Intestinal inflammation in chickens can manifest unequally along the gastrointestinal tract, yet how each region coordinates host–microbial alterations remain unclear. Using a dextran sulfate sodium (DSS)-induced enteritis model, we profiled the jejunum, ileum and cecum via integrated histology, plasma cytokine measurements, transcriptomics, 16S rRNA sequencing and correlation-based network analyses. DSS challenge elicited a systemic inflammatory phenotype, with markedly elevated IL-6, TNF-α, IFN-γ and IL-10, superimposed on anatomically divergent outcomes: the jejunum underwent pronounced structural remodeling and the most extensive transcriptional reprogramming; the ileum displayed a metabolically oriented expression shift accompanied by microbial expansion; and the cecum showed substantial taxonomic turnover and an epithelium- and lipid-metabolism-related transcriptomic signature despite limited morphometric change. PPAR-mediated lipid regulation emerged as a shared small-intestinal theme. Integrative analyses disclosed segment-specific microbe–gene couplings linking cecal taxa to epithelial barrier genes, ileal Enterococcus to metabolic regulators and jejunal Streptococcus to lipid transport, suggesting that local dysbiosis may steer host functional trajectories and influence the downstream effects of enteritis. These findings offer a spatial framework for gut inflammation and underscore intestinal location as a critical determinant of host–microbiota interplay in poultry.

To Cite This Article: Ran J, Du Y, Ning T, Li J, Fouad D, Iqbal MS, Xiao P, Huang W, 2026. Integrated transcriptome and microbiome analyses reveal segment-specific host–microbial responses to DSS-induced enteritis in chickens. Pak Vet J, 2026, 46(10): 2571-1581. http://dx.doi.org/10.29261/pakvetj/2026.243