“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, as reported by News-Medical.
Good gut bacteria produce a molecule that repairs damaged intestinal walls and triggers production of an anti-aging coenzyme, according to a study published in Science Advances. Researchers at Rutgers Health discovered that the compound (amide-)N-methylnicotinamide, or N-MNA, protects against severe inflammatory conditions by activating nicotinamide adenine dinucleotide, or NAD.
NAD levels naturally decline with age. Because NAD cannot cross cell walls directly, scientists look for precursor molecules that cells can absorb and convert. N-MNA acts as a direct precursor that human cells can easily convert back into the vital coenzyme.
Jiangmeng Han, a doctoral degree student in biological sciences at Rutgers University-Newark and first author of the study, tracked N-MNA after it entered human colon cells. The bacterial compound supplied roughly 22% of the total cellular NAD within 24 hours, according to Rutgers-Newark reporting.
Additional testing showed that human liver cells, kidney cells, and neurons also convert N-MNA into functional NAD. In animal trials, mice with inflamed and damaged colons that received untreated water lost 20% of their body weight and died. Mice injected with N-MNA lost only 5% of their body weight and recovered.
In fruit flies with damaged digestive tracts, administering the molecule raised the seven-day survival rate from 43% to 78%, Bioengineer.org reported. Histological examinations confirmed the precursor promoted healing by driving the rapid renewal of intestinal stem cells.
Researchers examined stool samples from 54 inflammatory bowel disease patients and 20 healthy volunteers. Patients with lower levels of N-MNA displayed significantly higher levels of gut inflammation markers.
“Patients with low levels of this metabolite showed a higher inflammatory activity,” Gao said.
Gao said that routine stool tests might eventually help physicians identify which patients will benefit most from specific probiotics. However, that clinical application remains several years away as researchers continue investigating basic cellular mechanisms.
The research team secured a five-year, $3.6 million grant from the National Institutes of Health. Scientists will use the funding to identify the specific human enzymes that process N-MNA.
Meanwhile, the lab of assistant professor of biological sciences Ching-On Wong is testing whether the molecule supports brain cell health and longevity. Gao’s lab is currently mapping the bacterial genes responsible for producing the compound.
Rutgers has filed a provisional patent application covering potential therapeutic uses of N-MNA. Han, Ferraris, Su, and Gao are listed as inventors on the filing.
Human cells take up N-MNA and convert it into NAD, an essential cellular coenzyme. Jiangmeng Han tracked the molecule and found it supplied about 22% of cellular NAD in human colon cells within 24 hours.
The research team received a five-year, $3.6 million grant from the National Institutes of Health. The funds support mapping bacterial genes and identifying human enzymes that process the molecule.
Tests confirmed that human colon cells, kidney cells, liver cells, and neurons assimilate N-MNA and convert it into functional NAD.
Worth a look