Reduced phosphatidylcholine level in the intestinal mucus layer of prediabetic NOD mice

Abstract

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 prediabetic 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 16 S rRNA sequencing. Jejunal mucus PC class levels were decreased in early prediabetic NOD vs C57BL/6 mice. In colonic mucus of NOD mice, the level of several PC species was reduced throughout prediabetes. In plasma, similar reductions of PC species were observed in early prediabetic 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 prediabetic 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 prediabetic NOD mice as well as reduced proportions of SCFA‐producing bacteria in cecal content at early prediabetes, possibly contributing to intestinal barrier dysfunction and T1D.

Metabolomics and Lipidomics Studies in Pediatric Type 1 Diabetes: Biomarker Discovery for the Early Diagnosis and Prognosis

“…Prominently, cholinecontaining lipid clusters, including PCs and SMs, possess a predictive potential for prediabetes state for demonstrating a decreasing pattern from birth in the case groups. In prediabetic nonobese diabetic mice, researchers identified a reduction of PC species compared to healthy C57BL/6 mice [42]. This change may imply the deficiency of choline in T1D progressors [27].…”

Mucus Perspective to Conduct the Molecular Concertation in Inflammatory Bowel Diseases

“…The chronic inflammation of IBD pathologies resides in a defective immune response triggered by unbalance between pro-and anti-inflammatory signals [113]. Phospholipids play a key role in this process, as they greatly contribute, together with bacteria, in modulating the mucus function of filtering [114]- [117]. In physiological condition, phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) are the two main phospholipid classes that are present in mucus, accounting together for more than 80% of total mucus phospholipids [114].…”