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Healthy plant-based diets rich in fermentable residues may induce gas-related symptoms, possibly mediated by the gut microbiota. We previously showed that consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria improved gastrointestinal (GI) comfort in response to a flatulogenic dietary challenge in healthy individuals. To study the effects of the FMP on gut microbiota activity from those participants, we conducted a metatranscriptomic analysis of fecal samples (n = 262), which were collected during the ingestion of a habitual diet and two series of a 3-day high-residue challenge diet, before and following 28-days of FMP consumption. Most of the FMP species were detected or found enriched upon consumption of the product. FMP mitigated the effect of a flatulogenic diet on gas-related symptoms in several ways. First, FMP consumption was associated with the depletion of gas-producing bacteria and increased hydrogen to methane conversion. It also led to the upregulation of activities such as replication and downregulation of functions related to motility and chemotaxis. Furthermore, upon FMP intake, metabolic activities such as carbohydrate metabolism, attributed to B. animalis and S. thermophilus, were enriched; these activities were coincidentally found to be negatively associated with several GI symptoms. Finally, a more connected microbial ecosystem or mutualistic relationship among microbes was found in responders to the FMP intervention. Taken together, these findings suggest that consumption of the FMP improved the tolerance of a flatulogenic diet through active interactions with the resident gut microbiota., This research was supported by a grant from Danone Nutricia Research. Danone Nutricia Research authors participated in the study design, interpretation of the data and in the writing of the report. Francisca Yáñez was supported by a fellowship from ANID, BECAS Chile, No. 72190278. Zixuan Xie received a fellowship from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Action, Innovative Training Network: FunHoMic; grant number 812969. CIBERHED is funded by the Instituto de Salud Carlos III.

Background: Sarcopenia, the age-related decrease in muscle mass and function can result in adverse health outcomes and subsequent loss of independence. Inadequate nutrition is an important contributor to the aetiology of sarcopenia, and dietary strategies are studied to prevent or delay this geriatric syndrome. Objective: The present study investigated whether there is an association between biochemical nutrient status markers, muscle parameters and sarcopenia in community-dwelling older adults. Design: Data from the cross-sectional Maastricht Sarcopenia study (MaSS) were used, in which skeletal muscle index (SMI), 4 meter gait speed, 5 times chair stand and handgrip strength were assessed among older adults (n=227). Sarcopenia was defined following the algorithm of the European Working Group on Sarcopenia in Older People. Fasted blood samples were analyses on amino acids levels, RBC phospholipid profile, 25-hydroxyvitamin D (25(OH)D), α-tocopherol, magnesium and homocysteine were determined in fasted blood levels. Generalized linear modelling and logistic regression were used for data analysis. Results: Lower blood levels of essential amino acids (EAA), total branched-chain amino acids (BCAA) and leucine were associated with lower SMI (P

International audience; The current study evaluates the safety and tolerance of a partially hydrolyzed whey protein-based infant formula (PHF) versus an in intact cow's milk protein formula (IPF). Breastfed infants were included as a reference group. In a multi-country, multicenter, randomized, double-blinded, controlled clinical trial, infants whose mothers intended to fully formula feed were randomized to PHF (n = 134) or IPF (n = 134) from ≤14 days to 17 weeks of age. The equivalence analysis of weight gain per day within margins of +/-3 g/d (primary outcome), the recorded adverse events, growth and gastro-intestinal tolerance parameters were considered for the safety evaluation. Equivalence of weight gain per day from enrolment until 17 weeks of age was demonstrated in the PHF group compared to the IPF group (difference in means -1.2 g/d; 90% CI (-2.42; 0.02)), with estimated means (SE) of 30.2 (0.5) g/d and 31.4 (0.5) g/d, respectively. No significant differences in growth outcomes, the number, severity or type of (serious) adverse events and tolerance outcomes, were observed between the two formula groups. A partially hydrolyzed whey protein-based infant formula supports adequate infant growth, with a daily weight gain equivalent to a standard intact protein-based formula; it is also safe for use and well-tolerated in healthy term infants.

ObjectiveTo systematically review the effect of oral intake of bacterial probiotics on 15 variables related to obesity, diabetes and non-alcoholic fatty liver disease.DesignSystematic review and meta-analysis.Data sourcesMedline, EMBASE and COCHRANE from 1990 to June 2018.Eligibility criteriaRandomised controlled trials (≥14 days) excluding hypercholesterolaemia, alcoholic liver disease, polycystic ovary syndrome and children ResultsOne hundred and five articles met inclusion criteria, representing 6826 subjects. In overweight but not obese subjects, probiotics induced improvements in: body weight (k=25 trials, d=−0.94 kg mean difference, 95% CI −1.17 to −0.70, I²=0.0%), body mass index (k=32, d=−0.55 kg/m², 95% CI −0.86 to −0.23, I²=91.9%), waist circumference (k=13, d=−1.31 cm, 95% CI −1.79 to −0.83, I²=14.5%), body fat mass (k=11, d=−0.96 kg, 95% CI −1.21 to −0.71, I²=0.0%) and visceral adipose tissue mass (k=5, d=−6.30 cm², 95% CI −9.05 to −3.56, I²=0.0%). In type 2 diabetics, probiotics reduced fasting glucose (k=19, d=−0.66 mmol/L, 95% CI −1.00 to −0.31, I²=27.7%), glycated haemoglobin (k=13, d=−0.28 pp, 95% CI −0.46 to −0.11, I²=54.1%), insulin (k=13, d=−1.66 mU/L, 95% CI −2.70 to −0.61, I²=37.8%) and homeostatic model of insulin resistance (k=10, d=−1.05 pp, 95% CI −1.48 to −0.61, I²=18.2%). In subjects with fatty liver diseases, probiotics reduced alanine (k=12, d=−10.2 U/L, 95% CI −14.3 to −6.0, I²=93.50%) and aspartate aminotransferases (k=10, d=−9.9 U/L, 95% CI −14.1 to -5.8, I²=96.1%). These improvements were mostly observed with bifidobacteria (Bifidobacterium breve, B. longum), Streptococcus salivarius subsp. thermophilus and lactobacilli (Lactobacillus acidophilus, L. casei, L. delbrueckii) containing mixtures and influenced by trials conducted in one country.ConclusionsThe intake of probiotics resulted in minor but consistent improvements in several metabolic risk factors in subjects with metabolic diseases.Trial registration numberCRD42016033273.

Background: The mechanisms responsible for calorie restriction-induced improvement in insulin sensitivity have not been fully elucidated. Greater insight can be achieved through deep biological phenotyping of subjects undergoing calorie restriction, and integration of big data.\ud \ud Materials and Methods: An integrative approach was applied to investigate associations between change in insulin sensitivity and factors from host, microbiota and lifestyle after a 6-week calorie restriction period in 27 overweight or obese adults (ClinicalTrials.gov: NCT01314690). Partial least squares regression was used to determine associations of change (week 6 – baseline) between insulin sensitivity markers and lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics in serum, urine and feces, and gut microbiota composition. ScaleNet, a network learning approach based on spectral consensus strategy (SCS, developed by us) was used for reconstruction of biological networks.\ud \ud Results: A spectrum of variables from lifestyle factors (10 nutrients), gut microbiota (10 metagenomics species) and host multi-omics (metabolic features: 84 from serum, 73 from urine, and 131 from feces; and 257 subcutaneous adipose tissue gene probes) most associated with insulin sensitivity were identified. Biological network reconstruction using SCS, highlighted links between changes in insulin sensitivity, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species. Linear regression analysis to model how changes of select variables over the calorie restriction period contribute to changes in insulin sensitivity, showed greatest contributions from gut metagenomic species and fiber intake.\ud \ud Conclusions: This work has enhanced previous knowledge on links between host glucose homeostasis, lifestyle factors and microbiota, and has identified potential biomarkers that may be used in future studies to predict and improve individual response to weight-loss interventions. Furthermore, this is the first study showing integration of the wide range of data presented herein, identifying 115 variables of interest with respect to insulin sensitivity from the initial input, consisting of 9,986 variables.

Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis reveal pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation demonstrate the bacterium’s intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Administration of the probiotic Lactobacillus rhamnosus CNCM I-3690 limits B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results suggest a new avenue for interventions against western diet-driven inflammatory and metabolic diseases., Lipid intake is known to promote Bilophila wadsworthia growth. Here the authors show that B. wadsworthia aggravates high fat diet induced metabolic dysfunctions and its suppression, both pharmacologically or mediated by Lactobacillus rhamnosus, limits the severity of metabolic impairment.

International audience; Respiratory tract infections such as flu cause severe morbidity and mortality and are among the leading causes of death in children and adults worldwide. Commensal microbiota is critical for orchestrating tissue homeostasis and immunity in the intestine. Probiotics represent an interesting source of immune modulators and several clinical studies have addressed the potential beneficial effects of probiotics against respiratory infections. Therefore, we have investigated the mechanisms of protection conferred by L. paracasei CNCM I-1518 strain in a mouse model of influenza infection. Notably, local myeloid cells accumulation is generated in the lungs after seven days feeding with L. paracasei prior to viral infection. L. paracasei-fed mice showed reduced susceptibility to the influenza infection, associated with less accumulation of inflammatory cells in the lungs, faster viral clearance and general health improvement. Interestingly, Allobaculum was significantly increased in L. paracasei-fed mice 7 days after influenza infection, even if the gut microbiota composition was not altered overall. L. paracasei-purified peptidoglycan partially recapitulated the protective phenotype observed with the entire bacteria. Collectively, our results demonstrate that oral consumption of L. paracasei CNCM I-1518 modulates lung immunity was associated with an improved control of influenza infection. These results further extend the beneficial role for certain lactobacilli to alleviate the burden of respiratory tract infections.

International audience; Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis ssp. lactis CNCM-I2494, a strain used in fermented dairy products. A chronic dinitrobenzene sulfonic acid (DNBS)-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability, and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations, and colonic cytokines were found to be altered. B. animalis ssp. lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations, and cytokine levels. Furthermore, tight junction (TJ) proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4+ lymphocyte alterations in both spleen and mesenteric lymphoid nodes. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4+ Th1 cells) by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5, and IL-10). Altogether, these data suggest that B. animalis ssp. lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability.

International audience; Candida albicans is a polymorphic yeast species that often forms part of the commensal gastrointestinal mycobiota of healthy humans. It is also an important opportunistic pathogen. A tripartite interaction involving C. albicans, the resident microbiota and host immunity maintains C. albicans in its commensal form. The influence of each of these factors on C. albicans carriage is considered herein, with particular focus on the mycobiota and the approaches used to study it, models of gastrointestinal colonization by C. albicans, the C. albicans genes and phenotypes that are necessary for commensalism and the host factors that influence C. albicans carriage.

Skeletal muscle mitochondrial function is the biggest component of whole-body energy output. Mitochondrial energy production during exercise is impaired in vitamin D-deficient subjects. In cultured myotubes, loss of vitamin D receptor (VDR) function decreases mitochondrial respiration rate and ATP production from oxidative phosphorylation. We aimed to examine the effects of vitamin D deficiency and supplementation on whole-body energy expenditure and muscle mitochondrial function in old rats, old mice, and human subjects. To gain further insight into the mechanisms involved, we used C2C12 and human muscle cells and transgenic mice with muscle-specific VDR tamoxifen-inducible deficiency. We observed that in vivo and in vitro vitamin D fluctuations changed mitochondrial biogenesis and oxidative activity in skeletal muscle. Vitamin D supplementation initiated in older people improved muscle mass and strength. We hypothesize that vitamin D supplementation is likely to help prevent not only sarcopenia but also sarcopenic obesity in vitamin D-deficient subjects.

International audience; Tailored dietary counseling could be specifically efficient during pregnancy, a period accompanied by a rise in nutrition awareness, but little is known about the expectations of pregnant women in this regard. We studied these expectations regarding tailored dietary advice in French women during their pregnancy, as well as their motivations and the perceived barriers and enablers. In French pregnant women, we evaluated the perceptions of tailored dietary advice provided by stepwise dietary counseling based on three types of dietary changes, consisting of: (1) a modification of the amounts consumed, (2) substitutions within the food subgroups, and (3) substitutions between food subgroups. A sequential explanatory mixed-method approach was designed. Using qualitative data from a focus group study (n = 40), we intended to explore in depth the women’s expectations regarding dietary advice and adherence to a tailored approach. These were combined with quantitative and qualitative data from a 6-week online longitudinal study (n = 115), using questionnaires designed to assess the modifications of dietary habits during pregnancy and to evaluate each type of dietary change. Both studies confirmed that most women in our samples did indeed intend to institute changes regarding healthier dietary practices during pregnancy. The principal motivation behind changes to their habits was to ensure the health and well-being of both their babies and themselves. The proposal of dietary advice that is tailored to both the current diet and the specific needs of pregnant women, but that is also positive and credible, was perceived as enabling implementing healthier dietary practices during pregnancy. Regarding the implementation of the dietary changes proposed, the enablers and barriers identified differed between modifications of the amounts consumed and substitutions. The women displayed interest in all types of dietary changes. This gave relevance to combining different types of changes in order to propose dietary counseling during pregnancy. Tailored dietary counseling was identified by French pregnant women in our samples as enabling them to adopt a healthier diet. However, perceived barriers might limit the implementation of dietary changes, especially when they involved marked modifications to their usual diet.

In drinking water production from groundwaters, biological rapid sand filters (RSFs) can be used for ammonium and manganese removal in aerobic conditions. However, in some boreholes, a start-up duration of several months is required to reach the required removal capacity, leading to significant water losses. Moreover, in specific industrial cases, no exogenous biomass under the form of backwash water or activated sludge can be added to accelerate the process, and different approaches are seldom considered in the literature. With the aim of saving water, start-up strategies coupling water temperature increase and substrate dosing were studied to accelerate the installation of biological activities in a pilot plant fed with borehole water. These set-ups enabled a substantial acceleration of nitrification but no improvement of manganese oxidation in the experimental conditions, although the experiments showed no clear negative influence of nitrification, through nitrite accumulation, on biological manganese oxidation. To further save energy and reduce water loss, outlet water recirculation at a rate of 75% during the start-up phase was validated. The proposed start-up strategy enabled the complete installation of active biofilms with a mean start-up time reduction of 36% and water use reduction of 84% compared to the reference natural conditions.

The potential of herbal extracts containing bioactive compounds to strengthen immunity could contribute to reducing antimicrobial use in poultry. This study aimed at developing a reliable and robust methodological pipeline to assess the ability of herbal extracts to strengthen chicken innate defenses, especially concerning inflammation and oxidative stress. This methodology was applied to Melissa officinalis L. (MEL) extract, recognized for its biological activities including antioxidant and anti-inflammatory properties. Different methods were used to (1). guarantee the quality of MEL extract and its capacity to stimulate the innate immune system; (2). evaluate the relevance of an ex vivo model to mimic inflammatory and oxidative stress challenges to replace LPS injection in chickens; (3). analyse the effects of feed supplemented with MEL extract on inflammation and oxidative stress induced ex vivo; (4). assess the effects of MEL extract on the redox balance, health, welfare and performance in broilers exposed to suboptimal starting conditions through a large-scale approach. The quality of MEL extract preparations, through phytochemical quantification of rosmarinic acid (RA), revealed varying concentrations of RA in the different MEL extracts. RA concentrations remained stable for at least 9 months and in feed three months after incorporating MEL extract. When incubated with chicken cell lines MEL extract showed potential metabolic activation and ability to stimulate immune functions but induced cytotoxicity at high concentrations. The original ex vivo model of inflammation developed on chicken blood cells enabled inflammation and oxidative stress biomarkers to be expressed and revealed antioxidative and anti-inflammatory properties of blood cells from chickens fed MEL extract. The experimental model of chicken suboptimal starting conditions validated beneficial effects of MEL extract on the redox balance and also evidenced improved performance during the growth phase, a tendency for fewer muscle defects but a higher severity of pododermatitis lesions without affecting other welfare indicators. This study grouped methods and tools that could be combined according to the plant extract, the needs of professionals working in poultry production systems and staff responsible for animal health, welfare and feeding.

Extensive microbial colonization of the infant gastrointestinal tract starts after parturition. There are several parallel mechanisms by which early life microbiome acquisition may proceed, including early exposure to maternal vaginal and fecal microbiota, transmission of skin associated microbes, and ingestion of microorganisms present in breast milk. The crucial role of vertical transmission from the maternal microbial reservoir during vaginal delivery is supported by the shared microbial strains observed among mothers and their babies and the distinctly different gut microbiome composition of caesarean-section born infants. The healthy infant colon is often dominated by members of the keystone genus Bifidobacterium that have evolved complex genetic pathways to metabolize different glycans present in human milk. In exchange for these host-derived nutrients, bifidobacteria’s saccharolytic activity results in an anaerobic and acidic gut environment that is protective against enteropathogenic infection. Interference with early-life microbiota acquisition and development could result in adverse health outcomes. Compromised microbiota development, often characterized by decreased abundance of Bifidobacterium species has been reported in infants delivered prematurely, delivered by caesarean section, early life antibiotic exposure and in the case of early life allergies. Various microbiome modulation strategies such as probiotic, prebiotics, synbiotics and postbiotics have been developed that are able to generate a bifidogenic shift and help to restore the microbiota development. This review explores the evolutionary ecology of early-life type Bifidobacterium strains and their symbiotic relationship with humans and discusses examples of compromised microbiota development in which stimulating the abundance and activity of Bifidobacterium has demonstrated beneficial associations with health., This research was funded by Danone Nutricia Research.

WOS:000528260100005.; International audience; Development can change the way organisms represent their environment and affect their behavior. In vision, complex stimuli are treated as the sum of their elements (elemental perception) in children or as a whole (configural perception) in adults. However, the influence of development in elemental/configural perception has never been tested in olfaction. Here we explored this issue in young rabbits, which are known to perceive during the neonatal period certain binary odor mixtures elementally and others weak configurally. Using conditioning and behavioral testing procedures, we set out six experiments evaluating the putative evolution of their odor perception between birth and weaning. Results highlighted that between postnatal days 2 and 9 the perception of an initially weak configural mixture became robust configural while that of two elemental mixtures did not. Additional switches from elemental to configural perception were observed at postnatal day 24. The use of a chemically more complex senary mixture resulted also in a shift from weak to robust configural perception between postnatal days 2 and 9. Thus, the perception of certain odor mixtures may rapidly evolve toward a more holistic mode in young rabbits, which may help simplifying their representation of the environment once out of the nest.

Background Provision of donor human milk is handled by established human milk banks that implement all required measures to ensure its safety and quality. Detailed human milk banking guidelines on a European level are currently lacking, while the information available on the actual practices followed by the European human milk banks, remains limited. The aim of this study was to collect detailed data on the actual milk banking practices across Europe with particular emphasis on the practices affecting the safety and quality of donor human milk. Materials and methods A web-based questionnaire was developed by the European Milk Bank Association (EMBA) Survey Group, for distribution to the European human milk banks. The questionnaire included 35 questions covering every step from donor recruitment to provision of donor human milk to each recipient. To assess the variation in practices, all responses were then analyzed for each country individually and for all human milk banks together. Results A total of 123 human milk banks completed the questionnaire, representing 85% of the European countries that have a milk bank. Both inter- and intra-country variation was documented for most milk banking practices. The highest variability was observed in pasteurization practices, storage and milk screening, both pre- and post-pasteurization. Conclusion We show that there is a wide variability in milk banking practices across Europe, including practices that could further improve the efficacy of donor human milk banking. The findings of this study could serve as a tool for a global discussion on the efficacy and development of additional evidence-based guidelines that could further improve those practices.

International audience; Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably 12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (

International audience; Objective.- The year 2020 marks the 10th consecutive year of the ePINUT study which is used for promoting awareness of hospital malnutrition in paediatric wards. The present article describes the methods and the studied population.Materials and methods. - ePINUT is a cross-sectional study gathering data each year over 2 weeks in March. Any child up to 18 years old, hospitalized except in neonatal and intensive care units could be included in this study. Length of hospitalization, weight variations and height were measured. An online calculator was made available for nutritional indices (http://www.epinut.fr/), in accordance with the French Paediatric Society guidelines. A geographic grouping was done based on university inter-regions.Results. - A total of 13,332 entries in France were included from 2010 to 2019. On a geographic level, 6 of the 7 regions contributed yearly to 10 to 15% of these entries, while the western region accounted for 25% of the entries (P < 0.001). Ninety-two cities participated, with 36% participating 5 to 9 years, 39% participating 2 to 4 years, and 26% participating once. The median age was 4 years old, 10.2% of children had a Weight-for-Height z-score smaller than -2 at admittance. These children stayed longer in the hospital (8.3 +/- 11.3 vs. 6.4 +/- 9.3 days, P = 0.02) and had a greater percent weight change during hospitalization (2.8 +/- 4.7 vs. 0.4 +/- 3.8%, P < 0.0001).Conclusion. - Such a long-term promotion of awareness about hospital malnutrition is unique. The future aim is to empower young patients and their parents and to get them involved in reducing hospital malnutrition in children. (c) 2021 Societe francophone nutrition clinique et metabolisme (SFNCM).

In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from available repositories, separating the genome of different virus strains from the Coronavirus family with considerable accuracy. The network’s behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are first validated on samples from other repositories, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets on existing datasets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from NGDC, separating the genome of different virus strains from the Coronavirus family with accuracy 98.73%. The network’s behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are validated on samples from NCBI and GISAID, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. The proposed methodology has a substantial added value over existing methods, as it is able to both identify promising primer sets for a virus from a limited amount of data, and deliver effective results in a minimal amount of time. Considering the possibility of future pandemics, these characteristics are invaluable to promptly create specific detection methods for diagnostics.

The present study reports the first structural characterization of protonated cyameluric acid ([CA + H]+) in the gas phase, which paves the way for prospective bottom-up research on the condensed-phase chemistry of CA in the protonated form. A number of [CA + H]+ keto-enol isomers can a priori be produced as a result of protonation at available N and O positions of precursor neutral CA tautomers, yet ab initio computations predict different reduced [CA + H]+ isomer populations dominating the solution and gas phases that are involved in the ion generation process (i.e., electrospray ionization). Infrared multiple photon dissociation spectra were recorded in the 990-1900 and 3300-3650 cm-1 regions and compared with theoretical [B3LYP/6-311++G(d,p)] IR absorption spectra of several [CA + H]+ isomers, providing a satisfactory agreement for the most stable monohydroxy form in the gas phase, [1358a]+, yet the contribution of its nearly isoenergetic OH rotamer, [1358b]+, cannot be neglected. This is indicative of the occurrence of [CA + H]+ isomer interconversion reactions, assisted by protic solvent molecules, during their transfer into the gas phase. The results suggest that available O positions on neutral CA are energetically favored protonation sites in the gas phase.

Digestive symptoms; Fermentable carbohydrates; Flatulence Sintomas digestivos; Carbohidratos fermentables; Flatulencia Símptomes digestius; Hidrats de carboni fermentables; Flatulència Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut–brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. As compared to a habitual diet, the flatulogenic diet increased the perception of digestive symptoms (flatulence score 7.1 ± 1.6 vs. 5.8 ± 1.9; p < 0.05) and the daily number of anal gas evacuations (22.4 ± 12.5 vs. 16.5 ± 10.2; p < 0.0001). FMP consumption reduced the flatulence sensation score (by –1.6 ± 2.2; p < 0.05) and the daily number of anal gas evacuations (by –5.3 ± 8.2; p < 0.0001). FMP consumption did not significantly alter the overall gut microbiota composition, but some changes in the microbiota correlated with the observed clinical improvement. The consumption of a product containing B. lactis CNCM I-2494 improved the tolerance of a healthy diet in patients with DGBI, and this effect may be mediated, in part, by the metabolic activity of the microbiota. This research was supported by an unrestricted grant from Danone Nutricia Research. Danone Nutricia Research authors participated in the study design, interpretation of the data and in the writing of the report. This work was supported in part by the Spanish Ministry of Economy and Competitiveness (Dirección General de Investigación Científica y Técnica, SAF 2016-76648-R). Ciberehd is funded by the Instituto de Salud Carlos III.

[EN] In vitro digestion studies often use animal digestive enzyme extracts as substitutes of human gastric and pancreatic secretions. Pancreatin from porcine origin is thus commonly used to provide relevant pancreatic enzymes such as proteases, amylase and lipase. Rabbit gastric extracts (RGE) have been recently introduced to provide gastric lipase in addition to pepsin. Before preparing simulated gastric and pancreatic extracts with targeted enzyme activities as described in in vitro digestion protocols, it is important to determine the activities of enzyme preparations using validated methods. The purpose of this inter-laboratory study within the INFOGEST network was to test the repeatability and reproducibility of lipase assays using the pH-stat technique for measuring the activities of gastric and pancreatic lipases from various sources. Twenty-one laboratories having different pH-stat devices received the same protocol with identical batches of RGE and two pancreatin sources. Lipase assays were performed using tributyrin as a substrate and three different amounts (50, 100 and 200 mu g) of each enzyme preparation. The repeatability results within individual laboratories were satisfactory with coefficients of variation (CVs) ranging from 4 to 8% regardless of the enzyme amount tested. However, the inter laboratory variability was high (CV > 15%) compared to existing standards for bioanalytical assays. We identified and weighted the contributions to inter-laboratory variability of several parameters associated with the various pH-stat equipment used in this study (e.g. reaction vessel volume and shape, stirring mode and rate, burette volume for the automated delivery of sodium hydroxide). Based on this, we established recommendations for improving the reproducibility of lipase assays using the pH-stat technique. Defining accurate and complete recommendations on how to correctly quantify activity levels of enzyme preparations is a gateway to promising comparison of in vitro data obtained from different laboratories following the same in vitro digestion protocol., The authors thank the European Commission COST Action FA1005 INFOGEST and INRAE for financing the meetings and conferences that enable the 21 laboratories to network and organise the work presented in this article. We also acknowledge the 'Healthy and Safe Food System (KB37) ' knowledge base program of the Dutch Ministry of Agriculture, Nature and Food Quality (LNV) , with grant number KB-37-001-007 for funding of this work performed at Wageningen Food & Biobased Research. We are grateful to Dr Sawsan Amara (CEO of Lipolytech SA., Marseille, France) for her generous gift of RGE and to Drs Jan Ludemann, Anja Jensen, Olaf Friedrich and Claus Middelberg from Nordmark Arzneimittel GmbH & Co. KG (Uetersen, Germany) for their generous gift of Nordmark pancreatin. Finally, we thank Drs Maria Fatima Cabral and Judite Costa from iBET for their technical support and discussion.

International audience; Lipid oxidation compromises the shelf-life of lipid-containing foods, leading to the generation of unpleasant off- flavours. Monitoring lipid oxidation under normal shelf-life conditions can be time-consuming (i.e. weeks or months) and therefore accelerated shelf-life conditions are often applied. However, little is known on their impact on the lipid oxidation mechanisms. In this study, different oxygen partial pressures (PO2; 10 and 21%), temperatures (20, 30 and 40 ◦C), and the removal of antioxidants through stripping of the oil were tested to accelerate lipid oxidation. Increasing the incubation temperature of stripped oil blends from 30 to 40 ◦C reduced the onset of lipid oxidation from 4 to 2 weeks, whereas the PO2 had no impact. Surprisingly, at room temperature, an increase in PO2 resulted in a longer onset time (10 weeks under 10% oxygen, 15 weeks under 21% oxygen). We hypothesize that this is due to a shift in (initiation) mechanism. In non-stripped oil, an increase in PO2 from 10 to 21% decreased the onset time from 16 to 10 weeks (40 ◦C). Temperature elevations and stripping led to a shift towards more trans–trans diene hydroperoxides, as compared to the cis–trans conformation. Additionally, oil stripping led to an increase in oxidized PUFAs with three or more double bonds in which the hydroperoxide group is located between the double bond pattern, instead of on the edge of it. Lastly, it was shown that small additions of LC-PUFAs (0, 0.3, 0.6, 1.2 and 2.3%, w/w) accelerate lipid oxidation, even in relatively stable stripped oils. In conclusion, increased PO2 and slightly elevated temperatures hold fair potential for accelerated shelf-life testing of non-stripped oils with a limited impact on the lipid oxidation mechanisms, whereas stripping significantly changes propagation mechanisms.

International audience; Proteins are widely used to stabilize emulsions, and plant proteins have raised increasing interest for this purpose. The interfacial and emulsifying properties of proteins depend largely on their molecular properties. We used fluorescence spectroscopy to characterize the conformation of food proteins from different biological origins (dairy or pea) and transformation processes (commercial or lab-made isolates) in solution and at the oil-water interface. The fourth derivative of fluorescence spectra provided insights in the local environment of tryptophan (Trp) residues and thus in the protein structure. In emulsions, whey proteins adsorbed with their Trp-rich region at the oil-water interface. Proteins in the commercial pea isolate were present as soluble aggregates, and no changes in the local environment of the Trp residues were detected upon emulsification, suggesting that these structures adsorb without conformational changes. The lab-purified pea proteins were less aggregated and a Trp-free region of the vicilin adsorbed at the oil-water interface.

Background Gastrointestinal (GI) discomfort is prevalent and known to be associated with impaired quality of life. Real-world information on factors of GI discomfort and solutions used by people is, however, limited. Social media, including online forums, have been considered a new source of information to examine the health of populations in real-life settings. Objective The aims of this retrospective infodemiology study are to identify discussion topics, characterize users, and identify perceived determinants of GI discomfort in web-based messages posted by users of French social media. Methods Messages related to GI discomfort posted between January 2003 and August 2018 were extracted from 14 French-speaking general and specialized publicly available online forums. Extracted messages were cleaned and deidentified. Relevant medical concepts were determined on the basis of the Medical Dictionary for Regulatory Activities and vernacular terms. The identification of discussion topics was carried out by using a correlated topic model on the basis of the latent Dirichlet allocation. A nonsupervised clustering algorithm was applied to cluster forum users according to the reported symptoms of GI discomfort, discussion topics, and activity on online forums. Users’ age and gender were determined by linear regression and application of a support vector machine, respectively, to characterize the identified clusters according to demographic parameters. Perceived factors of GI discomfort were classified by a combined method on the basis of syntactic analysis to identify messages with causality terms and a second topic modeling in a relevant segment of phrases. Results A total of 198,866 messages associated with GI discomfort were included in the analysis corpus after extraction and cleaning. These messages were posted by 36,989 separate web users, most of them being women younger than 40 years. Everyday life, diet, digestion, abdominal pain, impact on the quality of life, and tips to manage stress were among the most discussed topics. Segmentation of users identified 5 clusters corresponding to chronic and acute GI concerns. Diet topic was associated with each cluster, and stress was strongly associated with abdominal pain. Psychological factors, food, and allergens were perceived as the main causes of GI discomfort by web users. Conclusions GI discomfort is actively discussed by web users. This study reveals a complex relationship between food, stress, and GI discomfort. Our approach has shown that identifying web-based discussion topics associated with GI discomfort and its perceived factors is feasible and can serve as a complementary source of real-world evidence for caregivers.

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response. This work is conducted with support from the Advisory Board Members (California Institute of Technology, Winclove Probiotics, University of California Davis, Center for Autism and the Developing Brain, Ohio State University, the Autism Speaks Autism Treatment Network, Arizona State University, University College Cork), from the Consortium Partners: Fondazione EBRIS, in charge of project management and coordination and providing the gut permeability and immunological evaluation of the enrolled subjects; Nutricia Research Bv in charge of nutritional formulation development for interventional trial; Medinok Spa and Consiglio Nazionale Delle Ricerche (CNR) in charge of data analysis and multi-omics platform development; Bio Modeling Systems in charge of the mechanistic pathway hypothesis development; Euformatics in charge of analysis and the interpretation of the genomic variants of the patient material, and for the comparison of the variants from the different patient cohorts, Theoreo Srl and Imperial College Of Science in charge of metabolomics analysis and interpretation; National University of Ireland Galway, Azienda Sanitaria, Locale (ASL) Salerno and Massachusettse General Hospital for Children, in charge of enrollments for observation and interventional trials; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement in charge of analyzing the genomic and transcriptomic profiles of the host microbiota; Institut National de la Santé et de la Recherche Médicale, in charge of proteomics analysis; Utrecht University, in charge of pre-clinical studies; Tampereen Yliopisto, in charge of experimental design; Johns Hopkins University in charge of epigenomic evaluation and interpretation. Financial contributions were made by European Union. peer-reviewed

Evidence is accumulating that short chain fatty acids (SCFA) play an important role in the maintenance of gut and metabolic health. The SCFA acetate, propionate and butyrate are produced from the microbial fermentation of indigestible carbohydrates and appear to be key mediators of the beneficial effects elicited by the gut microbiome. Microbial SCFA production is essential for gut integrity by regulating the luminal pH, mucus production, providing fuel for epithelial cells and effects on mucosal immune function. SCFA also directly modulate host metabolic health through a range of tissue-specific mechanisms related to appetite regulation, energy expenditure, glucose homeostasis and immunomodulation. Therefore, an increased microbial SCFA production can be considered as a health benefit, but data are mainly based on animal studies, whereas well-controlled human studies are limited. In this review an expert group by ILSI Europe's Prebiotics Task Force discussed the current scientific knowledge on SCFA to consider the relationship between SCFA and gut and metabolic health with a particular focus on human evidence. Overall, the available mechanistic data and limited human data on the metabolic consequences of elevated gut-derived SCFA production strongly suggest that increasing SCFA production could be a valuable strategy in the preventing gastro-intestinal dysfunction, obesity and type 2 diabetes mellitus. Nevertheless, there is an urgent need for well controlled longer term human SCFA intervention studies, including measurement of SCFA fluxes and kinetics, the heterogeneity in response based on metabolic phenotype, the type of dietary fibre and fermentation site in fibre intervention studies and the control for factors that could shape the microbiome like diet, physical activity and use of medication. ispartof: BENEFICIAL MICROBES vol:11 issue:5 pages:411-455 ispartof: location:Netherlands status: published

International audience; Bifidobacteria are among the first colonisers of the gastrointestinal tract of breast-fed newborns due to, among other things, their ability to metabolise oligosaccharides naturally occurring in human milk. The presence of bifidobacteria in the infant gut has been shown to promote intestinal health and homeostasis as well as to preserve a functional gut barrier, thus positively influencing host health and well-being. Among human-associated gut commensals, Bifidobacterium bifidum has been described as the only species capable of the extracellular degradation of both mucin-type glycans and HMOs, thereby giving this species a special role as a commensal gut forager of both host and diet-derived glycans. In the present study, we assess the possible beneficial properties and probiotic potential of B. bifidum strain CNCM I-4319. In silico genome analysis and growth experiments confirmed the expected ability of this strain to consume HMOs and mucin. By employing various animal models, we were also able to assess the ability of B. bifidum CNCM I-4319 to preserve gut integrity and functionality from stress-induced and inflammatory damage, thereby enforcing its potential as an effective probiotic strain.

International audience; Background: The European study MetaCardis aims to investigate the role of the gut microbiota in health and cardiometabolic diseases in France, Germany, and Denmark. To evaluate long-term diet-disease relationships, a food frequency questionnaire (FFQ) was found to be the most relevant dietary assessment method for the MetaCardis study.Objective: The objectives of this study were to describe the development of three semiquantitative online FFQs used in the MetaCardis study-one FFQ per country-and to assess the relative validity of the French MetaCardis FFQ.Design: The layout and format of the MetaCardis FFQ was based on the European Prospective Investigation of Cancer (EPIC)-Norfolk FFQ and the content was based on relevant European FFQs. Portion size and nutrient composition were derived from national food consumption surveys and food composition databases. To assess the validity of the French MetaCardis FFQ, a cross-sectional study design was utilized.Participants/setting: The validation study included 324 adults recruited between September 2013 and June 2015 from different hospitals in Paris, France.Main outcome measures: Food intakes were measured with both the French MetaCardis FFQ and 3 consecutive self-administered web-based 24-hour dietary recalls (DRs).Statistical analyses performed: Several measures of validity of the French MetaCardis FFQ were evaluated: estimations of food groups, energy, and nutrient intakes from the DRs and the FFQ, Spearman and Pearson correlations, cross-classification, and Bland-Altman analyses.Results: The French MetaCardis FFQ tended to report higher food, energy, and nutrient intakes compared with the DRs. Mean correlation coefficient was 0.429 for food, 0.460 for energy, 0.544 for macronutrients, 0.640 for alcohol, and 0.503 for micronutrient intakes. Almost half of participants (44.4%) were correctly classified within tertiles of consumption, whereas 12.9% were misclassified in the opposite tertile. Performance of the FFQ was relatively similar after stratification by sex.Conclusions: The French MetaCardis FFQ was found to have an acceptable level of validity and may be a useful instrument to rank individuals based on their food and nutrient intakes.

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.