A combined aqueous extract of Psidium guajava L. and Tithonia diversifolia (Hemsl.) A. gray improves metabolic homeostasis and preserves intestinal integrity in experimental rabbit colibacillosis

BACKGROUND: Colibacillosis, caused by pathogenic Escherichia coli, remains a significant threat to rabbit production, particularly during the critical weaning period. With the emergence of multidrug-resistant strains limiting conventional antibiotic efficacy, there is an urgent need for sustainable phytotherapeutic alternatives. This study evaluated the therapeutic efficacy of a combined aqueous leaf extract of Psidium guajava L. and Tithonia diversifolia (Hemsl.) A. Gray on systemic biological markers and organ integrity in a rabbit model of colibacillosis. METHODS: Thirty healthy rabbits were randomly grouped into six cohorts: negative control (infected-untreated), healthy control (uninfected-untreated), positive control (infected-treated with Neomycin 10 mg/kg), immunodepressed (uninfected-cyclophosphamide), and two treatment groups (infected; receiving 400 or 800 mg/kg of the combined P. guajava and T. diversifolia extract). Colibacillosis was induced via oral administration of a pathogenic E. coli isolate (1 mL/100 g body weight; 10⁹ CFU/mL). Systemic recovery was assessed through hematological, biochemical, and antioxidant profiling, alongside histological examination and multivariate Principal Component Analysis (PCA). The data were analysed using OriginLab Pro 2025 and GraphPad Prism version 8.0.1 and all multivariate analyses and visualizations were performed in the R statistical environment (v4.4.3). RESULTS: E. coli infection triggered severe haematological, biochemical, and inflammatory dysregulation, characterized by significant increases in white blood cell counts, aspartate aminotransferase, creatinine, and triglycerides, concomitant with reduced red blood cell counts, haemoglobin, and albumin. The combined extract demonstrated dose-dependent efficacy. Notably, multivariate PCA mapping revealed that the 800 mg/kg dose achieved a superior therapeutic outcome, effectively resolving clinical diarrhoea and restoring biological profiles to states comparable to those of the healthy and Neomycin-treated cohorts. Furthermore, the extract significantly mitigated systemic oxidative stress and protected organ integrity. CONCLUSION: These findings demonstrate the therapeutic efficacy and potential of the combined P. guajava and T. diversifolia extract in managing colibacillosis and associated systemic inflammation in rabbits. This study supports the traditional ethnomedicinal use of these plants and demonstrate that these combined extracts could be develop as natural alternatives to synthetic antibiotics in veterinary medicine for managing colibacillosis in rabbits.