Journal of applied microbiology · 2025
Gut-organ axis is more fragmented in ulcerative colitis: a metaproteomics study.
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Yadav Asha, Shinde Pratik Balwant, Behl Arush, Singh Deepti, Kedia Saurabh, Ahuja Vineet, Sharma Krishna Kant
Аннотация
AIMS: The study aims to assess the gut microbiota function and the status of bidirectional relationship of gut with other body organs in ulcerative colitis (UC).
METHODS AND RESULTS: The proteomic analysis of fecal samples revealed the presence of 2072 microbial proteins and 243 human proteins. Microbial proteins for pentose phosphate pathway (PPP) increased significantly in UC samples; whereas, decrease in proteins related to energy metabolism, transmembrane transporters and membrane proteins, and protein folding was noted. Interestingly, expression of proteins related to iron metabolism and oxidative stress indicates an oxidative gut environment that favors the growth of pathogenic microbes, enteric infections, and intestinal damage. Over-expression of host proteins such as neutrophil defensin 3, lactotransferrin, neutrophil elastase, azurocidin, protein S100-A8, protein S100-A9, and cathepsin G further indicate inflammation, and microbial infection in UC gut. The microbial (Omp)-host (TLR4) protein interaction analysis by molecular docking suggests significant implications in immune modulation. Further, gas chromatography-mass spectrometry investigation revealed altered concentration of microbial short chain fatty acids.
CONCLUSION: The study revealed vital clues about the gut-organ homeostasis in UC that contribute to the host physiology, disease pathogenesis and 'gut-organ axis' fragmentation.
METHODS AND RESULTS: The proteomic analysis of fecal samples revealed the presence of 2072 microbial proteins and 243 human proteins. Microbial proteins for pentose phosphate pathway (PPP) increased significantly in UC samples; whereas, decrease in proteins related to energy metabolism, transmembrane transporters and membrane proteins, and protein folding was noted. Interestingly, expression of proteins related to iron metabolism and oxidative stress indicates an oxidative gut environment that favors the growth of pathogenic microbes, enteric infections, and intestinal damage. Over-expression of host proteins such as neutrophil defensin 3, lactotransferrin, neutrophil elastase, azurocidin, protein S100-A8, protein S100-A9, and cathepsin G further indicate inflammation, and microbial infection in UC gut. The microbial (Omp)-host (TLR4) protein interaction analysis by molecular docking suggests significant implications in immune modulation. Further, gas chromatography-mass spectrometry investigation revealed altered concentration of microbial short chain fatty acids.
CONCLUSION: The study revealed vital clues about the gut-organ homeostasis in UC that contribute to the host physiology, disease pathogenesis and 'gut-organ axis' fragmentation.