Wendy Garrett is the Irene Heinz Given Professor of Immunology and Infectious Diseases at the Harvard T. H. Chan School of Public Health and a Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School. She is co-director and co-founder of the Harvard Chan Microbiome in Public Health Center. Dr. Garrett’s team explores interactions between the gut microbiome and the immune system, both in physiological and pathological conditions, with a focus on inflammatory bowel diseases and colorectal cancer. Her team has identified microbial species, functions, and metabolites influencing host health and disease by using an interdisciplinary approach bridging meta’omics, microbiology, cellular immunology, biochemistry, cell biology, and cancer biology. The mission of Dr. Garrett’s lab is to identify basic biologic mechanisms to be applied to precision medicine.
Gut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort
As part of the Estonian Biobank, we established the Estonian Microbiome Cohort which includes stool, oral and plasma samples from 2509 participants and is supplemented with multi-omic measurements, questionnaires, and regular linkages to national electronic health records. Here we analyze stool data from deep metagenomic sequencing together with rich phenotyping, including 71 diseases, 136 medications, 21 dietary questions, 5 medical procedures, and 19 other factors. We identify numerous relationships (n = 3262) with different microbiome features. In this study, we extend the understanding of microbiome-host interactions using electronic health data and show that long-term antibiotic usage, independent from recent administration, has a significant impact on the microbiome composition, partly explaining the common associations between diseases.
Kertu Liis Krigul and Oliver Aasmets
Institute of Genomics, University of Tartu
Evaluation of microbiome enrichment and host DNA depletion in human vaginal samples using Oxford Nanopore’s adaptive sequencing
Metagenomic sequencing is promising for clinical applications to study microbial composition concerning disease or patient outcomes. Alterations of the vaginal microbiome are associated with adverse pregnancy outcomes, like preterm premature rupture of membranes, and preterm birth. Methodologically these samples often have to deal with low relative amounts of prokaryotic DNA and high amounts of host DNA (> 90%), decreasing the overall microbial resolution. Nanopore’s adaptive sampling method offers selective DNA depletion or target enrichment to directly reject or accept DNA molecules during sequencing without specialized sample preparation.
University Hospital Jena
C. difficile is overdiagnosed in adults and a commensal in infants
Clostridioides difficile is an urgent threat in hospital-acquired infections world-wide, yet the microbial composition associated with C. difficile, in particular in C. difficile infection (CDI) cases, remains poorly characterised. Here, we analysed 534 metagenomes from 10 publicly available CDI study populations. While we detected C. difficile in only 30% of CDI samples, multiple other toxigenic species capable of inducing CDI-like symptomatology were prevalent, raising concerns about CDI overdiagnosis. We further tracked C. difficile in 42,814 metagenomic samples from 253 public studies. We found that C. difficile prevalence, abundance and association with other bacterial species is age-dependent. In healthy adults, C. difficile is a rare taxon associated with an overall species richness reduction, while in healthy infants C. difficile is a common member of the gut microbiome and its presence is associated with a significant increase in species richness. More specifically, we identified a group of species co-occurring with C. difficile exclusively in healthy infants, enriched in obligate anaerobes and in species typically found in the gut microbiome of healthy adults. Overall, gut microbiome composition in presence of C. difficile in healthy infants is associated with multiple parameters linked to a healthy gut microbiome maturation towards an adult-like state. Our results suggest that C. difficile is a commensal in infants, and that its asymptomatic carriage is dependent on the surrounding microbial context.
Maternal metformin treatment persistently ameliorates high-fat diet-induced metabolic symptoms and modulates gut microbiota in rat offspring
Background: Maternal high-fat (HF) diet has long-term deleterious effect on offspring’s metabolic phenotype. The aim of this study was to evaluate whether maternal metformin (MT) administration ameliorates the negative effects of maternal HF diet on offspring and the role of gut microbiota and microbial bile acids (BAs) in it.
Methods: After mating, the pregnant Sprague-Dawley rats were randomly assigned to HF diet (60% fat) or standard CHOW diet (11.8% fat) group, and some of the HF diet group rats were co-treated with MT via drinking water (300 mg/kg/day), resulting in three groups according to maternal diet and MT treatment during gestation and lactation. All offspring were weaned on CHOW diet. The intestinal tissues and colon content of offspring rats were collected. In addition, offspring’s hypothalamus gene expression and BA content in plasma of adult male offspring was analyzed.
Results: Maternal HF diet resulted in increased body weight and adipose depots, increased intestinal and hypothalamic inflammation, changed gene expression of intestinal tight junctions and hypothalamic appetite markers in both male and female offspring at weaning, which continued into adulthood. The effects of maternal HF diet on offspring were alleviated by maternal MT administration. Interestingly, offspring’s microbiota composition in adulthood was profoundly influenced by maternal HF diet and MT administration. Furthermore, the plasma BA content was normalized by maternal MT administration in adult male offspring of HF-fed dams, and maternal MT administration significantly enriched the proportion of the beneficial Lactobacillus genera, which were negatively correlated with plasma unconjugated BA levels.
Conclusions: This study demonstrated the beneficial effects of maternal MT administration on offspring’s metabolic phenotype, focusing on the microbiota-BA-hypothalamus axis. The present study indicates that maternal MT administration could reshape the gut microbiota in adult offspring, normalize offspring’s plasma BA levels and gene expression of hypothalamic appetite markers, which may contribute to the beneficial effects of maternal MT exposure on offspring’s metabolic phenotype.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
Software testing in microbial bioinformatics: a call to action
Computational algorithms have become an essential component of microbiome research, with great efforts by the scientific community to raise standards on the development and distribution of code. Despite these efforts, sustainability and reproducibility are major issues since continued validation through software testing is still not a widely adopted practice. In the field of microbial bioinformatics, good software engineering practices are not yet widely adopted. Many microbial bioinformaticians start out as (micro)biologists and subsequently learn how to code. Without abundant formal training, a lot of education about good software engineering practices comes down to an exchange of information within the microbial bioinformatics community. Here, we report seven recommendations that help researchers implement software testing in microbial bioinformatics. These recommendations are: Establish software needs and testing goals; Use appropriate input test files; Use an easy-to-follow language format to implement testing; Try to automate testing; Test across multiple computational setups; and Encourage others to test your software. We propose collaborative software testing as an opportunity to continuously engage software users, developers, and students to unify scientific work across domains. As automated software testing remains underused in scientific software, our set of recommendations not only ensures appropriate effort can be invested into producing high quality and robust software but also increases engagement in its sustainability. We have developed these recommendations based on our experience from a collaborative hackathon organised prior to the American Society for Microbiology Next Generation Sequencing (ASM NGS) 2020 conference. We also present a repository hosting examples and guidelines for testing, available from https://github.com/microbinfie-hackathon2020/CSIS.
Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal