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The consumption of pectin, a dietary fiber, is associated with a reduced incidence of colorectal cancer. Papayas, rich in pectins, undergo accelerated ripening, modifying their fiber structure. Ripe papaya fiber has shown beneficial biological effects, like inhibiting cell proliferation in human colon cancer cell lines. However, pectin composition varies significantly among fruits, requiring modification protocols to standardize molecular size. This study evaluated the effect of thermally modified pectins from unripe (UP) and ripe (RP) papayas in the development of azoxymethane (AOM)-induced intestinal preneoplastic lesions in rats. Pectins were extracted from the pulp with 80% ethanol, thermally modified in an autoclave (120°C, 45 min), and incorporated (5%) into AIN-93G diets. Wistar rats (n = 28) were divided into four groups: negative control (NC, without AOM), positive control (PC, AOM 20 mg/kg), UP, and RP (AOM + modified pectin). For 11 weeks, body weight and food consumption were monitored. Cross sections of the colon were analyzed for aberrant crypt foci (ACF) via 0.2% methylene blue staining and optical microscopy (Zeiss Axiovert). Results showed a higher incidence of ACF in the distal portion (3.7% of the area) compared to the proximal portion (1.6%). UPF and RPF showed significantly (*p* < 0.05) lower ACF with ≥2 anomalies in the distal region compared to PCF. Thermal modification standardized the molecular weight of the pectins (~30 kDa) and increased the yield of the water-soluble fraction (WSF), enhancing colonic fermentation and the production of short-chain fatty acids with systemic antitumor action. There were no significant differences in final weight gain among groups. It is concluded that the modified UP and RP pectins exert a comparable protective effect against colorectal carcinogenesis, thereby overcoming natural variations in fruit ripening. These findings support the potential development of preventive and adjuvant dietary supplements for use in conjunction with chemotherapy.
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