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Nine experts discuss the challenges in translating current research on the human microbiome into strategies for disease prediction, diagnosis and therapy.

Here, the authors profile the respiratory microbiome of COVID-19 patients and link clinical practices, such as mechanical ventilation, with vast changes in the microbiota. In the lungs, oral bacteria are found physically associated with proinflammatory immune cells, thus possibly contributing to exacerbated immune responses in severe disease

Quantitative metagenomic analyses of gut microbiomes reveals kinship, together with current cohabitation, as drivers of microbial community transmission and persistence between family members over three to five generations.

Here, the authors use simulated quantitative gut microbial communities to benchmark the performance of 13 common data transformations in determining diversity as well as microbe-microbe and microbe-metadata associations, finding that quantitative approaches incorporating microbial load variation outperform computational strategies in downstream analyses, urging for a widespread adoption of quantitative approaches, or recommending specific computational transformations whenever determination of microbial load of samples is not feasible.

A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs.

The Human Microbiome Project put the health-associated microbes found in humans on centre stage. The project’s second phase shows how microbial disturbance in disease is linked to host processes.

Correlation of microbiome features with host quality of life and depression identified specific taxa and microbial pathways in two independent, large population cohorts, identifying links between microbial neuroactive potential and depression.

A microbiome genome-wide association study using three large European cohorts identified several significant study-wide and genome-wide correlations between human genetic variants and microbial traits, and used Mendelian randomization to estimate causal relationships between microbial traits and disease.

The intestinal microbiome has an important role in health and disease; however, the long-term effects of lifestyle choices on microbiome alterations are incompletely understood. Here, based on extensive lifestyle and medical data collected over 26 years, Si et al. demonstrate that long-term life history can predict current enterotype in older adults.

Here, the authors report quantitative daily gut microbiome variation of individual gut bacterial abundances in healthy individuals, linked to changes in transit time and diet, highlighting the potential need for multiple samplings for microbiome target identification and the development and application of reliable microbiome diagnostics.

Here, the authors apply quantitative microbiome profiling to a metagenomics data set comprising patients with primary sclerosing cholangitis and/or inflammatory bowel disease and identify microbial taxa associated with inflammation or specific disease indicators, which were validated in an independent inflammatory bowel disease cohort.

Are the dynamics of our microbial communities unique to us or does everyone's microbiota follow the same rules? The emerging insights into this question could be of relevance to health and disease. See Letter p.259

Metagenomics has enabled researchers to compile inventories of viruses, bacteria and archaea that inhabit specific niches. Here, the authors discuss the tools that are needed for us to progress to an integrated understanding of microbial ecosystems biology.

A manually curated metabolic module framework for (meta)genomic data analysis identifies species-function relationships in gut microbial genomes and microbiomes, revealing significant genus-level metabolic diversification linked to bacterial life-strategy.

Plankton communities in the top 150 m of the nutrient-depleted, oligotrophic global ocean that are most associated with carbon export include unexpected taxa, such as Radiolaria, alveolate parasites, and Synechococcus and their phages, and point towards potential functional markers predicting a significant fraction of the variability in carbon export in these regions.

Quantitive microbiome profiling reveals that total microbial load is an important determinant of enterotypes and may be a key driver of microbiota alterations in patients with Crohn’s disease.

Correlation and co-occurrence patterns found in metagenomic and phylogenetic data sets are increasingly being used to predict species interactions in the environment. Here, Faust and Raes describe the range of approaches for predicting microbial network models, the pitfalls that are associated with each approach and the future for developing ecosystem-wide models.

The gut microbiome field is shifting from association to modulation. Microbiota-based treatments come in many shapes and sizes, ranging from dietary intervention to live bacterial products. Recent methodological advances are instrumental to developing innovative new treatment strategies in microbiome-linked pathologies.

A large-scale study has been assessing microbial diversity by analysing DNA sequences from samples submitted by scientists around the globe. The initial results are now being used to create an open-access resource. See Article p.457

To therapeutically modulate gut microbial ecosystems, a better understanding of gut ecology is key. High-throughput in vitro ecology provides a tool with the necessary power to address these needs and interpersonal treatment response variation.

Faecal microbiota richness is considered a hallmark of gut health and stability. However, in healthy hosts, richness would primarily reflect the stage of ecosystem development through the gut, rather than community resilience. This Comment discusses the need to rethink microbiome biomarkers in the context of gut ecology.

The resilience of the microbiota can protect us from disease, but a resilient dysbiotic microbiota may also cause disease. This Opinion article discusses the concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications these have for human health.

Going from description of the diversity and disease associations of the human gut microbiota towards functional understanding and applications is challenging. In this Review, Raes and colleagues present synthetic ecology approaches that reduce the complexity and advance translation of human gut microbiota research.

This Perspective debates the concept of enterotypes and their use to characterize the gut microbiome, and provides a classifier and standardized methodology to aid cross-study comparisons.