1-methylnicotinamide attenuated inflammation and regulated flora in Necrotizing enterocolitis

TL;DR

1-MNA reduced inflammation and improved gut health in a rat model of NEC, suggesting it could be a promising treatment for this severe neonatal disease.

Contribution

This study is the first to demonstrate that 1-MNA can alleviate NEC by modulating inflammation, the TLR4-NF-κB pathway, and gut microbiota.

Findings

1-MNA reduced mortality and inflammation in NEC rats.

1-MNA inhibited the TLR4-NF-κB pathway activation.

1-MNA improved intestinal barrier function and modulated gut flora.

Abstract

Necrotizing enterocolitis(NEC) is a prevalent and destructive illness in neonates. Nicotinamide N-methyltransferase (NNMT) and its derivative, 1-methylnicotinamide (1-MNA), are known to be significant in conditions such as cardiovascular inflammation and renal tubular damage, and 1-MNA has been recognized for its anti-inflammatory effects in various diseases. However, the involvement of NNMT and 1-MNA in the development of NEC remains unclear.

We collected intestinal tissues and blood samples from children with NEC and control subjects for biochemical analysis. The NEC rats were induced by hypoxic cold stimulation and lipopolysaccharide, and control, NEC and NEC + 1-MNA groups were established. Neonatal rats were executed on the fourth day and blood, intestinal and fecal specimens were taken for subsequent testing.

Elevated NNMT and 1-MNA were found in NEC children and NEC rats. Exogenous supplementation of 1-MNA to NEC rats reduced mortality, pathological and inflammatory damage, and inhibited activation of the TLR4-NF-κB pathway in neonatal rats. In addition, 1-MNA improved intestinal barrier function and modulated intestinal flora in NEC rats.

1-MNA attenuated NEC injury by seemingly inhibiting the TLR4-NF-κB pathway, improving intestinal barrier function and modulating intestinal flora. These findings suggest a potential therapeutic role for 1-MNA in NEC management.

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