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Updated: Jul 6, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Fecal Supernatants from Patients with Crohn's Disease Induce Inflammatory Alterations in M2 Macrophages and
Frida Gorreja1, Mia Bendix2, Stephen T A Rush1
1Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
Abstract:
Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn's disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGFβ superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD.
Insights
Fecal supernatants from Crohn's disease (CD) patients alter intestinal macrophage and fibroblast responses, promoting inflammation but not fibrosis. Gut microbiota metabolites play a key role in CD inflammation.
Area of Science:
- Gastroenterology and Immunology
- Microbiome Research
- Cellular Biology
Background:
- Intestinal macrophages and fibroblasts are key players in Crohn's disease (CD) pathogenesis.
- The gut microbiome and its metabolites significantly influence the intestinal microenvironment.
Purpose of the Study:
- To investigate the impact of fecal supernatants (FSs) from CD patients on macrophage and fibroblast behavior.
- To understand how CD-associated fecal metabolites affect cellular functions related to inflammation and fibrosis.
Main Methods:
- Fecal supernatants (FSs) were collected from CD patients and healthy subjects (HS).
- Metabolite profiles of FSs were analyzed.
- Monocyte-derived M2 macrophages and fibroblasts were cultured with FSs.
- Analysis included secreted and surface proteins, gene expression, and macrophage efferocytosis.
Main Results:
- CD-FS exhibited a distinct metabolite profile compared to HS-FS.
- CD-FS induced an anti-inflammatory phenotype in M2 macrophages (increased IL-10, IL1RA, CD206) without altering efferocytosis.
- CD-FS increased pro-inflammatory mediators (IL-6, MCP-1) in fibroblasts but did not affect extracellular matrix production.
- Macrophage-conditioned media exposed to CD-FS modulated fibroblast gene expression, impacting TGFβ superfamily members and reducing IL-4.
Conclusions:
- M2 macrophages and fibroblasts exhibit aberrant responses to the CD fecal microenvironment.
- Altered protein expression suggests a role in inflammation perpetuation, not fibrosis, in CD.
- Gut microbiota metabolites are implicated in the development and/or maintenance of inflammation in Crohn's disease.
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