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.
Highlights
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) from normal fat diet (NFD) or high fat diet (HFD)-fed obese/diabetic KK-Ay (KK) mice or control C57BL/6J (BL) mice (Fig. 1A) were analyzed by headspace sampler-gas chromatography-mass spectrometry (HSS-GC-MS) without the solid-phase microextraction (SPME) procedure to identify proinflammatory metabolites associated with low-grade inflammation and identify biomarkers reflecting the progression of lifestyle-related disease
These fecal metabolites induced significant proinflammatory activity in mouse RAW264 cells. These results suggest that fecal VOCs might be potential biomarkers for the diagnosis of inflammation-associated lifestyle related diseases
Summary
When the microfloral composition deteriorates, it triggers low-level chronic inflammation associated with several lifestyle-related diseases including obesity and diabetic mellitus. Fecal VOCs from normal fat diet (NFD) or high fat diet (HFD)-fed obese/diabetic KK-Ay (KK) mice or control C57BL/6J (BL) mice (Fig. 1A) were analyzed by headspace sampler-gas chromatography-mass spectrometry (HSS-GC-MS) without the SPME procedure to identify proinflammatory metabolites associated with low-grade inflammation and identify biomarkers reflecting the progression of lifestyle-related disease. We detected up to ~80 fecal VOCs in mouse samples and found elevated levels of fecal VOCs such as phenol, acetone, nonanal and octanal were significantly associated with diet type (NFD vs HFD), mouse lineage (BL vs KK), the progression of disease state, and their interaction.
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