Abstract The One Health concept emphasizes the interdependence of human, animal, and ecosystem health. Against this broad backdrop, bile acids (BAs), as central products of host‐microbiota co‐metabolism, act far beyond their classical role in lipid emulsification. This review systematically summarizes BA biosynthesis, enterohepatic circulation, and gut microbiota‐mediated metabolic modification. We highlight how gut microbiota‐derived secondary BAs and farnesoid X receptor and Takeda G protein‐coupled receptor 5‐mediated BA signaling together shape BA homeostasis, glucose and lipid metabolism, intestinal barrier integrity, and immune homeostasis. We further discuss how population diversity, circadian rhythm, diet, behavior, environmental exposure, and surgical interventions dynamically shape systemic BA profiles. Finally, from a One Health perspective, we highlight the translational potential of BA‐targeted strategies in hepatobiliary diseases, metabolic disorders, neurodegenerative and retinal degenerative diseases, and intestinal infections, as well as their value in animal production as non‐antibiotic nutritional regulators. By improving animal health and reducing excessive drug use, residues, and risks of antimicrobial resistance at the source, BA‐based precision nutrition may contribute to food safety and ecosystem health. Overall, this review positions BAs as key molecular hubs in One Health, linking host metabolism, gut microbiota, immune regulation, and the integrated health of humans, animals, and ecosystems.
Abstract The artificial intelligence (AI)‐driven diet‐intestinal microbiota‐host health integration paradigm has emerged as a novel framework for advancing host health research. Intestinal microbiota serves as a key mediator linking dietary signals to host homeostasis, while AI enables efficient integration of multi‐omics data to construct microbial metabolic models, identify interaction patterns across biological scales, and support prediction‐informed modulation of diet‐microbiota interactions. This paradigm synergizes dietary intervention design, AI technology, intestinal microbiota modulation, and host health enhancement, offering innovative solutions for chronic disease management, animal health breeding, and food safety monitoring. In this review, we summarize the core mechanisms of the four‐dimensional interaction and the application value of AI‐driven informed optimization. This review also discusses the major challenges currently facing the field, including model interpretability, multi‐source data heterogeneity, and cross‐species translation, and further highlights that future research should focus on establishing interpretable and iterative AI‐driven closed‐loop systems. This integrated approach holds immense potential to revolutionize host wellness research and promote the development of nutritional health and related industries. Unlike existing diet‐microbiota‐host frameworks and AI‐assisted precision nutrition approaches that mainly focus on association analysis or outcome prediction, our proposed paradigm positions AI as an active coordination layer linking dietary inputs, microbial responses, and host outcomes. By integrating mechanism‐informed modeling with iterative feedback, this framework enables dynamic optimization of diet‐microbiota interactions and supports more precise host health regulation.
Abstract Conventional agricultural intensification has eroded the biological foundations of productive soil by disrupting the reciprocal interactions, plant‐soil feedback (PSF), through which plants actively shape and are continuously shaped by the soil microbiome. Although the molecular mechanisms governing PSF direction are increasingly well‐characterized, deliberate PSF management as a practical tool for resilient crop production remains underdeveloped. This is largely because no integrative framework has translated these ecological insights into state‐contingent, field‐deployable decision rules. This review addresses that gap by first synthesizing the molecular basis of microbiome assembly, encompassing host genetic control of root exudate chemistry, receptor‐mediated microbial recognition, and the bidirectional chemical dialogue between plant and rhizosphere. Building from this mechanistic foundation, we move beyond cataloging mechanisms to present a novel, integrative three‐pillar management framework for actively steering PSF. This framework operationalizes PSF management by strategically combining: (i) engineering the plant partner (leveraging genetics to recruit beneficial microbiomes), (ii) managing the soil habitat (using agronomic practices to engineer suppressive ecological legacies), and (iii) deploying advanced microbial consortia. Critically, we argue that the recent meta‐omics revolution, integrating metagenomics, metatranscriptomics, metaproteomics, and metabolomics, is the enabling technology that transforms this framework from a conceptual model into a quantifiable, diagnosable, and agriculturally deployable system. Multi‐omics tools provide the empirical foundation for diagnosing soil feedback states, monitoring intervention outcomes, and building predictive models. By bridging the lab‐field gap and evaluating key translational challenges, this review provides a coherent, actionable roadmap for harnessing PSF to achieve cultivated resilience in modern agriculture.
Abstract The gut‐mammary axis orchestrates bidirectional crosstalk linking intestinal homeostasis and mammary function through integrated neural, endocrine, and immune pathways. Dysregulation driven by gut microbiota dysbiosis or metabolic dysfunction compromises lactation performance and induces mastitis via pathogen translocation and epigenetic reprogramming. This review systematically discusses the molecular mechanisms underlying microbial metabolite‐mediated mammary development and lactation efficiency, evaluates the impact of gut‐derived pathogens on mammary barrier integrity and inflammatory cascades, explores maternal offspring microbiome transmission for neonatal immunity programming, and proposes precise nutritional strategies targeting microbial immune metabolic networks. Our synthesis of previous research findings aimed to optimize animal productivity, prevent mammary gland disorders, and provide insights for the advancement of the livestock industry.
Abstract Marine fish are paradoxically rich in polyunsaturated fatty acids (PUFAs) despite limited endogenous biosynthetic capacity, suggesting a critical contribution from the gut microbiota. Here, we first characterized the gut microbiota of Seriola dumerili, a PUFA‐rich marine fish, functionally enriched in the biosynthesis of unsaturated fatty acids. Further functional validation was performed using zebrafish as a model. Strain screening revealed the Bacillus thuringiensis strain Sd_h10 exhibited potent lipid utilization capacity in vitro and in zebrafish on a high‐fat diet, and remodeled transcription of lipid‐related pathways to promote lipid accumulation and PUFA biosynthesis. Notably, indole‐3‐butyric acid (IBA), a major metabolite of Sd_h10, was found in the intestinal tissue of S. dumerili and regulated peroxisome proliferator‐activated receptor gamma (PPARγ), mimicking the effects of the PPARγ agonist rosiglitazone in zebrafish. Long‐term IBA administration in conventional zebrafish increased body weight gain, hepatic lipid accumulation, and muscle docosahexaenoate (DHA) content, accompanied by upregulation of PPARγ downstream target genes, including dgat2, fads6, and elovl6l. Simultaneously, IBA reshaped the intestinal microbiota, depleting Burkholderiaceae while enriching Acidovorax abundance, accompanied by enrichment of functions related to fatty acid uptake, lipid utilization, and unsaturated fatty acid modification. These findings support a potential role for the microbiota‐derived metabolite IBA in modulating PPARγ‐associated signaling pathways linked to host DHA biosynthesis and accumulation. Our study provides additional evidence supporting microbiota‐host lipid metabolic interactions and highlights the potential application of probiotic‐associated microbial metabolites for improving lipid nutritional quality in marine fish.
Abstract Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide, characterized by dense desmoplastic stroma, profound immunosuppression, and poor responsiveness to conventional therapies. Accumulating evidence positions the intratumoral microbiome, encompassing bacteria as well as understudied fungal and viral components, as a critical regulator of PC pathogenesis, tumor microenvironment (TME) remodeling, and therapeutic efficacy. In this review, we synthesize the current understanding of the pancreatic intratumoral microbiome, including its distinct composition relative to normal pancreatic tissue, gut microbiota, and oral microbiota. The PC intratumoral microbiome is characterized by enrichment of validated pro‐tumorigenic drivers (e.g., Pseudomonas, Bacteroides species) alongside protective taxa (e.g., Lactobacillus species). These taxonomic profiles vary significantly based on disease stage, patient demographics, and treatment history. We dissected the mechanisms by which microbes and their derivatives drive PC initiation and progression, including immune suppression through modulation of myeloid‐derived suppressor cells and regulatory T cells, metabolic reprogramming involving short‐chain fatty acids and the tryptophan metabolite 3‐indoleacetic acid (3‐IAA), and stromal remodeling via activation of cancer‐associated fibroblasts. The influence of the microbiome on therapeutic response is examined, with particular emphasis on microbial‐mediated mechanisms that undermine treatment efficacy. We further summarize diagnostic and prognostic biomarkers, including salivary microbial signatures with moderate sensitivity and specificity, circulating microbial DNA, and composite microbial risk scores that integrate multiple bacterial species to predict survival. Therapeutic strategies targeting the microbiome are discussed, distinguishing clinically translatable approaches from experimental concepts requiring further validation. Finally, we outline challenges in standardizing profiling methods, validating microbial signatures across diverse populations, and translating preclinical insights to clinical practice, emphasizing the need for multi‐omics integration and interdisciplinary collaboration to advance microbiome‐driven PC management.
