Study reveals distinct metabolome differences in human upper intestinal tract using non-invasive sampling device

A study using an ingestible sampling device uncovered significant metabolome differences in the upper intestinal tract during routine daily digestion, highlighting the complex interplay between diet, host, and microbial metabolism. The study by Dr. Jacob Folz, Dr. Rebecca Culver, and many others was published on May 10 in Nature Metabolism.

A study, published in Nature Metabolism, conducted with 15 healthy participants has utilized an innovative non-invasive ingestible sampling device to investigate the spatiotemporal variations in the upper intestinal luminal contents during daily digestion. The research, which involved the collection and analysis of 274 intestinal samples and 60 corresponding stool homogenates, employed a combination of mass spectrometry assays and 16S rRNA sequencing, ultimately identifying 1,909 metabolites, including sulfonolipids and fatty acid esters of hydroxy fatty acids (FAHFA) lipids. The findings revealed significant differences between stool and intestinal metabolomes, with diet-derived and microbially linked metabolites accounting for the most substantial inter-individual variations. The study also shed light on the potential effects of antibiotics on intestinal bacteria and their metabolites, raising important questions about the implications for inflammation, diabetes, and inflammatory bowel disease.

According to the study, its results have significant implications for future research on digestion and intestinal diseases. It emphasizes the limitations of using stool as a surrogate for the gut intestinal tract, highlighting that stool primarily represents colonic contents. The study additionally demonstrates that over 50% of annotated metabolites exhibit significant differences between proximal and distal intestinal locations, underlining the complexity of the digestive process. The research points to the need for larger studies with a more diverse participant pool to draw comprehensive conclusions about gut metabolism across populations and to investigate potential links between antibiotics use and disruptions in sulfonolipid and FAHFA metabolism. Overall, this work showcases the potential of non-invasive sampling devices, combined with metabolomics and genomics, to advance the understanding of nutrition and human disease and enable more precise intervention and prevention strategies.

According to the research, in a related companion study, the same ingestible sampling device was used to explore variation in the intestinal environment using various omics approaches. This study found pronounced prophage induction in intestinal samples compared to stool, highlighting differences in the host proteome and bile acid profiles along the intestines. These findings, according to the study, complement the metabolome differences reported in the main study and collectively emphasize the significance of directly sampling from the intestines to enhance our understanding of the intricate relationship between human hosts and their commensal microbes, promising new insights into the field of gut microbiota research.

Springer Nature: Jacob Folz, et al., Human metabolome variation along the upper intestinal tract, Nature Metabolism (2023). https://doi.org/10.1038/s42255-023-00777-z