Some non-antibiotic drugs have been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Athanasios Typas and colleagues screened more than 1,000 marketed drugs and observed that a quarter of them inhibited the growth of at least one bacterial strain in vitro. Scrutiny of previous human cohort studies showed that human-targeted drugs with anticommensal activity have antibiotic-like side effects in humans. The new data provide a resource for future drug-therapy research.
The microbial communities that inhabit our gastrointestinal tract, termed the gut microbiota, are well known to play a fundamental role in many host processes, and our understanding of these complex communities continues to advance at a rapid pace. Research has characterized the gut microbiota in health and disease at increasing resolution, aided by the continuous development of tools and approaches. Greater mechanistic understanding of how our microbial partners, including the non-bacterial members, contribute to or protect against disease is a major focus of recent initiatives with the ultimate goal of translating these findings into clinical applications.
This collection brings together Research, Reviews and Comment published in several Nature journals covering key topics on the gut microbiota. The selected content has been published over the past year in Nature, Nature Microbiology, Nature Medicine, Nature Genetics, Nature Communications, Nature Reviews Microbiology, Nature Reviews Genetics and Nature Reviews Gastroenterology and Hepatology, some of which have been made freely available for 6 months, thanks to support from Yakult Honsha Co., Ltd.
Phospholipase Ds (PLDs) transform phosphatidylcholine to choline, which can then be converted to disease-associated trimethylamine. Here, PLDs are identified in gut bacteria that support growth of other bacteria and are potential therapeutic targets.
Infant diet and maternal gestational weight gain predict early metabolic maturation of gut microbiomes
Infant nutrition and maternal weight gain during pregnancy impact early-life acquisition and function of the gut microbiome .
Comprehensive fecal metabolic profiling in 786 individuals from TwinsUK provides insights into the influence of host genetics and gut microbial composition on metabolites that may mediate microbiome-associated phenotypes.
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.
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Metagenomic sequencing analysis of stool samples from 903 children as part of the TEDDY study shows that breastfeeding was the most important factor associated with microbiome structure, and the cessation of breast milk resulted in faster maturation of the gut microbiome.
An analysis of more than 10,000 metagenomes from the TEDDY study provides a detailed functional profile of the gut microbiome in relation to islet autoimmunity, and supports the protective effects of short-chain fatty acids in early-onset type 1 diabetes.
The authors compare human fecal viromes from three isolated villages of the Amazon rain forest with those from city dwellers. They report that the diversity of human viruses is not reduced in isolated villages, suggesting frequent viral introductions or increased susceptibility to enteric infections.
Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential
The effects of caesarean section delivery on mother-to-neonate transmission of microbiota are unclear. Here the authors show that caesarean section delivery can affect the transmission of specific microbial strains and the immunomodulatory potential of the microbiota.
Delayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation
Gut microbial dysbiosis in infancy is associated with childhood atopy and the development of asthma. Here, the authors show that gut microbiota perturbation is evident in the very earliest stages of postnatal life, continues throughout infancy, and can be partially rescued by Lactobacillus supplementation in high-risk for asthma infants.
Gut microbiota associations with common diseases and prescription medications in a population-based cohort
The human gut microbiome has been associated with many health factors, but variability between studies limits exploration of these effects. Here, Jackson et al. analyse gut microbiota associations for 38 common diseases and 51 medications within >2700 members of the TwinsUK cohort.
Recent microbiome genome-wide association studies have identified numerous associations between human genetic variants and the gut microbiome. Here, the authors review how genetic variation in the host can alter the composition of the gut microbiome towards a disease state, with a focus on disorders of immunity and metabolism.
A new bioinformatic tool identifies a candidate source of bloodstream infection for better management and prevention of hospital-acquired infections.
Lipopeptides secreted by Bacillus bacteria block quorum sensing by Staphylococcus aureus and thereby inhibit the growth of this opportunistic pathogen in the gut, suggesting why people in rural Thailand who are colonized by Bacillus are not also colonized by S. aureus.
Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome
Genome-wide and metagenome-wide association study of 92 cardiovascular-diseases-related proteins identifies genetic and microbial factors that explain 76.6% of inter-individual variation, highlighting the role of gut microbiome in cardiovascular disease.
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.
Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota
Antimicrobial peptide resistance genes are found to be widespread in the gut microbiome but are exchanged at lower rates compared to antibiotic resistance genes, with functional compatibility between bacteria being important for gene exchange.
Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis
Klebsiella pneumoniae from the gut microbiota of patients with primary sclerosing cholangitis (PSC) can damage the intestinal epithelial barrier, resulting in bacterial translocation and T helper 17 cell responses in the liver, indicating a role in PSC pathogenesis.
Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life
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.
The composition of the human gut microbiome is determined by many factors. Eran Segal and colleagues performed an extensive statistical analysis of the largest metagenomics-sequenced human cohort so far to determine the contribution of host genotype to microbiome composition. Host genetics has only a minor influence on microbiome variability, which is more strongly associated with environmental factors such as diet. The authors propose a 'microbiome-association index' that describes the association of the microbiome with host phenotype. Combining this measurement with host genetic and environmental data improves the accuracy of predictions about several human metabolic traits, such as glucose and obesity traits.
Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography
Stool microbiota composition correlates with the ethnic backgrounds of people living in the same city, suggesting that geographical location and ethnicity have distinct effects on microbiota.
Regional variation limits applications of healthy gut microbiome reference ranges and disease models
The definition of a 'healthy' microbiome is impacted by geographic regional variations.
Here the authors show that the human gut microbiome can recover after a clinically relevant, broad-spectrum antibiotic treatment and characterization of the resistome indicates that antibiotic resistance genes can impact the recovery process.
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.
Here the authors have characterized the growth of 96 human gut bacteria on a range of defined media, providing valuable insights into their metabolic capabilities and unique media for future studies.
Roseburia intestinalis is a butyrate-producing member of the gut microbiome that can use dietary plant polysaccharides to alter host metabolism, transcription and epigenetics, and lower inflammation and endotoxaemia, resulting in reduced atherosclerosis.
Preliminary evidence from two cases suggests that fecal microbiota transplantation may provide a viable treatment option for a severe adverse effect of immune checkpoint blockade therapy in patients with cancer.
Expansion of facultative anaerobic bacteria of the Enterobacteriaceae family in the gut is associated with dysbiosis—an imbalance in the microbiota—and inflammatory bowel disease. Sebastian Winter and colleagues show that tungstate treatment, which selectively inhibits molybdenum-cofactor-dependent microbial respiratory pathways that operate only during episodes of inflammation, mitigates inflammation in mouse models of colitis without causing any compositional alterations to the gut microbiota. This is a promising strategy for precision therapy of the microbiota in response to inflammatory disorders, but future work is needed to determine whether similar approaches could be relevant in humans.
Quantitative metagenomics reveals an altered bacteriophage community in a mouse model of colitis, which overlaps with that observed in humans with inflammatory bowel disease (IBD), providing a tool for interrogating phage dynamics in IBD.
Attention has turned to the gut microbiota in liver disease, including alcoholic and nonalcoholic fatty liver disease and hepatocellular carcinoma. This Review describes gut–liver communications, including evidence from animal and human studies, compares conditions within the liver disease spectrum and highlights key points for designing microbiome-based studies for liver disease research.
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.
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.
Comparing the microbiomes of great apes enables an evolutionary perspective on microbial communities. This approach is revealing not only new insights about humans and what differentiates us from our closest relatives but also the factors that influence microbiome composition and the ways in which microbiomes diverge.