Blood lactose after dairy product intake in healthy men.

The absence of a dedicated transport for disaccharides in the intestine implicates that the metabolic use of dietary lactose relies on its prior hydrolysis at the intestinal brush border. Consequently, lactose in blood or urine has mostly been associated with specific cases in which the gastrointestinal barrier is damaged. On the other hand, lactose appears in the blood of lactating women and has been detected in the blood and urine of healthy men, indicating that the presence of lactose in the circulation of healthy subjects is not incompatible with normal physiology. In this cross-over study we have characterised the postprandial kinetics of lactose, and its major constituent, galactose, in the serum of fourteen healthy men who consumed a unique dose of 800 g milk or yogurt. Genetic testing for lactase persistence and microbiota profiling of the subjects were also performed. Data revealed that lactose does appear in serum after dairy intake, although with delayed kinetics compared with galactose. Median serum concentrations of approximately 0·02 mmol/l lactose and approximately 0·2 mmol/l galactose were observed after the ingestion of milk and yogurt respectively. The serum concentrations of lactose were inversely correlated with the concentrations of galactose, and the variability observed between the subjects' responses could not be explained by the presence of the lactase persistence allele. Finally, lactose levels have been associated with the abundance of the Veillonella genus in faecal microbiota. The measurement of systemic lactose following dietary intake could provide information about lactose metabolism and nutrient transport processes under normal or pathological conditions

Biomarker of food intake for assessing the consumption of dairy and egg products

Foods of animal origin constitute one of the predominant food groups consumed in Western diets. They play an essential role in human nutrition as they represent an excellent source of high quality proteins, vitamins, minerals and fats. Foods of animal origin are highly diverse (e.g. meat, fish, dairy products and eggs) and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of specific foods of animal origin and health outcomes, it is important to identify reliable biomarkers of food intake (BFIs). BFIs provide a more accurate measure of intake and are independent of the memory and sincerity of the subjects as well as of their knowledge about the consumed foods. To date, only a very limited number of compounds have been proposed as biomarkers of the intake of foods of animal origin and further studies are necessary to validate them and to discover new candidate BFIs. We have, therefore, conducted a systematic search of the scientific literature to evaluate the current status of potential BFIs for each category of foods of animal origin commonly consumed in Europe. This review reports on candidate biomarkers for dairy products and eggs intake, while biomarkers for fish and meat intake will be published separately. Remarkably, validated BFIs for dairy products and eggs are not available. A series of challenges hinders their identification and validation, in particular the heterogeneous composition of each food within a product category and the lack of specificity of the markers identified so far. Untargeted metabolomic strategies may allow the identification of novel food biomarkers, that, when taken separately or in combination, could be used to assess the intake of dairy products and eggs

Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies

The life sciences are currently being transformed by an unprecedented wave of developments in molecular analysis, which include important advances in instrumental analysis as well as biocomputing. In light of the central role played by metabolism in nutrition, metabolomics is rapidly being established as a key analytical tool in human nutritional studies. Consequently, an increasing number of nutritionists integrate metabolomics into their study designs. Within this dynamic landscape, the potential of nutritional metabolomics (nutrimetabolomics) to be translated into a science, which can impact on health policies, still needs to be realized. A key element to reach this goal is the ability of the research community to join, to collectively make the best use of the potential offered by nutritional metabolomics. This article, therefore, provides a methodological description of nutritional metabolomics that reflects on the state‐of‐the‐art techniques used in the laboratories of the Food Biomarker Alliance (funded by the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL)) as well as points of reflections to harmonize this field. It is not intended to be exhaustive but rather to present a pragmatic guidance on metabolomic methodologies, providing readers with useful "tips and tricks" along the analytical workflow

Modulation of the peripheral blood transcriptome by the ingestion of probiotic yoghurt and acidified milk in healthy, young men

The metabolic health benefits of fermented milks have already been investigated using clinical biomarkers but the development of transcriptomic analytics in blood offers an alternative approach that may help to sensitively characterise such effects. We aimed to assess the effects of probiotic yoghurt intake, compared to non-fermented, acidified milk intake, on clinical biomarkers and gene expression in peripheral blood. To this end, a randomised, crossover study was conducted in fourteen healthy, young men to test the two dairy products. For a subset of seven subjects, RNA sequencing was used to measure gene expression in blood collected during postprandial tests and after two weeks daily intake. We found that the postprandial response in insulin was different for probiotic yoghurt as compared to that of acidified milk. Moreover changes in several clinical biomarkers were associated with changes in the expression of genes representing six metabolic genesets. Assessment of the postprandial effects of each dairy product on gene expression by geneset enrichment analysis revealed significant, similar modulation of inflammatory and glycolytic genes after both probiotic yoghurt and acidified milk intake, although distinct kinetic characteristics of the modulation differentiated the dairy products. The aryl hydrocarbon receptor was a major contributor to the down-regulation of the inflammatory genesets and was also positively associated with changes in circulating insulin at 2h after yoghurt intake (p = 0.05). Daily intake of the dairy products showed little effect on the fasting blood transcriptome. Probiotic yoghurt and acidified milk appear to affect similar gene pathways during the postprandial phase but differences in the timing and the extent of this modulation may lead to different physiological consequences. The functional relevance of these differences in gene expression is supported by their associations with circulating biomarkers

Os desafios do atendimento de pacientes com sequelas cardiovasculares decorrentes de trauma do tórax / Challenges in the care of patients with cardiovascular sequels resulting from chest trauma

Introdução: O tórax apresenta estruturas de diversos sistemas de sustentação da vida, dentre eles o respiratório e o cardiovascular. Por conter, estruturas nobres para a manutenção da vida, os potenciais para ocorrer lesões graves em decorrência de traumas são muito grandes, como dados mostram, 25% das mortes são secundárias a trauma torácico. Dentro deste contexto, questiona-se quais os desafios no atendimento de pacientes com sequelas cardiovasculares decorrentes de traumas torácicos? Portanto, esse estudo tem como objetivo identificar as dificuldades enfrentadas na assistência de saúde de pacientes com repercussões cardiovasculares devido a trauma de tórax, através da elaboração de um formulário baseado em revisão bibliográfica de dados da literatura científica publicados sobre esse tema. Metodologia: O trabalho baseia-se numa revisão integrativa de literatura, na qual foram analisados artigos publicados em revistas científicas, utilizando-se das bases de dados da BVS (Biblioteca Virtual da Saúde), como: Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e Scielo (Scientific Electronic Library Online). Resultados: Após as análises e seleção, restaram-se sete artigos para integrar a discussão. Os artigos selecionados, estão descritos na tabela, com autores, título, metodologia, resultados e conclusão. Em seguida, foi realizada uma discussão acerca destes artigos. Conclusão: Cada um dos casos revisados neste estudo demonstra a necessidade e a importância de acompanhamento cuidadoso de todos os pacientes que sofreram trauma torácico fechado, mesmo que a avaliação cardíaca inicial possa ser negativa.

Nat Genet

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.Comment in : Genetic differential calculus. [Nat Genet. 2015] Comment in : Scaling up phenotyping studies. [Nat Biotechnol. 2015

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Metabolic footprinting of fermented milks after ingestion by healthy subjects

Fermentation is a widely used method of natural food préservation that has conséquences on the texture, taste and nutritional value of the transformed food. With a consumption reaching to 23 and 30 kg per person per year in the United States and Europe respectively, fermented dairy products occupy nowadays an undeniable place in Western diets. Extensive nutritional investigations have been conducted regarding their ability to exert health benefits beyond their nutritional qualities, with particular interest in yoghurt, which represents around 40 % of consumed fermented dairy products. The present work is part of the project "F3 - Function of Fermented Food" jointly led by Agroscope (Bern, Switzerland) and Centre Hospitalier Universitaire Vaudois (CHUV, Lausanne, Switzerland). The aim of the F3 project is to evaluate the functional response of subjects exposed to a fermented dairy product. In a double-blinded, randomized crossover study, 14 healthy men consumed a probiotic yoghurt and a chemically acidified milk as a non-fermented control. The functional response to the ingestion of yoghurt was assessed in sérum using untargeted MS-based metabolomics, postprandially after the acute intake of the test products and in fasting sérum after a two-week daily intake period. In addition, the metabolic footprint of fermentation was assessed in the milk products. Multivariate statistical analysis revealed that the intake of yoghurt left a marked footprint in postprandial sérum metabolome compared to the non-fermented milk intake. Among the identified metabolites, sérum levels of four indoles derivatives were modulated and seven free amino acids presented higher sérum level after yoghurt intake. Non-fermented milk intake was characterized by higher postprandial levels of five bile acids. In addition, based on the postprandial results, fasting sérum samples after short-term daily intake could also be differentiated. Moreover, the acute intake of the dairy products was characterised by a postprandial increase of sérum lactose, in particular after milk intake. This increase was observed in each of the participants with a pronounced inter-individual variability. It appeared that the expression of the single nucleotide variant associated with lactase persistence was not primarily responsible for this variability, however, an association between postprandial galactose and several microbiota species was observed. Thus, the study allowed the identification in sérum of exogenous and endogenous metabolites that are modulated by the intake of a fermented milk, representing as many targets for future studies investigating health qualities of fermented dairy products. The present study also highlighted the relevance of the postprandial phase in nutritional intervention studies, as the investigation of this phase subsequently enabled the identification of metabolites that are regulated in fasting sérum after short-term intake. A global characterisation of the postprandial metabolome after the intake of the dairy products, compared to a non-dairy high-fat meal, revealed evident similarities. Nevertheless, this approach also revealed differentially regulated metabolites that are associated with metabolic health, and thus, can be proposed as a new strategy to identify nutritional biomarkers of health. -- La fermentation est un moyen naturel et largement répandu de conservation des aliments qui entraine une modification de la texture, du goût et de la valeur nutritionnelle du produit. Avec une consommation moyenne aux Etats-Unis et en Europe respectivement de 23 et 30 kg par personne et par an, les produits laitiers fermentés occupent une place non négligeable dans le régime alimentaire occidental. Le fait que leur consommation puisse avoir des effets bénéfiques sur la santé allant au-delà du simple apport nutritionnel a été le sujet de nombreuses études, et en particulier en ce qui concerne le yaourt qui représente environ 40 % de la consommation de produits laitiers fermentés. Le projet présenté ici a été réalisé dans le cadre du projet "F3 - Function of Fermented Food" mené conjointement par Agroscope (Berne, Suisse) et le Centre Hospitalier Universitaire Vaudois (CHUV, Lausanne, Switzerland). L'objectif du projet F3 étant d'évaluer la réponse fonctionnelle de sujets ayant consommé des produits laitiers fermentés. Une étude clinique croisée et randomisée a été menée sur 14 hommes sains ayant consommé, soit un yaourt probiotique, soit un lait acidifié chimiquement faisant office de contrôle non fermenté. Leur réponse fonctionnelle à l'ingestion du yaourt a été évaluée par une analyse métabolomique non-ciblée du sérum, d'abord en phase postprandiale suite à l'ingestion des produits tests, puis à jeun après deux semaines d'une consommation quotidienne. De même, le profil métabolique de chaque produit a également été évalué par une analyse métabolomique. Une analyse statistique multivariée a montré que, comparée à l'ingestion de lait non fermenté, la consommation de yaourt a laissé une « empreinte métabolique » spécifique dans le sérum des volontaires. Parmi les métabolites identifiés, les concentrations sériques postprandiales de quatre dérivés indole ont été modifiées et sept acides aminés ont présenté des niveaux sériques plus élevés suite à la consommation de yaourt. La consommation de lait non fermenté a notamment été caractérisée par des niveaux significativement plus élevés pour cinq acides biliaires. De plus, l'exploitation des résultats postprandiaux a permis une différenciation des sérums obtenus à jeun après deux semaines d'une consommation quotidienne de lait ou de yaourt. La consommation des produits laitiers fut également accompagnée d'une augmentation postprandiale de lactose dans le sérum, en particulier après l'ingestion de lait. Cette augmentation fut observée chez chacun des 14 participants malgré une importante variabilité interindividuelle. Cette variabilité n'était cependant pas expliquée par l'expression du polymorphisme lié à la tolérance au lactose, mais une association entre les niveaux postprandiaux de galactose et la présence de certaines espèces dans le microbiote intestinal a pu être établie. Cette étude a permis l'identification dans le sérum de métabolites spécifiques, endogènes ou exogènes, dont les niveaux sont modifiés lors de l'ingestion d'un produit laitier fermenté. Ces métabolites, et les voies métaboliques qui leurs sont associées, représentent autant de cibles potentielles pour de futures études nutritionnelles visant à décrire les effets des produits laitiers fermentés sur la santé. Ce projet souligne également l'importance à accorder à l'étude de la phase postprandiale lors de futures études nutritionnelles, celle-ci ayant été nécessaire ici à la différenciation des échantillons à jeun. Une comparaison globale des metabolomes postprandiaux après l'ingestion des produits laitiers, par rapport à un repas n'en contenant pas, a révélé d'évidentes similarités. Néanmoins, cette approche a également permis d'identifier certains métabolites différemment régulés et connus pour être associés à la santé métabolique ; ainsi, cette stratégie pourrait être envisagée pour la découverte de nouveaux biomarqueurs nutritionnels liés à la santé