Background and Aims
Anti‐Helicobacter pylori therapy may lead to the growth of pathogenic or antibiotic‐resistant bacteria in the gut. The study aimed to investigate the short‐term and long‐term ...impacts of H. pylori eradication with reverse hybrid therapy on the components and macrolide resistance of the gut microbiota.
Methods
Helicobacter pylori‐related gastritis patients were administered a 14‐day reverse hybrid therapy. Fecal samples were collected before treatment and at the end of week 2, week 8, and week 48. The V3–V4 region of the bacterial 16S rRNA gene in fecal specimens was amplified by polymerase chain reaction and sequenced on Illumina MiSeq platform. Additionally, amplification of erm(B) gene (encoding erythromycin resistance methylase) was performed.
Results
Reverse hybrid therapy resulted in decreased relative abundances of Firmicutes (from 62.0% to 30.7%; P < 0.001) and Actinobacteria (from 3.4% to 0.6%; 0.032) at the end of therapy. In contrast, the relative abundance of Proteobacteria increased from 10.2% to 49.1% (0.002). These microbiota alterations did not persist but returned to the initial levels at week 8 and week 48. The amount of erm(B) gene in fecal specimens was comparable with the pretreatment level at week 2 but increased at week 8 (0.025) and then returned to the pretreatment level by week 48.
Conclusions
Helicobacter pylori eradication with reverse hybrid therapy can lead to short‐term gut dysbiosis. The amount of erm(B) gene in the stool increased transiently after treatment and returned to the pretreatment level at 1‐year post‐treatment.
Helicobacter pylori induces immune tolerance and is associated with a lower risk for immune-mediated disorders, such as autoimmune and inflammatory bowel diseases (IBD). We aimed to determine the ...effects of treatment for H pylori infection on the incidence of autoimmune disease and IBD.
We collected data from the National Health Insurance Research Database in Taiwan on patients younger than 18 years old without a prior diagnosis of autoimmune disease or IBD. Patients with peptic ulcer disease (PUD) with treatment of H pylori infection (PUD+HPRx), PUD without H pylori treatment (PUD-HPRx), a urinary tract infection (UTI) treated with cephalosporin, or without PUD (controls) were matched for age, sex, insurance, and Charlson's comorbidity index score.
Of the 1 million patients we collected data from in 2005, we included 79,181 patients in the study. We compared the effects of treatment for H pylori infection on the risk of autoimmunity or IBD and found that PUD+HPRx has the highest adjusted hazard risk (aHR) for autoimmunity or IBD (aHR, 2.36), compared to PUD-HPRx (aHR, 1.91) or UTI (aHRs, 1.71) (P < .001). The increased risk of autoimmune disease was not completely accounted for by antibiotic therapy alone, because PUD+HPRx had a higher aHR than UTI (P < .001). A small but significant increase in mortality was observed in the PUD+HPRx cohort (aHR, 1.11; P = .001).
In an analysis of data from the National Health Insurance Research Database in Taiwan, we found that treatment for H pylori infection is associated with a significant increase in the risk for autoimmune disease, including IBD.
Macrophages (Mϕs) are known to be major producers of the anti-inflammatory cytokine interleukin-10 (IL-10) in the intestine, thus playing an important role in maintaining gastrointestinal ...homeostasis. Mϕs that reside in the small intestine (SI) have been previously shown to be regulated by dietary antigens, while colonic Mϕs are regulated by the microbiota. However, the role which resident Mϕs play in SI homeostasis has not yet been fully elucidated. Here, we show that SI Mϕs regulate the integrity of the epithelial barrier via secretion of IL-10. We used an animal model of non-steroidal anti-inflammatory drug (NSAID)-induced SI epithelial injury to show that IL-10 is mainly produced by MHCII
CD64
Ly6C
Mϕs early in injury and that it is involved in the restoration of the epithelial barrier. We found that a lack of IL-10, particularly its secretion by Mϕs, compromised the recovery of SI epithelial barrier. IL-10 production by MHCII
CD64
Ly6C
Mϕs in the SI is not regulated by the gut microbiota, hence depletion of the microbiota did not influence epithelial regeneration in the SI. Collectively, these results highlight the critical role IL-10-producing Mϕs play in recovery from intestinal epithelial injury induced by NSAID.
Studies on the association between rheumatoid arthritis (RA) and deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) are scarce. This study identifies the effects of RA on the risks of ...developing DVT and PE in a nationwide prospective cohort study.
We studied the entire Taiwan population from 1998 to 2008, with a follow-up period extending to the end of 2010. We identified patients with RA using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD). We also selected a comparison cohort that was randomly frequency-matched by age (each 5-year span), sex and index year from the general population. We analysed the risks of DVT and PE using Cox proportional hazards regression models, including sex, age and comorbidities.
From 23.74 million people in the cohort, 29 238 RA patients (77% women, mean age of 52.4 years) and 1 16 952 controls were followed 1 93 753 and 7 92 941 person-years, respectively. The risk of developing DVT and PE was 3.36-fold and 2.07-fold, respectively, in patients with RA compared with patients without RA, after adjusting for age, sex and comorbidities. The multiplicative increased risks of DVT and PE were also significant in patients with RA with any comorbidity.
This nationwide prospective cohort study demonstrates that DVT and PE risks significantly increased in patients with RA compared with those of the general population.
Background & Aims Dual oxidase 2 (DUOX2), a hydrogen-peroxide generator at the apical membrane of gastrointestinal epithelia, is up-regulated in patients with inflammatory bowel disease (IBD) before ...the onset of inflammation, but little is known about its effects. We investigated the role of DUOX2 in maintaining mucosal immune homeostasis in mice. Methods We analyzed the regulation of DUOX2 in intestinal tissues of germ-free vs conventional mice, mice given antibiotics or colonized with only segmented filamentous bacteria, mice associated with human microbiota, and mice with deficiencies in interleukin (IL) 23 and IL22 signaling. We performed 16S ribosomal RNA gene quantitative polymerase chain reaction of intestinal mucosa and mesenteric lymph nodes of Duoxa−/− mice that lack functional DUOX enzymes. Genes differentially expressed in Duoxa−/− mice compared with co-housed wild-type littermates were correlated with gene expression changes in early-stage IBD using gene set enrichment analysis. Results Colonization of mice with segmented filamentous bacteria up-regulated intestinal expression of DUOX2. DUOX2 regulated redox signaling within mucosa-associated microbes and restricted bacterial access to lymphatic tissues of the mice, thereby reducing microbiota-induced immune responses. Induction of Duox2 transcription by microbial colonization did not require the mucosal cytokines IL17 or IL22, although IL22 increased expression of Duox2. Dysbiotic, but not healthy human microbiota, activated a DUOX2 response in recipient germ-free mice that corresponded to abnormal colonization of the mucosa with distinct populations of microbes. In Duoxa−/− mice, abnormalities in ileal mucosal gene expression at homeostasis recapitulated those in patients with mucosal dysbiosis. Conclusions DUOX2 regulates interactions between the intestinal microbiota and the mucosa to maintain immune homeostasis in mice. Mucosal dysbiosis leads to increased expression of DUOX2, which might be a marker of perturbed mucosal homeostasis in patients with early-stage IBD.
Background
Bismuth quadruple therapy is the treatment of choice for the first‐line therapy of Helicobacter pylori infection in areas of high clarithromycin resistance. Currently, the impact of the ...promising treatment on gut microbiota remains unclear.
Aim
To investigate the short‐term and long‐term impacts of bismuth quadruple therapy on gut microbiota.
Methods
Adult patients with H. pylori‐related gastritis were treated with 14‐day bismuth quadruple therapy. Fecal samples were collected before treatment at week 2, week 8, and week 48. Nucleic acid extraction from fecal samples was performed. The V3‐V4 region of the bacterial 16S rRNA gene was amplified by polymerase chain reaction and sequenced with the MiSeq followed by data analysis using Qiime pipeline.
Results
Eleven patients received complete follow‐up. Before treatment, the most abundant phyla were Firmicutes (45.3%), Bacteroidetes (24.3%), Proteobacteria (9.9%), and Actinobacteria (5.0%). At the end of bismuth therapy, the relative abundances of Bacteroidetes and Actinobacteria decreased to 0.5% (P < .001) and 1.3% (P = .038), respectively. Additionally, the relative abundance of Verrucomicrobia also decreased from 3.2% to 1.11E−3% (P = .034). In contrast, the relative abundances of Proteobacteria and Cyanobacteria increased (P < .001 and P = .003, respectively). At week 8, the relative abundances of all phyla restored to the levels at baseline. The relative abundances of all phyla at week 48 also did not significantly differ from those at baseline. During eradication therapy, 6 patients (55%) reported at least 1 adverse event. The relative abundance of phylum Proteobacteria in patients with adverse effects was more than that in patients without adverse effects (68.7% ± 8.8% vs 43.4% ± 25.5%; P = .048).
Conclusions
Bismuth quadruple therapy for H. pylori eradication can lead to short‐term dysbiosis of gut microbiota. The increase in Proteobacteria in gut microbiota may attribute to the development of adverse effects during bismuth quadruple therapy.
Eosinophilic esophagitis is a chronic allergen driven immune mediated disease that is increasingly recognized as a leading cause of dysphagia and foregut symptoms in children and adults. Much ...knowledge has been gained in recent years on the genetic and environmental risk factors for this disease, the associated inflammatory milieu, and the long term complications from esophageal remodeling. In this review we will highlight recent progress made in research into this disease, focusing on adults. We will discuss ongoing efforts to develop a minimally invasive technique that may obviate the need for repeated endoscopic assessment of disease activity. Moreover, we will review studies using novel tools such as mucosal impedance and functional lumen imaging as potential surrogate markers for mucosal integrity and esophageal remodeling. With regard to the treatment of eosinophilic inflammation, we will discuss the controversies surrounding responsiveness to proton pump inhibitors in some patients. Therapeutic trials continue to support the use of topical glucocorticoids and empiric food elimination diets as first line treatments. We will discuss ongoing efforts to optimize the elimination diet protocol to decrease the level and duration of food restrictions. Looking ahead, our growing knowledge on the pathogenesis of eosinophilic esophagitis has enabled further advancement of promising targeted biologic therapies.
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