Experimentally induced visceral pain, variation in the microbiome, and host gene expression in irritable bowel syndrome

Authors

• NH Fourie
• D Wang
• PA Smyser
• SK Abey
• EG Ferguson
• LB Sherwin
• B Rahim-Williams
• WA Henderson

Abstract

Abdominal pain is a principal symptom of irritable bowel syndrome (IBS). Subclinical inflammation and microbial dysregulation are implicated in the etiology of IBS. We examined the relationship between induced abdominal pain, peripheral gene expression, and the oral microbiome, as minimally invasive sources of information about host biology. 18 healthy volunteers (HV) and 16 IBS patients drank a gastrointestinal (GI) four probe sugar test solution. Resulting abdominal pain was assessed using the Gastrointestinal Pain Pointer. Whole blood gene expression was determined with Affymetrix GeneChip® Human Genome U133 Plus 2.0 Arrays. Oral mucosal microbiome was characterized using PhyloChip™ Version G3 (SecondGenome). 258 bacteria were significantly correlated to pain severity. Negative correlations were dominated by the Lachnospiraceae (25%). Positive correlations were dominated by Lachnospiraceae (18%), Prevotellaceae (12%) and Veillonellaceae (11%). 508 genes were correlated to pain. Seven bacterial families (Lachnospiraceae, Prevotellaceae, Rikenellaceae, Bacillaceae, Veillonellaceae, Moraxellaceae and Psuedomonodaceae) dominated correlations with pain correlated genes. Functional molecular themes included cytokine pathways, Rho signaling and the PI3K/AKT pathway. The expression of several known opportunistic pathogens associated with extra-oral inflammatory pathologies were significantly associated with inflammation related genes and pain. Over expression of Prevotellaceae and Veillonellaceae in IBS and inflammatory bowel disease have been previously described. Their positive relationship with abdominal pain and strong correlation to inflammation associated genes suggest that they may be key drivers of systemic inflammation and gastrointestinal symptoms. Decreased expression of Lachnospiraceae with increasing pain severity may point to changing availability of butyrate, which is essential to epithelial health.

Scientific Focus Area: Microbiology and Infectious Diseases

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