Elevated levels of proinflammatory volatile metabolites in feces of high fat diet fed KK-Ay mice

Sci Rep. 2020 Mar 30;10(1):5681. doi: 10.1038/s41598-020-62541-7.

Abstract

When the microfloral composition deteriorates, it triggers low-level chronic inflammation associated with several lifestyle-related diseases including obesity and diabetic mellitus. Fecal volatile organic compounds (VOCs) have been found to differ in gastrointestinal diseases as well as intestinal infection. In this study, to evaluate a potential association between the pathogenesis of lifestyle-related diseases and VOCs in the intestinal tract, fecal VOCs from obese/diabetic KK-Ay mice (KK) or controls (C57BL/6J mice; BL) fed a normal or high fat diet (NFD or HFD) were investigated using headspace sampler-GC-EI-MS. Principal component analysis (PCA) of fecal VOC profiles clearly separated the experimental groups depending on the mouse lineage (KK vs BL) and the diet type (NFD vs HFD). 16 s rRNA sequencing revealed that the PCA distribution of VOCs was in parallel with the microfloral composition. We identified that some volatile metabolites including n-alkanals (nonanal and octanal), acetone and phenol were significantly increased in the HFD and/or KK groups. Additionally, these volatile metabolites induced proinflammatory activity in the RAW264 murine macrophage cell line indicating these bioactive metabolites might trigger low-level chronic inflammation. These results suggest that proinflammatory VOCs detected in HFD-fed and/or diabetic model mice might be novel noninvasive diagnosis biomarkers for diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Feces / chemistry
  • Gastrointestinal Microbiome / genetics
  • Inflammation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / metabolism*
  • RAW 264.7 Cells
  • RNA, Ribosomal, 16S / genetics
  • Volatile Organic Compounds / analysis*

Substances

  • Biomarkers
  • RNA, Ribosomal, 16S
  • Volatile Organic Compounds