A cellular energy molecule reshaped gut bacteria and colitis genes in mice

If you or someone you love deals with a condition like ulcerative colitis or Crohn's disease, you have probably read that gut bacteria and inflammation are tangled together in ways doctors still do not fully understand. A new laboratory study offers one more thread to pull: a molecule your cells already use to manage energy and repair, called NAD+ (nicotinamide adenine dinucleotide), and its supplement precursor NMN, appear to shift both the gut microbiome and inflammation-related gene activity in mice with colitis. It is early, mechanistic work, done entirely in animals and cells, but it adds a concrete biological pathway to a molecule that is already being sold over the counter as an anti-aging supplement.

Key takeaways

• In mice with chemically induced colitis, giving the NAD+ precursor NMN (nicotinamide mononucleotide) before and during the illness was linked to changes in hundreds of genes tied to inflammation, tissue repair, and fibrosis (scarring) in the colon.
• NMN treatment also shifted the makeup of gut bacteria in the same mice, based on stool sample sequencing.
• In a longer, 15-week feeding experiment and a separate cancer-risk model, NMN changed immune-related gene activity but did not significantly change how many tumors formed.
• This is an animal-only, single-lab study with small group sizes and no human data. It has not been independently replicated, and it does not establish that NMN treats or prevents IBD in people.

NMN Supplementation Altered Colitis-Related Gene Activity in Mice

Researchers at Kindai University in Japan found that giving mice the NAD+ precursor nicotinamide mononucleotide (NMN, a molecule the body converts into NAD+, a coenzyme cells rely on for energy metabolism and DNA repair) before and during chemically induced colitis was associated with widespread changes in gene activity in the colon, alongside a shift in gut bacteria. In mice with colitis, NMN treatment was linked to 451 genes turning up their activity and 878 genes turning down, including genes tied to a signaling protein called TGF-beta (transforming growth factor beta, a molecule that both calms inflammation and drives scarring, depending on context) and to tissue fibrosis. In a separate lab-dish experiment on mouse connective-tissue cells, NMN partially reversed some of the gene-expression changes normally triggered by TGF-beta itself, altering activity of genes including Lgr5, Naprt, Nt5e and Enpp1.

Why People Managing IBD Are Watching the Gut-Inflammation-Microbiome Link

Inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease, affects roughly 4.1 million adults in the United States, or about 1.6% of the adult population, according to the CDC's National Center for Health Statistics. Both conditions involve a mix of immune dysregulation, chronic inflammation, and disrupted gut bacteria (dysbiosis), and patients with long-standing IBD also carry a higher risk of colitis-associated colorectal cancer. TGF-beta sits at the center of that picture: it is produced partly in response to gut bacteria, and it both restrains excess immune activity and, when overactive, drives the fibrosis (scar tissue buildup) that can narrow the intestine in long-term Crohn's disease. A 2017 review in the Journal of Gastroenterology describes TGF-beta as a key regulator connecting immune cells, the gut lining, and the microbiota in IBD, which is why a treatment that nudges this pathway, even in mice, draws attention from researchers working on the disease.

How the Mice Were Studied

The researchers used three separate mouse experiments. First, they triggered acute colitis in mice with dextran sulfate sodium (DSS, a chemical that damages the gut lining to mimic colitis) after giving some mice NMN in their drinking water for a week beforehand and throughout the illness; colon tissue was then analyzed with RNA sequencing (a method for measuring which genes are active) in groups of 3 mice, and gut bacteria were profiled by 16S rRNA gene sequencing in groups of 4 mice. Second, a separate group of mice received NMN continuously for 15 weeks (roughly 100 days) without colitis, to look at longer-term effects on the colon, with 5 mice per group. Third, the team used a colitis-associated cancer model, combining a cancer-triggering chemical with repeated rounds of DSS, to see whether NMN changed tumor development. The doses used were high relative to typical human supplement use, roughly 166 to 470 milligrams per kilogram of body weight per day depending on the experiment, delivered continuously through the mice's drinking water rather than as a periodic dose.

What This Means If You Are Watching Your Own Gut Health

NMN is already marketed as an over-the-counter anti-aging supplement, and some people managing gut or inflammatory conditions may be curious whether it could help. This study does not answer that question for humans. It shows a plausible biological mechanism, NAD+ availability shaping TGF-beta-linked gene activity and the gut microbiome, in mice given doses far higher than typical commercial NMN supplement labels recommend for people. Separately, a placebo-controlled human safety trial published in Scientific Reports found that oral NMN at doses up to 1,250 milligrams a day for four weeks was well tolerated in healthy adults, but that trial measured general safety and blood markers, not colitis or IBD outcomes. Nothing here should be read as evidence that NMN treats, prevents, or manages IBD, and anyone considering a supplement for a diagnosed condition should raise it with a gastroenterologist rather than self-treat based on mouse data.

What the Study Cannot Tell Us Yet

The experiments used small numbers of mice per group, as few as 2 to 5 depending on the analysis, which limits statistical power and makes individual results easier to overturn with a larger sample. All of the findings described here are associations between NMN treatment and gene activity or bacterial composition, not proof that NMN caused the biological changes through the pathways the researchers propose, and the paper's own language repeatedly describes results as "associated with" rather than establishing direct causation. In the cancer-risk experiment, NMN changed immune gene activity within tumors but did not significantly reduce how many tumors formed, a reminder that gene-level effects do not always translate into a meaningful disease outcome. The gut bacteria findings also relied on three different statistical methods for detecting which bacterial genera changed, because these methods do not always agree with each other, a sign of how unsettled the analysis of microbiome data still is. No independent lab has yet reproduced these findings, and there is no human trial testing NMN in IBD.

Where This Research Goes Next

The authors frame this as early, exploratory work meant to map a possible NAD+ to TGF-beta to microbiome circuit rather than to demonstrate a treatment. The logical next steps, which the paper does not report having done, would be replication in independent labs, testing in a model of chronic (not just acute) colitis, and eventually human trials that measure disease activity rather than gene expression. Until then, this remains a hypothesis-generating mouse study rather than a signal that NMN supplements affect human IBD.

Common Questions

Does this study show NMN treats colitis or IBD in humans? No. It was conducted entirely in mice and mouse cells, using a chemically induced colitis model that mimics some, but not all, features of human IBD, and no human colitis or IBD data was collected.

What is the difference between NAD+ and NMN? NAD+ is a coenzyme every cell needs for energy metabolism and DNA repair; NMN is one of the molecules the body converts into NAD+, and it is sold as a supplement intended to raise NAD+ levels.

Is it safe for a person to take NMN for gut health? A separate human safety trial found oral NMN well tolerated at doses up to 1,250 milligrams daily for four weeks in healthy adults, but that trial tested general safety and blood markers, not IBD or colitis outcomes, so there is no established safe or effective dose for gut disease specifically.

Why did the researchers also test a cancer model? Long-standing IBD raises the risk of colitis-associated colorectal cancer, so the researchers wanted to check whether boosting NAD+ with NMN might unintentionally affect tumor development; in their model it did not significantly change tumor numbers.

References

Hisayuki Amano, Akiyoshi Komuro, Kazushige Ota, et al. (2026). NAD+ metabolism influences TGF-β–associated transcriptional programs and the gut microbiota in murine models of colitis. Biochemistry and Biophysics Reports. https://doi.org/10.1016/j.bbrep.2026.102752