Probiotic co-administration attenuates developmental cafeteria diet-induced cellular stress and NLRP3 inflammasome...

Early life exposure to obesogenic diets is increasingly associated with persistent immunometabolic dysregulation. However, the effects of such dietary stress on splenic apoptosis, autophagy, and inflammasome signaling during the developmental period remain insufficiently characterized. This study investigated whether probiotic supplementation modulates cafeteria diet (Cd)-induced molecular alterations in splenic tissue during the post-weaning period.

Twenty-one-day-old male Wistar rats were randomly assigned to four groups (n = 7/group): Control (Cnt), Cafeteria diet (Cd), SCD Probiotics (Prb), and Cafeteria diet plus probiotic (Cd+Prb). Interventions were maintained from postnatal day 21 to 56. Splenic apoptosis, autophagy, and inflammasome related markers were evaluated using RT-qPCR and immunohistochemistry.

Cafeteria diet exposure shifted the spleen toward a pro-apoptotic state, characterized by a relative decrease in BCL2 fold-change pattern and relative increases in BAK and Caspase-3 fold-change patterns, while protein analysis confirmed marked elevations in Caspase-3 and BAX (both p < 0.0001). Autophagy-related alterations included reduced ATG5 expression and marked p62 accumulation, consistent with impaired autophagic regulation, with corresponding protein-level differences for ATG5 and p62 (both p < 0.0001). Inflammasome-associated signaling was reflected by relative increases in NLRP3 and IL-18 fold-change patterns together with higher protein-level immunoreactivity, with strong protein-level significance (p < 0.0001). Probiotic administration exerted context-dependent effects on inflammasome-related gene expression, whereas probiotic co-administration attenuated several Cd-induced alterations, including partial normalization of BCL2 and IL-18 fold-change patterns and reduction of NLRP3 protein levels compared with the Cd group (p < 0.0001), although complete normalization was not achieved across all markers.

Developmental exposure to a cafeteria diet was associated with alterations in splenic apoptotic, autophagy-associated, and inflammasome-related markers, consistent with immune dysregulation during the post-weaning period. Concurrent probiotic supplementation partially and context-dependently modulated several of these alterations.