Cover Story Current Issue

Maternal nutrition exerts profound and lasting effects on infant development, with implications extending beyond somatic growth to long-term brain function and metabolic health. For example, newborns from mothers with obesity or diabetes exhibit increased susceptibility to metabolic disorders, including insulin resistance (IR) and type 2 diabetes (T2D), often emerging in childhood or adolescence. While genetic inheritance contributes to this intergenerational risk, early-life nutritional exposures are increasingly recognized as primary drivers of persistent metabolic programming. Among key classes of nutrients, branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—have emerged as potent modulators of metabolic health in human adults. Elevated circulating BCAAs are among the most accurate predictors of future insulin resistance (IR) and T2D, with a two-fold increase in serum levels conferring a 2.5-fold risk of diabetes onset within 6–10 years. This elevation can directly cause organ toxicity, exacerbating metabolic deficits in a feed-forward loop. However, the extent to which maternal BCAA overnutrition during gestation and lactation impacts offspring metabolic programming and predisposes to dysfunction remains unclear.

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Current Issue

Gut microbiota shape diurnal rhythms of amino acid metabolism in the mouse prefrontal cortex

Gabriel S.S. Tofani, John F. Cryan

Gut microbiota shape diurnal rhythms of amino acid metabolism in the mouse prefrontal cortex

 

Objectives

The gut microbiota plays a key role in maintaining brain health and homeostasis. Previous studies have demonstrated that metabolites in the brain respond to alterations in gut microbial composition. In this study we aimed to explore how depletion of the gut microbiota is associated with alterations in the diurnal rhythmicity of metabolites in the brain.

Methods

We used antibiotic-induced microbial depletion in mice to examine the impact of the gut microbiota on the rhythmicity of metabolites in the prefrontal cortex. Metabolite profiles were assessed across multiple timepoints using untargeted metabolomics.

Results

Microbial depletion was associated with alterations in the rhythmic profile of metabolites in the prefrontal cortex, with amino acids showing a robust inversion of their normal rhythm. These alterations were specific to the prefrontal cortex, with hippocampus and amygdala showing minimal changes. This altered gut microbial environment was associated with potential consequences for neurotransmitter production, including glutamate and serotonin.

Conclusions

These findings provide further evidence that the gut microbiota shapes rhythmic diurnal processes in the brain. Future studies are warranted to investigate how such microbial effects influence actual neurotransmitter levels and behavioral phenotypes associated with the prefrontal cortex.

 

 

Articles in Press

Gut microbiota shape diurnal rhythms of amino acid metabolism in the mouse prefrontal cortex

Gabriel S.S. Tofani, John F. Cryan

Gut microbiota shape diurnal rhythms of amino acid metabolism in the mouse prefrontal cortex

 

Objectives

The gut microbiota plays a key role in maintaining brain health and homeostasis. Previous studies have demonstrated that metabolites in the brain respond to alterations in gut microbial composition. In this study we aimed to explore how depletion of the gut microbiota is associated with alterations in the diurnal rhythmicity of metabolites in the brain.

Methods

We used antibiotic-induced microbial depletion in mice to examine the impact of the gut microbiota on the rhythmicity of metabolites in the prefrontal cortex. Metabolite profiles were assessed across multiple timepoints using untargeted metabolomics.

Results

Microbial depletion was associated with alterations in the rhythmic profile of metabolites in the prefrontal cortex, with amino acids showing a robust inversion of their normal rhythm. These alterations were specific to the prefrontal cortex, with hippocampus and amygdala showing minimal changes. This altered gut microbial environment was associated with potential consequences for neurotransmitter production, including glutamate and serotonin.

Conclusions

These findings provide further evidence that the gut microbiota shapes rhythmic diurnal processes in the brain. Future studies are warranted to investigate how such microbial effects influence actual neurotransmitter levels and behavioral phenotypes associated with the prefrontal cortex.

 

 

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13th
Helmholtz Diabetes Conference 
Munich, 21-23. Sep 2026                                                                                                                             

2024 impact factor: 6.6

You are what you eat

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