ARF1 maintains intestinal homeostasis by modulating gut microbiota and stem cell function

Area of Science:

• Cell Biology
• Microbiology
• Gastroenterology

Background:

• The small GTPase ARF1 is implicated in lipolysis and stem cell regulation in Drosophila.
• Its function in mammalian intestinal homeostasis is largely unknown.
• Investigating ARF1's role in intestinal epithelial cells (IECs) is critical.

Purpose of the Study:

• To explore the role of ARF1 in IECs.
• To elucidate the mechanisms underlying ARF1's function in intestinal homeostasis.
• To identify ARF1's impact on intestinal stem cell (ISC) behavior.

Main Methods:

• Utilized an IEC-specific ARF1 deletion mouse model.
• Performed immunohistochemistry, immunofluorescence, and organoid culture for ISC analysis.
• Conducted 16S rRNA sequencing, antibiotic treatments, and RNA sequencing to assess microbial and transcriptomic changes.
• Induced colitis using dextran sulfate sodium (DSS) to evaluate disease susceptibility.

Main Results:

• ARF1 is essential for ISC proliferation and differentiation.
• ARF1 deficiency exacerbates DSS-induced colitis and leads to gut microbial dysbiosis.
• Antibiotic-induced microbiota depletion partially rescued intestinal abnormalities.
• RNA-seq revealed significant alterations in metabolic pathways upon ARF1 deletion.

Conclusions:

• ARF1 plays a vital role in maintaining gut homeostasis.
• ARF1 deficiency impacts intestinal stem cell function and microbial balance.
• Findings offer new insights into intestinal disease pathogenesis and potential therapeutic targets.