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Maternal H. pylori is associated with differential fecal microbiota in infants born by vaginal delivery.
Hernandez, CD, Shin, H, Troncoso, PA, Vera, MH, Villagran, AA, Rodriguez-Rivera, SM, Ortiz, MA, Serrano, CA, Borzutzky, A, Dominguez-Bello, MG, et al
Scientific reports. 2020;(1):7305
Abstract
Helicobacter pylori colonization may affect the mucosal immune system through modification of microbiota composition and their interactions with the host. We hypothesized that maternal H. pylori status affects the maternal intestinal microbiota of both mother and newborn. In this study, we determine the structure of the fecal microbiota in mothers and neonates according to maternal H. pylori status and delivery mode. We included 22 mothers and H. pylori infection was determined by fecal antigen test. Eleven mothers (50%) were H. pylori-positive (7 delivering vaginally and 4 by C-section), and 11 were negative (6 delivering vaginally and 5 by C-section). Stool samples were obtained from mothers and infants and the fecal DNA was sequenced. The fecal microbiota from mothers and their babies differed by the maternal H. pylori status, only in vaginal birth, not in C-section delivery. All 22 infants tested negative for fecal H. pylori at 15 days of age, but those born vaginally -and not those by C-section- showed differences in the infant microbiota by maternal H. pylori status (PERMANOVA, p = 0.01), with higher abundance of Enterobacteriaceae and Veillonella, in those born to H. pylori-positive mothers. In conclusion, the structure of the infant fecal microbiota is affected by the maternal H. pylori status only in infants born vaginally, suggesting that the effect could be mediated by labor and birth exposures.
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Pharmacokinetics and Safety of Triple Therapy with Vonoprazan, Amoxicillin, and Clarithromycin or Metronidazole: A Phase 1, Open-Label, Randomized, Crossover Study.
Sakurai, Y, Shiino, M, Okamoto, H, Nishimura, A, Nakamura, K, Hasegawa, S
Advances in therapy. 2016;(9):1519-35
Abstract
INTRODUCTION Vonoprazan (TAK-438) is a novel potassium-competitive acid blocker that inhibits gastric H(+), K(+)-ATPase. The objectives of this study were to evaluate the influence of triple therapy with vonoprazan-amoxicillin-clarithromycin or vonoprazan-amoxicillin-metronidazole on the pharmacokinetics of each component of the triple therapies (primary) and to evaluate the safety and tolerability of vonoprazan-based triple therapies (secondary) in healthy adults. METHODS In this single-center, phase 1, open-label, randomized, four-way crossover study, Helicobacter pylori-negative, healthy Japanese male subjects were randomly assigned to 1 of 4 treatment sequences in two cohorts (12 subjects per cohort). Each treatment sequence comprised four treatment periods separated by a washout period of 7 or 14 days. Pharmacokinetic parameters for vonoprazan, amoxicillin, clarithromycin and metronidazole in single therapy or triple therapies were assessed. All adverse events were recorded. RESULTS Compared with single therapy, triple therapy with vonoprazan-amoxicillin-clarithromycin increased the area under the plasma concentration-time curve from time 0-12 h (AUC0-12) and maximum plasma concentration (C max) of plasma vonoprazan free base by 1.846- and 1.868-fold, respectively, and increased the AUC0-12 and C max of plasma clarithromycin by 1.450- and 1.635-fold, respectively. Triple therapy with vonoprazan-amoxicillin-metronidazole had no influence on the pharmacokinetics of vonoprazan or metronidazole. The pharmacokinetics of amoxicillin was not influenced by vonoprazan-based triple therapies. Seven adverse events were reported. Two subjects discontinued because of an adverse event (rash, liver function test abnormal); both events were considered to be study drug-related. CONCLUSION In healthy Japanese male subjects, triple therapy with vonoprazan-amoxicillin-clarithromycin increased vonoprazan and clarithromycin exposure. The safety and tolerability profile of triple therapy with vonoprazan-amoxicillin-clarithromycin or vonoprazan-amoxicillin-metronidazole was favorable in this population. FUNDING Takeda Pharmaceutical Company Ltd. TRIAL REGISTRATION JapicCTI-153102.
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Lactobacillus reuteri in the treatment of Helicobacter pylori infection.
Dore, MP, Cuccu, M, Pes, GM, Manca, A, Graham, DY
Internal and emergency medicine. 2014;(6):649-54
Abstract
Probiotics have proven to be useful in the treatment of a number of gastrointestinal diseases. Probiotics may compete directly with Helicobacter pylori, possibly by interference with adherence or by the production of antimicrobial molecules. Lactobacillus reuteri has been shown to inhibit H. pylori in vitro and in vivo, and theoretically may play a role in eradication therapy. The aim of this study was to examine the efficacy of L. reuteri in H. pylori eradication therapy. This was an open label single center study. H. pylori infection was defined as positive gastric histopathology and (13)C-UBT. Intervention consisted of L. reuteri (DSM 17938) 10(8) cfu plus pantoprazole 20 mg twice a day for 8 weeks. Eradication was defined as a negative (13)C-UBT, 4-6 weeks post therapy. Compliance was considered good if at least 90% of the total number of the pills were taken. 21 of 22 subjects completed the study without protocol violation (mean age 52 years; 36% men). L. reuteri plus pantoprazole twice a day cured 13.6% (3/22; 95% CI 2.9-34.9%) of patients with H. pylori infection by ITT analysis and 14.2% (3/21; 95% CI 3.0-36%) by PP analysis. Overall urease activity assessed before and 4-6 weeks post therapy showed a significant reduction with a difference of mean of 38.8 vs. 25.4 by one-tailed test (P = 0.002). In conclusion, L. reuteri may have a potential role in H. pylori eradication therapy if the cure rate can be improved by changes in dose, dosing interval, or duration of therapy.
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Effects of mastic gum Pistacia lentiscus var. Chia on innate cellular immune effectors.
Kottakis, F, Kouzi-Koliakou, K, Pendas, S, Kountouras, J, Choli-Papadopoulou, T
European journal of gastroenterology & hepatology. 2009;(2):143-9
Abstract
BACKGROUND The essential oil and Chios mastic gum (CMG) are natural antimicrobial agents currently broadly used in medicine owing to their antimicrobial, antioxidant, and hepatoprotective properties. The aim of this study was to investigate the effect of CMG-extracted arabinogalactan proteins (AGPs/CMG) both in vitro and in vivo, under the presence of Helicobacter pylori neutrophil-activating protein (HP-NAP), on the innate cellular immune effectors (neutrophils activations) comparing H. pylori-infected patients and healthy controls. PATIENTS AND METHODS The in-vivo effect of AGPs/CMG under the presence of HP-NAP in neutrophil activation was investigated in five H. pylori-infected patients and three healthy volunteers who received 1 g daily consumption of CMG for 2 months. All participants did not receive any immunosuppressive medication before or during the trial; patients with infectious diseases that could modify their immunologic status were excluded. In-vitro studies with pull-down experiments to assess the effect of AGPs/CMG under the presence of HP-NAP on the neutrophil activation were also carried out. Neutrophil activation was estimated by nicotinamide adenine dinucleotide phosphate-oxidase assays and optical microscopy methods by measurement of cytochrome C reduction. RESULTS Neutrophil activation was reduced when incubated in vitro with HP-NAP (P=0.0027) and AGP plus HP-NAP (P=0.0004) in H. pylori-positive patients who consumed AGP for 2 months. Similar results were also obtained when neutrophils were incubated with AGP plus HP-NAP (P=0.0038) in controls. Pull-down experiments showed a specific binding of AGPs to two membrane proteins of neutrophils, possibly suggesting inhibition of neutrophil activation. CONCLUSION AGPs/CMG inhibit neutrophil activation in the presence of HP-NAP, playing a crucial role in H. pylori-associated pathologies in gastric mucosa.
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Inhibition of Helicobacter pylori infection in humans by Lactobacillus reuteri ATCC 55730 and effect on eradication therapy: a pilot study.
Francavilla, R, Lionetti, E, Castellaneta, SP, Magistà, AM, Maurogiovanni, G, Bucci, N, De Canio, A, Indrio, F, Cavallo, L, Ierardi, E, et al
Helicobacter. 2008;(2):127-34
Abstract
BACKGROUND Several studies report an inhibitory effect of probiotics on Helicobacter pylori. AIM: To test whether Lactobacillus reuteri ATCC 55730 reduces H. pylori intragastric load in vivo, decreases dyspeptic symptoms, and affects eradication rates after conventional treatment. MATERIALS AND METHODS In a double-blind placebo-controlled study, 40 H. pylori-positive subjects were given L. reuteri once a day for 4 weeks or placebo. All underwent upper endoscopy, (13)C-urea breath test, and H. pylori stool antigen determination at entry and (13)C-urea breath test and H. pylori stool antigen (used as both qualitative and semiquantitative markers) after 4 weeks of treatment. Sequential treatment was administered subsequently to all. RESULTS In vivo, L. reuteri reduces H. pylori load as semiquantitatively assessed by both (13)C-urea breath test delta-value and H. pylori stool antigen quantification after 4 weeks of treatment (p < .05). No change was shown in patients receiving placebo. L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale as compared to pretreatment value (p < .05) that was not present in those receiving placebo (p = not significant). No difference in eradication rates was observed. CONCLUSIONS L. reuteri effectively suppresses H. pylori infection in humans and decreases the occurrence of dyspeptic symptoms. Nevertheless, it does not seem to affect antibiotic therapy outcome.
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High concentrations of D-amino acids in human gastric juice.
Nagata, Y, Sato, T, Enomoto, N, Ishii, Y, Sasaki, K, Yamada, T
Amino acids. 2007;(1):137-40
Abstract
The concentrations of free D- and L-amino acids were determined in the gastric juice from four groups: patients suffering from early gastric carcinoma with or without Helicobacter pylori infection, and patients without carcinoma but with peptic ulcers, duodenal ulcers or chronic gastritis with or without H. pylori infection. H. pylori is a bacterium associated with gastric inflammation and peptic ulcers and is a risk factor for stomach cancer. The highest D-amino acid ratios (free D-amino acid concentration to the total corresponding free D- and L-amino acid concentration) were 29%, 26%, 18%, 4% and 1% for proline, alanine, serine, aspartate and glutamate, respectively. The gastric juice levels of L-alanine, L-serine, L-proline, L-glutamate and D-alanine in the samples obtained from subjects bearing early gastric carcinoma and H. pylori were significantly higher than in the samples from the other three groups. Except for D-alanine, there was no correlation between the D-amino acid concentrations and presence of carcinoma or H. pylori.
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Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis.
Centanni, M, Gargano, L, Canettieri, G, Viceconti, N, Franchi, A, Delle Fave, G, Annibale, B
The New England journal of medicine. 2006;(17):1787-95
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Abstract
BACKGROUND Malabsorption of thyroxine has been described in patients treated with drugs that modify an acidic environment. We determined whether there is an increased need for thyroxine in patients with euthyroid multinodular goiter and impaired secretion of gastric acid. METHODS We assessed the dose of thyroxine required to obtain a low level of thyrotropin (0.05 to 0.20 mU per liter) in 248 patients with multinodular goiter. Of these 248 patients, 53 also had Helicobacter pylori-related gastritis and 60 had atrophic gastritis of the body of the stomach (31 with evidence of H. pylori infection and 29 without such evidence). The reference group comprised 135 patients with multinodular goiter and no gastric disorders. In addition, variation in the level of serum thyrotropin was prospectively studied in 11 patients treated with thyroxine before and after H. pylori infection and both before and during treatment with omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux. RESULTS The daily requirement of thyroxine was higher (by 22 to 34 percent) in patients with H. pylori-related gastritis, atrophic gastritis, or both conditions than in the reference group. In prospective studies, the occurrence of H. pylori infection in the 11 patients treated with thyroxine led to an increase in the level of serum thyrotropin (P=0.002), an effect that was nearly reversed on eradication of H. pylori infection. In a similar way, omeprazole treatment was associated with an increase in the level of serum thyrotropin in all 10 patients treated with thyroxine, an effect that was reversed by an increase in the thyroxine dose by 37 percent. CONCLUSIONS Patients with impaired acid secretion require an increased dose of thyroxine, suggesting that normal gastric acid secretion is necessary for effective absorption of oral thyroxine.
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In vivo tests of natural therapy, Tibetan yogurt or fresh broccoli, for Helicobacter pylori infection.
Opekun, AR, Yeh, CW, Opekun, JL, Graham, DY
Methods and findings in experimental and clinical pharmacology. 2005;(5):327-9
Abstract
Plants and probiotics have a long history in the treatment of gastrointestinal ailments. Our aim was to evaluate the effectiveness of Tibetan yogurt and fresh broccoli tips in Helicobacter pylori- (H. pylori) infected volunteers, using the urea breath test (UBT) to assess the effect on H. pylori. Clinical trials consisted of ingestion of approximately 135 g of fresh, finely minced juvenile broccoli tips (var. Emperor) in commercial plain yogurt t.i.d, for ten servings (3.3 days) or ingestion of freshly made Tibetan yogurt whey (120 ml) given twice a day for 3.5 days. Urea breath testing was done before and after the natural therapies. Five volunteers received broccoli tips and seven received Tibetan yogurt. No trend for a beneficial effect was seen; the UBT results (delta over baseline) before and after yogurt (35.5+/-12.8 vs. 40.7+/-12.2) (p=0.76) or broccoli (15.8 vs. 19.4) (p=1.0) were unchanged. Antimicrobial end products derived from Tibetan yogurt or broccoli tips have little or no anti-H. pylori effect in vivo. It appears that the gastric mucosal microenvironment apparently shielded H. pylori. In vitro studies suggesting anti-H. pylori activity of compounds should be considered as hypotheses to be tested.
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Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy--a placebo-controlled, double-blind randomized pilot study.
Myllyluoma, E, Veijola, L, Ahlroos, T, Tynkkynen, S, Kankuri, E, Vapaatalo, H, Rautelin, H, Korpela, R
Alimentary pharmacology & therapeutics. 2005;(10):1263-72
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BACKGROUND H. pylori is the major cause of chronic gastritis, and a risk factor for peptic ulcer and gastric cancer. AIM: To investigate the effect of probiotic supplementation on the tolerance and efficacy of H. pylori eradication treatment in a randomized, double-blind, placebo-controlled trial. METHODS A total of 338 volunteers were screened for H. pylori infection. The eligibility criteria were met by 47 subjects whose H. pylori infection was verified at the outset and re-evaluated after the treatment by the 13C-urea breath test and by enzyme immunoassay serology. The subjects were randomized to receive probiotic therapy (Lactobacillus rhamnosus GG, L. rhamnosusLC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii ssp. shermanii JS) or a placebo during H. pylori eradication and for 3 weeks following the treatment, and recorded their daily symptoms in a standardized diary. RESULTS When the frequencies of new or aggravated symptoms were evaluated, no significant differences were found between the two groups for individual symptoms. However, the probiotic group showed less treatment-related symptoms as measured by the total symptom score change (P = 0.038) throughout the H. pylori eradication therapy in contrast to the placebo group. The H. pylori eradication rate was non-significantly higher in the group receiving probiotic therapy (91% vs. 79%, P = 0.42). In this group the recovery of probiotic bacteria in the faeces increased significantly (P < 0.001). CONCLUSIONS In this pilot study, probiotic supplementation did not diminish significantly the frequency of new or aggravated symptoms during H. pylori eradication. However, our data suggest an improved tolerance to the eradication treatment when total symptom severity was taken into account. Furthermore, the results show that probiotic bacteria are able to survive in the gastrointestinal tract despite the intensive antimicrobial therapy.
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Treatment of Helicobacter pylori infection using a novel antiadhesion compound (3'sialyllactose sodium salt). A double blind, placebo-controlled clinical study.
Parente, F, Cucino, C, Anderloni, A, Grandinetti, G, Bianchi Porro, G
Helicobacter. 2003;(4):252-6
Abstract
BACKGROUND AND AIM 3' sialyllactose sodium salt (3'SL) is an oligosaccharide that occurs naturally in human and bovine milk. It can inhibit the adhesion of H. pylori to human epithelial cells in vitro. The aim of this study was to test whether this oligosaccharide can suppress or cure H. pylori colonization in vivo and to determine its safety in humans. METHODS Seventy-one consecutive dyspeptic patients with H. pylori infection documented by histology and 13C-Urea Breath Test (UBT) were initially recruited to this study. Patients with UBT values <15 were excluded, thus reducing the enrollment to 65 patients. They were given two different dosages of 3'SL (10 g or 20 g/day) in three daily administrations before meals or placebo for 4 weeks, according to a randomised double-blind protocol. A standardized 13C-UBT (using 100 mg of 13C labelled urea) was repeated in all patients at fixed intervals during treatment (at the end of weeks 1, 2 and 4) and 4 weeks after treatment withdrawal. Patients compliance and side-effects were evaluated at each weekly visit. RESULTS Five patients were excluded from the PP analysis due to violation of the protocol (noncompliance, lost to follow-up), whereas 61 patients completed correctly the study: 17 received 3'SL 10 g/day, 22 were treated with 3'SL 20 g/day and 21 were given placebo. The three treatment groups did not significantly differ in demographic or clinical patient characteristics. No serious adverse events were observed during therapy in any of the three groups. No patients became UBT negative (<4) during or after treatment but UBT values decreased significantly during the study period in both treatment groups and placebo. CONCLUSIONS Antiadhesive therapy was safe and well tolerated but did not suppress or cure H. pylori colonization in humans. The observed decrease in UBT values could be explained by a regression towards the mean effect.