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| Status |
Public on May 26, 2024 |
| Title |
Gut Microbiota Metabolite Indole-3-Acetic Acid Maintains Intestinal Epithelial Homeostasis Through Mucin Sulfation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The incidence and prevalence of inflammatory bowel disease (IBD) is gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and HFD-fed mice is observed. HFD induces a significant decrease in indole-3-acetic acid (IAA) and lead to intestinal barrier damage. Furthermore, IAA supplementation enhances the intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including Papss2 and Slc35b3, the synthesis enzyme and the transferase of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), via the Aryl Hydrocarbon Receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (LactobacillusΔiaaM) and the ability to produce IAA fails to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through AHR, contributing to the protection of intestinal homeostasis.
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| Overall design |
RNA-seq was performed in the colonic tissues from DSS-treated mice with or without IAA
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| Contributor(s) |
Li M |
| Citation missing |
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| |
| Submission date |
Dec 12, 2023 |
| Last update date |
May 26, 2024 |
| Contact name |
Mengfan Li |
| E-mail(s) |
mengfannn@tmu.edu.cn
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| Phone |
18838980065
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| Organization name |
Tianjin Medical University General Hospital
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| Street address |
154 Anshan Road, Heping District, Tianjin
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| City |
Tianjin |
| ZIP/Postal code |
300000 |
| Country |
China |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1051583 |
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