Impact of Gut R. torques on Type 2 Diabetes in Selenium‐deficient Mice

Abstract

Selenium (Se), an essential trace element, is involved in a variety of biological functions through optimized levels of dietary intake. Obesity and type 2 diabetes have been characterized by altered gut microbiota, inflammation, and gut barrier disruption. We have previously demonstrated that suboptimal Se intake at levels <23% of nutritional needs increases susceptibility to type 2 diabetes in middle‐aged mice. Furthermore, results of 16S rRNA amplicon sequencing analyses show a profound impact of dietary Se deficiency on gut microbiota, inducing an increased abundance of Lachnospiraceae in old mice. Lachnospiraceae, a family of anerobic and spore‐forming bacteria in the phylum Firmicutes, can degrade mucins and are associated with inflammation of the gut and insulin resistance. In particular, many studies link the R. torques species of the Lachnospiraceae family to type 2 diabetes. Thus, we hypothesized that dietary Se deficiency reshaped gut microbiota to modulate type 2 diabetes. The objective of this study was to determine whether and how R. torques and dietary Se interacted to influence type 2 diabetes. Weaning female C57BL/6J mice were fed either a Se‐deficient or a Se‐adequate diet for 27 weeks, and half of them were given an oral gavage of R. torques (2 ×108 CFU in 0.2 mL) daily between weeks 22 and 25. Mice were terminated at week 27. Neither dietary Se deficiency nor R. torquesenrichment influenced body weight or food intake during the time course. Dietary Se deficiency induced (P < 0.05) glucose intolerance (13%) and insulin insensitivity (16%) in the female mice aged 7 months. Although R. torquesenrichment did not aggravate or improve these two type 2 diabetes‐like symptoms, it affected the abundance of Lactobacillus, Faecalibacterium prausnitzii, Roseburia spp./E. rectale, and E. coli in the fecal and/or cecal samples. R. torquesenrichment 1) decreased selenoprotein P and glutathione peroxidase 1 in the liver but not skeletal muscle in Se‐adequate mice; 2) increased liver glutathione peroxidase 1 at the protein level in Se‐deficient mice. Altogether, R. torquesenrichment does not restore dietary Se deficiency‐induced glucose intolerance or insulin resistance in mature female mice despite changed protein expression of two key selenoproteins in Se metabolism.