Milestones in human microbiota research

These milestones present a historical perspective of the breakthroughs in the human microbiota field.

Research into human-associated microbiota has come a long way since Antonie van Leeuwenhoek first began to study microorganisms back in the 17th century. What advances allowed researchers to move from seeing single cells to studying complex microbial communities? In this audio, we hear from microbiologist David Relman, who spoke with Anand Jagatia.

Where is microbiota research headed? What needs to be done for this field to live up to its promise? In a roundtable discussion, Anand Jagatia puts these questions to Rochellys Heijtz, Jennifer Wargo and Eran Elinav, three researchers at the cutting-edge of the discipline.

Culturomics was developed to culture and identify unknown bacteria that inhabit the human gut. In this Review, Raoult and colleagues discuss the development of culturomics and how it has extended our understanding of bacterial diversity, and highlight the potential implications for human health.

Intestinal regulatory T cells (T_regcells) are distinct from those in other organs and function to maintain tolerance to harmless dietary antigens and commensal microorganisms. The unique features of these cells, as well as the signals involved in their development and maintenance, are discussed in this Review.

Current nutritional approaches to prevent and treat various diseases have limited effectiveness. Here, Zmora et al. review the major principles underlying effects of dietary constituents on the gut microbiota, resolving aspects of the diet–microbiota–host crosstalk, and present the promises and challenges of incorporating microbiome data into dietary planning.

Complex microbial communities shape the dynamics of various environments. In this Review, Knight and colleagues discuss the best practices for performing a microbiome study, including experimental design, choice of molecular analysis technology, methods for data analysis and the integration of multiple omics data sets.

The microbiota can influence host behaviour through the gut–brain axis. In this Opinion, Johnson and Foster explore the evolution of this relationship and propose that adaptations of competing gut microorganisms may affect behaviour as a by‑product, leading to host dependence.

Faecal microbiota transplantation (FMT) has emerged as a successful treatment forClostridium difficileinfection (CDI). Here, the authors describe the latest information on the mechanisms of action of FMT in the context of CDI and how it might restore the gut microbial community and structure. They also explore future applications of FMT beyond CDI.

The gut microbiota, traditionally studied in the context of disease, has emerged as a key regulator during normal homeostasis. Here, Sommer and Bäckhed discuss how the gut microbiota promotes the development and homeostasis of the immune system and orchestrates several aspects of human physiology, including tissue morphogenesis, metabolism and even behaviour.

In this Review, Turnbaugh and colleagues discuss several mechanisms by which the human gut microbiome affects the metabolism of xenobiotics, including drugs and dietary compounds, and explore how this knowledge can be applied to improve the treatment of human disease.

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.

Over ten years, the Human Microbiome Project has provided resources for studying the microbiome and its relationship to disease; this Perspective summarizes the key achievements and findings of the project and its relationship to the broader field.

Colonization of the infant gut by viruses, bacteriophages and bacteria over the first two years of life.

The human gut microbiome from a large cohort of more than 500 indivduals living on three continents with three distinct cultures is analysed, emphasizing the effect of host age, diet and environment on the composition and functional repertoire of fecal microbiota.

Whole-genome shotgun sequencing and sequencing of the gene encoding the 16S rRNA in samples from a variety of body sites in a large cohort of mothers and their infants reveals that, during the 6 weeks after birth, changes in the composition and function of the microbiome are driven by body site but not by the mode of delivery.

Integration of longitudinal gut metagenomic datasets from children in Finland, Estonia and Russian Karelia reveals high strain-level diversity, which consequently impacts the functional capabilities of the early life microbiome.

Bacterial species whose representation defines healthy postnatal assembly of the gut microbiota in Bangladeshi children during their first 2 years are identified, and a model is constructed to compare healthy children to those with severe acute malnutrition (SAM); results show that SAM is associated with microbiota immaturity that is only partially ameliorated by existing nutritional interventions.

A framework for metagenomic variation analysis to explore variation in the human microbiome is developed; the study describes SNPs, short indels and structural variants in 252 faecal metagenomes of 207 individuals from Europe and North America.

Metagenomic and metatranscriptomic analyses of stool samples from 308 individuals over time indicate that longitudinal sampling is important for detecting dynamic functional features of the gut microbiome.

Bacteroides fragilis is a member of the human intestinal microbiota. It is reported that a single molecule produced by this bacterium, polysaccharide A, can suppress the intestinal inflammatory response and thus protect from experimental colitis.

The effect of deficiency of MyD88 on the generation of type 1 diabetes (T1D) has been investigated through the generation of congenic strains in the non-obese diabetic (NOD) mouse model. It is found that in specific pathogen-free conditions, MyD88-deficiency attenuates T1D, indicating that the interaction of intestinal microbes with the innate immune system is a critical factor in modifying susceptibility to type 1 diabetes.

Finely tuned control of strain engraftment and abundance in the mouse gut microbiota was achieved using the marine polysaccharide porphyran, which could exclusively be used by an introduced subset of wild-type or genetically modified Bacteroides strains.

Bifidobacteria are natural inhabitants of the human gut and are known to provide protection from infection. It is now shown that certain features of bifidobacterial metabolism that ultimately lead to the production of acetate are involved in this effect.

A fraction of the intestinal microbiota as precise as a single bacterial species confers infection resistance by synthesizing Clostridium difficile-inhibiting metabolites from host-derived bile salts.

Using metabolomics and shotgun metagenomics on stool samples from individuals with and without inflammatory bowel disease, metabolites, microbial species and genes associated with disease were identified and validated in an independent cohort.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

Statistical analyses of a metagenomics-sequenced human cohort identify a relatively minor role for genetics in determining microbiome composition and show that several human phenotypes are as strongly associated with the gut microbiome as with host genetics.

As part of the second phase of Human Microbiome Project, the Multi-Omic Microbiome Study: Pregnancy Initiative presents a community resource to help better understand how microbiome and host profiles change throughout pregnancy as well as to identify new opportunities for assessment of the risk of preterm birth.

Deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, alongside changes in the microbiome, in samples from individuals with and without prediabetes reveal insights into inter-individual variability and associations between changes in the microbiome and other factors.

The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.

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.

Gut microbes influence our health and may contribute to human adaptation to different lifestyles. Here, the authors describe the gut microbiome of a community of hunter-gatherers and identify unique features that could be linked to a foraging lifestyle.

This study identifies 17 strains of human-derived Clostridia capable of inducing the accumulation and functional maturation of regulatory T cells; it is suggested that these strains may be useful candidates for the future development of oral bacterial therapeutics to treat human inflammatory disorders.

In mice, provision of butyrate—a short-chain fatty acid produced by commensal microorganisms during starch fermentation—facilitates extrathymic generation and differentiation of Foxp3⁺ regulatory T cells, demonstrating that metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells.

The nasal commensal bacterium Staphylococcus lugdunensis produces a novel cyclic peptide antibiotic, lugdunin, that inhibits colonization by S. aureus in animal models and is associated with a significantly reduced S. aureus carriage rate in humans, suggesting that human commensal bacteria could be a valuable resource for the discovery of new antibiotics.

Growing evidence from metagenome-wide association studies link multiple common disorders to microbial dysbiosis but effects of drug treatment are often not accounted for; here, the authors re-analyse two previous metagenomic studies of type 2 diabetes mellitus patients together with a novel cohort to determine the effects of the widely prescribed antidiabetic drug metformin and highlight the need to distinguish the effects of a disease from the effects of treatment on the gut microbiota.

A consortium of 11 bacterial strains from the healthy human gut microbiota can strongly induce interferon-γ-producing CD8 T cells in the intestine, and enhance both resistance to bacterial infection and the therapeutic efficacy of immune checkpoint inhibitors.

The known species repertoire of the collective human gut microbiota is substantially expanded with the discovery of 1,952 uncultured bacterial species that greatly improve classification of understudied African and South American samples.

Draft prokaryotic genomes from faecal metagenomes of diverse human populations enrich our understanding of the human gut microbiome by identifying over two thousand new species-level taxa that have numerous disease associations.