Publikationsdatenbank

Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Avery, Ellen G.

Haag, Lea-Maxie

McParland, Victoria

Kedziora, Sarah M.

Zigra, Gabriel J.

Valdes, Daniela S.

Kirchner, Marieluise

Popp, Oliver

Geisberger, Sabrina

Nonn, Olivia

Karlsen, Tine V.

N’Diaye, Gabriele

Yarritu, Alex

Bartolomaeus, Hendrik

Bartolomaeus, Theda U. P.

Tagiyeva, Nurana A.

Wimmer, Moritz I.

Haase, Nadine

Zhang, Yiming D.

Wilhelm, Andreas

Grütz, Gerald

Tenstad, Olav

Wilck, Nicola

Forslund, Sofia K.

Klopfleisch, Robert (WE 12)

Kühl, Anja A.

Atreya, Raja

Kempa, Stefan

Mertins, Philipp

Siegmund, Britta

Wiig, Helge

Müller, Dominik N.

Quelle

Cardiovascular research : journal of the European Society of Cardiology

Bandzählung: 121

Heftzählung: 5

Seiten: 803 – 816

ISSN: 0008-6363

Sprache

Englisch

Verweise

URL (Volltext): https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvae267/7953155

DOI: 10.1093/cvr/cvae267

Pubmed: 39804196

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Aims
The 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 results
Here, 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.
Conclusion
Collection 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.