Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus...

Area of Science:

• Biomedical Science
• Neuroscience
• Gastroenterology

Background:

• Diabetes Mellitus induces systemic oxidative stress and enteric nervous system neuropathy, leading to chronic gastrointestinal dysmotilities.
• Diabetic autonomic neuropathy affects up to 75% of patients, causing altered gut transit times (constipation or diarrhea).
• Streptozotocin-induced diabetic rats model Type I Diabetes Mellitus and its associated gastrointestinal dysmotilities.

Purpose of the Study:

• To investigate the effects of nicotinamide riboside (NR), a NAD+ precursor, on diabetic-induced dysmotility in rats.
• To determine if fecal microbiota transplant (FMT) could replicate the therapeutic effects of NR on diabetic enteric neuropathy.

Main Methods:

• Diabetic rats were treated with NR intraperitoneally every 48 hours for 6 weeks.
• Gastrointestinal transit time was measured weekly using the carmine red method.
• Fecal microbiota transplant was performed between NR-treated and untreated diabetic rats.

Main Results:

• Nicotinamide riboside (NR) administration improved overall gastrointestinal transit time in diabetic rats.
• 16S microbiome sequencing revealed decreased alpha and beta diversity in diabetic rats, with no change in FMT recipients.
• NR treatment led to increased myenteric plexus ganglia density in the small and large intestines of diabetic rats.

Conclusions:

• NR treatment functionally improved gastrointestinal transit time in diabetic rats.
• NR demonstrated neuroprotective effects on the myenteric plexuses, suggesting a benefit for diabetic enteric neuropathy.
• NR treatment improved gut transit and nerve density in streptozotocin-induced diabetic rats.