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When is Helicobacter pylori acquired in populations in developing countries? A birth-cohort study in Bangladeshi children

Kienesberger, Sabine; Perez-Perez, Guillermo I; Olivares, Asalia Z; Bardhan, Pradip; Sarker, Shafiqul A; Hasan, Kh Zahid; Sack, R Bradley; Blaser, Martin J
Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.
PMID: 29494270
ISSN: 1949-0984
CID: 2965982

Helicobacter pylori the Latent Human Pathogen or an Ancestral Commensal Organism

Li, Jackie; Perez-Perez, Guillermo I
We dedicated this review to discuss Helicobacter pylori as one of the latest identified bacterial pathogens in humans and whether its role is mainly as a pathogen or a commensal. Diseases associated with this bacterium were highly prevalent during the 19th century and gradually have declined. Most diseases associated with H. pylori occurred in individuals older than 40 years of age. However, acquisition of H. pylori occurs mainly in young children inside the family setting. Prevalence and incidence of H. pylori has had a dramatic change in the last part of the 20th century and beginning of the 21th century. In developed countries there is a clear interruption of transmission and the lowest prevalence is observed in children younger than 10 years in these countries. A similar decline is observed but not at the same level in developing countries. Here we discuss the impact of the presence or absence of H. pylori in the health status of humans. We also discuss whether it is necessary or not to establish H. pylori eradication programs on light of the current decline in H. pylori prevalence.
PMID: 29666614
ISSN: 1664-302x
CID: 3039622

Corrigendum: Description of two novel members of the family Erysipelotrichaceae: Ileibacterium valens gen. nov., sp. nov. and Dubosiella newyorkensis, gen. nov., sp. nov., from the murine intestine, and emendation to the description of Faecalibacterium rodentium

Cox, Laura M; Sohn, Jiho; Tyrrell, Kerin L; Citron, Diane M; Lawson, Paul A; Patel, Nisha B; Iizumi, Tadasu; Perez-Perez, Guillermo I; Goldstein, Ellie J C; Blaser, Martin J
PMID: 29022554
ISSN: 1466-5034
CID: 2731632

A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity

Ruiz, Victoria E; Battaglia, Thomas; Kurtz, Zachary D; Bijnens, Luc; Ou, Amy; Engstrand, Isak; Zheng, Xuhui; Iizumi, Tadasu; Mullins, Briana J; Muller, Christian L; Cadwell, Ken; Bonneau, Richard; Perez-Perez, Guillermo I; Blaser, Martin J
Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased.High or multiple doses of macrolide antibiotics, when given early in life, can perturb the metabolic and immunological development of lab mice. Here, Ruiz et al. show that even a single macrolide course, given early in life, leads to long-lasting changes in the gut microbiota and immune system of mice.
PMID: 28894149
ISSN: 2041-1723
CID: 2701542

Alpha1-antitrypsin deficiency and c-JUN [Letter]

Ponzetto, Antonio; Perez-Perez, Guillermo I; Figura, Natale
PMID: 28437866
ISSN: 1527-3350
CID: 2544042

Description of two novel members of the family Erysipelotrichaceae: Ileibacterium valens gen. nov., sp. nov. and Dubosiella newyorkensis, gen. nov., sp. nov., from the murine intestine, and emendation to the description of Faecalibacterium rodentium

Cox, Laura M; Sohn, Jiho; Tyrrell, Kerin L; Citron, Diane M; Lawson, Paul A; Patel, Nisha B; Iizumi, Tadasu; Perez-Perez, Guillermo I; Goldstein, Ellie J C; Blaser, Martin J
To better characterize murine intestinal microbiota, a large number (187) of Gram-positive staining, rod- and coccoid-shaped facultative and strictly anaerobic bacteria were isolated from small and large intestinal contents from mice. Based on 16S rRNA gene sequencing, a total 115 isolates formed three phylogenetically distinct clusters located within the family Erysipelotrichaceae. Group 1, as represented by strain NYU-BL-A3T, was most closely related to Allobaculum stercoricanis, with 16S rRNA gene similarity values of 87.7%. A second group, represented by NYU-BL-A4T, was most closely related to Faecalibaculum rodentium, with 86.6% 16S rRNA gene similarity. A third group had a nearly identical 16S rRNA gene sequence (99.9%) compared to the recently described Faecalibaculum rodentium, also recovered from a laboratory mouse; however, this strain had a few differences in biochemical characteristics, which are detailed in an emended description. The predominant (>10%) cellular fatty acids of strains NYU-BL-A3T were C16:0, and C18:0 and for NYU-BL-A4T were C10:0, C16:0, C18:0 and C18:1 omega9c. The two groups could also be distinguished by multiple biochemical reactions, with the group represented by NYU-BL-A4T being considerably more active. Based on phylogenetic, biochemical and chemotaxonomic criteria, two novel genera are proposed. Ileibacterium valens gen. nov., sp. nov. with NYU-BL-A3T (ATCC TSD-63 = DSM 103668) as the type strain and Dubosiella newyorkensis gen. nov., sp. nov. with NYU-BL-A4T (ATCC TSD-64 = DSM 103457) as the type strain.
PMID: 28100298
ISSN: 1466-5034
CID: 2413972

Helicobacter pylori colonization and pregnancies complicated by preeclampsia, spontaneous prematurity, and small for gestational age birth

den Hollander, Wouter J; Schalekamp-Timmermans, Sarah; Holster, I Lisanne; Jaddoe, Vincent W; Hofman, Albert; Moll, Henriette A; Perez-Perez, Guillermo I; Blaser, Martin J; Steegers, Eric A P; Kuipers, Ernst J
BACKGROUND: Preeclampsia (PE), small for gestational age (SGA), and spontaneous preterm birth (PTB) each may be complications of impaired placental function in pregnancy. Although their exact pathogenesis is still unknown, certain infectious agents seem to play a role. Helicobacter pylori (H. pylori) colonization has been associated with increased risk for PE. Our aim was to assess the association between H. pylori colonization and PE, SGA, and PTB. MATERIAL AND METHODS: We measured IgG anti-H. pylori and CagA antibodies in serum of pregnant women (median 20.5 weeks, range 16.5-29.4) who participated in a population-based prospective cohort study. Delivery and medical records were assessed. Information on demographics, education, and maternal risk factors was collected by questionnaire. We used multivariate logistic regression analyses to assess associations between H. pylori colonization and PE, SGA, and PTB. RESULTS: In total, 6348 pregnant women were assessed. H. pylori positivity was found in 2915 (46%) women, of whom 1023 (35%) also were CagA-positive. Pregnancy was complicated by PE, SGA, or PTB in 927 (15%) women. H. pylori colonization was associated with PE (aOR 1.51; 95%CI 1.03-2.25). Differentiation according to CagA status revealed the same risk. H. pylori was positively related with SGA, mainly explained by CagA-positive strains (aOR 1.34; 1.04-1.71). No association was observed between H. pylori and PTB. CONCLUSIONS: Our data suggest that H. pylori colonization may be a risk factor for PE and SGA. If these associations are confirmed by future studies and shown to be causal, H. pylori eradication may reduce related perinatal morbidity and mortality.
PMID: 27786400
ISSN: 1523-5378
CID: 2488282

Characterization of the Gastric Microbiota in a Pediatric Population According to Helicobacter pylori Status

Llorca, Laura; Perez-Perez, Guillermo; Urruzuno, Pedro; Martinez, Maria Josefa; Iizumi, Tadasu; Gao, Zhan; Sohn, Jiho; Chung, Jennifer; Cox, Laura; Simon-Soro, Aurea; Mira, Alex; Alarcon, Teresa
BACKGROUND: H. pylori colonizes the human stomach of approximately 50% of the world's population, and increases the risk of several gastric diseases. The goal of this study is to compare the gastric microbiota in pediatric patients with and without H. pylori colonization. METHODS: We studied 51 children that underwent gastric endoscopy due to dyspeptic symptoms (18 H. pylori-positive and 33 negative). Gastric biopsies were obtained for Rapid Urease Test, culture, histology and DNA extraction. H. pylori was quantified by qPCR and the gastric microbiome studied by V4-16S rRNA gene high-throughput sequencing. RESULTS: Bacterial richness and diversity of H. pylori-positive specimens were lower than those of negative and both groups were clearly separated according to beta diversity. Taxonomic analysis confirmed that H. pylori-positive subjects had a higher relative abundance of Helicobacter genus (66.3%) than H. pylori-negative subjects (0.45%). Four phyla (Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria) accounted for >97% of all reads in both groups. Within Proteobacteria, gamma- and beta-proteobacteria were the most abundant for H. pylori-negative patients, whilst epsilon-proteobacteria was for H. pylori positive. H. pylori-positive patients were associated with low Body Mass Index (BMI). In the group of underweight patients (BMI<18.5) there were 46.1% of H. pylori-positive patients compared with 24% in the non-underweight group (p=0.049). Patients with active superficial gastritis in H. pylori-positive patients had the lowest alpha diversity (p=0.035). CONCLUSIONS: We characterized the gastric microbiota for the first time in children with and without H. pylori and observed that when H. pylori is present, it tends to dominate the microbial community. In the H. pylori-negative patients, there was more relative abundance of Gamaproteobacteria, Betaproteobacteria, Bacteroidia and Clostridia classes and a higher bacterial richness and diversity.
PMID: 27820723
ISSN: 1532-0987
CID: 2304322

Rapid identification of Helicobacter pylori and assessment of clarithromycin susceptibility from clinical specimens using FISH

Demiray-Gurbuz, Ebru; Yilmaz, Ozlem; Olivares, Asalia Z; Gonen, Can; Sarioglu, Sulen; Soyturk, Mujde; Tumer, Sait; Altungoz, Oguz; Simsek, Ilkay; Perez Perez, Guillermo I
Helicobacter pylori remains one of the most common bacterial infections worldwide. Clarithromycin resistance is the most important cause of H. pylori eradication failures. Effective antibiotic therapies in H. pylori infection must be rapidly adapted to local resistance patterns. We investigated the prevalence of clarithromycin resistance due to mutations in positions 2142 and 2143 of 23SrRNA gene of H. pylori by fluorescence in situ hybridisation (FISH), and compared with culture and antimicrobial susceptibility testing in 234 adult patients with dyspepsia who were enrolled. Antrum and corpus biopsy specimens were obtained for rapid urease test, histopathology and culture. Epsilometer test was used to assess clarithromycin susceptibility. H. pylori presence and clarithromycin susceptibility were determined by FISH in paraffin-embedded biopsy specimens. We found that 164 (70.1%) patients were positive for H. pylori based on clinical criteria, 114 (69.5% CI 62.5-76.6%) were culture positive, and 137 (83.5% CI 77.8-89.2%) were FISH positive. Thus the sensitivity of FISH was significantly superior to that of culture. However specificity was not significantly different (91.4 versus 100.0%, respectively). The resistance rate to clarithromycin for both antrum and corpus was detected in H. pylori-positive patients; 20.2% by FISH and 28.0% by E-test.The concordance between E-test and FISH was only 89.5% due to the presence of point mutations different from A2143G, A2142G or A2142C. We conclude that FISH is significantly more sensitive than culture and the E-test for the detection of H. pylori and for rapid determinination of claritromycin susceptibility. The superior hybridisation efficiency of FISH is becoming an emerging molecular tool as a reliable, rapid and sensitive method for the detection and visualisation of H. pylori, especially when the management of H. pylori eradication therapy is necessary. This is particularly important for the treatment of patients with H. pylori eradication failure.
PMID: 28138399
ISSN: 2056-4538
CID: 2573032

Impact of the Microbiota and Gastric Disease Development by Helicobacter pylori

Alarcon, Teresa; Llorca, Laura; Perez-Perez, Guillermo
Microorganisms in humans form complex communities with important functions and differences in each part of the body. The stomach was considered to be a sterile organ until the discovery of Helicobacter pylori, but nowadays, it is possible to demonstrate that other microorganisms beyond H. pylori can colonize the gastric mucosa and that the diverse microbiota ecosystem of the stomach is different from the mouth and the esophagus, and also from the small intestine and large intestine. H. pylori seems to be the most important member of the gastric microbiota with the highest relative abundance when present, but when it is absent, the stomach has a diverse microbiota. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria are the most abundant phyla in both H. pylori-positive and H. pylori-negative patients. The gastric commensal flora may play some role in the H. pylori-associated carcinogenicity, and differences in the gastric microbiota composition of patients with gastric cancer, intestinal metaplasia, and chronic gastritis are described. The gastric microbiota changed gradually from non-atrophic gastritis to intestinal metaplasia, and to gastric cancer (type intestinal).
PMID: 28124157
ISSN: 0070-217x
CID: 2418582