![]() ![]() Historically, sampling the human intestinal tract without disturbance or contamination has been challenging 10. Thus, deeper understanding of how gut microorganisms impact human physiology and vice versa requires local sampling of the gut microbiome and its chemical environment in natural, unperturbed states. As a result, distinct microbial communities with specialized functions, metabolomes, immune niches and proteomes are present in each intestinal region 3, 4, 11. The regions of the gut distal to the stomach (duodenum, jejunum, ileum and colon) differ markedly in nutrient availability, pH, oxygen partial pressure, mucosal structure and flow rate 7. For example, key metabolites such as bile acids are altered upstream by microbial transformations and then substantially absorbed by the host before excretion 4. However, stool reflects waste products and downstream effluent, within which regional variation is lost. Because of difficulties in accessing and sampling the intestinal tract, stool has been the main source of information for human gut microbiome studies 10. An important yet often overlooked aspect of the gut is regional heterogeneity and how it impacts local physiology 9. Humans depend on their gut microorganisms for food digestion, immune system regulation and protection against pathogens, among other critical functions 1. The human intestinal tract harbours the vast majority of microorganisms residing in or on our bodies 1 their genetic content and biochemical transformation capabilities are hundreds of times larger than those encoded by the human genome 8. 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. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. 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. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. 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. 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. ![]() ![]() ![]() Nature volume 617, pages 581–591 ( 2023) Cite this article Profiling the human intestinal environment under physiological conditions ![]()
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