Fecal microbiome transplantation attenuates manganese-induced neurotoxicity through regulation of the apelin signaling pathway by inhibition of autophagy in mouse brain Original paper

What was studied?

This study focused on how fecal microbiome transplantation (FMT) can mitigate manganese (Mn)-induced neurotoxicity in mice. The researchers examined the molecular mechanisms involved, specifically the role of the apelin signaling pathway and autophagy regulation in the hippocampus. The study also explored the effects of Mn exposure on the gut microbiota and the potential therapeutic benefits of FMT in alleviating neurodegenerative changes induced by Mn.

Who was studied?

The study involved male BALB/c mice, divided into three groups: a control group, a manganese-exposed group (Mn), and a group that received fecal microbiome transplantation (Mn+FMT). The animals were exposed to manganese chloride (MnCl₂) in their drinking water for five weeks, and fecal matter from donor mice was administered to the Mn+FMT group through oral gavage.

What were the most important findings?

The study found that manganese exposure activated autophagy in the hippocampus, which contributed to neurotoxicity. The expression of autophagy-related proteins such as Beclin-1, LC-3B, p62, and PINK1 was significantly increased in the Mn-exposed group. FMT treatment, however, attenuated this autophagy activation, suggesting that gut microbiota modulation can reduce the neurotoxic effects of Mn. The researchers identified the apelin signaling pathway as the key pathway regulated by FMT, with significant changes in this pathway observed in the Mn+FMT group. Specifically, FMT reversed autophagy activation in the hippocampus by modulating the apelin pathway, which plays a role in neuroprotection through anti-inflammatory and anti-apoptotic effects. Additionally, transcriptomic and proteomic analyses revealed that the FMT intervention improved the overall brain protein profile, contributing to the reduction of neuroinflammation and mitigating the neurodegenerative effects induced by manganese exposure.

What are the greatest implications of this study?

The study provides compelling evidence that FMT can modulate the gut-brain axis to alleviate neurotoxicity caused by environmental pollutants like manganese. The findings suggest that gut microbiome manipulation could serve as a novel therapeutic approach for neurodegenerative diseases, particularly those associated with metal toxicity, such as Parkinson’s disease. The identification of the apelin signaling pathway as a target for FMT-induced protection highlights the potential for developing microbiome-based therapies to control autophagy and reduce oxidative stress in the brain. This study opens new avenues for managing metal-induced neurodegeneration through the regulation of microbial communities, providing a unique approach to neuroprotection.