Alternate‐Day Fasting Exacerbates Lung Inflammatory Disease Compared to High‐Sucrose Diet in Experimental Schistosomiasis Mansoni

Heterogeneous nutrient distribution, metabolic demand and immune responses can influence extrahepatic manifestations of Schistosoma mansoni infection. This study evaluated the effects of alternate-day fasting (ADF), high-sucrose diet (HSD) and praziquantel (PZQ) treatment on feeding motivation, anxiety-like behaviour and lung pathology in infected BALB/c mice. Infected animals received a standard diet (INF), or PZQ (300 mg/kg for 3 days), ADF, ADF + PZQ, HSD or HSD + PZQ. After 15 weeks of infection, behavioural parameters, parasite egg load, inflammatory infiltrate, macrophage accumulation and lung structure were analysed. Uninfected was used as control (Wild Type). ADF impaired motor and feeding-related behaviours compared to other groups. Infected mice under a standard diet or ADF showed higher egg deposition and larger pulmonary granulomas than HSD or PZQ-treated animals. Inflammatory infiltrate and alveolar collapse were more intense in INF and ADF groups, while macrophage accumulation increased with ADF but decreased after PZQ. Pulmonary fibrosis was reduced in ADF, HSD and PZQ groups compared to INF, though higher in ADF than in HSD or PZQ. Overall, ADF worsened lung pathology, promoting egg accumulation, granulomatous inflammation, fibrosis and alveolar collapse. These findings suggest that caloric restriction through ADF aggravates pulmonary disease in schistosomiasis, possibly by enhancing ectopic egg dissemination.