A network perspective on the ecology of gut microbiota and progression of type 2 diabetes: Linkages to keystone taxa in a Mexican cohort

IntroductionThe human gut microbiota (GM) is a dynamic system which ecological interactions among the community members affect the host metabolism. Understanding the principles that rule the bidirectional communication between GM and its host, is one of the most valuable enterprise for uncovering how bacterial ecology influences the clinical variables in the host.MethodsHere, we used SparCC to infer association networks in 16S rRNA gene amplicon data from the GM of a cohort of Mexican patients with type 2 diabetes (T2D) in different stages: NG (normoglycemic), IFG (impaired fasting glucose), IGT (impaired glucose tolerance), IFG + IGT (impaired fasting glucose plus impaired glucose tolerance), T2D and T2D treated (T2D with a 5-year ongoing treatment).ResultsBy exploring the network topology from the different stages of T2D, we observed that, as the disease progress, the networks lose the association between bacteria. It suggests that the microbial community becomes highly sensitive to perturbations in individuals with T2D. With the purpose to identify those genera that guide this transition, we computationally found keystone taxa (driver nodes) and core genera for a Mexican T2D cohort. Altogether, we suggest a set of genera driving the progress of the T2D in a Mexican cohort, among them Ruminococcaceae NK4A214 group, Ruminococcaceae UCG-010, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, Alistipes, Anaerostipes, and Terrisporobacter.DiscussionBased on a network approach, this study suggests a set of genera that can serve as a potential biomarker to distinguish the distinct degree of advances in T2D for a Mexican cohort of patients. Beyond limiting our conclusion to one population, we present a computational pipeline to link ecological networks and clinical stages in T2D, and desirable aim to advance in the field of precision medicine

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

DataSheet_1_A network perspective on the ecology of gut microbiota and progression of type 2 diabetes: Linkages to keystone taxa in a Mexican cohort.pdf

IntroductionThe human gut microbiota (GM) is a dynamic system which ecological interactions among the community members affect the host metabolism. Understanding the principles that rule the bidirectional communication between GM and its host, is one of the most valuable enterprise for uncovering how bacterial ecology influences the clinical variables in the host.MethodsHere, we used SparCC to infer association networks in 16S rRNA gene amplicon data from the GM of a cohort of Mexican patients with type 2 diabetes (T2D) in different stages: NG (normoglycemic), IFG (impaired fasting glucose), IGT (impaired glucose tolerance), IFG + IGT (impaired fasting glucose plus impaired glucose tolerance), T2D and T2D treated (T2D with a 5-year ongoing treatment).ResultsBy exploring the network topology from the different stages of T2D, we observed that, as the disease progress, the networks lose the association between bacteria. It suggests that the microbial community becomes highly sensitive to perturbations in individuals with T2D. With the purpose to identify those genera that guide this transition, we computationally found keystone taxa (driver nodes) and core genera for a Mexican T2D cohort. Altogether, we suggest a set of genera driving the progress of the T2D in a Mexican cohort, among them Ruminococcaceae NK4A214 group, Ruminococcaceae UCG-010, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, Alistipes, Anaerostipes, and Terrisporobacter.DiscussionBased on a network approach, this study suggests a set of genera that can serve as a potential biomarker to distinguish the distinct degree of advances in T2D for a Mexican cohort of patients. Beyond limiting our conclusion to one population, we present a computational pipeline to link ecological networks and clinical stages in T2D, and desirable aim to advance in the field of precision medicine.</p

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

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)