Profiling the human intestinal environment under physiological conditions

Dari Shalon, Rebecca Neal Culver, Jessica A. Grembi, Jacob Folz, Peter V. Treit, Handuo Shi, Florian A. Rosenberger, Les Dethlefsen, Xiandong Meng, Eitan Yaffe, Andrés Aranda-Díaz, Philipp E. Geyer, Johannes B. Mueller-Reif, Sean Spencer, Andrew D. Patterson, George Triadafilopoulos, Susan P. Holmes, Matthias Mann, Oliver Fiehn, David A. RelmanKerwyn Casey Huang

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

The spatiotemporal structure of the human microbiome 1,2, proteome 3 and metabolome 4,5 reflects and determines regional intestinal physiology and may have implications for disease 6. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals 7. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

Original languageEnglish (US)
Pages (from-to)581-591
Number of pages11
JournalNature
Volume617
Issue number7961
DOIs
StatePublished - May 18 2023

All Science Journal Classification (ASJC) codes

  • General

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