Adherent-invasive E. coli metabolism of propanediol in Crohn's disease regulates phagocytes to drive intestinal inflammation Journal Article
| Authors: | Viladomiu, M.; Metz, M. L.; Lima, S. F.; Jin, W. B.; Chou, L.; JRI Live Cell Bank; Guo, C. J.; Diehl, G. E.; Simpson, K. W.; Scherl, E. J.; Longman, R. S. |
| Article Title: | Adherent-invasive E. coli metabolism of propanediol in Crohn's disease regulates phagocytes to drive intestinal inflammation |
| 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. © 2021 Elsevier Inc. |
| Keywords: | adult; controlled study; gene sequence; human cell; nonhuman; flow cytometry; transcription factor foxp3; animal cell; phenotype; animal tissue; transcription factor gata 3; dendritic cell; interleukin 10; interleukin 1beta; animal experiment; animal model; enzyme linked immunosorbent assay; histology; escherichia coli; cd4+ t lymphocyte; cell isolation; enteritis; cytokine production; interleukin 17; th17 cell; intestine flora; cytokine release; rna 16s; interleukin 22; diphtheria toxin; phagocyte; crohn's disease; crohn disease; bacterial metabolism; fermentation; interleukin 23; nutrient availability; retinoid related orphan receptor gamma; mononuclear phagocyte; mononuclear phagocytes; bacterium adherence; enterobacteriaceae; carbon source; human; male; female; priority journal; article; fucose; microbial metabolism; propylene glycol; propionate; adherent-invasive e. coli; microbial metabolite-host immunity; propanediol dehydratase |
| Journal Title: | Cell Host & Microbe |
| Volume: | 29 |
| Issue: | 4 |
| ISSN: | 1931-3128 |
| Publisher: | Cell Press |
| Date Published: | 2021-04-14 |
| Start Page: | 607 |
| End Page: | 619.e8 |
| Language: | English |
| DOI: | 10.1016/j.chom.2021.01.002 |
| PROVIDER: | scopus |
| PMCID: | PMC8049981 |
| PUBMED: | 33539767 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 May 2021 -- Source: Scopus |
