Abstract:

This study aims to investigate the effects of different short-chain fatty acids (SCFAs) on the growth, behavior, microstructure of brain and liver, and the expression of inflammatory cytokines in young mice. The experimental subjects were newborn C57BL/6J pups (7 groups, 8 mice in each group). The pups in each group were from eight litters of different female mice, and were given gavage with different SCFAs concentrations for 28 consecutive days. The treatment groups were: CTL (0.9% saline), SF-900 group (900 mg·kg^-1 BW sodium formate), SF-1400 group (1 400 mg·kg^-1 BW sodium formate), SP-2 (20 mg·kg^-1 BW sodium propionate), SP-200 (200 mg·kg^-1 BW sodium propionate), SV-5 (5 mg·kg^-1 BW sodium valerate), and SV-20 (20 mg·kg^-1 BW sodium valerate). Body weight, brain index, and liver index were recorded, and spontaneous activity was assessed using the open-field test. Additionally, the expression levels of relevant genes in brain and liver tissues were measured. The results indicated that propionate (SP-2) and valerate (SV-5) significantly enhanced weight gain in young mice, with the propionate group (SP-2) showing the most significant weight increase by 12.83%. HE staining revealed that the microstructure of brain and liver tissues remained intact across all groups, with no significant pathological changes. Behavioral tests showed that formate-treated mice (SF-1400) and valerate-treated mice (SV-5, SV-20) exhibited significantly increased spontaneous activity and exploratory behavior, suggesting that these SCFAs might modulate behavioral responses through the central nervous system. Furthermore, the valerate-treated groups (SV-5, SV-20) regulated the expression of neurotrophic factors BDNF and TRKB in the brain, potentially promoting neuronal survival and synaptic plasticity through increased levels of neurotrophic factors and receptor signaling pathways (such as GPR41). RT-qPCR results revealed that propionate treatment significantly upregulated the expression of anti-inflammatory cytokines IL-4 and IL-10 in liver tissues, while downregulating pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ, indicating that propionate has a positive regulatory effect on liver immune function. In conclusion, SCFAs, particularly propionate and valerate, positively influence the growth and behavior of young mice by regulating immune responses and neurodevelopmental pathways. These findings support the potential role of SCFAs in improving immune function and promoting neurodevelopment.

Key words: short-chain fatty acids, growth and development, inflammatory cytokines, behavioral testing, microstructure