Abstract

In August, 2019, the US Department of Energy Office of Science awarded US$10 million to the National Microbiome Data Collaborative, the aim of which is to support the research community by providing open access to multidisciplinary microbiome data and a suite of bioinformatic tools for advanced analyses. The award reflects the vast amount of data that is being generated on the composition and function of the microbiome in an array of organisms and environments. Although studies of the human lung microbiome have trailed behind those of the gut, it is now clear that both have an important part to play in lung disease and critical illness. A concerted effort is needed to identify and address gaps in understanding to allow the microbiome to be targeted for the prevention and treatment of disease. Over the past two decades, the microbiome has been implicated in the pathogenesis and progression of a range of lung diseases, including those long thought to have a microbial basis (eg, asthma, chronic obstructive pulmonary disease, and cystic fibrosis) and conditions that were traditionally regarded as sterile (eg, idiopathic pulmonary fibrosis [IPF], acute respiratory distress syndrome, and lung cancer). For example, that early-life microbial exposures have long-term consequences in terms of asthma susceptibility is well established. Perhaps more surprising were the findings that lung microbiota are predictive of disease progression in IPF, and that crosstalk between commensal microbiota and the host immune system is linked to lung tumour development. The huge potential of the microbiome as a rich source of therapeutic targets and of diagnostic and prognostic markers of disease is now beyond question, but investment in and a commitment to new lines of research are needed to realise this potential in respiratory medicine and critical care. First-generation microbiome studies were descriptive, using 16S rRNA gene sequencing to characterise gut and lung microbiota in disease states. As the field has matured, the focus has shifted to mechanistic studies in vitro and in animal models, and longitudinal studies and randomised controlled trials in humans, which allow researchers to establish how the microbiome and host–microbiota interactions change over time in relation to disease states, therapies, and clinical outcomes. Ambitious multicentre, multidisciplinary consortium studies are the next step—including efforts to explore variations in the microbiome between populations and geographical regions—with a focus on standardisation and data sharing. New methods to characterise the microbiome (eg, nanopore sequencing and so-called culturomics) and to integrate and interrogate multi-omics data provide an opportunity to vastly expand our knowledge of the composition and function of the microbial community. A broadening of the scope of research is now needed, looking beyond bacteria to the roles of the virome and mycobiome. A Series of two papers in this issue highlights gaps in understanding and considers future directions for the study of the microbiome in respiratory disease. Charissa Naidoo and colleagues focus on the microbiome in tuberculosis. Although infectious diseases have been somewhat neglected compared with non-communicable diseases in studies of the microbiome, preliminary evidence suggests that microbiota of the respiratory tract and gut have a role in tuberculosis pathogenesis, treatment, and clinical outcomes. Tuberculosis treatment has long-term effects on human microbiome diversity, with health implications for patients in recovery, both during and after the completion of treatment. In a second paper, Kurtis Budden and colleagues review the mechanisms by which microbes interact with host immunity, their role in the pathogenesis and exacerbations of chronic respiratory diseases, and their interactions with common therapies. The next steps proposed by these groups of authors will be key to establishing directions of causality and understanding the clinical implications of findings in the field. The microbiome is increasingly recognised as a source of interindividual variability in the course of disease and response to treatment. In therapeutic trials, the microbiome should now be considered as an important component of patient heterogeneity. As data continue to accumulate, the challenge will be to translate research findings into clinical interventions for improved health outcomes. We are on the cusp of a new era of precision medicine, in which the microbiome informs diagnosis, prognosis, and risk stratification for therapies, and is a target of new therapeutic approaches.

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