Summary: In a groundbreaking study using Merino sheep, researchers uncovered that tiny genetic variations within gut microbes can influence brain-related behavior. By sequencing over 5,000 microbial genomes—including 3,500 never before reported—they linked single nucleotide variations (SNVs) in microbes to neurobehavioral traits and plasma metabolites tied to brain function.
These SNVs, mainly within Firmicutes and Bacteroidetes, were found to alter metabolites that affect neuroactive regulation and oxidative stress. The findings suggest that microbial genetics can subtly tune host metabolism and cognition, offering new insight into the microbiome-metabolism-brain connection.
Key Facts:
- Microbial Genome Discovery: Researchers reconstructed 5,253 gut microbial genomes, including 3,548 new species-level genomes.
- Microbe-Brain Link: Variations in microbial DNA (SNVs) were associated with changes in metabolites and exploratory behavior.
- Behavioral Insight: One microbial gene mutation correlated with brain-derived neurotrophic factor (BDNF) synthesis, affecting curiosity and exploration.
Source: Science China Press
The researchers used Merino sheep as an animal model, systematically collecting samples of their hindgut and ruminal microbiota, plasma metabolites, and neurocognitive behavioral phenotype data.
Based on metagenomic sequencing data from fecal and ruminal samples, the authors reconstructed 5,253 species-level metagenomic-assembled genomes (MAGs), including 3,548 previously unreported novel genomes, significantly expanding the microbial genome resources of ruminant digestive tracts.
Based on this database, the study characterized approximately 140 million single nucleotide variation (SNV) sites from 790 species.
By associating the phylogenetic evolutionary distances of the 790 species with 21 neurobehavioral trait phenotypes, the study found that hosts harboring different potential strains within the same species exhibited neurobehavioral differences.
Subsequently, by conducting an association analysis between microbial SNVs and host plasma metabolites, the study identified 34 significant associations between SNVs and metabolites, primarily enriched in the Firmicutes and Bacteroidetes phyla, many of which are potential novel species.
Metabolites associated with microbial SNVs are primarily related to key physiological processes such as neuroactive regulation and oxidative stress. The authors further integrated the associations between microbial SNVs, metabolites, and phenotypes, identifying 5 metabolites significantly associated with specific SNVs and exploratory behavior.
For example, at the 828 position in the bamb gene of Phocaeicola new416, the cytosine base was significantly different from the thymine base in plasma 4-anisic acid levels, and 4-anisic acid showed the strongest correlation with sheep exploratory duration. This mutation may alter protein structure, affecting the biosynthesis of brain-derived neurotrophic factor (BDNF), thereby regulating host exploratory behavior.
This study suggests that microbial genomic SNVs may be important drivers of host phenotypic differences, revealing that microbial genetic variation may influence host neurocognitive behavior by regulating host metabolism.
This finding expands our understanding of the “microbiome-metabolism-brain” axis and provides a theoretical foundation for the development of targeted interventions targeting the gut microbiome.
Key Questions Answered:
A: They found that small genetic mutations within gut microbes can influence host metabolism and neurocognitive traits, linking microbial DNA to behavior.
A: By sequencing thousands of microbial genomes and correlating specific SNVs with metabolites and behavioral traits in Merino sheep.
A: It suggests that microbial genetic variation—not just microbial composition—could play a key role in mood, cognition, and mental health, paving the way for precision microbiome-based therapies.
About this genetics and behavior research news
Author: Bei Yan
Source: Science China Press
Contact: Bei Yan – Science China Press
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Gut microbial genetic variations are associated with exploratory behavior via SNV-driven metabolic regulation in a sheep model” by Lianmin Chen et al. Science China Life Sciences
Abstract
Gut microbial genetic variations are associated with exploratory behavior via SNV-driven metabolic regulation in a sheep model
Host neurocognitive functions are influenced by the gut microbiome, but the role of microbial genetic variation in shaping host neural behavior remains unexplored.
Here, we profiled multi-omics data and neurobehavioral phenotypes in a model of 200 Merino sheep.
Genomic reconstruction of deeply sequenced fecal and ruminal samples generated 5,253 species-level metagenomic-assembled genomes, of which 3,548 were identified as novel species when compared with existing databases of sheep.
Association between strain-level genetic dissimilarities and host neurobehavioral traits showed that phylogenetic differences in 85% of species were associated with exploratory behavior (FDR<0.05).
We further associated 146 million microbial single nucleotide variations (SNVs) with 953 plasma metabolites and identified 34 study-wide significant associations (P<2.9×10−8), which involve potential microbial genetic regulation of host neuroactivity and oxidative stress-related metabolites, including 4-Anisic acid and D-galacturonate.
Integrated analysis revealed that microbial SNVs may regulate host cognitive exploration through regulating metabolites via structural modulation of encoded proteins.
For instance, we found that novel time- zone entry was associated with 4-Anisic acid, which was determined by SNV via structural regulation of membrane transporters.
Our findings suggest that microbial genetic variation plays a critical role in modulating host neurocognition, possibly through metabolite regulation, which provides novel insights for targeted interventions in neurometabolic disorders.
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