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Published on: July 13, 2016
Epithelial fucosylation regulates intestinal stem cell differentiation.
Haiqin Wu1,2,3, Chunlong Mu4, Xuan Li1,3
1Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Summary
Intestinal fucosylation is crucial for regulating intestinal stem cell (ISC) differentiation. Inhibiting fucosylation disrupts this balance, but supplementation with 2-fucosyllactose (2-FL) can restore normal ISC function and gut health.
Area of Science:
- Gastroenterology
- Developmental Biology
- Microbiome Research
Background:
- Human milk oligosaccharides (HMOs) are known to influence infant gut health.
- Fucosylated HMOs, like 2'-fucosyllactose (2'-FL), provide fucosylated glycans to the infant gut.
- The specific impact of HMOs on small intestinal fucosylation and intestinal stem cell (ISC) regulation is not fully understood.
Purpose of the Study:
- To investigate how inhibiting intestinal fucosylation affects ISC-mediated intestinal epithelial development in rats.
- To determine the role of 2'-FL in ameliorating the effects of fucosylation inhibition.
- To explore the long-term consequences of altered intestinal fucosylation on gut health.
Main Methods:
- Rats were treated with a fucosylation inhibitor (2F-Fuc) from postnatal day 4 to 21.
- ISC differentiation and Notch signaling pathways were analyzed in the jejunum.
- 2'-FL supplementation was administered after weaning (PN21) to assess its restorative effects.
- Changes in mucus-degrading microbiota were evaluated.
Main Results:
- Inhibition of jejunal fucosylation promoted ISC differentiation towards the secretory lineage by suppressing Notch signaling.
- Fucosylation inhibition led to persistent ISC differentiation deregulation in the jejunum, even after inhibitor withdrawal.
- 2'-FL supplementation post-weaning mitigated the long-term effects of fucosylation inhibition on ISC differentiation and microbiota composition.
Conclusions:
- Intestinal fucosylation is vital for maintaining the balance between ISC proliferation and differentiation.
- Targeted modification of intestinal fucosylation, potentially using 2'-FL, can enhance gut health, particularly in the small intestine.
- This study provides foundational insights into the interaction between intestinal fucosylation and ISC function.
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