Gut Bacteria Molecule N-MNA Rapidly Repairs Intestinal Damage in Mice, Flies and Human Cells

In mice whose colons had been inflamed and damaged, the difference came down to one injection. Animals that went untreated lost 20% of their body weight and died. Animals given a molecule called N-MNA lost only 5% and recovered. That contrast sits at the center of a study from Rutgers Health, published in Science Advances, describing a compound made by some gut bacteria that appears to heal the intestinal lining quickly.

The molecule's full name is (amide-)N-methylnicotinamide. It matters because of what it becomes inside cells: NAD, a coenzyme whose decline is thought to be a major driver of aging. NAD cannot enter cells directly, so scientists have long looked for precursors that cells can take up and convert. Some gut bacteria, including one sold in dietary supplements, already make an NAD precursor, which has fueled a market for products meant to raise it.

N-MNA is an unusual case. It is a near twin of a molecule human cells produce when they dispose of excess NAD building blocks, but the human version is a dead end. The bacterial one can be converted back into NAD. As Xiaoyang Su, an associate professor of medicine at Rutgers Robert Wood Johnson Medical School, put it, a tiny difference allows the bacterial compound to be turned back into NAD. Nan Gao, a professor of pharmacology, physiology and neuroscience at Rutgers New Jersey Medical School and a senior author, said humans do not appear to make this exact molecule, though some of the bacteria in our guts do.

First author Jiangmeng Han, a doctoral student in biological sciences at Rutgers University-Newark, followed the molecule into human colon cells, where it supplied about 22% of their NAD within 24 hours. It also became NAD in human neurons, liver cells and kidney cells, and in the bodies and heads of fruit flies that were given it. The tests showed that N-MNA sped repair of damaged guts by stimulating stem cell regeneration. In flies with damaged guts, seven-day survival rose from 43% to 78%.

The human evidence is indirect. The team analyzed stool samples from 54 patients with inflammatory bowel disease and 20 healthy volunteers. Patients with low N-MNA had significantly higher levels of gut inflammation markers. Gao said patients with low levels of this metabolite showed higher inflammatory activity. He added that a stool test might eventually help identify patients likely to benefit from probiotics, though he thinks that is probably some years away.

The limits are clear. The researchers did not test N-MNA as a treatment in IBD patients. Nor did they test whether eating probiotic strains that make it, including Lactobacilli in yogurt and oral supplements, raises NAD in people. Ching-On Wong, an assistant professor of biological sciences at Rutgers-Newark and a senior author, said the compound itself may be sufficient but that other, better compounds cannot be ruled out. Gao described the work as still focused on fundamentals, requiring a team of a biochemist, a geneticist and an intestinal biologist.

The next steps are funded. The team has a five-year, $3.6 million National Institutes of Health grant to identify the still-unknown human enzymes that process N-MNA. Wong's lab is testing whether the molecule supports brain cell health and longevity, while Gao's lab is mapping the bacterial genes that make it. Rutgers has filed a provisional patent application on uses of N-MNA, naming Han, Ferraris, Su and Gao as inventors. What to watch is whether the enzyme work and any first tests in patients follow.