Scientists at Rutgers Health have discovered a molecule produced by good gut bacteria that rapidly heals the intestinal lining, News-Medical reported on Saturday.
The compound protects against severe inflammatory diseases and triggers the production of a coenzyme that typically diminishes with age.
Published in Science Advances, tests across mice, fruit flies, and human cells showed that the molecule, (amide-)N-methylnicotinamide or N-MNA, activates nicotinamide adenine dinucleotide (NAD). This coenzyme’s age-related decline drives cellular aging, making its replenishment a primary target for regenerative therapies.
Because NAD cannot enter cells directly, researchers have sought precursors that cells can absorb and convert. N-MNA acts as a near twin of a molecule human cells make when disposing of excess NAD building blocks, but bacteria-produced N-MNA can be converted back into NAD.
“Humans do not appear to make this exact precursor molecule N-MNA, but some of the bacteria living in our gut do,” said Nan Gao, senior study author and professor of pharmacology, physiology and neuroscience at Rutgers New Jersey Medical School.
Jiangmeng Han, first author of the study and a doctoral degree student at Rutgers University-Newark, tracked N-MNA into human colon cells. The molecule supplied about 22% of their NAD within 24 hours.
The transformation also occurred in human neurons, liver cells, and kidney cells. Fruit flies and laboratory mice processed the compound identically across multiple organ systems.
Mice with inflamed and damaged colons experienced stark contrasts based on treatment. Untreated animals lost 20% of their body weight and died, while those injected with N-MNA lost only 5% and recovered.
Fruit flies with damaged guts saw their seven-day survival rate jump from 43% to 78% after receiving N-MNA. The molecule accelerated this healing by stimulating direct stem cell regeneration in the intestinal lining.
Researchers examined stool samples from 54 inflammatory bowel disease (IBD) patients and 20 healthy volunteers. Patients with low N-MNA levels had higher concentrations of gut inflammation markers.
“Patients with low levels of this metabolite showed a higher inflammatory activity,” Gao stated.
Stool tests might eventually help clinicians identify IBD patients who will benefit from specific probiotics, though that application remains years away. The current phase requires foundational biochemistry and genetic mapping.
“Right now, we’re still trying to understand the fundamentals, and this requires a multidisciplinary team of a biochemist, geneticist, and intestinal biologist,” Gao said.
The research team has secured a five-year, $3.6 million National Institutes of Health grant to identify the human enzymes responsible for processing N-MNA. Scientists did not test N-MNA treatment directly on IBD patients during this phase.
Investigators also did not test whether consuming commercial probiotic strains like Lactobacilli found in yogurt raises NAD levels in humans. Other bacterial compounds might eventually prove even more potent.
“This compound itself may be sufficient, but we cannot rule out the possibility that there are other, better compounds,” said Ching-On Wong, assistant professor of biological sciences at Rutgers-Newark and a senior author of the study.
Wong’s laboratory is currently testing whether N-MNA supports brain cell health and longevity. Meanwhile, Gao’s laboratory is mapping the specific bacterial genes responsible for producing the molecule.
Rutgers has filed a provisional patent application on the uses of N-MNA. Han, Ferraris, Su, and Gao are named as the primary inventors on the filing.
