Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research

Mass spectrometry (MS) techniques, because of their sensitivity and selectivity, have become methods of choice to characterize the human metabolome and MS-based metabolomics is increasingly used to characterize the complex metabolic effects of nutrients or foods. However progress is still hampered by many unsolved problems and most notably the lack of well established and standardized methods or procedures, and the difficulties still met in the identification of the metabolites influenced by a given nutritional intervention. The purpose of this paper is to review the main obstacles limiting progress and to make recommendations to overcome them. Propositions are made to improve the mode of collection and preparation of biological samples, the coverage and quality of mass spectrometry analyses, the extraction and exploitation of the raw data, the identification of the metabolites and the biological interpretation of the results

The Role of Host Genetics in Susceptibility to Influenza: A Systematic Review

Background: The World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted to summarize the current state of evidence on the role of host genetics in susceptibility to influenza (PROSPERO registration number: CRD42011001380). Methods and Findings: PubMed, Web of Science, the Cochrane Library, and OpenSIGLE were searched using a pre-defined strategy for all entries up to the date of the search. Two reviewers independently screened the title and abstract of 1,371 unique articles, and 72 full text publications were selected for inclusion. Mouse models clearly demonstrate that host genetics plays a critical role in susceptibility to a range of human and avian influenza viruses. The Mx genes encoding interferon inducible proteins are the best studied but their relevance to susceptibility in humans is unknown. Although the MxA gene should be considered a candidate gene for further study in humans, over 100 other candidate genes have been proposed. There are however no data associating any of these candidate genes to susceptibility in humans, with the only published study in humans being under-powered. One genealogy study presents moderate evidence of a heritable component to the risk of influenza-associated death, and while the marked familial aggregation of H5N1 cases is suggestive of host genetic factors, this remains unproven. Conclusion: The fundamental question ‘‘Is susceptibility to severe influenza in humans heritable?’ ’ remains unanswered. No

Counseling in isolated mild fetal ventriculomegaly

In this Review we aim to provide up-to-date and evidence-based answers to the common questions regarding the diagnosis of isolated mild fetal ventriculomegaly (VM). A literature search was performed to identify all reports of antenatal VM in the English language literature. In addition, reference lists of articles identified using the search were scrutinized to further identify relevant articles. Fetal mild VM is commonly defined as a ventricular atrial width of 10.0-15.0 mm, and it is considered isolated if there are no associated ultrasound abnormalities. There is no good evidence to suggest that the width of the ventricular atria contributes to the risk of neurodevelopmental outcome in fetuses with mild VM. The most important prognostic factors are the association with other abnormalities that escape early detection and the progression of ventricular dilatation, which are reported to occur in about 13% and 16% of cases, respectively. Most infants with a prenatal diagnosis of isolated mild VM have normal neurological development at least in infancy. The rate of abnormal or delayed neurodevelopment in infancy is about 11%, and it is unclear whether this is higher than in the general population. Furthermore, the number of infants that develop a real handicap is unknown. There are limitations of existing studies of mild VM. Although they address many of the relevant questions regarding the prognosis and management of fetal isolated mild VM, there is a lack of good-quality postnatal follow-up studies. The resulting uncertainties make antenatal counseling for this abnormality difficult

Stability in metabolic phenotypes and inferred metagenome profiles before the onset of colitis-induced inflammation.

Inflammatory bowel disease (IBD) is associated with altered microbiota composition and metabolism, but it is unclear whether these changes precede inflammation or are the result of it since current studies have mainly focused on changes after the onset of disease. We previously showed differences in mucus gut microbiota composition preceded colitis-induced inflammation and stool microbial differences only became apparent at colitis onset. In the present study, we aimed to investigate whether microbial dysbiosis was associated with differences in both predicted microbial gene content and endogenous metabolite profiles. We examined the functional potential of mucus and stool microbial communities in the mdr1a (-/-) mouse model of colitis and littermate controls using PICRUSt on 16S rRNA sequencing data. Our findings indicate that despite changes in microbial composition, microbial functional pathways were stable before and during the development of mucosal inflammation. LC-MS-based metabolic phenotyping (metabotyping) in urine samples confirmed that metabolite profiles in mdr1a (-/-) mice were remarkably unaffected by development of intestinal inflammation and there were no differences in previously published metabolic markers of IBD. Metabolic profiles did, however, discriminate the colitis-prone mdr1a (-/-) genotype from controls. Our results indicate resilience of the metabolic network irrespective of inflammation. Importantly as metabolites differentiated genotype, genotype-differentiating metabolites could potentially predict IBD risk