Fecal Supernatants from Patients with Crohn’s Disease Induce Inflammatory Alterations in M2 Macrophages and Fibroblasts
Journal article, 2024

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.


inflammatory bowel disease

fecal metabolites

M2 macrophages

Crohn’s disease


Frida Gorreja

University of Gothenburg

Mia Bendix

Regionshospitalet Randers

Stephen T.A. Rush

University of Gothenburg

Lujain Maasfeh

University of Gothenburg

Otto Savolainen

Chalmers, Life Sciences, Systems and Synthetic Biology

Anders Dige

Arhus Universitetshospital

Jorgen Agnholt

Arhus Universitetshospital

Lena Öhman

University of Gothenburg

Maria K. Magnusson

University of Gothenburg


2073-4409 (eISSN)

Vol. 13 1 60

Subject Categories

Gastroenterology and Hepatology





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