News & Events

Spatial-, temporal- and inter-subject variation of the metabolome across the upper and lower human gastrointestinal tract

Tuesday, September 13, 2022 - 12:45 to 14:00
Dr. Oliver Fiehn
UC Davis Genome Center - Metabolomics, UC Davis
Event Category: 
LMC - Lectures in Modern Chemistry
Dr. Tao Huan
Chemistry B250

Inflammatory bowel disease comprising ulcerative colitis and Crohn’s disease are conditions of the human intestines. Stool is an inadequate surrogate for intestinal microbiome or metabolome studies for these diseases. Peroral or endoscopic gut aspirates and mucosal biopsies are highly invasive, and are usually conducted in the fasted state.

We evaluated a novel, safe, ingestible sampling device that collects the luminal contents of various regions of the human intestinal tract during normal daily routine digestion. To demonstrate the biological and clinical utility of the capsule sampling device, we profiled the microbiome and metabolites present in the duodenum, jejunum, ileum, and ascending colon, in comparison to corresponding stool samples. 275 samples were taken from 15 healthy humans using four capsules after lunch and dinner over two subsequent days. Samples were analyzed using untargeted lipidomics and biogenic amines by CSH- and BEH amide LC with +/- ESI Orbitrap MS/MS and primary metabolites by trimethylsilylation and GC-TOF MS. Bile acids were targeted by C18-QTRAP 6500 MS/MS, and short chain fatty acids by derivatization/GC-MS. Data analysis was performed by MS-DIAL 4.8 with compound annotations using and NIST20 libraries.

We identified 1,909 metabolites, including novel bile acids, in addition to numerous unknown compounds. Stool metabolomes were dramatically different than intestinal tract samples. Trends in chemical abundance were observed based on intestinal location, subject-specific metabolite expression, and diet-linked factors. As expected, essential nutrients and dietary lipids decreased along the intestinal tract, while other diet related metabolites increased along the intestine. Interestingly, bile acids showed both expected and novel variations. Two subjects with antibiotic treatments up to 6 months prior to collection showed markedly different metabolome patterns. Exposome metabolism could be readily followed in different modifications along the intestinal tract. For the first time, the metabolome of the human intestine was analyzed to reveal subject specific chemical phenotypes.