Balanced intestinal retinoic acid concentrations are essential to maintain immune homeostasis in the gut. In this issue of Cell Host & Microbe, Bonakdar et al, sheds light on metabolic host-microbiota interactions and elegantly links diet, microbiota and host functions at the molecular level in the context of vitamin A metabolism.

In this issue of Cell Host & Microbe, Tsai et al. (2022) provide evidence that Staphylococcus aureus should be numbered among the pathogens for which original antigenic sin governs subsequent immune responses. Their approach may restore the utility of murine models in staphylococcal vaccine development.

The plant hormone salicylic acid plays an important role in balancing plant immunity and growth. In this issue of Cell Host & Microbe, Liu et al. (2022) discovered that a long non-coding RNA, lncSABC1, promotes growth in uninfected plants and unleashes defenses when pathogens attack by transcriptionally regulating salicylic acid biosynthesis.

The gut microbiome is a critical modulator of systemic physiology, including infectious disease susceptibility. Although this niche is a reservoir for uropathogenic Escherichia coli, knowledge of its role in urinary tract infections (UTIs) is limited. We discuss two recent studies, Thänert et al. (2022) and Worby et al. (2022), that interrogate the roles of the gut-bladder axis in UTIs.

In this issue of Cell Host & Microbe, Li et al. unveil an association between HLA-B∗46:01 and HIV disease progression in Asian populations. The distinct natural killer (NK) cell signature identified in individuals carrying HLA-B∗46:01 strongly suggests that NK cell inhibition plays a role in loss of HIV control.

Tackling the ancient infectious foe of malaria, Xie et al. (2022) uncover a novel class of nucleoside analogs that selectively hijack and inhibit the tyrosine tRNA synthase of the parasite. With high potency, good oral bioavailability, and minimal host cell toxicity, these inhibitors show promise as next-generation antimalarials.

Tissue damage and persistent inflammation are distinctive features of antibiotic-resistant chronic infections. In this issue of Cell Host & Microbe, Tang et al. demonstrate that anti-folate antibiotics trigger the synthesis of a bacterial second messenger, which induces an exuberant immune response and establishes a paradigm for chronic infection.

The pathogenicity of disease-associated microbes varies widely between individuals. In this issue of Cell Host & Microbe, Rice et al. demonstrate that interactions between intestinal commensals reciprocally modulate the host immune response to each microbe, ameliorating the inflammation caused by one and dampening antibody responses to the other.

Type 1 CD8 T cells (Tc1s) have been implicated in liver injury in autoimmune hepatitis (AIH) through mechanisms that have so far been unclear. In this issue of Cell Host & Microbe, Pandey et al. show that the aryl hydrocarbon receptor ligand-producing pathobiont Lactobacillus reuteri induces Tc1-mediated AIH-like pathology in mice with Tet-methylcytosine-dioxygenase-2 deficiency.

Broad-spectrum antibiotics should prevent disease, right? In this issue of Cell Host & Microbe, Drummond et al. turn logic on its head and show they actually drive more deadly invasive fungal-bacterial systemic co-infection. Prophylactic antibiotics increase susceptibility to these infections by targeting the commensal microbes required for gut-derived IL-17-mediated immunity.

Gut microbiota transcripts are notoriously hard to record accurately during perturbations because it is difficult to collect the signals near the source and at the time of variation. A recent study by Schmidt et al. in Science demonstrates a technology that overcomes these barriers.

The human gut virome, which is often referred to as the “dark matter” of the gut microbiome, remains understudied. A better understanding of the composition and variations of the gut virome across populations is critical for exploring its impact on diseases and health. A series of advances in the characterization of human gut virome have unveiled high genetic diversity and various functional potentials

Viruses are obligate intracellular parasites. Despite their dependence on host cells, viruses are evolutionarily autonomous, with their own genomes and evolutionary trajectories locked in arms races with the hosts. Here, we discuss a simple functional logic to explain virus macroevolution that appears to define the course of virus evolution. A small core of virus hallmark genes that are responsible

In this issue of Cell Host & Microbe, Le et al. discover that addition of exogenous Bacteroides sphingolipids can reverse lipid accumulation in the liver in a mouse model of hepatic steatosis. An elegant labeling strategy also revealed a unique microbially produced sphingolipid that was able to transit to the liver.

The gut microbial ecosystem is governed by complex microbe-microbe interactions, with most documented as interspecies relationships. In this issue of Cell Host & Microbe, Özçam et al. identified intraspecies competition among related strains of the gut symbiont Limosilactobacillus reuteri that are mediated via the antimicrobial activity of polyketide synthase (PKS).

In the complex gastrointestinal tract landscape, competition for resources is fierce among microbes. One way to avoid conflict is migration to a different microhabitat. In this issue of Cell Host & Microbe, Liou et al. demonstrate how a commensal and pathogen differ in how and where they acquire nitrate.

Inter-individual variability in the gut microbiome confounds efforts to understand host responses to dietary fiber. In this issue of Cell Host & Microbe, Lancaster et al. report individual and generalized host and microbiome responses in an interventional study of fiber supplements, motivating consideration of an alternative classification of fiber.

Given the worldwide epidemic of diet-related chronic diseases, evidence-based dietary recommendations are fundamentally important for health promotion. Despite the importance of the human gut microbiota for the physiological effects of diet and chronic disease etiology, national dietary guidelines around the world are just beginning to capitalize on scientific breakthroughs in the microbiome field

In a recent Cell paper, Fu et al. bridge descriptive cancer microbiome research with mechanistic and functional insight. With savvy use of antibiotics, the authors demonstrate divergent roles of the gut and intratumoral microbiome in breast tumor growth and metastasis, providing potentially actionable tools for better breast cancer management.

Bacterial pathogens must maintain a delicate balance between acquiring novel genetic material and preserving their well-engrained cell physiology. In the recent study by Jaskólska et al., an astonishing example of this sophisticated phenomenon was found in Vibrio cholerae,with the pandemic strain encoding systems within two horizontally acquired pathogenicity islands that degrade incoming DNA.

Preterm birth can have long-term health consequences, and the gut microbiome is an important contributor to infant health. In this issue of Cell Host & Microbe, Samara et al. explore the effects of probiotics treatment on the infant gut microbiome of extremely premature infants.

Success of live biotherapeutics depends upon sustained and durable engraftment of beneficial microbes with robust functional output. In this issue of Cell Host & Microbe, Button et al. (2022) report that a human milk oligosaccharide-Bifidobacterium synbiotic delivers by supporting functional engraftment in healthy adults without antibiotic administration.

The first malaria vaccine has been recently approved for children living in malaria-endemic areas. While this is long-awaited and welcome news, the modest efficacy of the vaccine highlights several areas that require further attention. Here, we describe the likely impact of the vaccine and where clinical and basic discovery research will still be required.

Maternal-child microbial seeding interventions expose Cesarean-section (C-section)-delivered infants to the maternal microbiome they bypass during Cesarean delivery. It is theorized such interventions restore the microbiome and normalize immune development to reduce the occurrence of C-section-associated inflammatory conditions. Here we discuss the rationale, evidence, and controversies surrounding

Necrotizing enterocolitis (NEC), a cause of death among premature babies, has defied therapeutics for decades. Bacterial analyses have expanded insights into NEC pathophysiology and roles of the gut microbiome. We discuss the contribution of the gut microbiome and potential therapeutics, notably lactadherin, that may promote gut homeostasis to alleviate NEC.

Forty-five percent of deaths among children under 5 years of age are associated with undernutrition. Globally, almost 200 million children exhibit the two major forms of undernutrition—wasting (low weight-for-height) or stunting (low height-for-age), with many affected by both. Undernutrition is not due to food insecurity alone. Growing evidence indicates that perturbed postnatal gut microbiome development

At birth, neonates provide a vast habitat awaiting microbial colonization. Microbiome assembly is a complex process involving microbial seeding and succession driven by ecological forces and subject to environmental conditions. These successional events not only significantly affect the ecology and function of the microbiome, but also impact host health. While the establishment of the infant microbiome

Associations between the global microbiome and diseases of children have been studied extensively; however, research on the viral component of the microbiome, the “virome,” is less advanced. The analysis of disease associations with the virome is often technically challenging, requiring a close examination of the “virome dark matter.” The gut is a particularly rich source of viral particles, and now

Secretory immunoglobulin A (SIgA) in human milk plays a central role in complex maternal-infant interactions that influence long-term health outcomes. Governed by genetics and maternal microbial exposure, human milk SIgA shapes both the microbiota and immune system of infants. Historically, SIgA-microbe interactions have been challenging to unravel due to their dynamic and personalized nature, particularly

The maternal immune system protects developing offspring against pathogens before birth via transplacental transfer and after birth through secreted milk. This transferred maternal immunity influences each generation’s susceptibility to infections and responsiveness to immunization. Thus, boosting immunity in the maternal-neonatal dyad is a potentially valuable public health strategy. Additionally

Intestinal host-microbiota interactions during the first year of life are critical for infant development. Early-life antibiotic exposures disrupt stereotypical gut microbiota maturation and adversely affect childhood health. Furthermore, antibiotics increase the abundance of resistant bacteria and enrich the resistome—the compendium of antibiotic resistance genes—within the gut microbiota. Here, we

Our skin is the interface through which we mediate lifelong interactions with our surrounding environment. Initial development of the skin’s epidermis, adnexal structures, and barrier function is necessary for normal cutaneous microbial colonization, immune development, and prevention of disease. Early life microbial exposures can have unique and long-lasting impacts on skin health. The identity of