Regulating homeostasis through glia in the “brain inside your gut”

Biology achieves permanence through change. Nowhere is this more striking than in the gut, where an autonomous nervous system - embedded within the intestine itself -maintains rhythm and balance even in the absence of the brain. This “brain inside your gut” continuously integrates mechanical, microbial, metabolic, and immune signals to preserve homeostasis. Yet we do not understand how its glial cells orchestrate this resilience, or how their dysfunction may initiate disease.

My laboratory will define the functional logic of enteric glial diversity and establish how distinct glial subtypes regulate homeostasis in health and across neurodegeneration. We will determine how these functional states shift at the earliest stages of disease, before brain pathology emerges, and identify the molecular safeguards across evolution that allow glia to endure extreme metabolic stress without triggering inflammation.

By integrating single-cell genomics, engineered intestine-on-chip systems, transgenic models, and human stem cell-derived organs, we will move beyond describing cell states to predicting how and when homeostasis destabilizes.

This work will reveal early biomarkers and mechanistic drivers of neurodegeneration rooted in the gut. Ultimately, it will shift therapeutic strategy, from attempting to rescue dying neurons to preserving the systems that prevent degeneration from beginning at all.

Dr. Marissa Scavuzzo, is an Assistant Professor in the Institute for Glial Sciences at Case Western Reserve University School of Medicine. Her research asks a fundamental biological question: how do cells maintain balance in a world defined by constant change? Focusing on the enteric nervous system, or the “brain inside your gut,” her lab investigates how enteric glial cells sense environmental signals and regulate homeostasis amid continuous mechanical, microbial, and metabolic flux.

Long overlooked as passive support cells, glia in the brain are now recognized as essential regulators of neural function. Dr. Scavuzzo is leading a similar transformation in the gut. Her laboratory identified a previously unknown, functionally specialized glial subtype that senses force and helps keep the gut in rhythm. This discovery challenges the prevailing view of enteric glia as uniform support cells and suggests that distinct glial subtypes may differentially shape motility, inflammation, metabolism, and gut-brain signaling.

By developing innovative genetic and stem cell–based tools, her team defines how glial diversity sustains balance, how inflammatory signaling drives dysfunction, and what safeguards preserve resilience under stress. Through this work, Dr. Scavuzzo aims to redefine enteric glial biology and uncover new therapeutic avenues for gastrointestinal and neurological conditions.

"Stability is not the absence of change, but the ability to adapt to it.”

In biology, this principle is called homeostasis - the ability of cells and tissues to preserve balance amid constant change. Nowhere is this challenge more relentless than in the gut, where cells must continuously adapt to dietary inputs, microbial activity, and mechanical stress. To meet this demand, evolution endowed the intestine with its own nervous system, the enteric nervous system (ENS). Within it, enteric glia are abundant, dynamic, and uniquely positioned to regulate stability, yet their biology remains largely uncharted.

History offers a lesson: for decades, glia in the brain were dismissed as passive support cells, until research revealed them as active regulators of neural function and central players in neurological disease. We believe enteric glia are poised for a similar transformation.

Our work brings new tools to uncover how these overlooked cells preserve balance, what happens when their safeguards fail, and how some species have evolved unusual resilience. By tracing this continuum, from stability to breakdown to adaptation, we aim to uncover fundamental rules of cellular homeostasis.

The implications reach far beyond gut physiology. Understanding how enteric glia sense, regulate, and adapt to change could open new therapeutic opportunities across disorders where metabolism, inflammation, and the nervous system collide. Enteric glia represent a new frontier in neuroscience, one that may reshape how we think about health and disease at the intersection of the gut and brain.

"The MIND Prize will enable us to move beyond describing the gut–brain axis and begin predicting how and when homeostasis destabilizes. By defining the earliest cellular changes in the enteric nervous system, we aim to identify actionable windows for intervention before neurodegeneration takes hold."