Human metabolome variation along the upper intestinal tract

Area of Science:

• Gastroenterology
• Metabolomics
• Microbiome Research

Background:

• The small intestine is crucial for processing diet, with metabolites arising from host secretions, ingested substances, and microbial activity.
• Understanding the dynamic changes in the upper intestinal environment is key to deciphering host-microbe-diet interactions.

Purpose of the Study:

• To investigate the spatiotemporal variations of metabolites in the upper intestinal lumen during normal digestion.
• To correlate these findings with dietary intake and microbial composition.

Main Methods:

• Utilized a non-invasive, ingestible sampling device to collect 274 intestinal and 60 stool samples.
• Employed five mass spectrometry assays and 16S rRNA sequencing for comprehensive metabolite and microbial analysis.

Main Results:

• Identified 1,909 metabolites, including novel sulfonolipids and fatty acid esters of hydroxy fatty acids (FAHFA).
• Observed significant differences between intestinal and stool metabolomes, with diet-derived and microbially influenced metabolites driving inter-individual variability.
• Linked luminal keto acids to fruit intake and identified potential roles for Blautia species in FAHFA metabolism.

Conclusions:

• Non-invasive in vivo sampling provides unprecedented insights into human small intestinal and ascending colon physiology.
• Demonstrated clear links between diet, host, and microbial metabolism within the upper gastrointestinal tract.
• Highlighted the impact of factors like antibiotic use on bioactive metabolite profiles.