Pyrogallol Modulates Abscopal Tumour and Gut Microbial Responses to Localized Irradiation in an Ehrlich Ascites Carcinoma Model

Radiotherapy’s clinical utility is often limited by radio-resistance, enterotoxicity, and intestinal dysbiosis. This study evaluated pyrogallol—a plant-derived vicinal trihydroxybenzene—as a dual-action radiosensitizer and mucosal protectant in an Ehrlich ascites carcinoma (EAC) BALB/c mouse model subjected to targeted LINAC irradiation (8 Gy). By combining transcriptomic profiling with whole-genome metagenomic sequencing, we interrogated the underlying host-microbiome interactions. Pyrogallol co-treatment significantly augmented radiotherapeutic efficacy, driving marked tumour regression through the upregulation of pro-apoptotic effectors ( Bax , Casp3 , Casp7 ) and p53 -mediated tumour suppressors ( Tp53 , p21 ), alongside Bcl2 repression. Concurrently, pyrogallol blunted oncogenic progression by arresting proliferation ( Cdk4 , Pcna ), inhibiting epithelial-mesenchymal transition ( N-cadherin , vimentin ), downregulating fibrotic remodelling ( Tgf-β , Col1A1 , Fibronectin ), and attenuating radiation-induced pro-inflammatory cytokine surges ( Il-1α , Il-6 , Il-12 ). At the gut interface, radiation degraded colonization resistance by depleting homeostatic short-chain fatty acid producers and Clostridium scindens , while fuelling pathobiont blooms ( Acinetobacter baumannii , Clostridioides difficile ). Pyrogallol reversed this dysbiosis through a distinct ecological shift; despite a reduction in total species richness, the intestinal niche became dominated by the next-generation probiotic Parabacteroides distasonis (∼94% relative abundance; Berger-Parker index: 0.94). Integrated Spearman’s rank correlations demonstrated that host proliferative, EMT, fibrotic, and inflammatory markers aligned positively with pathobiont clusters ( Bacteroides caecimuris , B. faecium , A. baumannii ). Conversely, tumour regression and anti-inflammatory signatures correlated strongly with pathobiont restriction and P. distasonis enrichment. Overall, pyrogallol emerges as a compelling therapeutic adjuvant that synergistically enhances tumour radiosensitivity while remodelling the gut microbiome into a protective, anti-inflammatory state.