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Helicobacter Pylori and Antibiofilm Enzymes
H. pylori resides within biofilm overlying and within gastric mucus.49 Biofilm microorganisms are 10 to over 1000 times more resistant to antibiotics than their free-living kindred.45 A biofilm matrix is primarily composed of exopolysacchrides. Cellulose, a polymer of b-(1®6) linked D-glucose sugars associated with plants, is a particularly ubiquitous component of biofilms made by gram-negative microorganisms.62 A nutraceutical enzyme formulation has been developed that combines cellulase with other carbohydrases and proteases. This formulation has broad antibiofilm activities against an array of pathogenic biofilms including H. pylori.63 It has been shown in the laboratory to have significant synergism against H. pylori with amoxicillin, tetracycline, and clarithromycin, but not with metronidazole. The observed synergistic effects suggest the enzyme formulation may be combined with standard triple therapy with clarithromycin and amoxicillin to accomplish more effective eradication of gastric H. pylori populations.
Helicobacter Pylori and Lactoferrin
Lactoferrin, a copious glycoprotein constituent of human external secretions, binds iron.64 Lactoferrin has been shown to have antibiofilm properties.65 It also has direct antimicrobial activities against H. pylori.66 A meta-analysis of nine randomized trials comparing lactoferrin supplementation to placebo or no treatment during anti-H. pylori therapies found that lactoferrin significantly increased eradication rates to 87% compared with 74% as well as reducing side effects.67 The addition of lactoferrin to standard as well as adjunctive complementary therapies for H. pylori has great potential to improve outcomes in patients requiring treatment for H. pylori colonization.
Helicobacter Pylori and N-Acetyl-L-Cysteine
N-Acetyl-L-cysteine, the N-acetyl derivative of L-cysteine, is the rate-limiting precursor for glutathione synthesis. Oral N-acetyl-L-cysteine has been used to disrupt H. pylori biofilm and mitigate H. pylori antibiotic resistance. In a small study involving 40 subjects who had failed at least four prior courses of standard therapies, N-acetyl-L-cysteine in addition to a culture-guided antibiotic program was associated with a cure rate of 65% versus a rate of 20% without N-acetyl-L-cysteine.68 The addition of N-acetyl-L-cysteine has significant potential in the treatment of H. pylori, particularly in patients who have failed prior courses of therapy.
Helicobacter Pylori and Quercetin
Quercetin is a potent polyphenolic bioflavonoid water-soluble antioxidant found in many foods including kale, watercress, onions, apples, green tea, and black tea.69 Quercetin has a variety of activities including anti-allergic, anti-inflammatory properties and activation of cellular pathways that lead to the prevention of many pathological conditions such as cancer and cardiovascular and neurodegenerative disease.70 Quercetin has significant in vitroanti-H. pylori effects that are pH independent.71 In an animal study, quercetin reduced H. pylori gastric mucosa infection and decreased inflammatory response and lipid peroxidation.72 This suggests that quercetin may have a useful role in moderating excessive inflammatory responses to H. pylori colonization and in increasing treatment success rates.
Conclusion
H. pylori has been a human gastric commensal microbe for the entire history of the species. It is clearly associated with significant disease, but only a minority of colonized people ever develop disease. H. pylori appears to confer health benefit, and declining colonization rates are associated with increases in esophageal diseases and allergies. The traditional "test and treat" strategy may be excessive, and more focused treatment indications are being preferred. Standard antimicrobial regimens have low and declining success rates. Adjunctive, complementary interventions such as probiotics, antibiofilm enzymes, lactoferrin, N-acetyl-L-cysteine, and quercetin offer the opportunities to improve H. pylori treatment success rates and reduce side effects.
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Notes
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Stephen Olmstead, MD, is chief science officer at ProThera Inc., where he directs clinical trials of ProThera and Klaire Labs nutraceutical products. His current research focus is the use of enzymes and chelating agents to disrupt pathogenic GI biofilm. Dr. Olmstead graduated from the University of New Mexico with distinction in biology and chemistry. He attended the University of New Mexico School of Medicine and trained at Harvard Medical School, Massachusetts General Hospital. He is board certified in both internal medicine and cardiovascular diseases.
Kathleen Burns, MSN, RN, NP, senior technical associate at ProThera Inc., provides scientific technical support to ProThera and Klaire Labs health-care professional customers. She received her master's degree in nursing from Massachusetts General Hospital Institute of Health Professions, Boston, and is a board certified pediatric nurse practitioner.
Dennis E. Meiss, PhD, is a founder of ProThera Inc. and acts as president and CEO. He is the primary formulator of ProThera and Klaire Labs products and directs the company's management team. Dr. Meiss received his PhD in neurobiology from the University of Connecticut.
Janet Ralston, BS, is a founder of ProThera Inc. She serves as vice president of the company, where she directs marketing efforts and client service programs. She is a graduate of the University of California, Davis, Nutrition and Dietetics program.
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