In this Review, Ruff, Greiling and Kriegel discuss the mechanisms through which the microbiota contributes to the predisposition, initiation and perpetuation of immune-mediated diseases, and explore the therapeutic avenues that either target the microbiota, the barrier surfaces or the host immune system to restore tolerance and homeostasis.
Diet, microbiome and immune homeostasis
Nutrition and diet influence human health and development through their effects on the gut microbiome and host immune homeostasis. These mechanisms are involved in a wide range of conditions and diseases, such as metabolic syndrome and immune-mediated diseases. This Collection contains Reviews from Nature Reviews Microbiology, Nature Reviews Gastroenterology & Hepatology and Nature Reviews Immunology that explore the relationship between diet, the microbiome and immunity, and the potential for novel diagnostic, preventive and therapeutic interventions.
Exclusion diets are popular in the management of irritable bowel syndrome (IBS). This Review outlines the mechanisms by which food might lead to symptoms in IBS and discusses different approaches to how exclusion diets can be evaluated in randomized controlled trials.
Alterations in the gut microbiota and metabolite profiles of patients with IBD have been described. In this Review, Lavelle and Sokol discuss these alterations and their pathophysiological basis, and identify future targets for precision therapeutic modulation.
This Review describes the breakdown of ‘mucosal firewalls’ in patients with inflammatory bowel disease, involving immunological pathways that regulate microbial recognition and killing, immune responses to microorganisms and the reinforcement of the intestinal barrier.
In this Review, Kolodziejczyk, Zheng and Elinav describe the latest advances in understanding diet–microbiota interactions, the individuality of gut microbiota composition and how this knowledge could be harnessed for personalized nutrition strategies to improve human health.
Here, the authors describe how metabolic disorders, such as type 2 diabetes and nonalcoholic fatty liver disease, are driven by alterations in the composition of the intestinal microbiota and its metabolites, which translocate from the gut across a disrupted intestinal barrier and contribute to metabolic inflammation.
The gut microbiota has been implicated in a range of diseases. This Review describes current understanding of probiotics and prebiotics as a means to manage the microbiota to improve host health, including mechanisms of actions and potential for clinical use.
In this Opinion article, Sonnenburg and Sonnenburg explore whether individuals in the industrialized world may be harbouring a microbial community that is now incompatible with human biology, and they hypothesize that the modern, industrial lifestyle has contributed to alterations in the microbiota that may be linked to the deterioration of human health.
The intestinal microbiota profoundly shapes host physiology through its production of small molecules and metabolites. Here, Honda and colleagues discuss how these microbial products shape immune function. They further consider the potential of ‘mining’ the microbiota for new microbial and metabolite-based immunotherapies.
Dietary salt can have direct effects on immune cell subsets as well as indirect effects through intestinal dysbiosis. We are beginning to appreciate that high salt diets not only are associated with increased risk of cardiovascular disease but also have marked effects on immune responses.
Clostridium difficile is an intestinal pathogen and a major cause of antibiotic-associated diarrhoea. In epidemics in recent years, hypervirulent ribotypes that cause severe disease have emerged, but the factors that contribute to their emergence are unclear. In this study, Robert Britton and colleagues show that two phylogenetically distinct hypervirulent ribotypes, RT027 and RT078, have independently acquired mechanisms to metabolize low concentrations of the disaccharide trehalose. The team also show that this ability to metabolize trehalose correlates with disease severity in a humanized mouse model. These data suggest a correlation between the emergence of these ribotypes and the widespread adoption and use of trehalose as a sugar additive in the human diet.
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.
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 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.
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 gut commensal Blautia producta secretes a lantibiotic that reduces colonization of the gut by the major pathogen vancomycin-resistant Enterococcus faecium, and transplantation of microbiota with high abundance of the lantibiotic gene enhances resistance to colonization in mice.
Screening of a library of bile acid metabolites revealed two derivatives of lithocholic acid that act as regulators of T helper cells that express IL-17a and regulatory T cells, thus influencing host immune responses.
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 biosynthetic pathway that produces the secondary bile acids DCA and LCA in human gut microbes has been fully characterized, engineered into another bacterial host, and used to confer DCA production in germ-free mice—an important proof-of-principle for the engineering of gut microbial pathways.
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.
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 .
A proof-of-concept clinical study shows that perturbations to the gut microbiome affect nutrient absorption in humans.
Members of the Enterobacteriaceae, including adherent invasive Escherichia coli, reprogram their metabolism to preferentially consume dietary serine during periods of inflammation in the gut to promote their growth and outcompete other microbiome members.
Cooked and raw plant diets cause different changes in gut microbiome composition and function, including mechanisms of starch digestibility and xenobiotic availability, and consequently impact host energy status.
Klebsiella michiganensis transmission enhances resistance to Enterobacteriaceae gut invasion by nutrition competition
Co-housing mice is shown to induce resistance against enterobacterial infection after antibiotic treatment through the ability to retain or share Klebsiella michiganensis, which is necessary and sufficient to prevent infection through competition for nutrients.
c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis
An intricately linked homeostasis exists between the gut microbiome and host immune system. Scheffold and colleagues show that intestinal Treg cells upregulate the transcription factor c-Maf in response to specific signals from the gut microenvironment to establish host–microbiota homeostasis.
The gut microbiota and their proximate immune cells engage in a dialog of reciprocal regulation. James and colleagues describe how immune cell and microbiotal populations vary along the length of the human colon.
Engineered commensal microbes that transform natural compounds present in cruciferous vegetables into an anticancer molecule prevent carcinogenesis and promote the regression of colorectal cancer in mice fed with the microbes and the vegetables.
Gut microbiome composition is remodeled using small peptides.
Intermittent fasting (IF) has been shown beneficial in reducing metabolic diseases. Here, using a multi-omics approach in a T2D mouse model, the authors report that IF alters the composition of the gut microbiota and improves metabolic phenotypes that correlate with cognitive behavior.
Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease
Inflammatory bowel disease (IBD) has been linked to host-microbiota interactions. Here, the authors investigate mucosa-associated microbiota using endoscopically-targeted biopsies from inflamed and non-inflamed colon in patients with Crohn’s disease and ulcerative colitis, finding associations with inflammation and host epigenomic alterations.
Maternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring
Incidence of food allergy in westernized populations is associated with low abundance of Prevotella. Here, the authors analyse the microbiome of a mother-infant prebirth cohort and find that maternal carriage, but not infant carriage, of P. copri during pregnancy predicts the absence of food allergy in the offspring.
Ceramides are a type of sphingolipid (SL) that have been shown to play a role in several metabolic disorders. Here, the authors investigate the effect of SL-production by gut Bacteroides on host SL homeostasis and show that microbiome-derived SLs enter host circulation and alter ceramide production.