Title | Adherent-invasive E. coli metabolism of propanediol in Crohn's disease regulates phagocytes to drive intestinal inflammation. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Viladomiu M, Metz ML, Lima SF, Jin W-B, Chou L, Guo C-J, Diehl GE, Simpson KW, Scherl EJ, Longman RS |
Corporate Authors | JRI Live Cell Bank |
Journal | Cell Host Microbe |
Volume | 29 |
Issue | 4 |
Pagination | 607-619.e8 |
Date Published | 2021 04 14 |
ISSN | 1934-6069 |
Keywords | Animals, Bacterial Adhesion, Crohn Disease, Escherichia coli, Escherichia coli Infections, Female, Host-Pathogen Interactions, Humans, Immunity, Inflammation, Interleukin-1beta, Intestinal Mucosa, Intestines, Male, Mice, Phagocytes, Propylene Glycols, Th17 Cells |
Abstract | Adherent-invasive E. coli (AIEC) are enriched in the intestinal microbiota of patients with Crohn's disease (CD) and promote intestinal inflammation. Yet, how AIEC metabolism of nutrients impacts intestinal homeostasis is poorly defined. Here, we show that AIEC encoding the large subunit of propanediol dehydratase (PduC), which facilitates the utilization of fucose fermentation product 1,2-propanediol, are increased in the microbiome of CD patients and drive AIEC-induced intestinal T cell inflammation. In murine models, CX3CR1+ mononuclear phagocytes (MNP) are required for PduC-dependent induction of T helper 17 (Th17) cells and interleukin-1β (IL-1β) production that leads to AIEC-induced inflammatory colitis. Activation of this inflammatory cascade requires the catalytic activity of PduC to generate propionate, which synergizes with lipopolysaccharide (LPS) to induce IL-1β by MNPs. Disrupting fucose availability limits AIEC-induced propionate production and intestinal inflammation. These findings identify MNPs as metabolic sensors linking AIEC metabolism with intestinal inflammation and identify microbial metabolism as a potential therapeutic target in Crohn's disease treatment. |
DOI | 10.1016/j.chom.2021.01.002 |
Alternate Journal | Cell Host Microbe |
PubMed ID | 33539767 |
PubMed Central ID | PMC8049981 |
Grant List | DP2 HD101401 / HD / NICHD NIH HHS / United States R01 DK120985 / DK / NIDDK NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 AR071302 / AR / NIAMS NIH HHS / United States R01 AI125264 / AI / NIAID NIH HHS / United States R01 DK114252 / DK / NIDDK NIH HHS / United States |