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Differences in Prevalence of Histologic Gastric Cancer Subtypes Between Mestizo and Mayan Populations in Guatemala
Villagrán Blanco, Carmen I; Hernández, Elisa; Wellmann, Irmgardt Alicia; Une, Clas; Mendez-Chacón, Erika; Perez-Perez, Guillermo; Daniels, Michael; Fernandez-Botran, Rafael
PURPOSE/OBJECTIVE:CagA seropositivity. MATERIALS AND METHODS/METHODS:Participants included 65 patients with GC and 135 age-/sex-matched controls. Data on ethnicity, H. pylori and CagA seropositivity status, as well as tumor subtype (diffuse or intestinal) were collected. Logistic regression models were fitted to examine the relationship between predictor variables (age, sex, ethnicity, H. pylori, and CagA) and the binary response variable (tumor type). Model selection was based on the Akaike information criterion. RESULTS:The prevalence of diffuse GC was found to be significantly higher in the Mayan compared with the Mestizo population in Guatemala. Although seropositivity for CagA was significantly higher in patients with GC, there were no significant differences between the two GC subtypes. CONCLUSION/CONCLUSIONS:This study suggests that there are differences in the prevalence of intestinal and diffuse GC histologic subtypes between the two main ethnic groups in Guatemala. Further studies are warranted, given the potential higher prevalence of the more severe GC subtype in the most vulnerable population.
PMID: 39208384
ISSN: 2687-8941
CID: 5702012
Oral and gastric microbiome in relation to gastric intestinal metaplasia
Wu, Fen; Yang, Liying; Hao, Yuhan; Zhou, Boyan; Hu, Jiyuan; Yang, Yaohua; Bedi, Sukhleen; Sanichar, Navin Ganesh; Cheng, Charley; Perez-Perez, Guillermo; Tseng, Wenche; Tseng, Wenzhi; Tseng, Mengkao; Francois, Fritz; Khan, Abraham R; Li, Yihong; Blaser, Martin J; Shu, Xiao-Ou; Long, Jirong; Li, Huilin; Pei, Zhiheng; Chen, Yu
Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.
PMID: 34664721
ISSN: 1097-0215
CID: 5043202
Campylobacter
Chapter by: Kienesberger, Sabine; Perez-Perez, Guillermo Ignacio
in: Foodborne Infections and Intoxications by
[S.l.] : Elsevier, 2021
pp. 165-186
ISBN: 9780128195192
CID: 5199132
A 500-year tale of co-evolution, adaptation, and virulence: Helicobacter pylori in the Americas
Muñoz-Ramirez, Zilia Y; Pascoe, Ben; Mendez-Tenorio, Alfonso; Mourkas, Evangelos; Sandoval-Motta, Santiago; Perez-Perez, Guillermo; Morgan, Douglas R; Dominguez, Ricardo Leonel; Ortiz-Princz, Diana; Cavazza, Maria Eugenia; Rocha, Gifone; Queiroz, Dulcienne M M; Catalano, Mariana; Palma, Gerardo Zerbeto de la; Goldman, Cinthia G; Venegas, Alejandro; Alarcon, Teresa; Oleastro, Monica; Vale, Filipa F; Goodman, Karen J; Torres, Roberto C; Berthenet, Elvire; Hitchings, Matthew D; Blaser, Martin J; Sheppard, Samuel K; Thorell, Kaisa; Torres, Javier
Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region.
PMID: 32879462
ISSN: 1751-7370
CID: 4596122
Editorial: Current Perspectives of Antimicrobial Resistance in Campylobacteraceae and Helicobacteraceae [Editorial]
Levican, Arturo; Perez-Perez, Guillermo; Oleastro, Monica; Fernández, Heriberto; Ferreira, Susana
PMCID:8821808
PMID: 35145927
ISSN: 2235-2988
CID: 5156912
MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer
Ding, Lin; Li, Qian; Chakrabarti, Jayati; Munoz, Andres; Faure-Kumar, Emmanuelle; Ocadiz-Ruiz, Ramon; Razumilava, Nataliya; Zhang, Guiying; Hayes, Michael H; Sontz, Ricky A; Mendoza, Zoe Elena; Mahurkar, Swapna; Greenson, Joel K; Perez-Perez, Guillermo; Hanh, Nguyen Thi Hong; Zavros, Yana; Samuelson, Linda C; Iliopoulos, Dimitrios; Merchant, Juanita L
The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM).
PMID: 31980446
ISSN: 1468-3288
CID: 4274112
A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis
Ozkul, Ceren; Ruiz, Victoria E; Battaglia, Thomas; Xu, Joseph; Roubaud-Baudron, Claire; Cadwell, Ken; Perez-Perez, Guillermo I; Blaser, Martin J
BACKGROUND:There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD). METHODS:By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS. RESULTS:A single PAT course early-in-life exacerbated later DSS-induced colitis by both perturbing the microbial community and altering mucosal immune cell composition. By conventionalizing germ-free mice with either antibiotic-perturbed or control microbiota obtained 40 days after the challenge ended, we showed the transferrable and direct effect of the still-perturbed microbiota on colitis severity in the DSS model. CONCLUSIONS:The findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.
PMCID:7382806
PMID: 32711559
ISSN: 1756-994x
CID: 4546182
Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection
Roubaud-Baudron, Claire; Ruiz, Victoria E; Swan, Alexander M; Vallance, Bruce A; Ozkul, Ceren; Pei, Zhiheng; Li, Jackie; Battaglia, Thomas W; Perez-Perez, Guillermo I; Blaser, Martin J
Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (β-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens.IMPORTANCE The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility.
PMID: 31874917
ISSN: 2150-7511
CID: 4244222
Gut microbiome of treatment-naïve MS patients of different ethnicities early in disease course
Ventura, R E; Iizumi, T; Battaglia, T; Liu, Menghan; Perez-Perez, G I; Herbert, J; Blaser, M J
Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium, compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.
PMCID:6841666
PMID: 31705027
ISSN: 2045-2322
CID: 4186622
Development and Assessment of a Helicobacter pylori Medication Adherence and Stomach Cancer Prevention Curriculum for a Chinese American Immigrant Population
Kwon, Simona C; Kranick, Julie A; Bougrab, Nassira; Pan, Janet; Williams, Renee; Perez-Perez, Guillermo Ignacio; Trinh-Shevrin, Chau
Chinese American immigrants are at increased risk for Helicobacter pylori infection and stomach cancer. Despite their increased risk, very few prevention strategies exist which target this vulnerable population. The purpose of this article is to present the stakeholder engaged development, review, assessment, refinement, and finalization of a H. pylori treatment adherence and stomach cancer prevention curriculum specifically designed to engage vulnerable, limited English proficient Chinese Americans in New York City.
PMCID:6098981
PMID: 29460136
ISSN: 1543-0154
CID: 2963612