From Microbiome Associations to Deployable Precision Probiotics in Animals: A Critical Narrative Review and Proposed Causal Evidence Framework for Next-Generation Probiotic Development

Next-generation probiotics (NGPs) are promoted as precision tools for animal health, yet the term is often applied to uncommon taxa before causality, safety and target-species efficacy are established. This critical narrative review reframes animal NGPs as a development pathway rather than a taxonomic category. A structured PubMed search was last run on 14 September 2026 with a publication date cutoff of 1 September 2026 and was supplemented by citation tracing and targeted searches of authoritative sources. From the screened literature, 45 representative and conceptually informative sources were purposively selected for the final narrative synthesis; the review was not intended to provide systematic or exhaustive coverage. The detailed synthesis focused on terrestrial farm and companion animals, whereas equine, rabbit and aquaculture studies were treated as boundary evidence. We evaluate how strain-resolved metagenomics, culturomics, metatranscriptomics, metaproteomics, metabolomics, host transcriptomics, machine learning, metabolic modeling and perturbation systems can move discovery beyond association. Studies across animal sectors show many biomarkers but limited causal validation, strain tracking, formulation data, multisite trials and ecological safety assessment. We propose an author-developed conceptual framework comprising a cumulative evidence ladder, from reproducible associations to field-ready deployment, and the ANIMAL-NGP reporting checklist (Animal endotype, Native ecological fit, Identity and genomic safety, Mechanism, Administration and manufacturing, and Longitudinal validation). These tools are intended to align claims with evidence and require prospective application and external validation. Multi-omics should therefore function as an evidence-navigation system, not as a substitute for causality.