Cited by 484Gut microbiota and healthGastrointestinal motility and disordersBacteriophages and microbial interactions

Profiling the human intestinal environment under physiological conditions

Open access
Shalon, Dari, Culver, Rebecca Neal, Grembi, Jessica A., Folz, Jacob, Treit, Peter V., Shi, Handuo, Rosenberger, Florian A., Dethlefsen, Les +13 more·2023·Nature

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41586-023-05989-7

Cites

82 of 82 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • BBAAs are abundant in the gastrointestinal tract and have been associated with human inflammatory bowel disease.

    “Furthermore, bacterial bile acid amidates (BBAAs) are abundant in the gastrointestinal tract18 and have been associated with human inflammatory bowel disease3.”
  • Reduced concentrations of DCA and LCA are detected in intestinal and fecal samples of individuals who had recently used antibiotics, albeit with a small sample size.

    “Moreover, reduced concentrations of DCA and LCA were detected in the intestinal and fecal samples of individuals who had recently used antibiotics, albeit with the caveat of a small sample size.354”
  • Recent development of non-invasive, ingestible sampling devices makes it possible to collect luminal contents throughout the intestinal tract, potentially overcoming limitations of stool samples in reflecting regional variation of gut microbiota.

    “Notably, the recent development of non-invasive, ingestible sampling devices has made it possible to collect luminal contents throughout the intestinal tract, potentially overcoming the limitations of stool samples in reflecting the regional variation of gut microbiota.354,753”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Shalon, D., Culver, R. N., Grembi, J. A., Folz, J., Treit, P. V., Shi, H., Rosenberger, F. A., Dethlefsen, L., Meng, X., Yaffe, E., Aranda-Díaz, A., Geyer, P. E., Mueller-Reif, J. B., Spencer, S., Patterson, A. D., Triadafilopoulos, G., Holmes, S. P., Mann, M., Fiehn, O., Relman, D. A., & Huang, K. C.
Affiliations
  • Stanford Medicine (US)
  • University of California, Davis (US)
  • Max Planck Institute of Biochemistry (DE)
  • Chan Zuckerberg Biohub San Francisco (US)
  • Stanford University (US)
  • Pennsylvania State University (US)
  • VA Palo Alto Health Care System (US)
Corresponding author
  • Culver, Rebecca Neal
  • Fiehn, Oliver
  • Relman, David A.
  • Huang, Kerwyn Casey
Venue
Nature
Published
2023-05-10
Volume
617
Issue
7961
Pages
581-591
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W4376132136
Cited by
484
References
82
Citations by year
2026: 112 · 2025: 159 · 2024: 162 · 2023: 51
FWCI
43.08
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Science Foundation (1936687)
  • Bill and Melinda Gates Foundation (INV-037857)
  • Fund for Astrophysical Research
  • National Institutes of Health (NIH T32, AI147023)
  • School of Medicine, Stanford University
  • National Defense Science and Engineering Graduate
  • Stanford Research Computing Center, Stanford University
  • National Institute of General Medical Sciences (RM1GM135102)
  • National Institute of Allergy and Infectious Diseases (R01AI147023)
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007056)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
Keywords
human gut microbiome, intestinal tract, ingestible devices, non-invasive sampling, intestinal physiology, bile acids, bile acid deconjugation, prophage induction, host proteome, gut metabolome, microbial distribution, multi-omics
MeSH terms
Gastrointestinal Microbiome, Bacteria, Bacteriophages, Bile Acids and Salts, Digestion, Feces, Humans, Intestines, Proteome, Metabolome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review