Researchers from Baylor College of Medicine, Tongji University, and several other institutes have found that weaning a child from milk and transitioning to solid foods at an early age not only changes their diet but also reprograms the gut immune system, creating long-term protection that persists into adulthood.

The study, published in Nature Microbiology, showed that in mice, weaning alters the gut microbiome—the community of microorganisms living in the intestines—and “trains” intestinal stem cells to respond more effectively to microbes in the future, reducing the risk of inflammatory diseases.

According to Professor of Pediatrics and Nutrition Lanlan Shen, weaning represents a sudden shift for the body: the gut is exposed to a much greater diversity of microbes. This surge in microbial diversity triggers a short-term, controlled inflammatory response called the “weaning reaction.” In this case, inflammation acts like a form of “training”—intense and temporary, but necessary to prepare the immune system for future challenges.

The researchers found that microbial signals during weaning modify DNA epigenetic marks in intestinal stem cells. These changes—for example, reduced methylation of MHC class II genes—make the cells easier to activate later, creating long-term “immune memory” directly within the intestinal epithelium. Even after stem cells mature into fully differentiated intestinal cells, they retain this “imprint” and respond faster and stronger to immune signals.

The training effect depends on microbial composition: Gram-positive bacteria stimulate the production of IFN-γ and short-chain fatty acids, which support epigenetic reprogramming.

Experiments also showed that early use of antibiotics disrupts this process, reducing immune protection and increasing the risk of inflammatory diseases and colorectal cancer in adulthood. Crucially, this occurs during an early life “window”: later in life, reprogramming was weak or absent, highlighting a critical period for establishing long-term gut immune memory.