Simplified Helicobacter pylori therapy for patients with penicillin allergy: a randomised controlled trial of vonoprazan-tetracycline dual therapy.

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. METHODS: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. RESULTS: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). CONCLUSIONS: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. TRIAL REGISTRATION NUMBER: ChiCTR2300074693.

Influence of Helicobacter pylori Infection and Eradication on Small Intestinal Bacterial Overgrowth and Abdominal Symptoms.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and small intestinal bacterial overgrowth (SIBO) has attracted attention recently. AIMS: To analyze the influence of H. pylori infection and eradication on SIBO, IMO, and abdominal symptoms. METHODS: Patients with gastrointestinal symptoms were tested for 13C urea breath test and if positive, treated with bismuth-based quadruple therapy. Lactulose hydrogen methane breath test (HMBT) was performed and symptoms were assessed using gastrointestinal symptom rating scale (GSRS) before and 6 weeks after eradication. RESULTS: Of the 102 subjects, 53 were H. pylori positive. The prevalence of SIBO and IMO were higher in patients with H. pylori infection than in those without infection (49.1% vs 24.5%, P = 0.019 for SIBO; 24.5% vs 8.2%, P = 0.027 for IMO). GSRS scores were similar between H. pylori-infected and uninfected patients (2 (IQR: 1;3) vs 2 (IQR: 1;2), P = 0.211). Patients with SIBO or IMO presented higher GSRS scores than patients with both SIBO and IMO negative (2 (IQR: 2;3), 2 (IQR: 2;3) vs 2 (IQR: 1;2), P = 0.011, 0.001, respectively). For the 50 patients who successfully eradicated H. pylori, the response rates for SIBO and IMO were 66.7% and 76.9%, respectively. GSRS scores also significantly decreased (2 (IQR: 1;3) to 0 (IQR: 0;1), P < 0.001) after eradication. CONCLUSION: Helicobacter pylori infection was associated with higher prevalence of SIBO and IMO, both of which led to more pronounced abdominal symptoms. H. pylori eradication also achieved therapeutic effects on SIBO and IMO, accompanied by relief of abdominal symptoms.

Ulcerative colitis overall disease severity index predicts colectomy: a prospective cohort study.

BACKGROUND: ulcerative colitis (UC) overall disease severity index (DSI) has been established. A prospective cohort study was performed to find the value of DSI to predict colectomy within one and four years and explored the association between DSI and other indexes. METHODS: the hospitalized UC patients were enrolled from March 2018 to January 2019 in this single center study. DSI, Truelove and Witts criteria, Mayo index and Seo index were assessed by medical records. Outcome was whether to undergo colectomy within one and four years and was obtained by telephone survey or medical records. Index values of predicting colectomy within one and four years were evaluated using receiver operating characteristics (ROC) curves. RESULTS: one hundred and thirty-eight of 233 hospitalized UC patients were enrolled. Within one year, the follow-up period was less than one year for six patients and two patients had died. A further nine patients underwent colectomy. The Spearman correlation coefficient between DSI and Truelove and Witts criteria, Mayo index and Seo index were 0.730, 0.839 and 0.843, respectively. Using these indices to predict colectomy within one and four years, the area under the curve of DSI was more than those of other indices and the cut-off value of DSI was 79. CONCLUSIONS: a good correlation of DSI with other indexes was demonstrated. DSI can be used to predict the need for colectomy within one or four years.

A real-world exploratory study on the feasibility of vonoprazan and tetracycline dual therapy for the treatment of Helicobacter pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies.

BACKGROUND: The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin. OBJECTIVE: To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies. DESIGN: Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13 C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing. RESULTS: A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline. CONCLUSIONS: For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin.

Application of a New Hemostatic Clip to Prevent Delayed Bleeding After Endoscopic Sphincterotomy: A Propensity Score-matched Analysis.

BACKGROUND AND AIM: Delayed bleeding after endoscopic sphincterotomy (ES) is a serious adverse event of endoscopic retrograde cholangiopancreatography. The aim of this study is to evaluate the effect of prevent delayed bleeding of hemostatic clip (Sureclip) after ES. METHODS: Consecutive patients diagnosed with common bile duct stones with a high risk of delayed bleeding who received ES from January 1, 2013, to July 31, 2022, were analyzed retrospectively. A 1:1 propensity score-matching analysis and logistic regression analysis were used. The patients were allocated into the hemostatic clip and control groups. The rate of delayed bleeding, hyperamylasemia, pancreatitis, and hemostatic clip closing the bile duct or pancreatic duct by mistake were compared between the 2 groups. RESULTS: Overall, 161 and 232 patients were allocated to the control and hemostatic clip groups, respectively, propensity score matching created 120 matched pairs. The rate of delayed bleeding was significantly lower in the hemostatic clip group than in the control group (1.67% vs. 7.5%, P=0.031). After adjusting for confounding factors, logistic regression showed hemostatic clip was associated with decreased odds of delayed bleeding (0.134, 95% CI: 0.025-0.719). No case of hemostatic clip closing the bile duct or pancreatic duct by mistake occurred in the hemostatic clip group. No significant differences were observed in postoperative hyperamylasemia and pancreatitis between the 2 groups. CONCLUSIONS: This study indicated that the prophylactic application of a hemostatic clip is associated with a significantly reduced rate of delayed bleeding after ES in high-risk patients. This approach did not increase the risk of adverse event.

Eradication rate and safety of a "simplified rescue therapy": 14-day vonoprazan and amoxicillin dual regimen as rescue therapy on treatment of Helicobacter pylori infection previously failed in eradication: A real-world, retrospective clinical study in China.

BACKGROUND: The currently recommended quadruple regimens as rescue therapy on Helicobacter pylori infection were not as effective as being supposed, especially in those who had failed two or more times. Dual regimen composed of vonoprazan (a potassium-competitive acid blocker) and amoxicillin might be an option since it's effective in eradication therapy as first-line treatment. OBJECTIVE: As a real-world retrospective study, data were collected to evaluate the efficacy and safety of vonoprazan and amoxicillin dual regimen as rescue therapy in Helicobacter pylori positive patients who had failed one or more times in their previous treatment. METHODS: From May 2020 to June 2021, the clinical data of patients who had failed in Helicobacter pylori infection treatment were collected in GI department of Peking University First Hospital, Beijing, China. Patients were given vonoprazan 20 mg or 40 mg per day and amoxicillin 3000 mg per day (VA dual therapy) for 14 days as rescue treatment. Helicobacter pylori status was evaluated by 13 C-urease breath test 6 weeks after treatment. All adverse effects during treatment were recorded. RESULTS: A total of 186 patients were enrolled, including 67 males and 119 females. All of them had failed for 1 ~ 7 times in their previous treatment. Successful eradication was achieved in 172 patients (92.5%, 172/186). The adverse effects (referring to skin rash, abdominal pain, diarrhea, and headache), mainly mild and did not cause quit of treatment, occurred in 14 patients (7.5%, 14/186) and all symptoms relieved spontaneously. CONCLUSIONS: Dual regimen composed of vonoprazan and amoxicillin for 14 days was effective and safe as rescue therapy in Helicobacter pylori infection treatment. It could be chosen as a "simplified rescue therapy" with relatively high eradication rate no matter how many times the patients had failed and what regimens they had used previously.

The effect of previous eradication failure on antibiotic resistance of Helicobacter pylori: A retrospective study over 8 years in Beijing.

BACKGROUND: Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. MATERIALS AND METHODS: This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. RESULTS: The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. CONCLUSIONS: The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multiple-resistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.

Menstrual blood-derived mesenchymal stem cells attenuate inflammation and improve the mortality of acute liver failure combining with A2AR agonist in mice.

BACKGROUND AND AIM: Acute liver failure (ALF) poses a serious public health issue. The menstrual blood-derived mesenchymal stem cells (MenSCs) have been applied to cure various liver-related diseases. However, the efficacy and mechanism are far from clear. This study aims to explore the efficacy and potential mechanism of MenSCs to cure ALF. METHODS: We investigate the potential mechanism of MenSCs on the ALF in vitro and in vivo. A2A adenosine receptor (A2AR) activation was investigated as the potential reinforcer for MenSCs treatment. Lipid polysaccharide/d-galactosamine (d-GalN) was employed to induce ALF. Diverse techniques were used to measure the inflammatory cytokines and key signaling molecules. Hematoxylin-eosin stain and aminotransaminases were applied to evaluate the liver injury. Flow cytometry was employed to assess the T cells. RESULTS: The MenSCs can decrease the lipid polysaccharide-induced inflammatory cytokine elevation and related signaling molecules in ALF, including TLR4, phosphorylated-NF-kBp65 (p-NF-kBp65), PI3K, and p-AKT, p-mTOR and p-IKK in vitro. Moreover, MenSCs also can significantly reverse the liver injury, inflammatory cytokines elevation and related signaling molecules increase, and Treg/Th17 ratio decrease in vivo. In addition, MenSCs plus A2AR agonist can enhance the above changes. CONCLUSIONS: The MenSCs can attenuate the ALF-induced liver injury via inhibition of TLR4-mediated PI3K/Akt/mTOR/IKK signaling. Then, this inhibits the p-NF-κBp65 translocate into nuclear, which causes a decrease of inflammatory cytokines release. Moreover, A2AR agonist can play a synergic role with MenSCs and enhance the above-mentioned effects.

Imbalanced mucosal microcirculation in the remission stage of ulcerative colitis using probe-based confocal laser endomicroscopy.

BACKGROUND: Microcirculatory disturbance is an important factor in the pathogenesis of Inflammatory Bowel Disease (IBD) but there have been few studies in this field. Confocal Laser Endomicroscopy (CLE) has been used over the last 10 years and has made it possible to explore the changes in microcirculation of the colonic mucosa. METHODS: We retrospectively selected patients who underwent probe-based Confocal Laser Endomicroscopy (pCLE) between 2014 and 2016. There were 7 patients with ulcerative colitis (UC) in clinical remission and 7 healthy subjects included in this study; all the UC patients' medical data were reviewed. For each patient, three segments of the colon were examined using pCLE including the ascending, transverse/descending and sigmoid colon. In each segment, the representative pCLE images of the three sites were selected for analysis. Four indicators, including Mean Vessel Diameter (MVD), Diameter Standard Deviation (DSD), Functional Capillary Density-long (FCDL) and Functional Capillary Density-area (FCDA), were measured with a specially designed detection software algorithm. The four indicators were compared between UC patients and healthy subjects. According to the different blood flow patterns, three types of distribution were established: the Around (A), Cobweb (C) and Deficiency (D) type. The relationships between the recurrence and blood flow patterns of UC patients were analyzed. RESULTS: MVD, DSD, FCDL and FCDA were 10.62 ± 0.56 µm, 2.23 ± 0.26, 0.030 ± 0.019 µm and 0.289 ± 0.030 for the healthy subjects and 11.06 ± 1.10 µm, 2.68 ± 0.29, 0.026 ± 0.005 µm and 0.272 ± 0.034 for the UC patients, respectively. Compared with healthy subjects, DSD was significantly increased and FCDA was significantly decreased (P < 0.01 for both). There was no difference in MVD and FCDL between UC patients and healthy subjects. The type A and type C blood flows were observed in healthy subjects (66.67 and 33.33%, respectively) while type C appears more in UC patients (71.3%) and type D blood flow could only be found in UC patients (14.29%) P < 0.01. UC patients who showed Type D blood flow had a shorter recurrence interval. CONCLUSIONS: Some local mucosal capillary density in UC patients was decreased, particularly in the inflammation-affected segment. The three mucosal blood flow patterns can be used as an indicator of mucosal healing.

Helicobacter pylori induces caudal-type homeobox protein 2 and cyclooxygenase 2 expression by modulating microRNAs in esophageal epithelial cells.

Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori. The role of H. pylori in esophageal disease has not been clearly defined. We previously reported that H. pylori esophageal colonization promotes the incidence of Barrett's esophagus and esophageal adenocarcinoma in vivo. Here, we studied the direct effects of H. pylori on the transformation of esophageal epithelial cells, with particular focus on whether H. pylori exerts its effects by modulating miRNAs and their downstream target genes. The normal human esophageal cell line HET-1A was chronically exposed to H. pylori extract and/or acidified deoxycholic acid for up to 36 weeks. The miRNA profiles of the esophageal epithelial cells associated with H. pylori infection were determined by microarray analysis. We found that chronic H. pylori exposure promoted acidified deoxycholic acid-induced morphological changes in HET-1A cells, along with aberrant overexpression of intestinal metaplasia markers and tumorigenic factors, including caudal-type homeobox protein 2 (CDX2), mucin 2, and cyclooxygenase 2 (COX2). Helicobacter pylori modified the miRNA profiles of esophageal epithelial cells, particularly aberrant silencing of miR-212-3p and miR-361-3p. Moreover, in biopsies from Barrett's esophagus patients, esophageal H. pylori colonization was associated with a significant decrease in miR-212-3p and miR-361-3p expression. Furthermore, we identified COX2 as a target of miR-212-3p, and CDX2 as a target of miR-361-3p. Helicobacter pylori infection of esophageal epithelial cells was associated with miRNA-mediated upregulation of oncoprotein CDX2 and COX2. Our observations provide new evidence about the molecular mechanisms underlying the association between H. pylori infection and esophageal carcinogenesis.

SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGFß-mediated epithelial to mesenchymal transition in human lung cancer cell line A549.

A post-transcriptional pathway by which TGF-ß modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-ß for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-ß induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-ß treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-ß-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma.

[Non-bismuth quadruple therapy versus standard triple therapy for Helicobacter pylori eradication: a randomized controlled study].

OBJECTIVE: To compare the efficacies of non-bismuth quadruple therapy for 7 days versus standard triple therapy for 7 or 10 days in initial treatment of Helicobacter pylori (H.pylori) . METHODS: A randomized, open-labeled, controlled trial comparing non-bismuth quadruple therapy with standard triple therapy was performed at Peking University First Hospital from August 2010 to July 2012. A total of 246 patients with a diagnosis of H.pylori infection by (13)C-urea breath test and receiving no eradication therapy were randomly divided into non-bismuth quadruple therapy and standard triple therapy for 7 or 10 days. There were 110 males and 136 females with an age range of 18-75 years. Among them, 81 patients received non-bismuth quadruple therapy (esomeprazole 20 mg, amoxicillin 1 000 mg, clarithromycin 500 mg and tinidazole 500 mg given twice daily for 7 days); 82 standard triple therapy (esomeprazole 20 mg, amoxicillin 1 000 mg and clarithromycin 500 mg given twice daily) for 7 days and 83 standard triple therapy for 10 days. The efficacies were examined at Week 4 post-therapy by (13)C-urea breath test. The incidence of adverse drug reactions was recorded. RESULTS: Among them, 242 patients completed the follow-up. The eradication rates for non-bismuth quadruple therapy and standard triple therapy for 7 or 10 days were 91.4% (74/81), 79.3% (65/82) and 79.5% (66/83) as determined by intention-to-treat analysis (ITT). The eradication rates were 92.5% (74/80), 81.3% (65/80) and 80.5% (66/82) respectively as determined by per-protocol analysis (PP).Non-bismuth quadruple therapy was superior to standard triple therapy for 7 days (ITT analysis P = 0.029, PP analysis P = 0.035) and 10 days (ITT analysis P = 0.032, PP analysis P = 0.026). The differences for the eradication rates between standard triple therapy for 7 days and for 10 days were insignificant (ITT analysis P = 0.968, PP analysis P = 0.902): Adverse reaction rates for non-bismuth quadruple therapy (8.8%, 7/80) and standard triple therapy for 7 days (7.5%, 6/80) and 10 days (9.8%, 8/82) were not significantly different (P = 0.872). CONCLUSION: Non-bismuth quadruple therapy for 7 days is both effective and safe for the first-line eradication of H.pylori.

Lactobacillus reuteri compared with placebo as an adjuvant in Helicobacter pylori eradication therapy: a meta-analysis of randomized controlled trials.

Background: Given the growing problem of antibiotic resistance, it is crucial to improve Helicobacter pylori (H. pylori) treatment interventions or provide adjunctive therapy. The objective of this meta-analysis was to evaluate whether Lactobacillus reuteri (L. reuteri) could improve H. pylori eradication rate, reduce the incidence of adverse events (AEs), and alleviate gastrointestinal symptoms. Design: A meta-analysis of randomized controlled trials (RCTs) comparing L. reuteri supplementation therapy with placebo was conducted. Sources and methods: We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate, and the scores on the Gastrointestinal Symptom Rating Scale and AEs were secondary outcomes. Results: Eight RCTs including 1087 patients were included in this analysis. The L. reuteri supplementation group showed significantly higher H. pylori eradication rates in both intention-to-treat (ITT) and per-protocol (PP) analysis [ITT: 80.0% versus 72.6%; p = 0.005, relative risk (RR): 1.10; 95% confidence interval (CI): 1.03-1.17; number needed to treat (NNT) = 14; PP: 81.8% versus 75.0%; p = 0.006, RR: 1.09; 95% CI: 1.03-1.16; NNT = 15]. Patients treated with L. reuteri showed greater improvements in gastrointestinal symptoms (pooled mean difference: -2.43, 95% CI: -4.56 to -0.29, p = 0.03). The incidence of AEs was significantly reduced in the L. reuteri supplementation group based on ITT and PP analysis (ITT: p < 0.00001, RR: 0.72, 95% CI: 0.67-0.78; PP: p < 0.00001, RR: 0.70, 95% CI: 0.65-0.77). Conclusion: The present meta-analysis demonstrated that supplementation with L. reuteri was beneficial for improving the eradication rate of H. pylori, reducing the overall incidence of side effects, and relieving gastrointestinal symptoms in patients during treatment. The findings provide new insights into clinical decision-making. Trial registration PROSPERO: CRD42023424052.

Lactobacillus reuteri compared with placebo as an adjuvant in Helicobacter pylori eradication therapy: a meta-analysis of randomized controlled trials Given the growing problem of antibiotic resistance, it is crucial to improve Helicobacter pylori (H. pylori) treatment interventions or provide adjunctive therapy. Eight randomized controlled trials (RCTs) including 1087 patients were included in this analysis. The present meta-analysis demonstrated that supplementing with L. reuteri tends to increase the eradication rate of H. pylori, reduce the overall incidence of antibiotic-related side effects, and alleviate gastrointestinal symptoms in patients during treatment, providing new insights for clinical decision-making.

Efficacy and safety of vonoprazan-amoxicillin dual therapy for Helicobacter pylori first-line treatment: a single-center, randomized, controlled trial.

Background: With the increase in antibiotic resistance, the success rate of Helicobacter pylori (H. pylori) eradication therapy has declined in recent years. Vonoprazan-amoxicillin (VA) dual therapy has been reported to be a promising regimen. Objectives: To compare the efficacy and safety of VA dual therapy and bismuth quadruple therapy containing amoxicillin and clarithromycin for H. pylori first-line eradication, and to further analyze the effects of clarithromycin resistance on eradication rate. Design: This study was a single-center, open-label, randomized controlled trial. Methods: Treatment-naïve H. pylori-infected patients were randomly allocated 1:1 to the VA group (vonoprazan 20 mg twice daily and amoxicillin 750 mg four times daily, for 14 days) or the RBAC group (rabeprazole 10 mg, bismuth potassium citrate 220 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily, for 14 days). H. pylori clarithromycin resistance and CYP2C19 gene polymorphisms were detected with real-time polymerase chain reaction (PCR) technique. The eradication rates and adverse events were analyzed. Results: A total of 151 patients were enrolled. The intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) eradication rates and their 95% confidence intervals (95% CIs) were 94.6% (86.0-98.3%), 98.6% (91.3-99.9%), and 98.5% (90.9-99.9%) for VA group and 87.0% (77.0-93.3%), 91.8% (82.3-96.6%), and 93% (83.7-97.4%) for RBAC group. The eradication rate of the VA group was noninferior to the RBAC group in ITT, mITT, and PP analyses (p < 0.0001). In patients infected with strains of clarithromycin resistance point mutation, the eradication rate of the RBAC group decreased to lower than 90%, but the difference from the VA group did not achieve statistical significance (ITT eradication rate: 81.5% in the RBAC group and 96.2% in the VA group, p = 0.192). The incidence of adverse events in the VA group was 39.2%, which was significantly lower than that in the RBAC group (79.2%, p = 0.000). Conclusion: The efficacy of VA dual therapy is noninferior to RBAC in H. pylori first-line eradication, with fewer adverse reactions. Registration: This study was registered at the Chinese Clinical Trial Registry (ChiCTR2100052550) on 30 October 2021.

Drinking water quality and inflammatory bowel disease: a prospective cohort study.

Environmental factors, such as drinking water and diets, play an important role in the development of inflammatory bowel disease (IBD). This study aimed to investigate the associations of metal elements and disinfectants in drinking water with the risk of inflammatory bowel disease (IBD) and to assess whether diet influences these associations. We conducted a prospective cohort study including 22,824 participants free from IBD from the Yinzhou cohort study in the 2016-2022 period with an average follow-up of 5.24 years. The metal and disinfectant concentrations were measured in local pipeline terminal tap water samples. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). During an average follow-up period of 5.24 years, 46 cases of IBD were identified. For every 1 standard deviation (SD) increase in the concentration of manganese, mercury, selenium, sulfur tetraoxide (SO4), chlorine, and nitrate nitrogen (NO3_N) were associated with a higher risk of IBD with the HRs of 1.45 (95% CI: 1.14 to 1.84), 1.51 (95% CI: 1.24-1.82), 1.29 (95% CI: 1.03-1.61), 1.52 (95% CI: 1.26-1.83), 1.26 (95% CI: 1.18-1.34), and 1.66 (95% CI: 1.32-2.09), whereas zinc and fluorine were inversely associated with IBD with the HRs of 0.42 (95% CI: 0.24 to 0.73) and 0.68 (95% CI: 0.54-0.84), respectively. Stronger associations were observed in females, higher income groups, low education groups, former drinkers, and participants who never drink tea. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of IBD. We found significant associations between exposure to metals and disinfectants and IBD. Diets regulated the associations to some extent.

Probiotic Escherichia coli Nissle 1917 Expressing Elafin Protects Against Inflammation and Restores the Gut Microbiota.

Intestinal mucosal inflammation and epithelial barrier dysfunction have been implicated as pathological factors in inflammatory bowel disease (IBD). An emerging area of IBD research focuses on probiotics. The probiotic Escherichia coli Nissle 1917 (EcN) is an excellent choice for engineering therapeutic microbes. Elafin is an endogenous specific inhibitor of neutrophil elastase (NE) and proteinase 3, and we previously found Elafin can effectively suppress the development of colitis. Here, we genetically engineered EcN to deliver Elafin (EcN-Elafin) directly to the colonic mucosa and explored the protective effects of EcN-Elafin against colitis in mice. EcN-Elafin significantly alleviated dextran sodium sulfate (DSS) induced colitis. Compared with wild-type EcN, oral administration of EcN-Elafin displayed better effects on loss of weight, colon length shortening, elevated expression of myeloperoxidase (MPO), and proinflammatory cytokines and chemokine in colonic tissues. In addition, EcN-Elafin restored the expression and distribution of tight junction protein ZO-1 in colonic tissues back to normal. In a damaged colonic epithelial model utilizing Caco-2 cells stimulated with TNF-α, EcN-Elafin efficiently downregulated the activation level of NF-κB signaling. EcN-Elafin was also found to have restored the dysbiosis in gut caused by DSS administration. Moreover, EcN-Elafin significantly enhanced the concentrations of butyrate and valerate in the gut lumen. Thus, our findings demonstrated that EcN-Elafin enhanced the colonic epithelial barrier, promoted the resolution of inflammation, modulated the gut microbiota, and elevated concentrations of short-chain fatty acids (SCFAs) in the gut. EcN-Elafin may be a potential therapeutic method for IBD.

Efficacy of Sucralfate-Combined Quadruple Therapy on Gastric Mucosal Injury Induced by Helicobacter pylori and Its Effect on Gastrointestinal Flora.

BACKGROUND: This study explored the therapeutic efficacy of standard triple therapy combined with sucralfate suspension gel as well as the mechanisms of action in mouse models of H. pylori infection. MATERIALS AND METHODS: C57BL/6J mice were randomly divided into 5 groups: NC (natural control), HP (H. pylori infection), RAC (rabeprazole, amoxicillin, and clarithromycin), RACS (RAC and sucralfate suspension gel), and RACB (RAC and bismuth potassium citrate). HE staining and electron microscopy were performed to estimate histological and ultrastructural damages. The IL-8, IL-10, and TNF-α of gastric antrum tissues were measured by immunohistochemistry and qRT-PCR. ZO-1 and Occludin were also detected with immunohistochemistry. The genomes of gastric and fecal microbiota were sequenced. RESULTS: The eradication rate of H. pylori in the RACS group was higher than the RAC group. RACS therapy had protective effects on H. pylori-induced histological and ultrastructural damages, which were superior to the RAC group. RACS therapy reduced the protein and mRNA levels of IL-8 compared with the RAC group. The expression of Occludin in the RACS group was significantly higher than that of the RAC group. The composition of gastric and fecal microbiota for RACS was similar to the RACB group according to PCA. CONCLUSIONS: The RACS regimen eradicated H. pylori infection effectively and showed RACS had protective effects against H. pylori-induced histological and ultrastructural damage. The mechanisms of RACS effects included decreasing IL-8, enhancing Occludin, and transforming gastric microbiota. Moreover, RACS and RACB have a similar effect on gastrointestinal flora.

Gain of Function of Ion Channel TRPV1 Exacerbates Experimental Colitis by Promoting Dendritic Cell Activation.

Dysregulated mucosal immunity plays an essential role in the pathophysiology of inflammatory bowel disease (IBD). Transient receptor potential vanilloid 1 (TRPV1) is a Ca2+-permeable ion channel that is implicated in modulating immune responses. However, its role in the pathogenesis of intestinal inflammation remains elusive. Here, we found that TRPV1 gain of function significantly increased the susceptibility of mice to experimental colitis, and that was associated with excessive recruitment of dendritic cells and enhanced Th17 immune responses in the lamina propria of colon. TRPV1 gain of function promoted dendritic cell activation and cytokine production upon inflammatory stimuli, and consequently enhanced dendritic cell-mediated Th17 cell differentiation. Further mechanistic studies showed that TRPV1 gain of function in dendritic cells enhanced activation of calcineurin/nuclear factor of activated T cells (NFATc2) signaling induced by inflammatory stimuli. Moreover, in patients with IBD, TRPV1 expression was increased in lamina propria cells of inflamed colon compared with healthy controls. Our findings identify an important role for TRPV1 in modulating dendritic cell activation and sustaining Th17 responses to inflammatory stimuli, which suggest that TRPV1 might be a potential therapeutic target in controlling mucosal immunity and IBD.

High Expression and Clinical Significance of Elafin in Colorectal Cancer.

OBJECTIVE: The decrease of Elafin is associated with several inflammatory diseases. Exogenous Elafin may be a treatment for IBD. Little data has shown the expression of Elafin in patients of colorectal cancer. Here, we tried to explore Elafin expression in human tissues of colorectal cancer. METHODS: We examined the protein expression of Elafin in human tissues of adjacent nontumor and colorectal tumor by immunohistochemistry (IHC) or quantitative real-time polymerase chain reaction (qRT-PCR), then analyzed the clinical and RNA-seq data presented in The Cancer Genome Atlas (TCGA) database to confirm the relationship between Elafin levels and colorectal tumor. RESULTS: Of the 88 paired samples, 68 colorectal cancer tissues indicated a high expression of Elafin compared with 52 matched adjacent noncancerous tissues. And the mRNA levels of Elafin in 35 paired tissues showed a similar trend. The RNA-seq and clinical data were available in 438 colorectal cancer tissues and 41 normal tissues in TCGA database. The RNA-seq data showed that Elafin mRNA was upregulated about twofold in colorectal cancer samples as compared to adjacent noncancerous samples (176.42 ± 402.13 vs. 96.75 ± 150.07; P = 0.208). No statistically significant correlation was found between the Elafin expression and the age, gender, tumor invasive stage, lymph node metastasis, and distant metastasis both at the protein and mRNA levels. However, the Elafin expression was correlated with clinical stage based on the AJCC guidelines at protein levels but not mRNA levels. CONCLUSIONS: Elafin was upregulated in patients of colorectal cancer, resulting to potential limitations for exogenous Elafin treatment.

Protective effect of Saccharomyces boulardii on intestinal mucosal barrier of dextran sodium sulfate-induced colitis in mice.

BACKGROUND: The effect and mechanism of Saccharomyces boulardii (Sb) in inflammatory bowel disease are unclear. The objective of the study was to evaluate the impact of Sb on intestinal mucosal barrier and intestinal flora in a colitis mouse model. METHODS: Forty C57BL/6J male mice were randomly assigned to five groups: normal control group (A), pathologic control group (B), Sb treatment group (C), mesalazine treatment group (D), and Sb combined with mesalazine treatment group (E). Colitis was induced by the addition of 2.5% (wt/vol) dextran sodium sulfate (DSS) in the drinking water ad libitum for 7 days. The general condition, weight change, stool property, and bloody stool level of mice were observed to evaluate the disease activity index. The expression of zona occludens-1 (ZO-1) and occludin in intestinal tissue were measured by immunohistochemistry. The level of tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 in plasma was measured by enzyme linked immunosorbent assay. Inter-cellular tight junctions were observed by transmission electron microscopy. The feces and intestinal contents were collected sterilely, and intestinal flora was analyzed by 16S rRNA sequencing. RESULTS: Compared with group B, Sb reduced the disease activity index and histological score of group C (disease activity index: group B 2.708 ±â€Š0.628, group C 1.542 ±â€Š0.616, PBC = 0.005; histological score: group B 9.875 ±â€Š3.271, group C 4.750 ±â€Š1.832, PBC = 0.005) in DSS-induced colitis in mice. Sb exerted a protect effect on the expression of ZO-1 (group B 2.075 ±â€Š1.176, group C 4.225 ±â€Š1.316, PBC = 0.019) and occludin (group B 2.200 ±â€Š0.968, group C 3.525 ±â€Š1.047, PBC = 0.023). Compared with group B, Sb decreased the level of TNF-α and IL-8 of group C (TNF-α: group B 716.323 ±â€Š44.691 ng/L, group C 521.740 ±â€Š90.121 ng/L, PBC = 0.001; IL-8: group B 128.992 ±â€Š11.475 pg/mL, group C 106.283 ±â€Š15.906 pg/mL, PBC = 0.012). Treatment with Sb preserved the tight junctions and ameliorated microvilli and inter-cellular space. Treatment with Sb also showed its own characteristics: a higher percentage of Bacteroidetes and a lower percentage of Firmicutes, with significant differences or a significant trend. The proportion of the S24-7 family was increased significantly in the Sb treatment group. CONCLUSIONS: Sb shows an anti-inflammatory effect and has a protective effect on the intestinal mucosal mechanical barrier. Sb may up-regulate the abundance of family S24-7 specifically, and maybe a mechanism underlying its function.