Gut–microbiome dialogue: the unexpected role of epithelial cells

By Elodie Vaz | Published on April 14, 2026 | 4 min read


Interactions between the gut and the intestinal microbiome are essential for proper physiological function. These interactions largely rely on the immune system, which regulates the coexistence between the host and microbial communities.  

However, these mechanisms remain poorly understood during early life, a period when the immune system is still immature. As Professor Pedro Hernandez Cerda, researcher at Inserm and Institut Curie, noted in a press release, “it is precisely during these early stages that the interactions shaping intestinal function are established.” Understanding these early processes is crucial, particularly for better grasping the emergence of digestive or inflammatory disorders.  

Exploring immune mechanisms at the dawn of life  

In a study published on April 2, 2026, in Science, a multidisciplinary team from Institut Curie, Inserm, and CNRS sought to decipher the cellular mechanisms governing gut–microbiome interactions early in life. The objective was to determine how these interactions are established in the absence of a fully functional immune system, and which cell types might compensate for this immaturity.  

Zebrafish: a model for early-life interactions  

To address this question, researchers used zebrafish as an experimental model. This choice is based on a key feature: from the first day after hatching, these animals are exposed to environmental microorganisms while their immune system is not yet mature.  

This early window makes it possible to observe initial interactions between the microbiome and intestinal tissue in a physiological context comparable to neonatal stages in vertebrates. Researchers thus analyzed the molecular and cellular mechanisms involved in this early dialogue.  

Epithelial cells at the heart of a novel immune circuit  

The results reveal a central role for enteroendocrine cells, specialized epithelial cells of the intestine. Contrary to previous understanding, these cells are capable of producing a key immune cytokine, interleukin-22 (IL-22), previously thought to be exclusively produced by lymphocytes.  

This IL-22 production is triggered by the microbiome itself, via a tryptophan-derived metabolite. In turn, IL-22 modulates the composition of the microbiome by inducing the expression of antimicrobial genes in the intestinal epithelium.  

“A cycle is therefore established: the microbiome appears to exploit its host, via IL-22, to control its own composition, which in turn influences intestinal function,” explains Professor Pedro Hernandez Cerda.  

This bidirectional circuit also contributes to the regulation of intestinal motility. In animals deficient in IL-22, researchers observed slowed intestinal transit, associated with decreased levels of ghrelin, a hormone involved in appetite regulation.  

The study further shows that ghrelin can partially compensate for the effects of IL-22 deficiency on intestinal motility.  

A new target for early-life disorders  

These findings highlight a novel mechanism by which intestinal epithelial cells directly participate in immune regulation, particularly in early life. “This circuit involving enteroendocrine cells appears to act specifically during early life. It could therefore represent a therapeutic target for certain motility or inflammatory disorders at early stages of life,” the researcher suggests.  

Beyond this perspective, the study underscores the plasticity and previously unrecognized capabilities of intestinal epithelial cells, long considered merely as physical barriers.

Researchers now plan to explore their role in more extreme contexts, particularly during severe intestinal injury, to assess their potential in tissue regeneration.  

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