Reduced phosphatidylcholine level in the intestinal mucus layer of pre-diabetic NOD mice.

Type 1 diabetes (T1D) is an autoimmune disease with rising incidence. Pre- and manifest T1D is associated with intestinal barrier dysfunction, skewed microbiota composition, and serum dyslipidemia. The intestinal mucus layer protects against pathogens and its structure and phosphatidylcholine (PC) lipid composition may be compromised in T1D, potentially contributing to barrier dysfunction. This study compared pre-diabetic Non-Obese Diabetic (NOD) mice to healthy C57BL/6 mice by analyzing the intestinal mucus PC profile by shotgun lipidomics, plasma metabolomics by mass spectrometry and nuclear magnetic resonance, intestinal mucus production by histology, and cecal microbiota composition by 16S rRNA sequencing. Jejunal mucus PC class levels were decreased in early pre-diabetic NOD vs C57BL/6 mice. In colonic mucus of NOD mice, the level of several PC species was reduced throughout pre-diabetes. In plasma, similar reductions of PC species were observed in early pre-diabetic NOD mice, where also increased beta-oxidation was prominent. No histological alterations were found in jejunal nor colonic mucus between the mouse strains. However, the β-diversity of the cecal microbiota composition differed between pre-diabetic NOD and C57BL/6 mice, and the bacterial species driving this difference were related to decreased short-chain fatty acid (SCFA)-production in the NOD mice. This study reports reduced levels of PCs in the intestinal mucus layer and plasma of pre-diabetic NOD mice as well as reduced proportions of SCFA-producing bacteria in cecal content at early pre-diabetes, possibly contributing to intestinal barrier dysfunction and T1D.