Sodium propionate oral supplementation ameliorates depressive-like behavior through gut microbiome and histone 3 epigenetic regulation.

Major depressive disorder (MDD) is a global health concern, affecting over 250 million individuals worldwide. In recent years, the gut-brain axis has emerged as a promising field for understanding the pathophysiology of MDD. Microbial metabolites, such as short-chain fatty acids (SCFAs)-acetate, butyrate, and propionate-, have gained attention for their potential to influence epigenetic modifications within the host brain. However, the precise mechanisms through which these metabolites participate in MDD pathophysiology remain elusive. This study was designed to investigate the effects of oral SCFA supplementation in adult male Wistar rats subjected to chronic unpredictable mild stress (CUMS). A subset of control and CUMS-exposed rats received different supplementations: sodium acetate (NaOAc) at a concentration of 60 mM, sodium butyrate (NaB) at 40 mM, sodium propionate (NaP) at 50 mM, or a mixture of these SCFAs. The gut microbiome was assessed through 16S rRNA sequencing, and epigenetic profiling was performed using Western blot analysis. Results demonstrated that NaP supplementation significantly alleviated anhedonia in stressed animals, as evidenced by improved performance in the sucrose consumption test. This ameliorative effect was potentially associated with the modulation of gut bacterial communities, accompanied by the attenuation of the region-specific epigenetic dysregulation in the brain of the animals exposed to chronic stress. These findings suggest a potential association between gut dysbiosis and stress response, and NaP could be a promising target for future MDD interventions. However, further studies are needed to fully elucidate the underlying mechanisms of these effects.

Transgenerational inheritance of methylmercury and vitamin A-induced toxicological effects in a Wistar rats environmental-based model.

Mercury (Hg) and vitamin A (VitA) are two environmental factors with potential health impacts, especially during pregnancy and early childhood. Fish and seafood may present elevated levels of methylmercury (MeHg), the major Hg derivative, and VitA. This study aimed to evaluate the transgenerational effects of exposure to MeHg and/or VitA on epigenetic and toxicological parameters in a Wistar rat model. Our findings revealed persistent toxicological effects in generations F1 and F2 following low/mild doses of MeHg and/or VitA exposure during dams' (F0) gestation and breastfeeding. Toxicological effects observed in F2 included chronic DNA damage, bone marrow toxicity, altered microglial content, reduced neuronal signal, and diminished male longevity. Sex-specific patterns were also observed. Co-exposure to MeHg and VitA showed both synergistic and antagonistic effects. Additionally, the study demonstrated that MeHg and VitA affected histone methylation and caused consistent effects in F2. While MeHg exposure has been associated with transgenerational inheritance effects in other organisms, this study provides the first evidence of transgenerational inheritance of MeHg and VitA-induced toxicological effects in rodents. Although the exact mechanism is not yet fully understood, these findings suggest that MeHg and VitA may perpetuate their impacts across generations. The study highlights the need for remedial policies and interventions to mitigate the potential health problems faced by future generations exposed to MeHg or VitA. Further research is warranted to investigate the transgenerational effects beyond F2 and determine the matrilineal or patrilineal inheritance patterns.