Voluntary wheel running modulates murine gut microbiome during hyperammonemic stress

Area of Science:

• Microbiology
• Exercise Physiology
• Metabolic Disease

Background:

• Ammonia, a gut microbiome-derived metabolite, causes cellular hyperammonemic stress (HAS) in chronic diseases.
• Exercise can modulate the gut microbiome, but its effects during HAS are not well understood.
• Chronic diseases often involve impaired ammonia metabolism, potentially exacerbated by exercise.

Purpose of the Study:

• To investigate the impact of voluntary wheel running (VWR) on the gut microbiome (GMB) in a mouse model of HAS.
• To determine if exercise can ameliorate HAS-induced changes in GMB composition and diversity.
• To explore exercise-mediated GMB modulation as a strategy for managing HAS.

Main Methods:

• Male C57BL/6J mice were treated with ammonium acetate (AmAc) or vehicle for 6 weeks.
• Mice were assigned to either VWR or usual activity (UA) groups.
• Stool samples were analyzed using 16S rRNA sequencing for GMB composition and diversity.

Main Results:

• VWR partially ameliorated HAS-induced GMB instability and loss of beneficial taxa.
• Alpha-diversity was highest in AmAc-VWR mice.
• Exercise reversed the decline of Akkermansia and increased Clostridium sensu stricto 1 and Eubacterium ventriosum in AmAc-treated mice.

Conclusions:

• HAS induces GMB instability, characterized by a reduction in short-chain fatty acid-producing bacteria.
• VWR can partially restore GMB homeostasis and beneficial bacteria during HAS.
• Exercise-induced GMB modulation may offer a therapeutic strategy for HAS-related complications in chronic diseases.