Towards a comprehensive characterisation of the human internal chemical exposome: Challenges and perspectives

The holistic characterisation of the human internal chemical exposome using high-resolution mass spectrometry (HRMS) would be a step forward to investigate the environmental AE tiology of chronic diseases with an unprecedented precision. HRMS-based methods are currently operational to reproducibly profile thousands of endogenous metabolites as well as externally-derived chemicals and their biotransformation products in a large number of biological samples from human cohorts. These approaches provide a solid ground for the discovery of unrecognised biomarkers of exposure and metabolic effects associated with many chronic diseases. Nevertheless, some limitations remain and have to be overcome so that chemical exposomics can provide unbiased detection of chemical exposures affecting disease susceptibility in epidemiological studies. Some of these limitations include (i) the lack of versatility of analytical techniques to capture the wide diversity of chemicals; (ii) the lack of analytical sensitivity that prevents the detection of exogenous (and endogenous) chemicals occurring at (ultra) trace levels from restricted sample amounts, and (iii) the lack of automation of the annotation/identification process. In this article, we discuss a number of technological and methodological limitations hindering applications of HRMS-based methods and propose initial steps to push towards a more comprehensive characterisation of the internal chemical exposome. We also discuss other challenges including the need for harmonisation and the difficulty inherent in assessing the dynamic nature of the internal chemical exposome, as well as the need for establishing a strong international collaboration, high level networking, and sustainable research infrastructure. A great amount of research, technological development and innovative bio-informatics tools are still needed to profile and characterise the "invisible" (not profiled), "hidden" (not detected) and "dark" (not annotated) components of the internal chemical exposome and concerted efforts across numerous research fields are paramount

Standardisation of a new model of H9N2/Escherichia coli challenge in broilers in the Lebanon

Primary infection by low pathogenic avian influenza (LPAI) predisposes for secondary infection by Escherichia coli in poultry, leading to significant economic losses. Future research in control of this ailment requires the establishment of a successful controlled challenge by avian influenza virus (AIV)/E. coli. Six groups of broilers (6 birds/group) were included for the standardisation of the controlled challenge by AIV/E. coli. Birds in groups 1, 2, 3, 4 and 5 received an intra-tracheal challenge of 0.5 ml of two haemagglutinating units of H9N2 virus at 20 days of age. At the age of 23 days, birds in group 1 received an intra-thoracic (right air sac)-E. coli challenge equivalent to 1.6 × 109 colony-forming units (cfu)/0.5 ml/bird, while birds in groups 2, 3, 4 and 5 received E. coli by the same route and in the following respective decreasing order of viable cells: 1.6 × 106, 1.6 × 105, 1.6 × 104 and 1.6 × 103 cfu. Birds in control group 6 were deprived of H9N2 and E. coli challenge. Results showed significant early mortality in group 1 that was challenged with the highest number of E. coli, in comparison to groups 2-6 (p0.05). The frequencies of four signs at 2 days and at 5 days post E. coli challenge (conjunctivitis, diarrhoea, ocular exudates and rales) in the surviving birds of groups 2-5 were most often higher than those observed in control group 6 (p<0.05). These four signs and five gross lesions (abdominal airsacculitis, left thoracic airsacculitis, pericarditis, right thoracic airsacculitis and tracheitis) had a decreasing pattern of frequency related to a decrease in the E. coli count used in the challenge