The role of matrix metalloproteinase 28 and gut microbiome in the regulation of obesity and metabolic disorders

Abstract

Matrix metalloproteinase 28 is a member of the matrix metalloproteinases family. In preliminary studies, the absence of it was found to relate to obesity. Obesity increases the risk of many health issues, including type 2 diabetes, both considered challenges to the global economy. In this study, we hypothesise that Mmp28 knock-out (KO) mice have altered metabolism influenced by the gut microbiome, and changing the living conditions will mitigate these effects. We aim to investigate whether the deletion of the Mmp28 gene is a crucial factor through which environmental management can affect the composition of gut microbiota, resulting in improved metabolism. Mmp28-KO and wild-type C57BL/6J mice were on a standard chow diet in specific pathogen-free (SPF) conditions and transferred to the conventional mouse room (CMR) for five weeks. Mice were fasted overnight and sacrificed at 30 weeks old. The livers were used for histology, and metabolic indicators were analysed using RT-qPCR and biochemical assays, while the faecal samples were used for microbiome analysis using 16s rRNA sequencing. When housed in SPF, Mmp28-KO mice had dyslipidaemia and fatty livers in addition to increased body weights and insulin resistance. They also had lower levels of the carbohydrate-digesting bacterium Bifidobacterium and higher levels of the Firmicutes phylum and its genus, Lachnospiraceae. The five weeks transfer to CMR caused weight loss, improved insulin resistance and reduced fatty liver in the mice. There was a rise in the abundance of Oscilibacter and a decline in the quantity of Firmicutes following decreased circulating butyrate. These results suggest Mmp28 is vital in regulating body weight and metabolism via alterations to the gut microbiome. They also show a change of sanitation conditions for five weeks can rebalance the gut microbiome and reshape body metabolism and obesity in genetically susceptible individuals. There are lessons to learn and study in humans.