GUT–IMMUNE AXIS RELATIONSHIP IN POULTRY

The gut–immune axis is presented here as a functional framework describing probiotic interaction with intestinal epithelium, microbiota, and GALT, rather than as a generalized theoretical concept. The poultry digestive tract not only functions in digestion and nutrient absorption, but also plays a key role in immune system regulation through the gut–immune axis [117]. This concept describes the dynamic relationship between the gut microbiota, intestinal epithelial cells, and GALT, which collectively maintain immune stability and regulate responses to pathogens [118]. Through this system, poultry are able to balance tolerance to commensal microbes while activating defense mechanisms when encountering pathogenic microorganisms [119].

However, it is important to acknowledge that several detailed signaling pathways commonly cited in gut–immune discussions are extrapolated from mammalian models, while avian-specific molecular validation remains relatively limited. Thus, although functional outcomes, such as improved IgA production, balanced cytokine expression, and reduced pathogen load, are supported by poultry studies, mechanistic depth at receptor and transcriptomic levels in birds is still evolving [120].

The gut microbiota plays a key role as a link in the gut–immune axis. A balanced microbial community is capable of producing various bioactive metabolites, including SCFAs, vitamins, and antimicrobial peptides that serve as signals for the immune system [121]. SCFAs, for example, play a role in promoting the differentiation of regulatory T lymphocytes (Tregs), reducing the production of pro-inflammatory cytokines, and increasing the expression of tight junction proteins in the intestinal epithelium [122]. However, the majority of mechanistic data regarding SCFA-mediated immune modulation has been characterized in mammalian models, with fewer direct functional studies available in poultry. In particular, molecular characterization of SCFA receptors, downstream transcription factors, and epigenetic regulation in avian immune cells is still limited. In this way, the microbiota helps maintain the strength of the mucosal barrier and influences the regulation of both innate and adaptive immune responses [123].

The intestinal epithelium serves as both a physical barrier and a crucial point of communication between the microbiota and the immune system [124]. Epithelial cells produce mucus, antimicrobial peptides, and immune signaling molecules that can activate dendritic cells and macrophages [125]. Dendritic cells that capture antigens from the intestinal lumen then guide the differentiation of T and B lymphocytes within the GALT, thus promoting the formation of mucosal antibodies and activating effector T cells. Again, many of these epithelial–immune interaction pathways have been extensively described in mammals, and equivalent avian mechanisms are still under active investigation [126]. Comprehensive transcriptomic, proteomic, and receptor-level analyses in poultry remain relatively underrepresented compared with mammalian research.

The GALT is a key structure that carries out immune responses at mucosal surfaces. Probiotics modulate GALT activity by enhancing dendritic cell maturation, increasing expression of co-stimulatory molecules, and promoting regulatory T cell (Treg) differentiation, thereby strengthening immune tolerance while maintaining effective pathogen defense [127]. This lymphoid tissue, including Peyer’s patches, bursa of Fabricius, pharyngeal tonsils, and cecal tonsils, facilitates recognition of antigens from the lumen, stimulation of B cells to produce IgA, and coordination of T lymphocyte activity in regulating local and systemic immune responses [128]. GALT activity is also influenced by metabolites and microbiota components, including probiotics, which can enhance specific immune responses without causing excessive inflammation. Nevertheless, direct mechanistic confirmation of several probiotic–GALT interactions in poultry remains less comprehensive compared with mammalian systems. Thus, while functional outcomes have been observed, detailed molecular validation in avian species is still evolving [129].

Harmonious interactions within the gut–immune axis play a crucial role in maintaining resistance to pathogens, controlling inflammatory responses, and supporting optimal performance in poultry. Through targeted interaction with GALT, probiotics enhance mucosal antibody production, improve post-vaccination antibody titers, and contribute to controlled inflammatory responses that favor growth efficiency in poultry [130]. However, given the current reliance on extrapolated mammalian data, further avian-specific mechanistic studies are needed to validate these proposed pathways. An imbalance in any one element, for example, microbial dysbiosis or damage to the intestinal epithelium, can trigger an excessive immune response, prolonged inflammation, or reduced growth efficiency [131]. Therefore, various nutritional and management approaches, including the administration of probiotics, prebiotics, and synbiotics, aim to maintain the stability of the gut–immune axis, strengthen intestinal barrier function, and regulate innate and adaptive immune activity [132]. As shown in Figure 2[84–135], the poultry immune system involves coordinated interactions between innate and adaptive immune components leading to antibody production. Furthermore, the figure highlights the dynamic interplay between gut microbiota, intestinal epithelium, and GALT, as well as the proposed gut–immune–climate axis under heat stress conditions [117–129, 133–135].

Figure 2: Innate and adaptive immunity in poultry, illustrating the gut–immune axis and proposed gut–immune–climate axis. This schematic illustration was conceptually developed based on published evidence [84–135] and generated using artificial intelligence tools (ChatGPT 5.2), then subsequently modified by the authors.

Furthermore, we propose extending this concept to a “Gut–Immune–Climate Axis” to emphasize the role of probiotics in climate resilience. Recent studies from 2025 indicate that heat stress and high ambient temperatures disrupt microbial balance, impair epithelial integrity, and suppress immune function in poultry [133]. Heat-stable probiotic strains, nanoparticle-encapsulated formulations, or multi-strain blends may mitigate these effects by preserving gut microbiota stability, enhancing mucosal immunity, and reducing stress biomarkers such as heterophil-to-lymphocyte ratio and corticosterone [134]. Integrating environmental and management factors, such as stocking density and thermal load, within this axis provides a framework for linking gut–immune modulation to climate-adaptive poultry production, aligning with broader sustainability goals [135]. Future research should test these predictions under controlled heat stress conditions and in commercial settings to quantify probiotic-mediated resilience.