Manganese-induced sex-specific gut microbiome perturbations in C57BL/6 mice Original paper

What was studied?

This study explored how manganese (Mn) exposure affects the gut microbiome in a sex-specific manner in C57BL/6 mice. The researchers used high-throughput sequencing, metagenomics, and metabolomics to investigate the changes in the gut bacterial composition, functional genes, and fecal metabolites in both male and female mice exposed to manganese chloride (MnCl₂). The study aimed to understand the impact of Mn on the gut microbiome and its possible contribution to neurotoxicity, as well as how these changes could be influenced by sex differences.

Who was studied?

The study involved C57BL/6 mice, with both male and female mice exposed to manganese chloride in their drinking water over a period of 13 weeks. The research analyzed changes in the gut microbiome and fecal metabolomes of these mice, comparing control groups with those exposed to Mn. Additionally, the study looked at specific bacterial genes and metabolic pathways that were altered due to manganese exposure.

What were the most important findings?

The study revealed significant, sex-specific changes in the gut microbiome following manganese exposure. In males, Mn exposure led to a notable increase in the relative abundance of the phylum Firmicutes and a decrease in Bacteroidetes. In contrast, females exhibited an opposite pattern, with Firmicutes decreasing and Bacteroidetes increasing. At the genus level, manganese exposure significantly altered the abundance of key bacteria involved in neurotransmitter metabolism, such as tryptophan and GABA pathways. Genes related to LPS synthesis, oxidative stress, and DNA repair were more upregulated in female mice, while male mice exhibited greater changes in bacterial motility and chemotaxis genes. Furthermore, manganese exposure altered the metabolic profiles of both male and female mice, with female mice showing a stronger perturbation in antioxidant levels like α-tocopherol and γ-tocopherol. These findings suggest that manganese exposure affects both the microbial composition and metabolic pathways, influencing gut-brain communication, with notable sex-dependent effects.

What are the greatest implications of this study?

This study has significant implications for understanding how environmental exposure to metals like manganese can influence gut health, particularly through the gut microbiome. The sex-specific differences observed highlight the importance of considering gender when studying the toxicological effects of metals. The alterations in microbial composition and metabolism, particularly those affecting neurotransmitter pathways and inflammatory mediators, suggest that manganese exposure could influence brain health through the gut-brain axis. These findings offer potential insights into how metal toxicity contributes to neurological diseases and could lead to new therapeutic approaches for managing manganese-related neurotoxicity. Moreover, the study underscores the need to consider the gut microbiome as an important player in the overall effects of environmental exposures on health.