Rapid modulation of gut microbiota composition by hypothalamic circuits in mice

Area of Science:

• Neuroscience
• Microbiology
• Metabolism

Background:

• The gut microbiota influences brain functions, including energy balance, through metabolites.
• Hormones like leptin and ghrelin signal energy status to the brain, particularly the hypothalamus.
• The influence of the hypothalamus on gut microbiota composition is not well understood.

Purpose of the Study:

• To investigate whether the hypothalamus can modulate gut microbiota composition.
• To explore the timescale and mechanisms of brain-gut axis communication regarding microbiota.

Main Methods:

• Chemogenetic manipulation of hypothalamic neurons (POMC and AgRP) in male mice.
• Central administration of leptin or ghrelin.
• 16S rRNA gene sequencing for gut microbiota analysis.
• Transcriptomic analysis of duodenal tissue.

Main Results:

• Hypothalamic interventions rapidly (2-4 hours) altered gut microbiota composition anatomically.
• These changes correlated with duodenal neuronal/synaptic pathway reconfiguration and increased sympathetic tone.
• Diet-induced obesity diminished leptin's effect on microbiota and sympathetic activation.

Conclusions:

• A novel brain-gut axis acutely regulates gut microbiota composition on fast timescales.
• This axis plays a role in meal-to-meal adjustments and systemic energy balance.
• Obesity may impair this brain-gut communication pathway.