Complementary intestinal mucosa and microbiota responses to caloric restriction

Area of Science:

• Gastroenterology and Nutrition
• Microbiology and Immunology
• Molecular Biology

Background:

• The intestine plays a crucial role in nutrient absorption and host-microbiota interactions.
• Intestinal response to caloric restriction (CR) is complex and involves metabolic and immune regulation.
• Understanding CR's impact on the intestine is vital for metabolic and inflammatory disease research.

Purpose of the Study:

• To investigate the effects of CR on gene expression and metabolite profiles in the mouse duodenum.
• To identify key transcription factors involved in the intestinal response to CR.
• To determine the role of gut microbiota in mediating CR-induced intestinal changes.

Main Methods:

• Mice underwent 25% CR for 14 days.
• Gene expression analysis of duodenum mucosa.
• Metabolomic profiling of duodenum and feces.
• Experiments with germ-free mice and microbiota transfer.

Main Results:

• CR induced a polarization of duodenum gene expression, upregulating metabolic and downregulating immune/inflammatory pathways.
• Transcription factors like PPAR and IRF families, particularly Pparα and Isgf3, were implicated.
• CR altered duodenum and fecal metabolites, with changes dependent on microbiota density.
• Microbiota depletion and transfer experiments revealed that the observed gene expression polarization is microbiota-independent.

Conclusions:

• CR significantly alters intestinal mucosal gene expression and metabolite profiles.
• The host's intestinal response to CR, including gene expression changes, is largely independent of the gut microbiota.
• This study highlights the intricate host-centric regulatory mechanisms governing the intestinal response to CR.