Helicobacter pylori eradication: Not only early consequences
2018; Elsevier BV; Volume: 35; Linguagem: Inglês
10.1016/j.ebiom.2018.08.051
ISSN2352-3964
Autores Tópico(s)Gastrointestinal disorders and treatments
ResumoA lot of physicians treating Helicobacter pylori (Hp)-positive patients with extra-alimentary disorders as well as gastroenterological symptoms have often deliberated: “to kill or not to kill Hp?” Today, evidence-based indications for starting Hp eradication are available in the Maastricht V/Florence Consensus Report [[5]Malfertheiner P. Megraud F. O'Morain C.A. Gisbert J.P. Kuipers E.J. Axon A.T. et al.Management of Helicobacter pylori infection - the maastricht V/Florence consensus report.Gut. 2017; 66: 6-30https://doi.org/10.1136/gutjnl-2016-312288Crossref PubMed Scopus (1789) Google Scholar]. However, clinical decisions are not always easy. Sometimes, Hp eradication is demanded by a patient who read on the internet that Hp infection is a first-class carcinogen. Other times, the physician loses patience and recommends Hp eradication as a desperate therapy for a difficult patient with functional dyspepsia or heartburn resistant to the standard treatment, expecting the patient either to change doctors or to experience symptom relief. However, the study by Chen et al. [[1]Chen L. Xu W. Lee A. He J. Huang B. Zheng W. et al.The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.EBioMedicine. 2018; 35: 87-96Summary Full Text Full Text PDF PubMed Scopus (82) Google Scholar] shows that recommending 14-day bismuth-containing quadruple therapy may not only eradicate Hp, but could also change gut microbiota (examined using 16S rRNA sequencing in stool samples). They found that induced enteral dysbiosis can be maintained as much as 8 weeks after beginning therapy with antibiotics. However, it should also be taken into consideration that changes in gut microbiota after Hp eradication are not only the result of antibiotics acting, but can also be due to long-lasting alterations in saliva secretion, gastric acidity, gastric motility, mucosal immunological response, changes in metabolic pathways and the loss of a direct effect of Hp infection on other microorganisms living in the human digestive tract [[3]Goderska K. Agudo Pena S. Alarcon T. Helicobacter pylori treatment: antibiotics or probiotics.Appl Microbiol Biotechnol. 2018; 102: 1-7https://doi.org/10.1007/s00253-017-8535-7Crossref PubMed Scopus (105) Google Scholar]. We now know that these effects of Hp eradication last longer than 8 weeks. The effects may potentially affect the course of several diseases related to gut dysbiosis (e.g. inflammatory bowel disease, food allergies, and diabetes mellitus), as well as the absorption of nutrition and drugs. However, long-term clinical complications of dysbiosis other than pseudomembranous colitis induced by Hp-eradicative therapy need confirmation in further study. In my opinion, confirmation of late Hp-eradication complications, e.g. sub forms of changes in the prevalence of clinical end-points, would have similar practical importance to identifying the effects of diabetogenic statins, which induced physicians to be more cautious in recommending lipid-lowering drugs in individuals with primary prevention of cardiovascular disorders as an indication. However, the study by Chen et al. [[1]Chen L. Xu W. Lee A. He J. Huang B. Zheng W. et al.The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.EBioMedicine. 2018; 35: 87-96Summary Full Text Full Text PDF PubMed Scopus (82) Google Scholar] shows not only the potential unfavorable action of quadruple eradicative therapy, but also points to an effective method of patient protection against undesirable symptoms and dysbiosis associated with antibiotic therapy, which is the supplementing of 14-day bismuth-containing quadruple therapy with Clostridium butyricum, bacteria that produce a butyrate, short fatty-acid modulating inflammation response and protective enteric barrier [[2]Chen G. Ran X. Li B. Li Y. He D. Huang B. et al.Sodium butyrate inhibits inflammation and maintains epithelium barrier integrity in a TNBS-induced inflammatory bowel disease mice model.EBioMedicine. 2018; 30: 317-325https://doi.org/10.1016/j.ebiom.2018.03.030Summary Full Text Full Text PDF PubMed Scopus (211) Google Scholar]. The authors found that this supplementation also improved the ratio of favorable-to-detrimental bacteria in gut microflora, although its effect on Hp-eradication rate did not reach statistical significance. In the light of still ineffective trials on vaccinations for the prevention of Hp contamination [[6]Malfertheiner P. Selgrad M. Wex T. Romi B. Borgogni E. Spensieri F. et al.Efficacy, immunogenicity, and safety of a parenteral vaccine against Helicobacter pylori in healthy volunteers challenged with a Cag-positive strain: A randomised, placebo-controlled phase ½ study.Lancet Gastroenterol Hepatol. 2018; (pii: S2468-1253(18)30125-0. [Epub ahead of print])https://doi.org/10.1016/S2468-1253(18)30125-0Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar], the use of alternative therapies that could improve antibiotic activity, modulate inflammatory response, and improve enteric barrier integrity in supporting Hp-eradicative therapy seems to be reasonable [[3]Goderska K. Agudo Pena S. Alarcon T. Helicobacter pylori treatment: antibiotics or probiotics.Appl Microbiol Biotechnol. 2018; 102: 1-7https://doi.org/10.1007/s00253-017-8535-7Crossref PubMed Scopus (105) Google Scholar,[4]Hungin A.P.S. Mitchell C.R. Whorwell P. Mulligan C. Cole O. Agréus L. et al.Systematic review: Probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus.Aliment Pharmacol Ther. 2018; 47: 1054-1070https://doi.org/10.1111/apt.14539Crossref PubMed Scopus (84) Google Scholar]. Such treatment mainly consists of probiotics (e.g. Lactobacillus acidophilus, L. gasseri, L. reuteri, Saccharomyces boulardii, Bifidobacterium spp., B. clausii), fermented food (e.g. milk, cucumber, or cabbage) and/or phytomedicines, e.g. with traditional Chinese medicines, berberine, green tea, catechins, cranberry juice, garlic extract, propolis, and sialic acid [[3]Goderska K. Agudo Pena S. Alarcon T. Helicobacter pylori treatment: antibiotics or probiotics.Appl Microbiol Biotechnol. 2018; 102: 1-7https://doi.org/10.1007/s00253-017-8535-7Crossref PubMed Scopus (105) Google Scholar,[4]Hungin A.P.S. Mitchell C.R. Whorwell P. Mulligan C. Cole O. Agréus L. et al.Systematic review: Probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus.Aliment Pharmacol Ther. 2018; 47: 1054-1070https://doi.org/10.1111/apt.14539Crossref PubMed Scopus (84) Google Scholar,[8]Yang J.C. Lu C.W. Lin C.J. Treatment of Helicobacter pylori infection: Current status and future concepts.World J Gastroenterol. 2014; 20: 5283-5293https://doi.org/10.3748/wjg.v20.i18.5283Crossref PubMed Scopus (105) Google Scholar,[10]Zhang D. Ke L. Ni Z. Chen Y. Zhang L.H. Zhu S.H. et al.Berberine containing quadruple therapy for initial Helicobacter pylori eradication: An open-label randomized phase IV trial.Medicine (Baltimore). 2017; 96e7697https://doi.org/10.1097/MD.0000000000007697Crossref Scopus (16) Google Scholar]. However, an evaluation of the clinical outcomes of the use of these substances requires further study. It also seems to be worth performing both basic and clinical research on the usefulness of prebiotics (e.g. fiber, fructo-oligosaccharides, galacto-oligosaccharides, inulin, pectins, rhamnose, lactose, polyphenols, polyols), protozoa, fermented food, as well as diets rich or poor in fermented products or fermentable oligosaccharides, disaccharides, monosaccharides and polyols (high or low FODMAP) as media for improving the eradication rate and reducing the side effects of Hp eradication. The study by Chen et al. [[1]Chen L. Xu W. Lee A. He J. Huang B. Zheng W. et al.The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.EBioMedicine. 2018; 35: 87-96Summary Full Text Full Text PDF PubMed Scopus (82) Google Scholar] left some important questions unanswered. As stated above, the later clinical consequences of Hp eradication, e.g. risk of diabetes mellitus, autoimmune diseases, inflammatory bowel disease should be further explained. As this study showed that Hp eradication may be harmful in some patients, it also seems reasonable to evaluate in detail the eradication of which strain of Hp (cagA-positive or vacA-positive) is associated with the most favorable clinical outcome and the most detrimental clinical consequences. Such evidenced data might help in the individualization of Hp-eradicative therapy, as well as in the observation of its potential complications. Before exploring these questions, every physician ought, before recommending Hp-eradicative therapy, to take into consideration that such therapy may evoke not only early but also later and long-lasting complications related to enteric dysbiosis [[4]Hungin A.P.S. Mitchell C.R. Whorwell P. Mulligan C. Cole O. Agréus L. et al.Systematic review: Probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus.Aliment Pharmacol Ther. 2018; 47: 1054-1070https://doi.org/10.1111/apt.14539Crossref PubMed Scopus (84) Google Scholar,[7]Park A.M. Omura S. Fujita M. Sato F. Tsunoda I. Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer's disease: 10 pitfalls of microbiome studies.Clin Exp Neuroimmunol. 2017; 8: 215-232https://doi.org/10.1111/cen3.12401Crossref PubMed Scopus (35) Google Scholar]. This seems to be the key message of the articles by Chen et al. [[1]Chen L. Xu W. Lee A. He J. Huang B. Zheng W. et al.The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.EBioMedicine. 2018; 35: 87-96Summary Full Text Full Text PDF PubMed Scopus (82) Google Scholar] and Yildiz et al. [[9]Yildiz S.S. Yalinay M. Karakan T. Bismuth-based quadruple Helicobacter pylori eradication regimen alters the composition of gut microbiota.Infez Med. 2018; 26: 115-121PubMed Google Scholar]. The author declared no conflicts of interest. The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trialWhile H. pylori infection may not be necessarily detrimental in all patients, eradication of H. pylori was associated with widespread changes in gut microbial ecology and structure. Probiotic supplementation could relieve more gastrointestinal symptoms by inducing alterations in gut microbiota and host immune responses. As such, the decision to eradicate H. pylori should be based on comprehensive analysis of individual patients. Full-Text PDF Open Access
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