NMN May Relieve Acute Pancreatitis

Acute pancreatitis (AP) is an inflammatory disease in which pancreatic tissue digests itself due to abnormal activation of pancreatic enzymes. Generally speaking, most APs are mild and can recover spontaneously within a few days, but 20% of them are moderate or severe, and the mortality rate of these cases is high.

The most direct manifestation of acute pancreatitis is the impairment of pancreatic exocrine function, which may cause an imbalance of intestinal flora, which in turn leads to increased intestinal barrier permeability and bacterial translocation, aggravating pancreatic damage and inflammatory response, forming a vicious circle. This is the key factor leading to death in moderate and severe acute pancreatitis.

Previous studies have found that intestinal flora can promote host NMN-related metabolism. We know that NMN and NAD+ can reduce oxidative stress and inflammatory responses, which are the key pathogenic factors of AP. Therefore, scientists speculate that alleviating intestinal flora imbalance through fecal transplantation (FMT) may be a potential strategy for the treatment of acute pancreatitis.

Recently, Harbin Medical University published a paper in the "British journal of pharmacology". They found that the intestinal flora after fecal transplantation can induce more NMN and reach the pancreas to transform into NAD+, thereby activating the expression of SIRT3 and PRDX5 proteins , thereby reducing the severity of AP.

The researchers first induced the mice to develop acute pancreatitis (AP), and then divided them into two groups, and transplanted the mucosal and fecal microorganisms (FMT) of normal mice into one of the mice. The results showed that the mice in the FMT group Pancreatic tissue damage was significantly reduced, and serum markers of pancreatitis were significantly reduced, suggesting that FMT attenuated the severity of AP.

The researchers further investigated the effect of fecal transplantation (FMT) on the gut microbiota of AP mice. The results showed that FMT restored the Simpson diversity index decreased by AP, and even the diversity exceeded that of the control group, indicating that the diversity of intestinal flora increased significantly after FMT.

Firmicutes and Bacteroidetes were the most dominant phyla in the gut microbiota, and the results showed that FMT reduced the AP-induced increase in Firmicutes/Bacteroidetes ratio. These evidences all suggest that FMT attenuates the severity of AP by altering the dysbiosis of intestinal flora.

In order to explore the mechanism behind FMT slowing down AP, the researchers analyzed serum metabolites and found that the metabolism of niacin and nicotinamide is the most abundant during AP, and NMN is the key substance in this metabolic pathway.

The researchers found that long-term mild treatment with FMT produced more serum NMN and significantly enhanced NAD+ biosynthesis in the pancreas. Combined with the previous conclusions, we can speculate that FMT may produce more NMN by regulating the composition of intestinal flora.

To confirm this speculation, the researchers gave mice 500 mg/kg per day of NMN or PBS (control) for 4 weeks, and then induced AP. The results showed that compared with the control group, the NMN treatment group significantly reduced the pancreatic tissue damage, and the pancreatic damage indicators such as serum amylase and lipase decreased significantly.

The researchers found that NMN levels in serum were negatively correlated with inflammatory indicators such as white blood cells and neutrophils, suggesting that we may be able to predict the severity of pancreatitis based on NMN levels.

Secondly, this study clarified the internal mechanism of fecal transplantation to alleviate acute pancreatitis. Fecal transplantation produces more NMN by changing the intestinal flora, thereby activating SIRT3, increasing the expression of PRDX5, and reducing the oxidative damage and mitochondrial function of acinar cells obstacle.

At the same time, this study also suggests that the NMN produced by our intestinal flora should not be underestimated, and its role is greater than we imagined.

Tag: NMN

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