Host-microbiome interactions in nicotinamide mononucleotide (NMN) deamidation

Area of Science:

• Biochemistry
• Microbiology
• Aging Research

Background:

• Nicotinamide adenine dinucleotide (NAD+) is crucial for cellular processes and declines with age.
• Nicotinamide mononucleotide (NMN) is a NAD+ precursor investigated for age-related diseases.
• The gut microbiome's role in NMN metabolism is largely unknown.

Purpose of the Study:

• To investigate the metabolic fate of orally administered NMN.
• To determine the influence of the gut microbiome on NMN bioavailability and NAD+ metabolism.
• To explore alternative pathways for NMN incorporation into NAD+.

Main Methods:

• Oral administration of NMN to rodents.
• Treatment with antibiotics to deplete the gut microbiome.
• Analysis of NAD+ metabolites in host tissues.
• Tracing NMN incorporation pathways.

Main Results:

• Orally delivered NMN can be deamidated and incorporated into NAD+ via the de novo pathway in mammalian tissues.
• This pathway's activity is reduced in animals lacking a gut microbiome due to antibiotic treatment.
• Antibiotic treatment increased host availability of NAD+ metabolites, suggesting microbiome competition.
• The gut microbiome may compete with the host for dietary NAD+ precursors.

Conclusions:

• Oral NMN metabolism involves host de novo synthesis, influenced by the gut microbiome.
• The gut microbiome plays a role in modulating NAD+ precursor availability.
• Interactions between NMN, the gut microbiome, and host NAD+ metabolism are significant for aging research.