The JNK2-microbiome axis modulates gut barrier integrity through microbial acetate.

Area of Science:

• Gastroenterology
• Microbiology
• Immunology

Background:

• Weaning shifts diet from milk to solids, impacting metabolism, microbiota, and gut immunity.
• The role of continued milk intake post-weaning on gut epithelial homeostasis is not well understood.

Purpose of the Study:

• To investigate the effects of post-weaning milk supplementation on gut barrier function and immune response.
• To determine the impact of timing for milk supplementation on these effects.

Main Methods:

• Utilized a mouse model to study the effects of milk-based feeding versus high-fat diets post-weaning.
• Administered dextran sodium sulfate (DSS) to induce mild inflammation.
• Analyzed the role of specific signaling pathways (JNK2, P38) and bacterial enrichment (Dubosiella newyorkensis).

Main Results:

• Milk-based feeding post-weaning enriched Dubosiella newyorkensis, promoting acetate production and activating JNK2 signaling.
• This activation enhanced intestinal barrier integrity and suppressed DSS-induced inflammation.
• High-fat diets or JNK2 inhibition led to P38 activation, barrier disruption, and inflammation.
• Beneficial effects of milk were only observed when initiated during the weaning period.

Conclusions:

• Immediate post-weaning milk supplementation maintains a beneficial gut microbiome and enhances gut barrier integrity.
• A delay of even one week in initiating milk supplementation eliminates these protective effects.
• Timing of nutritional intervention during weaning is crucial for preserving intestinal health.