NAD precursors cycle between host tissues and the gut microbiome

Area of Science:

• Microbiology
• Metabolic Science
• Nutritional Science

Background:

• Nicotinamide adenine dinucleotide (NAD) is a vital redox cofactor for mammalian and microbial life.
• Understanding NAD+ metabolism in the gut microbiome is crucial for host health.

Purpose of the Study:

• To investigate the origins of NAD+ precursors available to the mouse gut microbiome.
• To elucidate the metabolic interplay between host and gut microbes concerning NAD+ synthesis.

Main Methods:

• Utilized isotope tracing to track NAD+ precursor metabolism in vivo.
• Analyzed nutrient absorption and microbial conversion pathways within the gastrointestinal tract.

Main Results:

• Dietary NAD+ precursors are absorbed in the upper gastrointestinal tract, unavailable to distal gut microbes.
• Circulating host nicotinamide is utilized by the gut microbiome for NAD+ synthesis.
• The microbiome converts host nicotinamide to nicotinic acid, supporting host NAD+ levels and metabolic flexibility.
• Nicotinamide riboside, a popular nutraceutical, is primarily converted to nicotinic acid by the gut microbiome for host NAD+ utilization.

Conclusions:

• The gut microbiome utilizes host-derived nicotinamide to synthesize NAD+.
• Microbial transformation of host-derived nicotinamide is essential for maintaining host NAD+ homeostasis and metabolic flexibility.
• The gut microbiome plays a key role in processing nutraceuticals like nicotinamide riboside for host benefit.