By Elodie Vaz | Published on April 14, 2026 | 4 min readInteractions 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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About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.
