Evidence map›Paper›PMID 39804196›Full record

ArticleCardiovascular research2025

Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface.

Ellen G Avery, Lea-Maxie Haag, Victoria McParland, Sarah M Kedziora, Gabriel J Zigra, Daniela S Valdes, Marieluise Kirchner, Oliver Popp, Sabrina Geisberger, Olivia Nonn and 22 more

Abstract read
In one paragraph

Article in Cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors.

Ellen G AveryMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Lea-Maxie HaagDepartment for Medicine (Gastroenterology, Infectious Diseases, Rheumatology) Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Victoria McParlandMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Sarah M KedzioraMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Gabriel J ZigraDepartment for Medicine (Gastroenterology, Infectious Diseases, Rheumatology) Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Daniela S ValdesMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Marieluise KirchnerCore Unit Proteomics, Berlin Institute of Health at Charite-Universitätsmedizin Berlin, Berlin, Germany.
Oliver PoppProteomics Platform, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Sabrina GeisbergerMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Olivia NonnMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Tine V KarlsenDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway.
Gabriele N'DiayeExperimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Alex YarrituMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Hendrik BartolomaeusMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID 0000-0003-4288-3828
Theda U P BartolomaeusMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Nurana A TagiyevaMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Moritz I WimmerMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Nadine HaaseMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID 0000-0003-0727-1738
Yiming D ZhangMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Andreas WilhelmCheckImmune GmbH, BerlinBioCube, Robert-Rössle Str. 10, Berlin 13125, Germany.
Gerald GrützCheckImmune GmbH, BerlinBioCube, Robert-Rössle Str. 10, Berlin 13125, Germany.
Olav TenstadDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway.ORCID 0000-0001-5833-2620
Nicola WilckMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID 0000-0003-3189-5364
Sofia K ForslundMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Robert KlopfleischDepartment of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Anja A KühlDepartment for Medicine (Gastroenterology, Infectious Diseases, Rheumatology) Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Raja AtreyaDepartment of Medicine 1, Friedrich-Alexander University, Erlangen, Germany.ORCID 0000-0002-8556-8433
Stefan KempaMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID 0000-0002-0696-9299
Philipp MertinsCore Unit Proteomics, Berlin Institute of Health at Charite-Universitätsmedizin Berlin, Berlin, Germany.
Britta SiegmundDepartment for Medicine (Gastroenterology, Infectious Diseases, Rheumatology) Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.ORCID 0000-0002-0055-958X
Helge WiigDepartment of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway.ORCID 0000-0002-7740-8210
Dominik N MüllerMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID 0000-0003-3650-5644

Funding

Bundesministerium für Bildung und Forschung (BMBF) funding Multimodal Clinical Mass Spectrometry to Target Treatment Resistance (MSTARS)Charité-Universitätsmedizin Berlin and the Berlin Institute of Health at Charité (BIH)Corona Foundation in the German StifterverbandDeutsche Forschungsgemeinschaft (DFG, German Research Foundation) DFG-SFB-1365/A01Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) DFG-SFB1449Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) DFG-SFB1470/A05Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) DFG-TRR 241Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) SFB1340Deutsches Zentrum für Herz-Kreislauf-Forschung 81Z0100110DZGIF (DZG Innovation Fund)European Research Council under the European Union's Horizon 2020 research and innovation program 852796Norwegian Health AssociationResearch Council of Norway 262079The German Ministry of Education and Research (BMBF) 01EJ2202AThe German Ministry of Education and Research (BMBF) 01EJ2202DWestern Norway Regional Health Authority 912168Western Norway Regional Health Authority F-12546
6 · The paper itself

Abstract

aimsThe gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health. Variation in bacterial load and composition along the GI tract may influence the mucosal microenvironment and thus be reflected its interstitial fluid (IF). Characterization of the segment-specific microenvironment is challenging and largely unexplored because of lack of available tools. METHODS AND

resultsHere, we developed methods, namely tissue centrifugation and elution, to collect IF from the mucosa of different intestinal segments. These methods were first validated in rats and mice, and the tissue elution method was subsequently translated for use in humans. These new methods allowed us to quantify microbiota-derived metabolites, mucosa-derived cytokines, and proteins at their site-of-action. Quantification of short-chain fatty acids showed enrichment in the colonic IF. Metabolite and cytokine analyses revealed differential abundances within segments, often significantly increased compared to plasma, and proteomics revealed that proteins annotated to the extracellular phase were site-specifically identifiable in IF. Lipopolysaccharide injections in rats showed significantly higher ileal IL-1β levels in IF compared to the systemic circulation, suggesting the potential of local as well as systemic effect.

conclusionCollection of IF from defined segments and the direct measurement of mediators at the site-of-action in rodents and humans bypasses the limitations of indirect analysis of faecal samples or serum, providing direct insight into this understudied compartment.

Indexed as

BacteriaColonExtracellular FluidGastrointestinal MicrobiomeHost Microbial InteractionsIntestinal MucosaAnimalsCentrifugationCytokinesFatty Acids, VolatileFemaleHumansMaleMetabolomicsMiceMice, Inbred C57BLCytokinesFatty Acids, VolatileFluid isolationHumansInterstitial fluidIntestinal microenvironmentIntestineMicrobiomeRodents

Identifiers

PMID39804196
PMCPMC12101326

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.