A Good Gut Feeling: Study Finds NMN Boosts Healthy Gut Bacteria and Supports a Strong Intestinal Lining in Mice

Housing upwards of 100 trillion bacteria, the human intestine is like a lush rainforest with a wide diversity of microbes — both good and bad. Once thought to solely play a role in digesting food and synthesizing certain vitamins, research over the past two decades has exploded with new insights into how these microbes affect human health. 

One key aspect of a healthy gut is the integrity of our intestinal mucosa — the innermost layer of the intestinal lining that provides a physical barrier between the gut and the rest of the body. Damage to this lining is common, causing gaps between its one-cell-thick layer of epithelial cells to grow further and further apart. Increased intestinal permeability leads to harmful bacteria overgrowth, metabolic dysfunction, and unwanted compounds entering the body.

As poor gut health is a growing problem, many researchers look for ways to combat this intestinal “leakiness.” Now, researchers out of China find the compound nicotinamide mononucleotide (NMN) may be one way to support both gut bacteria diversity and a strong intestinal lining, providing evidence that NMN plays a role in supporting gut health. 

Why We Need NAD+

NMN is a compound that has been recently rising in popularity for its potential use in supporting longevity and overall health with age — and now, research shows it may be used to support gut health, too. One of the most well-known functions of NMN is its status as a precursor to NAD+ (nicotinamide adenine dinucleotide) — a vital coenzyme needed by every cell in the body. Despite its essentiality, NAD+ levels decline with age, accelerating aging and contributing to poor health outcomes. 

Previous research has found that NMN supports metabolic and cardiovascular function. However, not many studies have examined the involvement of this NAD+ precursor with gut health until this research authored by Huang and colleagues published in the journal Frontiers in Nutrition. 

Mighty Mucus and Beneficial Bile Acids

A strong and selectively permeable — meaning, it lets through things we need, like nutrients, while rejecting pathogens or large inflammatory proteins — intestinal lining is a vital component of not just gut health but the health of our bodies as a whole.

An essential component of the intestinal mucosa is, as the name suggests, mucus. While mucus doesn’t always seem like a good thing — especially when you’ve got a cold or sinus infection — mucus is crucial in our guts. Mucus provides the first line of defense against any invading microbes or toxins that aren’t wanted, as it’s so sticky that these infiltrating compounds become trapped before they can make their way into your body. This slimy, lubricating layer is also a rich source of nutrients for healthy gut bacteria to thrive and diversify. 

Another part of the gut health puzzle is adequate production of bile acids — byproducts of cholesterol metabolism that regulate cholesterol absorption and help us digest dietary fats. Bile acids also exhibit antibacterial effects, which prevent an overgrowth of unhealthy microbes in the gut. Previous cell-based research has found that NAD+ stimulates intestinal cells to produce and secrete more mucus, which sets the stage for using supplemental NMN similarly in human and animal studies. 

NMN Nurtures Healthy Gut Bacteria

In this study, Huang and colleagues tested the effects of NMN on gut bacterial abundance, bile acid production, and intestinal lining function in young female mice. The research team divided the mice into five groups — one control group plus four groups with differing concentrations of NMN in their drinking water, ranging from 0.1 mg of NMN per mL to 0.6 mg/mL. 

After 15 weeks, the mice who received NMN had higher levels of healthy gut bacteria and reduced abundance of several harmful bacteria. The best results were actually seen in the lowest NMN concentration (0.1 mg/mL), as the researchers found the higher NMN groups to show reduced gut microbe diversity. 

Specifically, the 0.1 mg/mL NMN group showed an increased prevalence of Ruminococcae, an anti-inflammatory microbe that reduces intestinal permeability or leakiness, and Prevotellaceae, a bacteria that produces butyrate. Butyrate is a short-chain fatty acid — a group of beneficial compounds made in the gut that regulate intestinal health and provide fuel for the epithelial cells of the intestinal lining. 

Supplemental NMN also boosted levels of the probiotic Akkermansia muciniphila, a bacteria that promotes mucin synthesis — the main protein found in mucus — and has been found to support healthy body weights. Lastly, NMN reduced the abundance of harmful bacteria called Bilophila and Oscillibacter, which are linked to intestinal inflammation and metabolic dysfunction. 

Supporting Stronger Gut Linings with NMN

After seeing the beneficial effects of NMN on bacterial diversity, Huang and colleagues looked at how the NAD+ precursor altered bile acid activity, mucus production, and intestinal thickness. Again, they found that the lowest NMN group showed more favorable results to these gut health markers than the higher NMN doses or the control group. 

Low-dose supplemental NMN increased the production of five types of bile acids and a bile acid metabolite called betaine, which benefits digestive enzymes and gut microbe diversity. NMN significantly increased mucus production and thickness in the intestinal lining, indicating reduced intestinal leakiness and a stronger gut lining.

This study indicates a new direction for using NMN — helping to support functional gut microbe diversity, mucus production, and intestinal lining strength. All of these gut-related factors are increasingly dysfunctional in our modern society, and this research provides evidence that boosting NAD+ levels through NMN may be one way to support these processes. 

However, it’s too soon to tell if low-dose supplemental NMN will benefit gut health in humans, as this study was only done with young female mice. As Huang and colleagues conclude, “In this study, [NMN] exerted a protective effect on the intestinal mucosa, which had a positive effect on intestinal health. This study indicates a new direction for the use of NMN. However, the mechanism by which NMN regulates the gut microbiota has not yet been clarified, and further research is needed.”

References: 

Huang P, Jiang A, Wang X, et al. NMN Maintains Intestinal Homeostasis by Regulating the Gut Microbiota. Front Nutr. 2021;8:714604. Published 2021 Jul 29. doi:10.3389/fnut.2021.714604

Hwang D, Jo H, Ma SH, Lim YH. Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells. Food Chem Toxicol. 2018;118:880-888. doi:10.1016/j.fct.2018.06.039