The fermented food microbiome comprises live microorganisms, their genetic elements and their metabolites, and represents an established dietary approach for modulating host–microbiome interactions through the consumption of fermented foods. Fermentation enhances food preservation and nutrient bioavailability, and supplies the host with probiotics, prebiotic substrates and postbiotic metabolites. These bioactive compounds can influence the oral and gut microbiota, modulate immune function and support metabolic resilience. Fibre-rich, plant-based fermented foods retain such components within structured matrices that enhance microbial viability and mucosal interactions more consistently than do fermented dairy foods. This Review explores how the fermented food microbiome affects the oral–gut axis via both transient microbial exposure and metabolite-mediated signalling. Drawing on clinical and preclinical evidence, we examine how fermented food intake alters resident microbiota and host physiology throughout the digestive tract. Despite growing evidence, the mechanisms through which fermented food might promote health remain insufficiently defined in humans owing to strain variability, inconsistency in microbial composition across fermented foods, heterogeneous clinical outcomes and regulatory ambiguity. Taking into account these limitations, we propose a roadmap to integrate the fermented food microbiome into precision nutrition as a feasible, personalized, diet-based strategy to promote health and prevent disease. The bioactive compounds and microbial consortia contained in plant-based fermented foods support oral and gut microbiota, host immune function and metabolic resilience. This Review describes the impact of the fermented food microbiome on the oral–gut axis and identifies a strategic roadmap to integrate this edible microbiome into precision nutrition practices to promote health.

Precise, reversible control of gene expression from self‑amplifying RNA (saRNA) remains difficult, limiting the therapeutic flexibility of this otherwise potent platform. Although alphavirus‑derived saRNAs encode non‑structural proteins that drive RNA replication and offer an intrinsic regulatory point, no existing approach has enabled direct, drug‑dependent control of this machinery for high‑fidelity modulation of expression. Here we engineer saRNA constructs whose replication is activated by the approved small‑molecule drug trimethoprim, using drug‑responsive degradation domains fused to individual non‑structural proteins to regulate self‑amplification. As each replication protein contributes differently to RNA copying, we systematically screened fusion configurations and identified an optimal design combining modified replication proteins with a regulated payload. This construct achieved more than a 104‑fold difference between on and off states with negligible background expression. In mice, oral trimethoprim enabled tunable, reversible and temporally programmed expression patterns. When encoding a human immunodeficiency virus antigen, an escalating trimethoprim regimen enhanced germinal centre responses, a key determinant of antibody affinity maturation. This drug‑regulated saRNA platform provides a controllable and clinically compatible strategy for vaccines, immunotherapies and gene therapies. A self-amplifying RNA circuit whose replication is activated by an FDA-approved small molecule enables precise, reversible and programmable control of RNA amplification and antigen expression for improved therapeutic and vaccine design.

The microbiome actively influences antimicrobial resistance (AMR) dynamics by shaping both ecological and evolutionary processes. However, the extent of its role in resistance emergence, transmission and persistence remains unclear. Traditional AMR research has mainly focused on genetic mechanisms and pathogen-level dynamics. In contrast, the intersection of AMR and the microbiome, including resistance-gene reservoirs, microbial competition and community-mediated selection, remains poorly represented, especially in a modelling context. Here we present a structured framework for incorporating microbiome–AMR interactions into predictive models. We identify key microbiome-mediated processes shaping AMR across different levels of complexity, describe how these can be quantitatively integrated into models, and identify critical data gaps that limit current approaches. By bridging microbiome ecology, AMR biology and mathematical modelling, we set out research priorities and strategies to improve resistance prediction and guide microbiome-targeted interventions. The microbiome plays a significant yet underexplored role in antimicrobial resistance by influencing ecological and evolutionary processes. This Perspective proposes a framework to integrate microbiome–AMR interactions into predictive models while highlighting key mechanisms and data gaps to improve resistance understanding and interventions.

Microbial inoculants are increasingly promoted as sustainable alternatives or complements to conventional agricultural inputs, yet their field performance remains highly variable. This review examines how ecological processes governing root microbiome assembly constrain inoculant establishment, persistence, and function across agricultural systems. We synthesize current evidence on the roles of environmental filtering, host-mediated selection, microbial interactions, and context dependency in shaping inoculant outcomes. We further evaluate the promise and limitations of core-microbiome concepts and synthetic communities as emerging strategies for microbiome-informed inoculant design, emphasizing that their practical translation remains challenged by methodological variability, ecological complexity, formulation constraints, and regulatory barriers. By integrating ecological theory with applied microbiology, this review highlights why many inoculants fail to deliver consistent agronomic benefits and outlines a more potential framework for developing context-aware, field-relevant microbiome-based solutions for sustainable agroecosystem management.

The Type VI CRISPR-Cas13 system, evolved from prokaryotic immunity, has become a versatile, programmable RNA-targeting platform with broad biotechnological potential. Guided by CRISPR RNA (crRNA), Cas13 cleaves single-stranded RNA via higher eukaryotic and prokaryotic nucleotide-binding domains, exerting specific (cis) and nonspecific (trans) collateral cleavage, which enables ultrasensitive nucleic acid detection while introducing cytotoxicity risks in eukaryotic cells. Diversification of Cas13 subtypes, including compact variants, enhances targetability and delivery compatibility, and inhibitory strategies (anti-CRISPR proteins, crRNA mimicry/degradation) enable activity modulation for improved safety. Building on mechanistic foundations, Cas13 is repurposed for targeted RNA knockdown, nucleic acid diagnostics, live-cell RNA imaging with catalytically inactive variants, programmable RNA base editing through deaminase fusions, splicing regulation, epitranscriptomic editing of multiple RNA chemical marks, interaction mapping of RNA–protein and RNA–RNA networks, and translational control, with preliminary clinical translation in antiviral therapies, pathogenic transcript correction, and cancer therapy. Furthermore, Cas13-integrated diagnostics and functional genomics are accelerating biomarker discovery and personalized treatment. Nevertheless, successful clinical translation hinges on overcoming critical bottlenecks, including tissue-specific delivery, mitigation of collateral cytotoxicity, and management of host immunogenicity. This review synthesizes Cas13 classification, structure–function principles, regulatory inhibitors, application modalities, and translational challenges to inform next-generation engineering and responsible deployment of RNA-targeted technologies.

Traditional proximity biotinylation approaches require extensive genetic engineering or intricate purification steps. Here, we introduce FISH+, a ready-to-use RNA proximity labeling method that relies on the recruitment of peroxidase to RNA targets, and facilitates in situ proximity biotinylation in fixed cells. This method permits concurrent visualization of RNA molecules and identification of RNA-interacting proteins. Using this method, we visualized 45S and NEAT1 RNA, and captured their proximal proteins, demonstrating the capability to concurrently visualize RNA and identify proximal proteins. By targeting PNCTR (~36 copies per cell), we observed distinctly bright RNA dots, representing the combined biotinylation signals from both RNA and proximal proteins in situ. This indicates the potential of the FISH+ method for enhanced RNA visualization. We further generalized the FISH+ method to explore XIST-interacting proteins, a number of reported interactors were significantly enriched, such as SPEN, CIZ1 and RBM15. Using quantitative mass spectrometry, we show that FISH+ correctly identifies known RNA-protein interactions in the nucleus of human cells. Overall, we established a watch-and-catch punctate RNA method through the integration of RNA fluorescence in situ hybridization (FISH) with proximity biotinylation. This method provides additional spatial information for the characterization of RNA-centric interactions in fixed, genetically unperturbed samples. FISH+ extends RNA FISH from visualization to protein identification through a simple, robust and highly accessible “watch-and-catch” proximity labeling method for punctate RNAs.

The twin-arginine translocation (Tat) system is a mechanistically unique protein transport pathway moving folded proteins across membranes. It is found in all domains of life and is essential for bacterial virulence and plant photosynthesis. The membrane proteins, TatA, TatB and TatC form a core complex to which substrate proteins bind, triggering the recruitment of additional TatA protomers to form the transport site. Here we present cryo-electron microscopy structures of the prototypical TatBC complex from E. coli and the atypical complexes from Nitratifactor salsuginis and Myxococcus xanthus in a resting state, alongside TatAC substrate-bound TatBC and TatABC complexes from E. coli in the early stages of transport. These structures demonstrate that substrate proteins associate with the core complex solely through their N-terminal signal peptides. The Tat targeting sequences of the signal peptides make specific contacts with TatC, and the peptide body is clamped by TatB. The core complex contains highly tilted transmembrane helices that drive extreme local membrane thinning. On the basis of our structures and biochemical and functional analyses, we propose a model for the early steps in Tat transport. Cryo-EM structural, biochemical and functional analyses of the bacterial twin-arginine translocation system for protein transport across membranes reveal mechanisms of substrate binding.