In intensive livestock and poultry production systems, animals are often exposed to environmental and physiological stressors that impair intestinal barrier function and growth performance. Akkermansia muciniphila (AKK) has gained attention as a next-generation probiotic. However, its practical application is often hindered by its strict anaerobic nature and sensitivity to feed processing conditions. In this review, the AKK secretome is defined as the total collection of bioactive factors released or shed into the extracellular space, encompassing functional proteins, extracellular vesicles, metabolic by-products, and cell envelope-derived fragments, which collectively constitute the cell-free supernatant. This review summarizes current knowledge on the molecular components of AKK secretome and discusses its potential application as a functional feed additive. At the mechanistic level, AKK secretome supports intestinal epithelial integrity by regulating tight junctions through TLR2 signaling and promoting mucosal repair via Wnt/β-catenin-dependent stem cell activity. Individual components of the secretome, including branched-chain phospholipids, the AmTARS protein, and Amuc_1100, contribute to immune homeostasis and Nrf2-mediated redox regulation, respectively, thereby increasing host tolerance to oxidative stress. For animal production applications, AKK secretome has several practical advantages over live bacterial preparations, such as improved thermal stability during processing and reduced biosafety concerns related to bacterial translocation and antibiotic resistance gene transfer. In conclusion, the AKK secretome represents a promising and practical strategy for translating mechanistic insights into effective interventions for stress mitigation in modern animal production systems.

This study explored the effects of different preparations of Akkermansia muciniphila (AKK) on the gut microbiota and jejunal transcriptome of lipopolysaccharide (LPS) challenged yellow-feathered broilers. A total of 100 one-day-old broilers were divided into five groups, including control group (Control), LPS injection (LPS), gavage of AKK broth culture plus LPS injection (AKK), gavage of viable AKK suspension plus LPS injection (Active) and gavage of heat-inactivated AKK suspension plus LPS injection (Inactive). Growth performance results showed that LPS significantly reduced the body weight of broilers. Alpha diversity showed no significant group differences. At the phylum level, Firmicutes was significantly lower in groups with AKK gavage. At the genus level, Bacteroides was relatively more abundant, whereas Streptococcus was numerically less abundant in AKK-treated groups. The Active group had the highest abundance of Akkermansia. Transcriptome analysis revealed the Inactive group had significantly lower Occludin. Combined KEGG and GO analyses revealed that the LPS challenge suppressed innate immunity by downregulating the Retinoic acid-inducible gene (RIG)-I-like receptor signaling pathway. In response, different interventions distinctly modulated the transcriptome. The AKK group counteracted this suppression by upregulating innate immune and antiviral defense responses. The Active group primarily influenced metabolism, downregulating pathways for drug and glutathione metabolism and xenobiotic responses while upregulating retinol metabolism. In addition, the Inactive group demonstrated an upregulation of ribosome biogenesis, and energy metabolism, suggesting a restoration of core cellular functions. In summary, all gavaged AKK preparations maintained broiler gut microbiome stability, while AKK broth culture demonstrated superior efficacy in alleviating LPS-induced jejunal stress.