In recent years, a growing body of research has highlighted the crucial role of the gut microbiota in maintaining overall health and slowing the aging process. From supporting immunity to regulating metabolism, these microscopic organisms are far more influential than we once believed.

But where does NMN (Nicotinamide Mononucleotide) fit into the picture? As a well-known NAD⁺ precursor linked to longevity, NMN is now being explored for another surprising benefit: its ability to restore balance within the gut microbiome.

So how exactly does NMN work to improve gut health? Let’s dive into the science behind this fascinating connection.


1. Specific Regulatory Effects of NMN on Gut Microbiota

Increasing the Abundance of Beneficial Bacteria

NMN raises NAD⁺ levels in the gut, activating longevity-related proteins such as SIRT1, which promotes the growth of beneficial bacteria like Bifidobacteria and Lactobacilli. For example, mouse studies have shown that NMN supplementation significantly increases the number of butyrate-producing bacteria (such as Akkermansia muciniphila). These bacteria produce short-chain fatty acids (SCFAs), which help maintain the integrity of the intestinal mucosa.


Inhibiting the Overgrowth of Harmful Bacteria

NMN modulates the metabolic environment to reduce the abundance of harmful bacteria such as Bilophila. For instance, in a sleep deprivation-induced gut dysbiosis model, NMN significantly decreased the levels of MRSA and Escherichia coli in mouse feces, thereby alleviating intestinal inflammation.


Optimizing Microbial Diversity

NMN helps restore gut microbiota α-diversity (species richness) and β-diversity (community structure differences). For example, in sleep-deprived mice supplemented with NMN, gut microbial diversity increased by 13.17%, and the ratio of Firmicutes to Bacteroidetes shifted closer to a healthy state.



2. NMN Improves Intestinal Barrier Function

Promoting Mucus Secretion

NMN enhances goblet cell metabolism, leading to increased mucus layer thickness and strengthening of the physical barrier. For example, in mouse studies, NMN supplementation significantly increased the thickness of the intestinal mucus layer and reduced the FD4 leakage area, indicating a protective effect on intestinal permeability.


Enhancing Tight Junction Protein Expression

NMN can upregulate the expression of tight junction proteins such as Occludin and ZO-1, helping to repair the damaged intestinal epithelial barrier. In mouse experiments, the NMN-treated group showed higher levels of tight junction proteins and improved FD4 retention, suggesting enhanced barrier function.


Regulating Autophagy Mechanisms

NMN promotes intestinal autophagy—such as by upregulating LC3 protein expression—to help remove damaged organelles and pathogens, thereby maintaining barrier integrity. For instance, in starvation models, NMN was shown to induce autophagy and strengthen tight junctions between cells.



3. NMN’s Anti-Inflammatory and Metabolic Regulatory Effects

Inhibiting Inflammatory Signaling Pathways

NMN helps suppress intestinal inflammation by modulating pathways such as NF-κB and reducing levels of pro-inflammatory cytokines like IL-6 and TNF-α. For example, in sleep-deprived mice, NMN supplementation significantly reduced inflammatory markers in the gut, alleviated colon atrophy, and eased mucosal congestion.


Regulating Bile Acid Metabolism

NMN promotes the synthesis of bile acid–related metabolites such as cholic acid (CA) and taurodeoxycholic acid (TDCA), which help inhibit excessive bacterial growth. Untargeted metabolomics analysis has shown increased bile acid levels in feces after NMN supplementation, suggesting a synergistic effect with gut microbiota modulation.


Improving Metabolic Disorders

By boosting NAD⁺ levels, NMN improves insulin resistance, fatty liver, and other metabolic issues, indirectly contributing to a healthier gut environment. Clinical studies have indicated that NMN can lower blood glucose and cholesterol levels, reducing the negative impact of metabolic diseases on gut microbiota.