Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice.
This animal study investigated whether treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with a low-fat diet (LD) switch produced distinct gut microbiome changes in diet-induced obese (DIO) mice, compared to mice maintained on a high-fat Western diet, switched to LD alone, or kept as lean controls. Researchers analyzed cecal microbiome profiles using amplicon sequence variant (ASV) sequencing across these groups. The study found that diet switch (regardless of NNMTi treatment) drove several microbiome differences at the genus and phylum levels relative to controls, while differences between lean and obese controls were minimal, suggesting adiposity alone had limited microbiome impact in this model. Alpha diversity did not significantly differ between groups, but beta diversity analyses indicated within-group similarity. K-means clustering revealed that NNMTi-treated LD-switched mice had a distinct microbiome pattern, characterized by decreased Erysipelatoclostridium and increased Lactobacillus—genera associated with metabolic regulation and body weight. Parasutterella abundance, elevated in both LD-switched groups, significantly correlated with several adipose tissue metabolites. The authors acknowledge this is a foundational, exploratory study in mice, limiting direct translation to human metabolic disease.