Human microbiome ecology
The Vieira-Silva Lab explores the ecology of host-associated microbial communities, with a focus on the human gastrointestinal tract. Our research focuses on understanding the ecological dynamics of human gut-associated microbial communities in healthy host-microbiome homeostasis and how their disturbance contributes to the risk of disease onset or progression. We apply quantitative approaches to population cohort studies and intervention trials to identify the mechanisms that drive the dynamics of the gut ecosystem in health, the determinants of its resilience to perturbations and the alterations that contribute to disease (dysbiosis).
The Vieira-Silva Lab explores gut microbiota dynamics in health and disease in population cohorts, pre- and post-clinical (therapeutic) interventions and across short-term perturbation studies. Our research aims to unravel the mechanisms that determine microbiota resilience or, on the other hand, those that contribute to an increased risk of disease development. We also focus on tracking the metabolic capacity of the gut microbiota and its symbiotic or deleterious association with the host, including through bidirectional interactions with the immune system. Our objectives are to identify and quantify the contribution of the gut microbiome to the risk of disease development and help develop microbiota remediation strategies for (combined) therapeutic interventions. For this aim, we favour hypothesis-driven experimental design and invest in developing experimental and computational approaches to study human-associated microbial communities. In particular, we invest in the continuous development of bioinformatic tools to extract interpretable traits from metagenomic data, as well as computational approaches to quantify ecological dynamics and host-microbiome interactions. In parallel, we develop novel experimental approaches, striving to obtain high-quality and high-resolution quantitative multi-omics and clinical data (notably strain-level quantitative microbiome profiling based on parallelisation of microbiome sequencing and quantifying total microbial density by flow cytometry).
Research track #1 – Ecological dynamics and resilience of human gut microbiota
The gut microbiota displays high variation, even in cross-sections of healthy human populations. Our research invests in defining the boundaries of gut microbiota variation in healthy individuals and disentangling host and lifestyle covariates that affect the composition and metabolic potential of the gut microbiota without necessarily causing disease. We exploit population-level prospective studies such as the Gutenberg Health Study (GHS, n=15,000, Mainz, Germany), which include both microbiome and extensive clinical monitoring of an average section of the population to characterise normal ecosystem (eubiosis) variation as a necessary step towards studying aberrant microbiota states (dysbiosis). Using quantitative metagenomic profiling of the microbiota composition, we disentangle host and lifestyle covariates that affect the composition and metabolic potential of gut communities without perturbing health.
Research track #2 – Microbiome resilience in healthy ageing
Microbiome disturbance, or the development of dysbiosis, is considered one of the hallmarks of ageing. After primary colonisation of the gut habitat in infancy, the colon microbiota of healthy individuals stabilises and fluctuates between a limited set of mature, eubiotic configurations. With age, the microbiota tends to steadily diversify, with the human host gradually acquiring a larger set of colonisers through diet, social interactions and environmental exposure. At the other end of the health spectrum, ageing is also associated with an increased prevalence of dysbiosis, characterised by an abrupt loss of microbial diversity and a dramatic reduction in the abundance of keystone species. Development of dysbiosis can be linked to disease susceptibility, a more pronounced systemic inflammatory tone and, specifically among elderly individuals, frailty and immunosenescence. By assessing microbiome variation across a range of ages in population cohorts, we aim to disentangle health- and lifestyle-associated environmental and microbiome-intrinsic drivers of gut ecosystem stability and resilience in healthy ageing. This in turn provides a valuable step towards the development of novel microbiota modulation strategies to prevent or counter the development of age-associated dysbiosis.
Research track #3 – Host-microbiome-drug interactions in disease
Both academics and pharmaceutical companies are currently carrying out drug intervention trials with microbiota monitoring to evaluate how microbiota composition impacts treatment response or to identify drugs with the potential to be repurposed for microbiota remediation. As part of the BMBF Cluster of Excellence CurATime, the Vieira-Silva Lab explores the contribution of the gut microbiome to the risk of cardiovascular disease and atherothrombosis development with age in cohorts that have been extensively clinically phenotyped. We aim to identify gender-specific microbiome signatures that will help stratify patients for better drug allocation and define early risk markers of disease progression or outcome, and in the long-term, contribute to the development of novel therapeutic approaches in cardiovascular disease.
Research track #4 - Mechanistic modelling of host-microbiota interactions
Mechanistic models allow us to test and obtain mechanistic insights and develop new hypotheses. Microbiome research itself has evolved to generate quantitative, reproducible and higher resolution data, making it possible to adopt modelling approaches. Our goal is to invest in building interpretable mechanistic models of host-microbiome interactions in order to unravel microbiota-host and microbe-microbe interactions of clinical importance. We focus in particular on microbiota-immune system interactions that are associated with metabolic and cardiovascular disease progression.
PhD students & postdocs: We foster a diverse environment to promote collaborative interdisciplinary research projects. If you are interested in working with us, please send an inquiry to sara.vieira-silva(at)uni-mainz.de, with the subject “[PhD or Postdoc] position at Vieira-Silva Lab”. Please include a CV and a brief motivation letter stating your past experience and research interests and why you would want to work with us.