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Irritable Bowel Syndrome, Intestinal Permeability, and Low-Grade Chronic Inflammation — Scientific Review

by luciano

(Related article no. 2: Irritable Bowel Syndrome (IBS) and Intestinal Permeability)
1. Introduction
Irritable Bowel Syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract characterized by abdominal pain and altered bowel habits, in the absence of evident structural abnormalities. It is classified as a Disorder of Gut–Brain Interaction (DGBI) and presents heterogeneous clinical phenotypes.

2. Intestinal Permeability and IBS: Scientific Evidence
2.1 Clinical Review on Intestinal Permeability
“Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review”
Hanning et al. (2021) — Review of 66 studies on the role of the intestinal barrier in IBS.
Summary: Increased intestinal permeability is observed in a significant proportion of IBS patients, particularly in diarrhea-predominant (IBS-D) and post-infectious IBS (PI-IBS), while it is less frequent in constipation-predominant IBS (IBS-C) and nearly absent in mixed IBS (IBS-M). Increased permeability is also associated with greater symptom severity. (PubMed)

2.2 Correlations Between Permeability and Clinical Factors
Anthropometric studies and challenge tests indicate that increased permeability is frequently associated with:
Alterations in tight junction proteins (e.g., occludin, ZO-1)
Visceral hypersensitivity
Local and systemic inflammatory markers
(as shown in reviews on IBS and other gastrointestinal models) (Springer Nature)

3. Intestinal Permeability and Low-Grade Chronic Inflammation
3.1 General Concept and Proposed Mechanisms
“Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review”
Di Vincenzo et al. (2023)
Summary: The intestinal barrier is a dynamic system integrated with the microbiota, nutrients, and immune system. Increased permeability (“leaky gut”) may facilitate the interaction between luminal antigens and immune cells, triggering pro-inflammatory activation. (MedNews Care)

3.2 Interaction Between Inflammation and Barrier Function
“Intestinal permeability – a new target for disease prevention and therapy”
BMC Gastroenterology
Summary: Barrier dysfunction is associated with low-grade inflammation, visceral sensitivity, and IBS symptoms. Local inflammation may contribute to degradation of tight junction proteins, promoting a self-perpetuating cycle of permeability and inflammation. (SpringerLink)

3.3 Bibliometrics and Research Trends
“Mapping research trends on intestinal permeability in IBS …”
Recent bibliometric analysis
Summary: There is growing research interest in microbiota, diet, intestinal permeability, and inflammation in IBS. Interactions among the intestinal barrier, microbiome, and nutritional/environmental factors represent major emerging topics. (PubMed)

4. Low-Grade Inflammation in IBS and Its Relationship with Permeability
4.1 Inflammatory Markers in IBS
Preview of meta-analysis (Digestive Diseases and Sciences, 2025)
Summary: Pro-inflammatory cytokines such as IL-6 and TNF-α are frequently elevated in IBS patients, together with intestinal dysbiosis, suggesting chronic immune activation. (Springer Nature)

4.2 Relationship Between Inflammation and Permeability
“Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?”
Summary: Although increased permeability is associated with inflammatory markers in several diseases, a mandatory causal relationship is not demonstrated. Permeability may accompany inflammation but does not inevitably generate it. (PubMed)

5. Synthesis: IBS Is Multifactorial — Permeability Is Not Mandatory
Main points of consensus:
1. Many IBS patients exhibit increased permeability, particularly IBS-D and PI-IBS, but many do not.
2. Low-grade chronic inflammation is common in IBS but not always accompanied by increased permeability.
3. Inflammation may contribute to barrier dysfunction, yet IBS-like symptoms can occur with normal permeability.
Emerging consensus model:
Intestinal permeability acts as a pathogenic amplifier in specific IBS subgroups, interacting with microbiota, diet, stress, and immune function, but it is not a universal prerequisite.

6. Examples of Relevant Studies (Rapid Summary)
Hanning et al., 2021 — IBS/barrier systematic review
Di Vincenzo et al., 2023 — Microbiota–permeability–inflammation narrative review
Digestive Diseases and Sciences, 2025 — Inflammation & microbiome meta-analysis
BMC Gastroenterology — Barrier loss, mild inflammation, visceral sensation
Bibliometric analysis — IBS/permeability research trends

7. Conceptual Conclusions
IBS is multifactorial, and its pathophysiology cannot be reduced to a single “barrier defect.”
Increased permeability and low-grade inflammation may co-occur but are not universal.
Their presence depends on clinical phenotype, microbiota composition, immune factors, diet, and psychobiological stress. Clinical assessment should consider biomarkers, microbiota, and immune-barrier interactions, not epithelial integrity alone.

Undigested Food → Low-Grade Intestinal Inflammation → Increased Intestinal Permeability

by luciano

(Related Article No. 3 – Series: Irritable Bowel Syndrome (IBS) and Intestinal Permeability)
Introduction
Recent scientific literature suggests that the presence of incompletely digested food within the intestinal lumen may, in specific contexts, contribute to low-grade chronic inflammatory processes and to increased intestinal permeability.
This relationship emerges particularly from the review by Riccio and Rossano (2019), which proposes that undigested food residues and the intestinal microbiota may cooperate in the pathogenesis of systemic inflammatory conditions, including those with possible neurological manifestations. In this model, loss of intestinal barrier integrity allows the passage of luminal molecules—food fragments, peptides, endotoxins, and microbial components—into the internal compartment, thereby promoting immune activation.
From this perspective, digestion is not merely a nutritional process, but also a fundamental biological defense mechanism.

The Concept of Dietary “Non-Self”
Before complete digestion, food retains a biological identity distinct from that of the host organism.
According to Riccio and Rossano:
Intact or partially digested food is biologically perceived as “non-self”
Only after complete breakdown into simple molecules (amino acids, monosaccharides, fatty acids) does it become “self”
The intestinal barrier therefore plays a crucial role in preventing the systemic passage of structurally complex material.
When this containment system weakens, partially digested food fragments may cross the epithelium and contribute to:
Intestinal inflammation
Chronic immune activation
Alterations of the microbiota
Potential systemic effects

Gastric Digestion as the First Level of Protection
Gastric digestion represents the first major filter against dietary antigenic load.
1. Protein Fragmentation
The acidic environment of the stomach:
Denatures proteins
Activates pepsin
Produces smaller, more manageable peptides
The more extensively proteins are hydrolyzed early, the smaller the amount of complex fragments reaching the small intestine.
This is relevant because: Macromolecular proteins are more immunogenic
Large peptides can interact with the mucosa
Excess protein residues increase intestinal digestive burden
2. Support of the Enzymatic Cascade
Adequate gastric acidity promotes efficient activation of pancreatic proteases (trypsin, chymotrypsin, elastase, carboxypeptidases).
If gastric digestion is inefficient:
Downstream enzymatic activity is reduced
The probability of incompletely degraded protein residues increases
Thus, the stomach functions as both a mechanical and chemical filter that reduces mucosal exposure to potentially immunogenic molecules.

Incomplete Digestion and Intestinal Permeability
When larger quantities of complex peptides reach the intestine:
Interaction with the epithelium increases
In the presence of a weakened barrier, the probability of translocation rises
Local immune activation is promoted
In “leaky gut” models, this is associated with:
Alterations of tight junctions
Increased paracellular permeability
Passage of peptides, endotoxins, and antigens
This may generate a vicious cycle:
Inefficient digestion → increased antigenic load → mucosal stress → increased permeability → increased inflammation

The Special Case of Gluten
Gluten represents a well-studied example of a partially digestible dietary protein.
Reviews by Cenni et al. (2023) and other studies show that:
Gluten is rich in proline and glutamine
Human digestion generates enzyme-resistant peptides
Some of these peptides can alter tight junctions via zonulin
In predisposed individuals (celiac disease, non-celiac gluten sensitivity):
Gluten peptides increase intestinal permeability
Facilitate bacterial translocation
Activate mucosal immune responses
It is important to emphasize that:
The human digestive system possesses proteases capable of degrading many gluten peptides
Nevertheless, some highly immunogenic fragments may persist
Therefore, gluten is not universally pathogenic, but may become clinically relevant in vulnerable contexts.

 

Monococcus wheat (einkorn wheat): why it is so important

by luciano

Summary of the main characteristics of the monococcus wheat (einkorn) which give it great potential to be used for the preparation of bakery products but also sweet ones for people who:
1. are genetically predisposed for celiac disease (but non safe for celiac people) (1) (2) (3) (4) (5),
2. must keep the glycemic index under control (6),
3. non-celiac gluten sensitive, reintroduce gluten after its exclusion (7),
4. have difficulty digesting gluten (8).
5. are sensitive to ATI -amylase trypsina inhibitors- (9),
Furthermore, the high nutritional qualities of einkorn wheat should be highlighted (10) (11).
(1) ………..omissis. “Conclusions: Our data show that the monococcum lines Monlis and ID331 activate the CD T cell response and suggest that these lines are toxic for celiac patients. However, ID331 is likely to be less effective in inducing CD because of its inability to activate the innate immune pathways”. Immunogenicity of monococcum wheat in celiac patients. Carmen Gianfrani et altri. Am J Clin Nutr 2012;96:1339–45.

(2) ………omissis. “D’altra parte, tenuto conto che l’incidenza e la gravità della celiachia dipende dalla quantità e dalla nocività delle prolamine e che alcuni genotipi di grano monococco hanno una elevata qualità panificatoria accoppiata con assenza di citotossicità e ridotta immunogenicità, è atteso che l’uso delle farine di monococco nella dieta della popolazione generale, all’interno della quale si trova una elevata percentuale di individui predisposti geneticamente alla celiachia ma non ancora celiaci, possa contribuire a contenere la diffusione di questa forma di intolleranza alimentare. Ciò lascia pensare che il grano monococco, riportato recentemente in coltivazione in Italia dai ricercatori del Consiglio per la Ricerca e la sperimentazione in Agricoltura (CRA) di Roma e San Angelo Lodigiano, potrà svolgere un ruolo importante nella prevenzione della celiachia, sia direttamente sotto forma di pane e pasta sia indirettamente come specie modello per lo studio del ruolo dell’immunità innata nell’insorgenza della celiachia”. Le nuove frontiere delle tecnologie alimentari e la celiachia Norberto Pogna, Laura Gazza (2013).

(3)-Extensive in vitro gastrointestinal digestion markedly reduces the immune-toxicity of Triticum monococcum wheat: Implication for celiac disease
Carmen Gianfrani, Alessandra Camarca, Giuseppe Mazzarella, Luigia Di Stasio, Nicola Giardullo, Pasquale Ferranti, Gianluca Picariello, Vera Rotondi Aufiero, Stefania Picascia, Riccardo Troncone, Norberto Pogna, Salvatore Auricchio
and Gianfranco Mamone. Mol. Nutr. Food Res. 2015, 00, 1–11
Scope: The ancient diploid Triticum monococcum is of special interest as a candidate low-toxic wheat species for celiac disease patients. Here, we investigated how an in vitro gastro-intestinal digestion, affected the immune toxic properties of gliadin from diploid compared to hexaploid wheat.
Method and results: Gliadins from Triticum monococcum, and Triticum aestivum cultivars were digested using either a partial proteolysis with pepsin-chymotrypsin, or an extensive degradation that used gastrointestinal enzymes including the brush border membrane enzymes. The immune stimulatory properties of the digested samples were investigated on T-cell lines and jejunal biopsies from celiac disease patients. The T-cell response profile to the Triticum mono coccum gliadin was comparable to that obtained with Triticum aestivum gliadin after the partial pepsin-chymotrypsin digestion. In contrast, the extensive gastrointestinal hydrolysis drastically reduced the immune stimulatory properties of Triticum monococcum gliadin. MS-based analy- sis showed that several Triticum monococcum peptides, including known T-cell epitopes, were degraded during the gastrointestinal treatment, whereas many of Triticum aestivum gliadin survived the gastrointestinal digestion.
Conclusion: he pattern of Triticum monococcum gliadin proteins is sufficiently different from those of common hexaploid wheat to determine a lower toxicity in celiac disease patients following in vitro simulation of human digestion.

(4) …….omissis. “Abstract. A growing interest in developing new strategies for preventing coeliac disease has motivated efforts to identify cereals with null or reduced toxicity. In the current study, we investigate the biological effects of ID331 Triticum monococcum gliadin-derived peptides in human Caco-2 intestinal epithelial cells. Triticum aestivum gliadin derived peptides were employed as a positive control. The effects on epithelial permeability, zonulin release, viability, and cytoskeleton reorganization were investigated. Our findings confirmed that ID331 gliadin did not enhance permeability and did not induce zonulin release, cytotoxicity or cytoskeleton reorganization of Caco-2 cell monolayers. We also demonstrated that ID331 ω-gliadin and its derived peptide ω(105–123) exerted a protective action, mitigating the injury of Triticum aestivum gliadin on cell viability and cytoskeleton reorganization. These results may represent a new opportunity for the future development of innovative strategies to reduce gluten toxicity in the diet of patients with gluten intolerance”. Protective effects of ID331 Triticum monococcum gliadin on in vitro models of the intestinal epithelium. Giuseppe Jacomino et altri 2016.

(5)………omissis. “Scientific research has several times supported and encouraged the use of grains with low toxicity in the prevention of celiac disease; in the research we are now presenting, some grains have been studied highlighting their profile regarding both the presence of peptides resistant to gastro-intestinal digestion and, among these, those containing the “toxic” fraction (table 3) “ ….omissis Even if none of them can be considered safe for CD patients, grain with reduced amount of major T-cell stimulatory epitopes may help in the prevention of CD, since previous studies demonstrated that the amount and duration to gluten exposure are strictly linked to the initiation of this pathology.” (A Comprehensive Peptidomic Approach to Characterize the Protein Profile of Selected Durum Wheat Genotypes: Implication for Coeliac Disease and Wheat Allergy. Rosa Pilolli , Agata Gadaleta, Luigia Di Stasio , Antonella Lamonaca, Elisabetta De Angelis , Domenica Nigro , Maria De Angelis , Gianfranco Mamone and Linda Monac. Published: 1 October 2019).

(6) ….omissis. Non tutto l’amido è rapidamente idrolizzato durante la digestione, la frazione che resiste alla digestione e all’assorbimento nell’intestino tenue umano è definita “amido resistente” e ha effetti fisiologici comparabili a quelli della fibra alimentare. Il grano monoccoco però ha un basso contenuto (0,2%) in “amido resistente” se confrontato con il grano tenero(0,4- 0,8%) (Abdel-Aal et al. 2008).

Benefits of Products Made with Einkorn Wheat

by luciano

The research “Integrated Evaluation of the Potential Health Benefits of Einkorn-Based Breads” can be considered the first integrated evaluation of the potential health benefits, linked to the excellent nutritional properties, of using einkorn flour in bread and baked goods. It also highlights how using whole-wheat flour and sourdough is essential to achieve the best results in terms of exploiting the potential of this grain. The choice of this grain is well summarized in one passage of the research: “Einkorn (Triticum monococcum L. ssp. monococcum) is an ancient crop. Compared to polyploid wheats it has a higher content of proteins, polyunsaturated fatty acids, fructans, and phytochemicals as tocols, carotenoids, alkylresorcinols, phytosterols, and a lower α-, β-amylase and lipoxygenase activities [15]. In addition, einkorn expresses very few T-cell stimulatory gluten peptides [16]. Einkorn could represent a valid alternative for producing functional baked products” [In-depth analysis “A”].

Einkorn Wheat (Triticum monococcum): Key Characteristics – Concise Summary

Why einkorn wheat is considered the ancestor of all wheats
“Einkorn wheat (Triticum monococcum) is one of the oldest wheat species cultivated by humans. Domesticated more than 10,000 years ago in the Fertile Crescent, it represents the simplest form of wheat that has survived to the present day and is considered the genetic ancestor of modern wheats.”
The renewed scientific interest in einkorn wheat arises from the need to understand how modern genetic selection has profoundly altered contemporary wheats, from a nutritional, technological, and immunological perspective.

Botanical and genetic characteristics
“Triticum monococcum is a diploid wheat species (2n = 2x = 14), unlike durum wheat (Triticum durum) and common wheat (Triticum aestivum), which are tetraploid and hexaploid, respectively. Its simpler genome reflects a lower degree of artificial selection over millennia.”
Scientific clarification:
The genomic simplicity of einkorn makes it an important model for studying cereal evolution and for analyzing differences between ancient and modern wheats.
Editorial note:
The term “ancient grains” has no official botanical definition but is widely used in scientific and popular literature to describe cereal species and varieties that have undergone limited modern genetic improvement.

Gluten, digestion, and immunogenicity
“Comparative in vitro studies show that einkorn gliadin peptides are digested more efficiently during simulated gastrointestinal digestion than those from modern wheats, resulting in reduced immunogenicity in cellular models.”
Scientific clarification:
These findings indicate that the structure of einkorn gluten proteins differs from that of modern wheats and may be more readily degraded by digestive enzymes [In-depth analysis “B”].
“In individuals with wheat-dependent exercise-induced anaphylaxis (WDEIA), einkorn wheat did not elicit significant skin reactivity and showed a different IgE profile compared to common wheat, suggesting potential interest for the development of hypoallergenic foods.”
Scientific clarification:
These are preliminary results that require confirmation through larger clinical studies, but they open promising perspectives in research on reduced-allergenicity foods.
⚠️ Fundamental clarification
“To date, there is no sufficient scientific evidence demonstrating the safety of einkorn wheat for individuals with diagnosed celiac disease. Einkorn contains gluten and cannot be considered a gluten-free cereal.”
Further note:
Some individuals with non-celiac wheat sensitivity (NCWS) report better tolerance to einkorn wheat, but available clinical data remain still limited [In-depth analysis “C”].

Nutritional value and metabolic health
“Einkorn wheat generally contains higher levels of proteins, carotenoids, tocols, and other bioactive compounds compared to modern wheats, resulting in a particularly interesting nutritional profile.”
Scientific clarification:
The high carotenoid and antioxidant content contributes to the characteristic deep yellow color of einkorn flour and enhances its nutritional appeal.
“In an animal model (pig), consumption of einkorn wheat bread resulted in more moderate glycemic and insulin responses compared to common wheat bread, along with favorable modifications of the intestinal microbiota.”
Scientific clarification:
In particular, an increase in microorganisms producing short-chain fatty acids (SCFAs)—key compounds for intestinal mucosal health—was observed.

Technological aspects and baking performance
“Einkorn wheat flours exhibit lower gluten strength and a less elastic dough structure compared to modern wheats, making processing more delicate.”
Scientific clarification:
Recent studies show that the use of selected varieties, longer fermentation times, and adapted technological processes can yield bread and pasta with high nutritional and sensory quality even when made from einkorn wheat.

Conclusions
Einkorn wheat represents a bridge between the past and the future of human nutrition. Ancient in both history and genetics, it is nevertheless highly relevant today due to the strong scientific interest it attracts in nutritional, digestive, and technological research.
In upcoming articles, we will further explore the relationship between einkorn wheat, gluten, gut microbiota, and wheat sensitivity, always maintaining a clear distinction between established scientific evidence and hypotheses that are still under investigation.

In-depth analysis “A”: Integrated Evaluation of the Potential Health Benefits of Einkorn-Based Breads”
“Omissis…..Several studies have shown a clear correlation between the consumption of wholegrain and a reduced risk of cardiovascular diseases [1,2], diabetes [3], and some types of cancer [4]. The beneficial properties of wholegrain are mainly ascribed to their micronutrient and phytochemical content [5–7]. Cereals are among the richest food in phenolic acids, their content being comparable with or even higher than that found in berries, fruits, and vegetables [8]. In addition, some cereals are rich in lutein and zeaxanthin [9,10]. Micronutrients and phytochemicals are chiefly concentrated in the outer layers of grains [11], and this could explain the preventive effects associated with high wholegrain consumption [12]. Nowadays, the higher nutritional value of wholegrain compared to refined ones is recognized [13], and there is an increasing interest in ancient crops as source of wholegrain flours [14]. Einkorn (Triticum monococcum L. ssp. monococcum) is an ancient crop. Compared to polyploid wheats it has a higher content of proteins, polyunsaturated fatty acids, fructans, and phytochemicals as tocols, carotenoids, alkylresorcinols, phytosterols, and a lower α-, β-amylase and lipoxygenase activities [15]. In addition, einkorn expresses very few T-cell stimulatory gluten peptides [16]. Einkorn could represent a valid alternative for producing functional baked products. In bakery, processing could contribute to functionality [17,18]. Sourdough fermentation, involving the inter-relation between microbial metabolism and cereal enzymes, has been shown to greatly affect the functional features of leavened baked goods [19]. This type of fermentation may produce new nutritionally active molecules such as functional peptides and amino acid derivatives [20,21], deriving from either the bacterial hydrolytic activity [20] or from their own synthetic pathways [22]. To exert a positive action in the human body, bioactive compounds must be hydrolyzed from the food matrix, and be absorbed in the intestine. The bioaccessibility of bioactive compounds, i.e., the percentage released from the food matrix and made available for uptake by the intestinal mucosa, is an important parameter that can be influenced by many different factors including the food matrix and the food processing [23,24]. Fermentation by lactic acid bacteria may improve nutrient bioaccessibility and produce compounds with anti-oxidant and anti-inflammatory activity [19]. Sourdough lactic acid bacteria have been reported to release or synthesize antioxidant and anti-inflammatory peptides during fermentation of cereal flours [20]. Integrated Evaluation of the Potential Health Benefits of Einkorn-Based Breads. Fabiana Antognoni, et al. Nutrients November 2017.” The numbers in square brackets refer to the bibliographic references present in the text of the cited research”.

In-depth analysis “B”

Einkorn’s gluten proteins form a simpler, weaker, and more water-soluble network compared to modern wheat, due to its diploid genetics (14 chromosomes vs. modern 42) and a different gliadin-to-glutenin ratio (around 2:1 vs. modern wheat’s 7:1), resulting in shorter protein strands and less elasticity. This structure makes einkorn’s gluten more digestible and less inflammatory for many, despite having similar total gluten content, creating a tighter crumb in baked goods

In-depth analysis “C”

The 33-mer peptide, a fragment of wheat’s alpha-gliadin, is considered a highly potent immune stimulator, especially for celiac disease, because it’s resistant to digestion, contains multiple T-cell epitopes, and forms active nanostructures that trigger innate immune responses via Toll-like receptors (TLRs) in macrophages, leading to inflammation. This proteolytically stable peptide, often deamidated by tissue transglutaminase (TG2), binds strongly to HLA-DQ2 and activates T-cells, driving the autoimmune reaction in celiac disease.”

Bibliographic references

1. Shewry P.R., Hey S.J. The contribution of wheat to human diet and health. Food and Energy Security, 2015.
2. Geisslitz S. et al. Comparative analysis of in vitro digestibility and immunogenicity of gliadin proteins from durum and einkorn wheat. Food Chemistry, 2020.
3. Zoccatelli G. et al. Immunoreactivity of Triticum monococcum in patients with wheat-dependent exercise-induced anaphylaxis. Molecular Nutrition & Food Research, 2015.
4. Costabile A. et al. In vivo effects of einkorn wheat bread on glycemic response and gut microbiota in the pig model. Nutrients, 2018.
5 .Hidalgo A., Brandolini A. Nutritional properties of einkorn wheat. Journal of Cereal Science, 2014.
6. Foschia M. et al. Breadmaking performance of elite einkorn lines. Foods, 2023.
7. Immunogenicità di gliadine di monococco vs. durum: digestione enzymatica più efficace, meno immunogenicità in modelli T-cell. ([PubMed][2]) 2015
8. Glutine più digeribile nel piccolo farro in studi CNR: potenziale minore tossicità (CNR, “glutine digeribile”). ([Consiglio Nazionale delle Ricerche][7]) 2018
9. Struttura dell’impasto e qualità del pane: caratteristiche diverse rispetto al grano moderno. ([OUP Academic][8]) 2018.
10. Trasformazione genetica ed utilizzo come modello di studio cerealicolo (genoma piccolo e interessante). ([SpringerLink][1]) 2025
11. Recente review su antichi cereali e IBS (con riferimento a proprietà nutrizionali e immunogeniche). ([Springer Nature][9])

Irritable Bowel Syndrome: Why Inflammation and “Leaky Gut” Are Not the Same Thing

by luciano

(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.

Long-Tail Keywords: difference between IBS and leaky gut, is IBS always inflammatory, intestinal inflammation without mucosal damage, causes of irritable bowel syndrome, IBS gut brain interaction explained, IBS without intestinal permeability