(related article n. 1 of Irritable Bowel Syndrome (IBS) and Intestinal Permeability)
In recent years, irritable bowel syndrome (IBS) has often been described as a direct consequence of an “inflamed” or “hyper-permeable” gut. While this narrative is appealing, it is incomplete. The most recent scientific literature describes IBS as a heterogeneous and multifactorial disorder, in which inflammation, intestinal permeability, the nervous system, and the gut microbiota interact differently from person to person. Understanding this complexity is essential to avoid reductionist explanations—and one-size-fits-all treatments.
IBS: A Disorder of Gut–Brain Interaction
According to current diagnostic criteria (Rome IV), IBS is classified as a Disorder of Gut–Brain Interaction (DGBI). This means that symptoms do not necessarily arise from visible structural damage to the intestine, but from altered communication between the gut, the nervous system, and the immune system.
Abdominal pain, bloating, and bowel habit changes may therefore occur even when:
the intestinal mucosa is structurally intact
inflammatory markers are within normal ranges
This is where many misunderstandings begin.
Intestinal Permeability: Important, but Not Universal
Some patients with IBS show increased intestinal permeability (the so-called leaky gut), particularly:
in diarrhea-predominant IBS (IBS-D)
in post-infectious IBS
In these cases, the intestinal barrier is less efficient and may facilitate immune system activation.
However, not all IBS patients exhibit increased permeability.
In subtypes such as constipation-predominant IBS (IBS-C) or mixed IBS (IBS-M), intestinal permeability is often comparable to that of healthy individuals.
This is a crucial point: increased permeability is not a universal feature of IBS.
Low-Grade Inflammation: Present, but Not Always “Visible”
Many studies show that IBS is frequently associated with chronic low-grade inflammation, characterized by:
mild increases in pro-inflammatory cytokines
activation of mast cells and immune cells
localized or systemic inflammatory signals
However, this inflammation:
may be submucosal or neuro-immune
may not directly involve the intestinal epithelium
may occur without altering intestinal permeability
In other words, inflammation does not automatically mean a “damaged gut.”
A Key Point Often Misunderstood
Current research supports a more realistic model:
Intestinal permeability is not a mandatory prerequisite for inflammation, but when present, it can amplify inflammatory processes.
This explains why:
some patients show inflammation without leaky gut
others have altered barrier function without significant symptoms
Clinical outcomes depend on multiple factors:
type of inflammation
gut microbiota composition
neuro-endocrine regulation
individual susceptibility
IBS Without Leaky Gut: How Are Symptoms Explained?
In patients with normal intestinal permeability, IBS symptoms are driven by other well-documented mechanisms:
Visceral Hypersensitivity
The gut becomes “over-sensitive”: normal stimuli are perceived as painful.
Altered Gut–Brain Axis
Chronic stress, anxiety, and neuro-endocrine dysregulation amplify gut signals.
Functional Dysbiosis
Qualitative changes in the microbiota and its metabolites influence the nervous and immune systems without damaging the barrier.
Neuro-Mucosal Immune Activation
Immune cells activated near nerve fibers release mediators that increase pain, even with an intact epithelium.
Why This Changes the Way IBS Should Be Treated
If IBS is not a single disease, it cannot have a single cause—or a single treatment.
Effective management must be:
personalized
based on the patient’s specific profile
attentive to the different mechanisms involved
Reducing IBS to “inflammation” or “leaky gut” risks:
excessive oversimplification
unrealistic therapeutic expectations
neglect of central components of the disorder
In Summary
❌ IBS does not always mean increased intestinal permeability
❌ Inflammation does not always mean mucosal damage
✅ IBS is a complex disorder of gut–brain interaction
Understanding this complexity does not make IBS more confusing—it makes it more accurate, more scientific, and more treatable.