem-Dabaghianet al. 2016, Rhandawa, 2008, Salem et
al. 2010, Tabassum & Ahmad, 2021, Wissam, 2019,
●Actions: anti-inflammatory, analgesic, antibacterial, antifungal, antiparasitic
●In vivo:
○2g daily with PPI x 2 weeks -66.7% (Stool antigen)
○6g daily with honey x 2 weeks –57% (UBT) with minimal s/e, significant ↓ in dyspepsia
○5g daily –significantly decreased HP levels and dyspepsia
○2g daily added to bismuth quad -↑ eradication and quality of life markers
●Potential anti-VacA& CagAactivity
●Safe up to 28g/kg in rabbits
Alizadeh-Nainiet al. 2020, Mohtashamiet al. 2015,
Hashem-Dabaghianet al. 2016, Rhandawa, 2008, Salem et
al. 2010, Tabassum & Ahmad, 2021, Wissam, 2019,
Licorice
●Traditional use for ulcers
●In vitro:
○significant anti-HP activity –incl. resistant strains
○Strong adhesion inhibition
●In vivo:
○Higher efficacy than bismuth when subbed into quadruple therapy
Fukaiet al., 2000, Wittschieret al. 2009, Momeniet al. 2014, Celik& Duran, 2019,
Kwon et al., 2020
●Traditional use for ulcers
●In vitro:
○significant anti-HP activity –incl. resistant strains
○Strong adhesion inhibition
●In vivo:
○Higher efficacy than bismuth when subbed into quadruple therapy
Fukaiet al., 2000, Wittschieret al. 2009, Momeniet al. 2014, Celik& Duran, 2019,
Kwon et al., 2020
Cranberry
●Inhibition of urease, adhesion
●Consider as monotherapy in asymptomatic children
●Category ”A” in pregnancy
●Potential BabAactivity
Shmuelyet al. 2016, Lee et al. 2008
●Inhibition of urease, adhesion
●Consider as monotherapy in asymptomatic children
●Category ”A” in pregnancy
●Potential BabAactivity
Shmuelyet al. 2016, Lee et al. 2008
Ginger
●Anti-ulcer, anti-inflammatory, DNA protective, carminative, digestive
●Category “A” in pregnancy
●CagAactivity
●In vitro:
○Inhibitory of HP growth
○Acts as natural potassium channel acid blocker
Shmuelyet al. 2016
●Anti-ulcer, anti-inflammatory, DNA protective, carminative, digestive
●Category “A” in pregnancy
●CagAactivity
●In vitro:
○Inhibitory of HP growth
○Acts as natural potassium channel acid blocker
Shmuelyet al. 2016
Curcumin
Shmuelyet al. 2016
●Anti-inflammatory
●Traditional use in healing peptic ulcers
●May be used to prevent HP growth
●In vivo:
○Minimal evidence for anti-HP activity in humans
○Eliminates HP in mice
○300mg 5x daily –decreased ulcers in 76% by 12 weeks.
■Symptom relief within 1-2 weeks
Shmuelyet al. 2016
●Anti-inflammatory
●Traditional use in healing peptic ulcers
●May be used to prevent HP growth
●In vivo:
○Minimal evidence for anti-HP activity in humans
○Eliminates HP in mice
○300mg 5x daily –decreased ulcers in 76% by 12 weeks.
■Symptom relief within 1-2 weeks
Isothiocyanates/Sulforaphane
●High urine levels had lowest occurrence of gastric cancer (n=18000)
●In vitro:
○Bactericidal against H. pylori
●In vivo:
○Decreases H. pylori colonization
○Mitigates mucosal inflammation
○Reverses NSAID-induced gastritis
○Decreases nitric oxide levels
Holubiuk& Imiela, 2016, Yanakaet al., 2017, Mirmiranet al., 2017
●High urine levels had lowest occurrence of gastric cancer (n=18000)
●In vitro:
○Bactericidal against H. pylori
●In vivo:
○Decreases H. pylori colonization
○Mitigates mucosal inflammation
○Reverses NSAID-induced gastritis
○Decreases nitric oxide levels
Holubiuk& Imiela, 2016, Yanakaet al., 2017, Mirmiranet al., 2017
Resveratrol & Red Wine
●Anti-VacA& -CagAactivity
●In vitro:
○Inhibits H. pylori growth
○Inhibits urease
Vale & Oleastro, 2014, Paulo et al. 2011, Mahadyet al., 2003, Tombola et al., 2003, Lee et al.
2008
●Anti-VacA& -CagAactivity
●In vitro:
○Inhibits H. pylori growth
○Inhibits urease
Vale & Oleastro, 2014, Paulo et al. 2011, Mahadyet al., 2003, Tombola et al., 2003, Lee et al.
2008
Green Tea
●Healing & anti-inflammatory in gastric tissue
●Urease inhibition
●Anti-adhesive
●Biofilm disruption
●Anti-vacAactivity
●Bactericidal in vitro & in vivo
Lee et al., 2008, Shmuelyet al. 2016
●Healing & anti-inflammatory in gastric tissue
●Urease inhibition
●Anti-adhesive
●Biofilm disruption
●Anti-vacAactivity
●Bactericidal in vitro & in vivo
Lee et al., 2008, Shmuelyet al. 2016
Other Botanicals/Neutraceuticals
●Garlic
●Berberis/Coptis
●Goldenseal
●Baicalskullcap
●Pelargonium
●Bacopa monierra
●Propolis
●Meadowsweet
●Agrimony
●Sage
●Cistus
●Cinnamon
●Burdock
●Bidens
●Lotus
●Nutmeg
●Sage
●Korean (red) ginseng
●Wormwood
●Rosemary
●Yarrow
●Fennel
●Passionflower
●Juniper
●Chamomile
●Lavender
●Cedar
●Silver fir
●Pine needle
●Lemon
●Tea tree
Ullah et al. 2021, Fahey et al. 2015, Min-Heeet al. 2007, Wu et al. 2008, Mahadyet al. 2005, Korona-
Glowniaket al., 2020, Shmuelyet al. 2016, Lee & Park, 2019, Tombola et al., 2003
●Garlic
●Berberis/Coptis
●Goldenseal
●Baicalskullcap
●Pelargonium
●Bacopa monierra
●Propolis
●Meadowsweet
●Agrimony
●Sage
●Cistus
●Cinnamon
●Burdock
●Bidens
●Lotus
●Nutmeg
●Sage
●Korean (red) ginseng
●Wormwood
●Rosemary
●Yarrow
●Fennel
●Passionflower
●Juniper
●Chamomile
●Lavender
●Cedar
●Silver fir
●Pine needle
●Lemon
●Tea tree
Ullah et al. 2021, Fahey et al. 2015, Min-Heeet al. 2007, Wu et al. 2008, Mahadyet al. 2005, Korona-
Glowniaket al., 2020, Shmuelyet al. 2016, Lee & Park, 2019, Tombola et al., 2003
Essential Oils
●Hericiumerinaceus
●Cinnamon
●Lemon verbena
●Carrot seed
●Thyme
●Rosegum
●Fool’s watercress
●Oregano
●Peppermint
●Caraway
●Ginger
●Turmeric
●Licorice
●Nutmeg
●Chili pepper
Fahey et al. 2015
●Hericiumerinaceus
●Cinnamon
●Lemon verbena
●Carrot seed
●Thyme
●Rosegum
●Fool’s watercress
●Oregano
●Peppermint
●Caraway
●Ginger
●Turmeric
●Licorice
●Nutmeg
●Chili pepper
Fahey et al. 2015
Urease Inhibitors
●Bismuth
●Resveratrol
●Red wine
●Sulforaphane
●Broccoli sprouts
●Cranberry
●Honey
●Cedar
●Low nickel diet
Fahey et al. 2013, Ge et al. 2012, Paulo et al., 2011
●Bismuth
●Resveratrol
●Red wine
●Sulforaphane
●Broccoli sprouts
●Cranberry
●Honey
●Cedar
●Low nickel diet
Fahey et al. 2013, Ge et al. 2012, Paulo et al., 2011
Biofilm Disruptors
●Cranberry
●Berberis/Mahonia
●Cinnamon
●Clove
●Curcumin
●Ginger
●Grapefruit juice
●Green tea
●Lemongrass
●Licorice
●Quercetin
●Resveratrol
●Black Cumin
●Enzymes
●Neem
●Manuka honey
●Thiols (NAC, ALA,
glutathione)
Shmuelyet al. 2016
●Cranberry
●Berberis/Mahonia
●Cinnamon
●Clove
●Curcumin
●Ginger
●Grapefruit juice
●Green tea
●Lemongrass
●Licorice
●Quercetin
●Resveratrol
●Black Cumin
●Enzymes
●Neem
●Manuka honey
●Thiols (NAC, ALA,
glutathione)
Shmuelyet al. 2016
Adhesion Inhibitors
●Bismuth
●Lactobacillus
●Licorice
●Berberine
●Catnip
●Cranberry
●Green Tea
Holubiuk& Imiela, 2016, Wittschieret al. 2009
●Bismuth
●Lactobacillus
●Licorice
●Berberine
●Catnip
●Cranberry
●Green Tea
Holubiuk& Imiela, 2016, Wittschieret al. 2009
Quorum Sensing Inhibitors
●Basil
●Berberis/Mahonia
●Berries
●Curcumin
●Garlic
●Ginger
●Grapefruit juice
●Green Tea
●Kale
●Quercetin
●Rosemary
●Thyme
●Basil
●Berberis/Mahonia
●Berries
●Curcumin
●Garlic
●Ginger
●Grapefruit juice
●Green Tea
●Kale
●Quercetin
●Rosemary
●Thyme
Diet and
H. pylori
H. pylori
Diet & H. pylori
●Diet can control growth, virulence and expression of HP
●Bactericidal
●Anti-adhesive
●Antioxidant
●Immune stimulatory
●Anti-inflammatory
Raeiet al. 2016, O’Mahoneyet al. 2005, Fahey et al. 2015
●Diet can control growth, virulence and expression of HP
●Bactericidal
●Anti-adhesive
●Antioxidant
●Immune stimulatory
●Anti-inflammatory
Raeiet al. 2016, O’Mahoneyet al. 2005, Fahey et al. 2015
What to avoid
●High salt
●High nickel
●Smoked, pickled, salt-preserved foods
●Nitrites
●Coffee, smoking, moderate alcohol don’t appear to be risk factors
Raeiet al. 2016, Ullah et al. 2021, Lohet al. 2007, Beeverset al. 2004, Sharma et al. 2013,
Murray et al., 2002
●High salt
●High nickel
●Smoked, pickled, salt-preserved foods
●Nitrites
●Coffee, smoking, moderate alcohol don’t appear to be risk factors
Raeiet al. 2016, Ullah et al. 2021, Lohet al. 2007, Beeverset al. 2004, Sharma et al. 2013,
Murray et al., 2002
HP Protective Diet
●Fresh Fruits
○Berries
○Cranberry
○Pomegranate
○Apple
○Grape
●Vegetables
○Broccoli sprouts
○Broccoli/cabbage/radish
○Cabbage juice
○Red bell peppers
○Garlic
○Algae/sea vegetables
Raeiet al. 2016, Fahey et al. 2015, Holubiuk& Imiela, 2016
●Fresh Fruits
○Berries
○Cranberry
○Pomegranate
○Apple
○Grape
●Vegetables
○Broccoli sprouts
○Broccoli/cabbage/radish
○Cabbage juice
○Red bell peppers
○Garlic
○Algae/sea vegetables
Raeiet al. 2016, Fahey et al. 2015, Holubiuk& Imiela, 2016
HP Protective Diet
●Oils
○PUFAs, esp. linolenic acid
○Fish oil
○Garlic oil
○Black currant seed
○Carrot seed
○Grapefruit seed oil
○Monolaurin
●Dairy
○Fermented dairy
○Lactoferrin
○Colostrum
○Cow’s milk
Raeiet al. 2016, Fahey et al. 2015, Thompson et al. 1994, Khulusiet al. 1995,
Jung & Lee, 2015, Bergssonet al. 2002
●Oils
○PUFAs, esp. linolenic acid
○Fish oil
○Garlic oil
○Black currant seed
○Carrot seed
○Grapefruit seed oil
○Monolaurin
●Dairy
○Fermented dairy
○Lactoferrin
○Colostrum
○Cow’s milk
Raeiet al. 2016, Fahey et al. 2015, Thompson et al. 1994, Khulusiet al. 1995,
Jung & Lee, 2015, Bergssonet al. 2002
HP Protective Diet
●Herbs & Spices
Raeiet al. 2016, Ullah et al. 2021, O’Mahoneyet al. 2005, Fahey et al. 2015
○Nutmeg
○Curcumin
○Black cumin seed
○Cumin
○Ginger
○Chili
○Borage
○Caraway
○Oregano
○Licorice
○Thyme
●Herbs & Spices
Raeiet al. 2016, Ullah et al. 2021, O’Mahoneyet al. 2005, Fahey et al. 2015
○Nutmeg
○Curcumin
○Black cumin seed
○Cumin
○Ginger
○Chili
○Borage
○Caraway
○Oregano
○Licorice
○Thyme
HP Protective Diet
●Probiotics
○Lactobacillus
○Bifidobacteria
○S. boulardii
●Nutrients
○Selenium
○Vitamin E
○Vitamin C
○Zinc carnosine
●Other
○Honey
○Manuka honey
○Propolis
○Resveratrol
○Red wine
Raeiet al. 2016, Ullah et al. 2021, Fahey et al. 2015, Biagiet al. 2009, Murray et al. 2002m, Hussain et al. 2018,
Dore et al., 2019, Cárdenas et al., 2020, Zhou et al., 2019, Colladoet al., 2005, Chenollet al., 2011, Chen et al.
2019, Ji & Yang, 2021, Plomeret al. 2020, Song et al. 2018
https://doi.org/10.1155/2018/9379480
●Probiotics
○Lactobacillus
○Bifidobacteria
○S. boulardii
●Nutrients
○Selenium
○Vitamin E
○Vitamin C
○Zinc carnosine
●Other
○Honey
○Manuka honey
○Propolis
○Resveratrol
○Red wine
Raeiet al. 2016, Ullah et al. 2021, Fahey et al. 2015, Biagiet al. 2009, Murray et al. 2002m, Hussain et al. 2018,
Dore et al., 2019, Cárdenas et al., 2020, Zhou et al., 2019, Colladoet al., 2005, Chenollet al., 2011, Chen et al.
2019, Ji & Yang, 2021, Plomeret al. 2020, Song et al. 2018
https://doi.org/10.1155/2018/9379480
Retesting
Retesting
●At least 4 weeks after finishing protocol
●Positive retest VERY common
●GI-MAP
●H. pylori Panel
●Pathogen Panel
●At least 4 weeks after finishing protocol
●Positive retest VERY common
●GI-MAP
●H. pylori Panel
●Pathogen Panel
Wrapping it
all up
all up
Summary
●Choose your treatment
○Antibiotics-serious, acute cases
○Botanical antimicrobials -low-grade symptomatic cases
○Long term management (diet, lifestyle, GI balancing)
■Asymptomatic/mildly symptomatic cases
■Pregnancy & young children
■Maintain remission
●Layer treatment modalities
●Retestand adjust protocol
●Choose your treatment
○Antibiotics-serious, acute cases
○Botanical antimicrobials -low-grade symptomatic cases
○Long term management (diet, lifestyle, GI balancing)
■Asymptomatic/mildly symptomatic cases
■Pregnancy & young children
■Maintain remission
●Layer treatment modalities
●Retestand adjust protocol
My Top Choices for Long Term
●Green tea
●Honey weekly
●Flaxseed oil
●Garlic
●Ginger
●Cranberry juice
●Blueberry juice
●Fermented foods
●Cruciferous veg
●Berries
●Fish oil
●Red wine
●Low salt
●Green tea
●Honey weekly
●Flaxseed oil
●Garlic
●Ginger
●Cranberry juice
●Blueberry juice
●Fermented foods
●Cruciferous veg
●Berries
●Fish oil
●Red wine
●Low salt
Questions?
Afrasiabian, H., Imanieh, M. H., Nejati, M. A., & Salehi, A. (2016). The effect of oral administration of Pistacia atlanticakurdicagum on
the eradication of Helicobacter pylori in patients with dyspepsia: A randomized clinical trial.Glob J Health Sci,9(2), 256.
Al-Habbal, M. J., Al-Habbal, Z., & Huwez, F. U. (1984). A double-blind controlled clinical trial of mastic and placebo in the treatment of
duodenal ulcer. Clinical and experimental pharmacology and physiology, 11(5), 541-544.
Alizadeh-naini, M., Yousefnejad, H., & Hejazi, N. (2020). The beneficial health effects of Nigella sativa on Helicobacter pylori
eradication, dyspepsia symptoms, and quality of life in infected patients: a pilot study.Phytotherapy Research,34(6), 1367-1376.
Alkim, H., Koksal, A. R., Boga, S., Sen, I., & Alkim, C. (2017). Role of bismuth in the eradication of Helicobacter pylori.American journal
of therapeutics,24(6), e751-e757.
Amieva, M. R., Salama, N. R., Tompkins, L. S., & Falkow, S. (2002). Helicobacter pylori enter and survive within multivesicular vacuoles
of epithelial cells.Cellular microbiology,4(10), 677-690.
Assaad, S., Chaaban, R., Tannous, F., & Costanian, C. (2018). Dietary habits and Helicobacter pylori infection: a cross sectional study at
a Lebanese hospital.BMC gastroenterology,18(1), 1-13.
Backert, S., & Clyne, M. (2011). Pathogenesis of Helicobacter pylori infection. Helicobacter, 16, 19-25.
the eradication of Helicobacter pylori in patients with dyspepsia: A randomized clinical trial.Glob J Health Sci,9(2), 256.
Al-Habbal, M. J., Al-Habbal, Z., & Huwez, F. U. (1984). A double-blind controlled clinical trial of mastic and placebo in the treatment of
duodenal ulcer. Clinical and experimental pharmacology and physiology, 11(5), 541-544.
Alizadeh-naini, M., Yousefnejad, H., & Hejazi, N. (2020). The beneficial health effects of Nigella sativa on Helicobacter pylori
eradication, dyspepsia symptoms, and quality of life in infected patients: a pilot study.Phytotherapy Research,34(6), 1367-1376.
Alkim, H., Koksal, A. R., Boga, S., Sen, I., & Alkim, C. (2017). Role of bismuth in the eradication of Helicobacter pylori.American journal
of therapeutics,24(6), e751-e757.
Amieva, M. R., Salama, N. R., Tompkins, L. S., & Falkow, S. (2002). Helicobacter pylori enter and survive within multivesicular vacuoles
of epithelial cells.Cellular microbiology,4(10), 677-690.
Assaad, S., Chaaban, R., Tannous, F., & Costanian, C. (2018). Dietary habits and Helicobacter pylori infection: a cross sectional study at
a Lebanese hospital.BMC gastroenterology,18(1), 1-13.
Backert, S., & Clyne, M. (2011). Pathogenesis of Helicobacter pylori infection. Helicobacter, 16, 19-25.
Bebb, J. R., Bailey-Flitter, N., Ala’Aldeen, D., & Atherton, J. C. (2003). Mastic gum has no effect on Helicobacter pylori load in vivo.
Journal of Antimicrobial Chemotherapy, 52(3), 522-523.
Beevers, D. G., Lip, G. Y., & Blann, A. D. (2004). Salt intake and Helicobacter pylori infection.Journal of hypertension,22(8), 1475-1477.
Benoit, S. L., Maier, R. J., Sawers, R. G., & Greening, C. (2020). Molecular hydrogen metabolism: a widespread trait of pathogenic
bacteria and protists.Microbiology and Molecular Biology Reviews,84(1), e00092-19.
Bergonzelli, G. E., Donnicola, D., Porta, N., & Corthésy-Theulaz, I. E. (2003). Essential oils as components of a diet-based approach to
management of Helicobacter infection.Antimicrobial agents and chemotherapy,47(10), 3240-3246.
Bergsson, G., Steingrı́msson, Ó., & Thormar, H. (2002). Bactericidal effects of fatty acids and monoglycerides on Helicobacter
pylori.International journal of antimicrobial agents,20(4), 258-262.
Biagi, M., Miraldi, E., Figura, N., & Giachetti, D. (2009). Antiradical activity and in vitro inhibition of Helicobacter pylori by Italian red
wines.Natural product communications,4(2), 1934578X0900400218.
Boltin, D., Levi, Z., Gingold-Belfer, R., Schmilovitz-Weiss, H., Shochat, T., Dickman, R., ... & Niv, Y. (2020). Comparative effect of proton-
pump inhibitors on the success of triple and quadruple therapy for Helicobacter pylori infection.Digestive Diseases,38(5), 408-414.
Journal of Antimicrobial Chemotherapy, 52(3), 522-523.
Beevers, D. G., Lip, G. Y., & Blann, A. D. (2004). Salt intake and Helicobacter pylori infection.Journal of hypertension,22(8), 1475-1477.
Benoit, S. L., Maier, R. J., Sawers, R. G., & Greening, C. (2020). Molecular hydrogen metabolism: a widespread trait of pathogenic
bacteria and protists.Microbiology and Molecular Biology Reviews,84(1), e00092-19.
Bergonzelli, G. E., Donnicola, D., Porta, N., & Corthésy-Theulaz, I. E. (2003). Essential oils as components of a diet-based approach to
management of Helicobacter infection.Antimicrobial agents and chemotherapy,47(10), 3240-3246.
Bergsson, G., Steingrı́msson, Ó., & Thormar, H. (2002). Bactericidal effects of fatty acids and monoglycerides on Helicobacter
pylori.International journal of antimicrobial agents,20(4), 258-262.
Biagi, M., Miraldi, E., Figura, N., & Giachetti, D. (2009). Antiradical activity and in vitro inhibition of Helicobacter pylori by Italian red
wines.Natural product communications,4(2), 1934578X0900400218.
Boltin, D., Levi, Z., Gingold-Belfer, R., Schmilovitz-Weiss, H., Shochat, T., Dickman, R., ... & Niv, Y. (2020). Comparative effect of proton-
pump inhibitors on the success of triple and quadruple therapy for Helicobacter pylori infection.Digestive Diseases,38(5), 408-414.
Bonilla, S., Mitchell, P. D., & Mansuri, I. (2021). Low adherence to society guidelines for the management of Helicobacter pylori among pediatric
gastroenterologists.Journal of Pediatric Gastroenterology and Nutrition,73(2), 178-183.
Boyanova, L., Markovska, R., & Mitov, I. (2019). Helicobacter pylori growth stimulation by adrenaline detected by two methods.Diagnostic microbiology and
infectious disease,93(1), 30-32
Bücker, R., Azevedo-Vethacke, M., Groll, C.et al.Helicobacter pyloricolonization critically depends on postprandial gastric conditions.Sci Rep2,994 (2012).
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doi:10.3748/wjg.v13.i18.2581
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complementary treatment of Helicobacter pylori infection on gut microbiome. European Journal of Clinical Microbiology & Infectious Diseases, 39(7), 1365-1372.
Caron, T. J., Scott, K. E., Fox, J. G., & Hagen, S. J. (2015). Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier.World Journal
of Gastroenterology: WJG,21(40), 11411.
Castillo-Juárez, I., González, V., Jaime-Aguilar, H., Martínez, G., Linares, E., Bye, R., & Romero, I. (2009). Anti-Helicobacterpylori activity of plants used in Mexican
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Boyanova, L., Markovska, R., & Mitov, I. (2019). Helicobacter pylori growth stimulation by adrenaline detected by two methods.Diagnostic microbiology and
infectious disease,93(1), 30-32
Bücker, R., Azevedo-Vethacke, M., Groll, C.et al.Helicobacter pyloricolonization critically depends on postprandial gastric conditions.Sci Rep2,994 (2012).
Caner, Vildanet al. “H pylori iceAalleles are disease-specific virulence factors.”World journal of gastroenterologyvol. 13,18 (2007): 2581-5.
doi:10.3748/wjg.v13.i18.2581
Cárdenas, P. A., Garcés, D., Prado-Vivar, B., Flores, N., Fornasini, M., Cohen, H., ... & Baldeón, M. E. (2020). Effect of Saccharomyces boulardiiCNCM I-745 as
complementary treatment of Helicobacter pylori infection on gut microbiome. European Journal of Clinical Microbiology & Infectious Diseases, 39(7), 1365-1372.
Caron, T. J., Scott, K. E., Fox, J. G., & Hagen, S. J. (2015). Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier.World Journal
of Gastroenterology: WJG,21(40), 11411.
Castillo-Juárez, I., González, V., Jaime-Aguilar, H., Martínez, G., Linares, E., Bye, R., & Romero, I. (2009). Anti-Helicobacterpylori activity of plants used in Mexican
traditional medicine for gastrointestinal disorders.Journal of ethnopharmacology,122(2), 402-405.
Celik, M. M., & Duran, N. (2019). An experimental in-vitro study to evaluate the anti-helicobacter activity of Glycyrrhetinicacid. RevistaRomânăde Medicinăde
LaboratorVol, 27(1).
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