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1. Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals

Author

Yi-Chun Yen, Arnaud Polizzi, Yuna Blum, Hervé Guillou, Marie Tremblay-Franco, Gilles Mithieux, Alexandra Montagner, Agata Korecka, Rémy Burcelin, Amandine Gautier-Stein, Sven Pettersson, Walter Wahli, Maha Al-Asmakh, Cécile Canlet, Hyunsoo Shawn Je, Sandrine Lagarrigue, Velmurugesan Arulampalam, Yannick Lippi, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Microbiology, Tumor and Cell Biology (MTC), Stockholm University, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Medicine, Division of Cardiology, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, U855, Nutrition et cerveau, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School [Singapore], Karolinska Institute, Department of Health Sciences, College of Arts and Sciences, Qatar University, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Université Européenne de Bretagne (UEB), Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], SCELSE microbiome centre, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Region Midi-Pyrenees, Swiss National Science Foundation, Bonizzi-Theler-Stiftung, 7th EU program TORNADO, Etat de Vaud, Nanyang Technological University Start-Up Grants, Merieux Foundation, Swedish Medical Research Council, SCELCE Microbiome Centre at NTU, Singapore, CIFAR Institute, Canada, ProdInra, Archive Ouverte, Lee Kong Chian School of Medicine (LKCMedicine), Singapore Centre for Environmental Life Sciences Engineering, University of California-University of California, Duke-NUS Graduate Medical School, AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Center for Integrative Genomics, Université de Lausanne, Guillou, Hervé, Pettersson, Sven, Wahli, Walter, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Nanyang Technological University (NTU)

Subjects
0301 basic medicine, Male, Gut microbiota, Intestinal, microbiota, Liver-disease, Ppar-alpha, Metabolism, Homeostasis, Modulation, Components, Expression, Health, [SDV]Life Sciences [q-bio], Circadian clock, Receptors, Cytoplasmic and Nuclear, Mice, 0302 clinical medicine, 2. Zero hunger, Regulation of gene expression, Multidisciplinary, Gastrointestinal Microbiome, 3. Good health, CLOCK, [SDV] Life Sciences [q-bio], Liver, Organ Specificity, Inactivation, Metabolic, Medicine, Female, Signal transduction, Erratum, Signal Transduction, medicine.medical_specialty, Cell biology, Animals, Biomarkers, Circadian Clocks/genetics, Gastrointestinal Tract/metabolism, Gastrointestinal Tract/microbiology, Gene Expression Profiling, Gene Expression Regulation, Gluconeogenesis/genetics, Inactivation, Metabolic/genetics, Liver/metabolism, Microbiota, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/metabolism, Transcriptome, Biology, Microbiology, Article, 03 medical and health sciences, Internal medicine, Circadian Clocks, medicine, Genetics, Microbiome, Gluconeogenesis, Gene expression profiling, Gastrointestinal Tract, 030104 developmental biology, Endocrinology, Liver function, 030217 neurology & neurosurgery
Abstract

The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function. Région Midi-Pyrénées to HG (Mathusalem) and to WW (Chaire d’Excellence Pierre de Fermat). This work was also supported by grants from the Swiss National Science Foundation (individual grants to WW), the Bonizzi-Theler-Stiftung (WW), the 7th EU program TORNADO (WW, SP), and by the Etat de Vaud and the Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grants. SP is also supported by grants from the Merieux Foundation, Swedish Medical Research Council, the SCELCE Microbiome Centre at NTU, Singapore, and CIFAR Institute, Canada.

Published
2016

2. Combination of exhaled breath condensate samples with lipoarabinomannan point of care assay for pulmonary tuberculosis (TB) diagnosis: protocol for a diagnostic accuracy study.

Author

Pouzol S, Khaja Mafij Uddin M, Islam A, Jabin MS, Nigou J, Banu S, and Hoffmann J

Subjects
Humans, Prospective Studies, Biomarkers analysis, Bangladesh, Adult, Point-of-Care Testing, Sensitivity and Specificity, Point-of-Care Systems, Male, Female, Adolescent, Mycobacterium tuberculosis isolation & purification, Sputum microbiology, Lipopolysaccharides analysis, Tuberculosis, Pulmonary diagnosis, Breath Tests methods
Abstract

Introduction: The WHO estimates a gap of about 30% between the incident (10.6 million) and notified (7.5 million) cases of tuberculosis (TB). Combined with the growing recognition in prevalence surveys of the high proportion of cases identified who are asymptomatic or paucisymptomatic, these data underscore how current symptom screening approaches and use of diagnostic tests with suboptimal performance on sputum miss large numbers of cases. Thus, the development of sputum-free biomarker-based tests for diagnosis is becoming necessary, which the WHO has already identified as a priority for new TB diagnostics.The objective of this study is to evaluate a combination of exhaled breath condensate (EBC) samples and mycobacterial lipoarabinomannan (LAM) as point-of-care (POC) assays to identify TB patients., Methods and Analysis: This prospective diagnostic accuracy study is conducted at the TB Screening and Treatment Centre of International Center for Diarrhoeal Disease Research, Bangladesh, on a cohort of adults and adolescents >11 years of age. A total of 614 individuals with presumptive pulmonary TB based on TB signs, symptoms and radiography are being recruited from 28 August 2023. Spot sputum is collected for standard reference testing (L-J culture, GeneXpert MTB/Rif, acid-fast Bacilli microscopy) to fine-tune categorisation of TB disease status for each participant, defined as (1) definite TB (at least one positive standard reference test); (2) probable TB (not microbiologically confirmed but under TB treatment); (3) possible TB (no TB treatment but signs, symptoms and radiography suggestive of TB); (4) other respiratory disease (microbiologically not confirmed and no radiography presenting abnormalities compatible with TB); and (5) unknown (no microbiological evidence with normal/no TB abnormalities with radiography). Urine and EBC specimens will be subjected to LAM POC testing and biobanked for further investigation. Statistical analyses will include an assessment of diagnostic accuracy by constructing receiver operating curves and calculating sensitivity and specificity, as well as post-test probabilities., Ethics and Dissemination: The study protocol was approved by the Research Review Committee as well as the Ethical Review Committee of icddr,b and recorded under a protocol reference number, PR-2301. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings, and shared with national and international policymaking bodies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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3. Rabies in the Middle East, Eastern Europe, Central Asia and North Africa: Building evidence and delivering a regional approach to rabies elimination.

Author

Taylor E, Del Rio Vilas V, Scott T, Coetzer A, Prada JM, Alireza G, Alqadi NA, Berry A, Bazzal B, Barkia A, Davlyatov F, Farahtaj F, Harabech K, Imnadze P, Mahiout F, Majeed MI, Nedosekov V, Nel L, Rich H, Soufi A, Vodopija R, Vranjes N, Picot VS, and Horton D

Subjects
Africa, Northern epidemiology, Animals, Dogs, Europe, Eastern, Middle East epidemiology, Dog Diseases epidemiology, Dog Diseases prevention & control, Rabies epidemiology, Rabies prevention & control, Rabies veterinary
Abstract

The Middle East, Eastern Europe, Central Asia and North Africa Rabies Control Network (MERACON), is built upon the achievements of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB). MERACON aims to foster collaboration among Member States (MS) and develop shared regional objectives, building momentum towards dog-mediated rabies control and elimination. Here we assess the epidemiology of rabies and preparedness in twelve participating MS, using case and rabies capacity data for 2017, and compare our findings with previous published reports and a predictive burden model. Across MS, the number of reported cases of dog rabies per 100,000 dog population and the number of reported human deaths per 100,000 population as a result of dog-mediated rabies appeared weakly associated. Compared to 2014 there has been a decrease in the number of reported human cases in five of the twelve MS, three MS reported an increase, two MS continued to report zero cases, and the remaining two MS were not listed in the 2014 study and therefore no comparison could be drawn. Vaccination coverage in dogs has increased since 2014 in half (4/8) of the MS where data are available. Most importantly, it is evident that there is a need for improved data collection, sharing and reporting at both the national and international levels. With the formation of the MERACON network, MS will be able to align with international best practices, while also fostering international support with other MS and international organisations., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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