A comparison of Helicobacter pylori and non-Helicobacter pylori Helicobacter spp. Binding to Canine Gastric Mucosa with Defined Gastric Glycophenotype

Background: The gastric mucosa of dogs is often colonized by non-Helicobacter pylori helicobacters (NHPH), while H. pylori is the predominant gastric Helicobacter species in humans. The colonization of the human gastric mucosa by H. pylori is highly dependent on the recognition of host glycan receptors. Our goal was to define the canine gastric mucosa glycophenotype and to evaluate the capacity of different gastric Helicobacter species to adhere to the canine gastric mucosa. Materials and Methods: The glycosylation profile in body and antral compartments of the canine gastric mucosa, with focus on the expression of histo-blood group antigens was evaluated. The in vitro binding capacity of FITC-labeled H. pylori and NHPH to the canine gastric mucosa was assessed in cases representative of the canine glycosylation pattern. Results: The canine gastric mucosa lacks expression of type 1 Lewis antigens and presents a broad expression of type 2 structures and A antigen, both in the surface and glandular epithelium. Regarding the canine antral mucosa, H. heilmannii s.s. presented the highest adhesion score whereas in the body region the SabA-positive H. pylori strain was the strain that adhered more. Conclusions: The canine gastric mucosa showed a glycosylation profile different from the human gastric mucosa suggesting that alternative glycan receptors may be involved in Helicobacter spp. binding. Helicobacter pylori and NHPH strains differ in their ability to adhere to canine gastric mucosa. Among the NHPH, H. heilmannii s.s. presented the highest adhesion capacity in agreement with its reported colonization of the canine stomach.We kindly thank Prof. Thomas Boren from the Department of Medical Biochemistry and Biophysics, Umea University, Sweden for providing the 17875/Leb and 17875babA1A2H. pylori strains. The authors thank Dr. Fernando Rodrigues, Dr. Ana Laura Saraiva, and Cristina Bacelar who kindly provided technical support. I. Amorim (SFRH/BD/76237/2011) and A. Magalhães (SFRH/BPD/75871/2011) acknowledge FCT for financial support. This study was partially funded by the Portuguese Foundation for Science and Technology (PTDC/CTM-BPC/121149/2010; PTDC/CVT/117610/2010; PTDC/BBB-EBI/0786/2012). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT

Obesity-induced hypoadiponectinaemia: the opposite influences of central and peripheral fat compartments

$\textbf{Background and Aims:}$ The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration. $\textbf{Methods:}$ To investigate the independent association of abdominal and gluteofemoral fat with adiponectin concentration, we used multivariable regression and data from 30-year-old adults from the 1982 Pelotas Birth Cohort ($n$ = 2,743). To assess the causal role of abdominal and gluteofemoral fat accumulation on adiponectin concentration, we used Mendelian randomization and data from two consortia of genome-wide association studies—the GIANT ($n$ > 210 000) and ADIPOGen consortia ($n$ = 29 347). $\textbf{Results:}$ In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: $\beta$ = -0.24 standard unit of log adiponectin per standard unit increase in abdominal fat; 95% confidence interval (CI) = -0.31, -0.18; $P$ = 8*10$^{-13}$; women: $\beta$ = -0.31; 95% CI = -0.36, -0.25; $P$ = 7*10$^{-27}$), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: $\beta$ = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; $P$ = 0.008; women: $\beta$ = 0.24; 95% CI = 0.17, 0.31; $P$ = 7*10$^{-11}$). In the Mendelian randomization analysis, genetically-predicted waist circumference was inversely related to blood adiponectin concentration ($\beta$ = -0.27 standard unit of log adiponectin per standard unit increase in waist circumference; 95% CI = -0.36, -0.19; $P$ = 2*10$^{-11}$), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration ($\beta$ = 0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI = 0.11, 0.24; $P$ = 1*10$^{-7}$). $\textbf{Conclusions:}$ These results support the hypotheses that there is a complex interplay between body fat distribution and circulating adiponectin concentration, and that whereas obesity-induced hypoadiponectinaemia seems to be primarily attributed to abdominal fat accumulation, gluteofemoral fat accumulation is likely to exert a protective effect.The study ‘Pelotas Birth Cohort, 1982’ is conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2004 to 2013, the Wellcome Trust supported the 1982 birth cohort study. The International Development Research Center, World Health Organization, Overseas Development Administration, European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq) and the Brazilian Ministry of Health supported previous phases of the study. M.C.B. receives financial support from the Brazilian National Research Council (CNPq) [144749/2014-9, 201498/2014-6 (Science Without Borders Program), and 163291/2015-2] and Coordenac¸~ao de Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES). K.K.O. is supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2]

Obesity-induced hypoadiponectinaemia: the opposite influences of central and peripheral fat compartments

$\textbf{Background and Aims:}$ The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration. $\textbf{Methods:}$ To investigate the independent association of abdominal and gluteofemoral fat with adiponectin concentration, we used multivariable regression and data from 30-year-old adults from the 1982 Pelotas Birth Cohort ($n$ = 2,743). To assess the causal role of abdominal and gluteofemoral fat accumulation on adiponectin concentration, we used Mendelian randomization and data from two consortia of genome-wide association studies—the GIANT ($n$ > 210 000) and ADIPOGen consortia ($n$ = 29 347). $\textbf{Results:}$ In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: $\beta$ = -0.24 standard unit of log adiponectin per standard unit increase in abdominal fat; 95% confidence interval (CI) = -0.31, -0.18; $P$ = 8*10$^{-13}$; women: $\beta$ = -0.31; 95% CI = -0.36, -0.25; $P$ = 7*10$^{-27}$), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: $\beta$ = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; $P$ = 0.008; women: $\beta$ = 0.24; 95% CI = 0.17, 0.31; $P$ = 7*10$^{-11}$). In the Mendelian randomization analysis, genetically-predicted waist circumference was inversely related to blood adiponectin concentration ($\beta$ = -0.27 standard unit of log adiponectin per standard unit increase in waist circumference; 95% CI = -0.36, -0.19; $P$ = 2*10$^{-11}$), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration ($\beta$ = 0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI = 0.11, 0.24; $P$ = 1*10$^{-7}$). $\textbf{Conclusions:}$ These results support the hypotheses that there is a complex interplay between body fat distribution and circulating adiponectin concentration, and that whereas obesity-induced hypoadiponectinaemia seems to be primarily attributed to abdominal fat accumulation, gluteofemoral fat accumulation is likely to exert a protective effect.The study ‘Pelotas Birth Cohort, 1982’ is conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2004 to 2013, the Wellcome Trust supported the 1982 birth cohort study. The International Development Research Center, World Health Organization, Overseas Development Administration, European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq) and the Brazilian Ministry of Health supported previous phases of the study. M.C.B. receives financial support from the Brazilian National Research Council (CNPq) [144749/2014-9, 201498/2014-6 (Science Without Borders Program), and 163291/2015-2] and Coordenac¸~ao de Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES). K.K.O. is supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2]

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-a levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology (PEst C/SAU/LA0003/2013). This work is funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (NORTE 07 0124 FEDER 000024; FCOMP-01-0124-FEDER028188; FCOMP-01-0124-FEDER 041276) and National Funds through the FCT-Foundation for Science and Technology (EXPL/CTM-BIO/0762/2013, PTDC/BBB-EBI/0786/2012) and acknowledges support by the EuropeanUnion (Seventh Framework Programme GastricGlycoExplorer project, grant number 316929). Grants were received from FCT, POPH (Programa Operacional Potencial Humano) and FSE (Fundo Social Europeu) (SFRH/BPD/75871/2011 to AM;SFRH/SINTD/60034/2009 to RMP; SFRH/BPD/84084/2012 to RMF; SFRH/BPD/89764/2012 to PO). AM acknowledges EMBO for a Short-Term Fellowship (EMBO ASTF 330-212). Transcript analysis was funded by NIH (grant P41GM103490) to KWM

Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

BACKGROUND:In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer. This finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. We have investigated CFS sufferers in the UK to determine if they are carriers of XMRV. METHODOLOGY:Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS. DNA extracted from blood samples of 186 CFS patients were screened for XMRV provirus and for the closely related murine leukaemia virus by nested PCR using specific oligonucleotide primers. To control for the integrity of the DNA, the cellular beta-globin gene was amplified. Negative controls (water) and a positive control (XMRV infectious molecular clone DNA) were included. While the beta-globin gene was amplified in all 186 samples, neither XMRV nor MLV sequences were detected. CONCLUSION:XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not