Effect of environmental variance-based resilience selection on the gut metabolome of rabbits

Background Gut metabolites are key actors in host-microbiota crosstalk with efect on health. The study of the gut metabolome is an emerging topic in livestock, which can help understand its efect on key traits such as animal resilience and welfare. Animal resilience has now become a major trait of interest because of the high demand for more sustainable production. Composition of the gut microbiome can reveal mechanisms that underlie animal resil ience because of its infuence on host immunity. Environmental variance (VE), specifcally the residual variance, is one measure of resilience. The aim of this study was to identify gut metabolites that underlie diferences in the resilience potential of animals originating from a divergent selection for VE of litter size (LS). We performed an untargeted gut metabolome analysis in two divergent rabbit populations for low (n=13) and high (n=13) VE of LS. Partial least square-discriminant analysis was undertaken, and Bayesian statistics were computed to determine dissimilarities in the gut metabolites between these two rabbit populations. Results We identifed 15 metabolites that discriminate rabbits from the divergent populations with a prediction performance of 99.2% and 90.4% for the resilient and non-resilient populations, respectively. These metabolites were suggested to be biomarkers of animal resilience as they were the most reliable. Among these, fve that derived from the microbiota metabolism (3-(4-hydroxyphenyl)lactate, 5-aminovalerate, and equol, N6-acetyllysine, and serine), were suggested to be indicators of dissimilarities in the microbiome composition between the rabbit populations. The abundances of acylcarnitines and metabolites derived from the phenylalanine, tyrosine, and tryptophan metabo lism were low in the resilient population and these pathways can, therefore impact the infammatory response and health status of animals. Conclusions This is the frst study to identify gut metabolites that could act as potential resilience biomarkers. The results support diferences in resilience between the two studied rabbit populations that were generated by selec tion for VE of LS. Furthermore, selection for VE of LS modifed the gut metabolome, which could be another factor that modulates animal resilience. Further studies are needed to determine the causal role of these metabolites in health and diseas

Selection for environmental variance shifted the gut microbiome composition driving animal resilience

Background. Understanding how the host’s microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant breeders. Currently, selection for resilience is considered a critical step in improving the sustainability of livestock systems. Environmental variance (VE), the withinindividual variance of a trait, has been successfully used as a proxy for animal resilience. Selection for reduced VE could effectively shift gut microbiome composition; reshape the inflammatory response, triglyceride, and cholesterol levels; and drive animal resilience. This study aimed to determine the gut microbiome composition underlying the VE of litter size (LS), for which we performed a metagenomic analysis in two rabbit populations divergently selected for low (n = 36) and high (n = 34) VE of LS. Partial least square-discriminant analysis and alpha- and beta-diversity were computed to determine the differences in gut microbiome composition among the rabbit populations. Results. We identified 116 KEGG IDs, 164 COG IDs, and 32 species with differences in abundance between the two rabbit populations studied. These variables achieved a classification performance of the VE rabbit populations of over than 80%. Compared to the high VE population, the low VE (resilient) population was characterized by an underrepresentation of Megasphaera sp., Acetatifactor muris, Bacteroidetes rodentium, Ruminococcus bromii, Bacteroidetes togonis, and Eggerthella sp. and greater abundances of Alistipes shahii, Alistipes putredinis, Odoribacter splanchnicus, Limosilactobacillus fermentum, and Sutterella, among others. Differences in abundance were also found in pathways related to biofilm formation, quorum sensing, glutamate, and amino acid aromatic metabolism. All these results suggest differences in gut immunity modulation, closely related to resilience. Conclusions. This is the first study to show that selection for VE of LS can shift the gut microbiome composition. The results revealed differences in microbiome composition related to gut immunity modulation, which could contribute to the differences in resilience among rabbit populations. The selection-driven shifts in gut microbiome composition should make a substantial contribution to the remarkable genetic response observed in the VE rabbit population

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Çédille, revista de estudios franceses

Presentació

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains

Presentation

El pasado mes de abril iniciamos una nueva etapa en Çédille, representada principalmente por su traslado a la plataforma Open Journal System (OJS) de la Universidad de La Laguna, así como por la renovación y reasignación de competencias del Consejo de Redacción. Durante este tiempo, hemos tenido que adaptarnos, experimentar y comprender, pacientemente, el funcionamiento de esta nueva herramienta que es OJS. Ello ha supuesto, en algunos casos, que se hayan producido determinadas dificultades de comunicación con nuestros lectores y evaluadores, o que se hayan ocasionado pequeños retrasos en la gestión de la revista. Como nuestros seguidores saben, muy recientemente hemos sufrido, además, un ataque informático que no solo impidió el acceso a la plataforma durante varios días (justo en el momento final de producción de este número), sino que obligó a trasladar nuestro sitio web a otro servidor y a implementar nuevas medidas de seguridad. Afortunadamente, gracias al buen hacer y profesionalidad de Juan Ascanio Amigó, asesor técnico de OJS para la Universidad de La Laguna, hemos logrado salir airosos de los problemas, complicaciones y secuelas que nos hemos ido encontrando en este tiempo. En este número que ahora ve la luz contamos con treinta y cuatro contri-buciones que superan, en total, las setecientas páginas. Así, Amelia Gamoneda Lanza y Francisco González Fernández se han encargado de coordinar una nueva entrega –la undécima– de la serie «Monografías», donde han reunido una ..

Global patterns and drivers of ecosystem functioning in rivers and riparian zones

Abstract River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth’s biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented “next-generation biomonitoring” by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)