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LC-MS analysis of lactulose challenge and the microbiome

Thursday, September 15, 2016 — Poster Session III

3:30 p.m. – 5:00 p.m.
FAES Terrace
NINR
MOLBIO-29

Authors

  • PV Joseph
  • NH Fourie
  • EG Ferguson
  • SK Abey
  • PJ Walter
  • LB Sherwin
  • B Rahim-Williams
  • L Leggio
  • WA Henderson

Abstract

Background: The synthetic sugar lactulose is used clinically to evaluate intestinal permeability (IP) and is known to stimulate visceral pain (VP) or sensitivity. The microbiome mediates IP, VP, and lactulose breakdown in the gut. In this study, we looked to calculate VP response to oral lactulose challenge using baseline microbiome. Methods: 18 participants were recruited (27.944.27 years, BMI 25.624.24, 66% female, 50% Caucasian), consented, and screened for active infections and organic disease. Participants’ microbiome sampling preceding ingestion of a lactulose-containing test solution. 5-hour urine was completed following ingestion. PhyloChip microbiome analysis, mass spectrometry urinary metabolism (Thermo Scientific Q-Exactive LC-MS), and self-reported VP (Gastrointestinal Pain Pointer) were measured. Results: 11/18 participants reported VP. Urinary/lactulose ratio was positively associated with VP (R2>0.5) and correlated to 65 OTUs (R2>0.25), and 45 were positively correlate. The Lactobacillaceae and Clostridiali are disproportionately represented among the group of 65 correlated bacteria compared to the overall richness profile. Discussion: Microbial OTU-specific association to VP/IP lactulose ratio provides a trend which can be utilized to predict response to lactulose ingestion as part of IP tests. Further, lactulose is absorbed by colonic bacteria to produce short-chain fatty acids, such as butyric acid, which are known to modulate the epithelial barriers in cell and animal models. Because alterations in IP and epithelial barriers are believed to provide to various pathologies, including those stemming from chronic inflammation. Future studies to elucidate the influence of microbes and their byproducts to epithelium health.

Category: Molecular Biology and Biochemistry