Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is a significant threat to poultry, with substantial economic and public health implications, especially with the emergence of multidrug-resistant APEC strains. In this comprehensive review, we present recent evidence that host lipids, both exogenous and endogenous, are increasingly recognized as important contributors in the regulation of host responses to APEC, via the complex interplay of mechanisms. We outline four complementary mechanisms of lipid-mediated protection: (1) direct down-regulation of APEC virulence genes, particularly through interactions of polyunsaturated fatty acids (PUFAs) such as arachidonic acid with bacterial regulators such as FadR; (2) modification of the microbiota to potentially enhance colonization resistance by promoting beneficial bacteria like Lactobacillus and Bifidobacterium and suppressing pathogenic Enterobacteriaceae; (3) enhancement of gut barrier function via increased tight junction protein expression and mucin secretion; and (4) modulation of pro-inflammatory and pro-resolving immune factors may contribute to improved pathogen clearance and tissue repair processes. Recent research has demonstrated that ω-3 PUFA supplementation in the diet reduced pathogen burden and improved gut health in experimental poultry systems, although the magnitude and reproducibility of these effects remain variable across studies. But critical research gaps exist, such as avian-specific mechanistic investigations, time-dependent effects of lipid-microbiota-pathogen interactions, and formulations suitable for commercial use in terms of stability, affordability and delivery efficiency. This review, which bridges lipid biology, microbiome research and immunology, offers a scientific foundation for precision nutrition approaches that can simultaneously modulate pathogens, microbiota and host immunity. These lipid interventions have great potential for sustainable APEC control in poultry.

To Cite This Article: Nawaz S, Shoaib M, Wang Z, Zhang H, Yan R, Sun M, Zhang J, Jiang W, Han X and Xiangjun S, 2026. Host lipids as modulators of avian pathogenic Escherichia coli infection: mechanisms of virulence suppression, microbiota-mediated colonization resistance, and therapeutic potential. Pak Vet J, 46(8): 1872-1882. http://dx.doi.org/10.29261/pakvetj/2026.191