Macrophage-specific TRAF6 deletion mitigates DSS-induced colitis and is associated with reduced Enterococcus abundance and altered arachidonic acid metabolism.
5 affiliations
- 1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China.
- 2The First Clinical Medical School, Ningxia Medical University, Yinchuan, China.
- 3Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, China. [email protected].
- 4Key lab of ministry of education for protection and utilization of special biological resources in western China, Ningxia University, Yinchuan, China. [email protected].
- 5Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China. [email protected].
Abstract
Inflammatory bowel disease (IBD) involves dysregulated host immunity, gut microbial dysbiosis, and metabolic disturbances. As key innate immune cells, macrophages play critical roles in inflammatory responses, epithelial barrier dysfunction, and host-microbiota interactions. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a key adaptor protein in pro-inflammatory signaling, but the role of macrophage TRAF6 in colitis-associated microbial and metabolic alterations remains unclear. Here, we used macrophage-specific Traf6 conditional knockout mice in a 3% DSS-induced colitis model. TRAF6 expression was increased in colonic tissues from DSS-treated mice and patients with IBD, with enhanced co-localization with CD68-positive macrophages. Macrophage-specific Traf6 deletion reduced colitis severity, inflammatory responses, and epithelial barrier injury. 16S rRNA gene sequencing showed substantial gut microbiota remodeling, including reduced Enterococcus abundance. Untargeted metabolomics identified alterations in arachidonic acid metabolism: prostaglandin A2 (PGA2) was significantly reduced in both fecal and serum samples, whereas 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid [12(S)-HHT] was significantly reduced in feces and showed a similar downward trend in serum. Enterococcus abundance was positively associated with PGA2 and 12(S)-HHT levels, and an independent human IBD cohort further showed enrichment of Enterococcus. Collectively, macrophage-specific Traf6 deletion ameliorated DSS-induced colitis and was associated with coordinated remodeling of the gut microbiota and host metabolism, supporting an association between macrophage TRAF6, reduced Enterococcus abundance, and altered arachidonic acid metabolism during intestinal inflammation.
Related
- 2-methylbutanal remodels arachidonic acid metabolism and antitumor immunity through ENO1 in colorectal cancer
- Jiegeng decoction ameliorates COPD-like pulmonary injury in association with changes in PPARγ expression, arachidonic acid metabolism, and gut microbial composition
- Genomic insight into Enterococcus faecium biofilm formation isolated from catheter associated urinary tract infection
- CISD1 suppresses COPD inflammation by recruiting ubiquitinated STING and altering macrophage metabolism
- Factors associated with clinical classification of BALF mNGS-detected Enterococcus faecium as infection rather than colonization in ICU patients
BibTeX
@article{ma2026macrophagespecific,
title = {{Macrophage-specific TRAF6 deletion mitigates DSS-induced colitis and is associated with reduced Enterococcus abundance and altered arachidonic acid metabolism.}},
author = {Qinmei Ma and Fang Li and Mingdi Wang and Xiuyi Fang and Jinhan Sun and Fang Wang and Xiaoling Wu and Yujing Gao},
journal = {BMC microbiology},
year = {2026},
month = aug,
doi = {10.1186/s12866-026-05536-0},
url = {https://europepmc.org/article/MED/43009771},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Macrophage-specific TRAF6 deletion mitigates DSS-induced colitis and is associated with reduced Enterococcus abundance and altered arachidonic acid metabolism.
AU - Qinmei Ma
AU - Fang Li
AU - Mingdi Wang
AU - Xiuyi Fang
AU - Jinhan Sun
AU - Fang Wang
AU - Xiaoling Wu
AU - Yujing Gao
PY - 2026
DA - 2026/08/13
JO - BMC microbiology
DO - 10.1186/s12866-026-05536-0
UR - https://europepmc.org/article/MED/43009771
AB - Inflammatory bowel disease (IBD) involves dysregulated host immunity, gut microbial dysbiosis, and metabolic disturbances. As key innate immune cells, macrophages play critical roles in inflammatory responses, epithelial barrier dysfunction, and host-microbiota interactions. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a key adaptor protein in pro-inflammatory signaling, but the role of macrophage TRAF6 in colitis-associated microbial and metabolic alterations remains unclear. Here, we used macrophage-specific Traf6 conditional knockout mice in a 3% DSS-induced colitis model. TRAF6 expression was increased in colonic tissues from DSS-treated mice and patients with IBD, with enhanced co-localization with CD68-positive macrophages. Macrophage-specific Traf6 deletion reduced colitis severity, inflammatory responses, and epithelial barrier injury. 16S rRNA gene sequencing showed substantial gut microbiota remodeling, including reduced Enterococcus abundance. Untargeted metabolomics identified alterations in arachidonic acid metabolism: prostaglandin A2 (PGA2) was significantly reduced in both fecal and serum samples, whereas 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid [12(S)-HHT] was significantly reduced in feces and showed a similar downward trend in serum. Enterococcus abundance was positively associated with PGA2 and 12(S)-HHT levels, and an independent human IBD cohort further showed enrichment of Enterococcus. Collectively, macrophage-specific Traf6 deletion ameliorated DSS-induced colitis and was associated with coordinated remodeling of the gut microbiota and host metabolism, supporting an association between macrophage TRAF6, reduced Enterococcus abundance, and altered arachidonic acid metabolism during intestinal inflammation.
SN - 1471-2180
ER -