Explore the vast range of titles available.

In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health.In this Review, Morais, Schreiber and Mazmanian discuss emerging and exciting evidence of intricate and potentially important connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to complex behaviours.

Key Points The gut microbiota is spatially stratified along the longitudinal and cross-sectional axes of the gut. Chemical and nutrient gradients, antimicrobial peptides and physical features of the gut contribute to differences in microbial community composition in different locations. The mucosal and lumenal microbiota of the gut represent distinct microbial communities. On a smaller scale, patchiness within these communities suggests that they are highly spatially organized. Diet imparts a large effect on microbial colonization and relative abundance, but some bacteria can thrive independently of dietary changes by living on host-derived nutrients such as mucin glycans. Therefore, the mucus layer can harbour a reservoir of bacteria that is maintained regardless of food intake. The appendix and colonic crypts may also be examples of such microbial reservoirs. Only a subset of gut symbionts are able to access the epithelial surface. Mucus, antimicrobial peptides and adaptive immune activity limit tissue accessibility. Direct interfacing between the host and microbial symbionts may be important for the maintenance of homeostasis. Immunomodulation by certain symbionts allows the host to tolerate intimate relationships with potentially beneficial microorganisms. This may be a way in which commensals distinguish themselves from pathogens and prevent their elimination by the immune system. Although many diseases have been associated with dysbiosis, an understanding of the function of the microbiota in health and disease requires the biogeography of the community to be considered. Recent studies in humans have found differences specific to the mucosal community in cases of inflammatory bowel disease and hepatic encephalopathy. The gut microbiota has a strong impact on host physiology. In this Review, Mazmanian and colleagues describe the mechanisms that control the biogeography of bacteria in the gut and discuss the importance of the spatial localization of the gut microbiota during health and disease. Animals assemble and maintain a diverse but host-specific gut microbial community. In addition to characteristic microbial compositions along the longitudinal axis of the intestines, discrete bacterial communities form in microhabitats, such as the gut lumen, colonic mucus layers and colonic crypts. In this Review, we examine how the spatial distribution of symbiotic bacteria among physical niches in the gut affects the development and maintenance of a resilient microbial ecosystem. We consider novel hypotheses for how nutrient selection, immune activation and other mechanisms control the biogeography of bacteria in the gut, and we discuss the relevance of this spatial heterogeneity to health and disease.

Candidate phyla radiation (CPR) bacteria and DPANN (an acronym of the names of the first included phyla) archaea are massive radiations of organisms that are widely distributed across Earth’s environments, yet we know little about them. Initial indications are that they are consistently distinct from essentially all other bacteria and archaea owing to their small cell and genome sizes, limited metabolic capacities and often episymbiotic associations with other bacteria and archaea. In this Analysis, we investigate their biology and variations in metabolic capacities by analysis of approximately 1,000 genomes reconstructed from several metagenomics-based studies. We find that they are not monolithic in terms of metabolism but rather harbour a diversity of capacities consistent with a range of lifestyles and degrees of dependence on other organisms. Notably, however, certain CPR and DPANN groups seem to have exceedingly minimal biosynthetic capacities, whereas others could potentially be free living. Understanding of these microorganisms is important from the perspective of evolutionary studies and because their interactions with other organisms are likely to shape natural microbiome function.

Honeybees (Apis mellifera) are key pollinators that support global agriculture and are long-established models for developmental and behavioural research. Recently, they have emerged as models for studying gut microbial communities. Earlier research established that hindguts of adult worker bees harbour a conserved set of host-restricted bacterial species, each showing extensive strain variation. These bacteria can be cultured axenically and introduced to gnotobiotic hosts, and some have basic genetic tools available. In this Review, we explore the most recent research showing how the microbiota establishes itself in the gut and impacts bee biology and health. Microbiota members occupy specific niches within the gut where they interact with each other and the host. They engage in cross-feeding and antagonistic interactions, which likely contribute to the stability of the community and prevent pathogen invasion. An intact gut microbiota provides protection against diverse pathogens and parasites and contributes to the processing of refractory components of the pollen coat and dietary toxins. Absence or disruption of the microbiota results in altered expression of genes that underlie immunity, metabolism, behaviour and development. In the field, such disruption by agrochemicals may negatively impact bees. These findings demonstrate a key developmental and protective role of the microbiota, with broad implications for bee health.In this Review, Motta and Moran explore recent research investigating the role of the gut microbiota in honeybee biology and health, as well as the environmental factors that can impair the microbiota and the potential strategies to restore a perturbed microbiota in honeybees.

Scleractinian corals’ microbial symbionts influence host health, yet how coral microbiomes assembled over evolution is not well understood. We survey bacterial and archaeal communities in phylogenetically diverse Australian corals representing more than 425 million years of diversification. We show that coral microbiomes are anatomically compartmentalized in both modern microbial ecology and evolutionary assembly. Coral mucus, tissue, and skeleton microbiomes differ in microbial community composition, richness, and response to host vs. environmental drivers. We also find evidence of coral-microbe phylosymbiosis, in which coral microbiome composition and richness reflect coral phylogeny. Surprisingly, the coral skeleton represents the most biodiverse coral microbiome, and also shows the strongest evidence of phylosymbiosis. Interactions between bacterial and coral phylogeny significantly influence the abundance of four groups of bacteria–including Endozoicomonas- like bacteria, which divide into host-generalist and host-specific subclades. Together these results trace microbial symbiosis across anatomy during the evolution of a basal animal lineage. Associations between corals and symbiotic microorganisms could be driven by the environment or shared evolutionary history. Here, the authors examine relationships between coral phylogenies and associated microbiomes, finding evidence of phylosymbiosis in microbes from coral skeleton and tissue, but not mucus.

Honeybees are highly social insects with a rich behavioral repertoire and are a versatile model for neurobiological research. Their gut microbiota comprises a limited number of host-restricted bacterial phylotypes that are important for honeybee health. However, it remains unclear how specific gut members affect honeybee behaviors. Here, we find that antibiotic exposure disturbs the gut community and influences honeybee phenotypes under field conditions. Using laboratory-generated gnotobiotic bees, we show that a normal gut microbiota is required for olfactory learning and memory abilities. Brain transcriptomic profiling reveals distinct brain gene expression patterns between microbiota-free and conventional bees. Subsequent metabolomic analyses of both hemolymph and gut samples show that the microbiota mainly regulates tryptophan metabolism. Our results indicate that host-specific Lactobacillus strains promote memory behavior by transforming tryptophan to indole derivatives that activate the host aryl hydrocarbon receptor. Our findings highlight the contributions of specific gut members to honeybee neurological processes, thus providing a promising model to understand host-microbe interactions. Eusocial honeybee is a versatile model for neurobiological research. Here, the authors established a link between honeybee gut Lactobacillus in bee learning and memory ability via indole derivatives that activate host’s aryl hydrocarbon receptor.

The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules 1 . Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins 2 . Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs 2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors 3 , 4 . These receptors have pivotal roles in shaping host innate immune responses 1 , 5 . However, the effect of this host–microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3 + regulatory T (T reg ) cells expressing the transcription factor RORγ. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this T reg cell population. Restoration of the intestinal BA pool increases colonic RORγ +  T reg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites. Both dietary and microbial factors influence the composition of the gut bile acid pool, which in turn modulates the frequencies and functionalities of RORγ-expressing colonic FOXP3 + regulatory T cells, contributing to protection from inflammatory colitis.

In modern oceans, eukaryotic phytoplankton is dominated by lineages with red algal-derived plastids such as diatoms, dinoflagellates, and coccolithophores. Despite the ecological importance of these groups and many others representing a huge diversity of forms and lifestyles, we still lack a comprehensive understanding of their evolution and how they obtained their plastids. New hypotheses have emerged to explain the acquisition of red algal-derived plastids by serial endosymbiosis, but the chronology of these putative independent plastid acquisitions remains untested. Here, we establish a timeframe for the origin of red algal-derived plastids under scenarios of serial endosymbiosis, using Bayesian molecular clock analyses applied on a phylogenomic dataset with broad sampling of eukaryote diversity. We find that the hypotheses of serial endosymbiosis are chronologically possible, as the stem lineages of all red plastid-containing groups overlap in time. This period in the Meso- and Neoproterozoic Eras set the stage for the later expansion to dominance of red algal-derived primary production in the contemporary oceans, which profoundly altered the global geochemical and ecological conditions of the Earth. There are several competing hypotheses for the acquisition of red algal-derived plastids by eukaryotic phytoplankton. Here, the authors use Bayesian molecular clock analyses to evaluate the chronological possibility of the proposed plastid origins and transmissions.

Virtually all plants and animals, including humans, are home to symbiotic microorganisms. Symbiotic interactions can be neutral, harmful or have beneficial effects on the host organism. However, growing evidence suggests that microbial symbionts can evolve rapidly, resulting in drastic transitions along the parasite–mutualist continuum. In this Review, we integrate theoretical and empirical findings to discuss the mechanisms underpinning these evolutionary shifts, as well as the ecological drivers and why some host–microorganism interactions may be stuck at the end of the continuum. In addition to having biomedical consequences, understanding the dynamic life of microorganisms reveals how symbioses can shape an organism’s biology and the entire community, particularly in a changing world.Symbiotic interactions can be neutral, harmful or have beneficial effects for host organisms. In this Review, Drew, Stevens and King discuss the evolutionary transitions of host–microorganism symbioses along the parasite–mutualist continuum, the mechanisms underlying evolutionary changes, the selective pressures involved and common empirical approaches for studying them.

Growing evidence indicates that the mammalian microbiome can affect behaviour, and several symbionts even produce neurotransmitters. One common explanation for these observations is that symbionts have evolved to manipulate host behaviour for their benefit. Here, we evaluate the manipulation hypothesis by applying evolutionary theory to recent work on the gut–brain axis. Although the theory predicts manipulation by symbionts under certain conditions, these appear rarely satisfied by the genetically diverse communities of the mammalian microbiome. Specifically, any symbiont investing its resources to manipulate host behaviour is expected to be outcompeted within the microbiome by strains that do not manipulate and redirect their resources into growth and survival. Moreover, current data provide no clear evidence for manipulation. Instead, we show how behavioural effects can readily arise as a by-product of natural selection on microorganisms to grow within the host and natural selection on hosts to depend upon their symbionts. We argue that understanding why the microbiome influences behaviour requires a focus on microbial ecology and local effects within the host.