Intestinal permeability, the gut–immune axis, and allergic disease: Clinical implications for practice

Allergic diseases are traditionally framed as disorders of inappropriate immune reactivity to environmental antigens such as pollen, foods, or house dust mite. However, a growing body of evidence suggests that gastrointestinal barrier integrity and gut microbial ecology play a central role in shaping allergic susceptibility and symptom expression.

Given that approximately 70–80% of immune tissue resides within the gut‑associated lymphoid tissue (GALT), even subtle disturbances in intestinal permeability or microbiota composition may influence immune tolerance and inflammatory tone far beyond the gastrointestinal tract (Wiertsema, 2021).

In this blog, nutritional therapist Ruth explores the mechanistic links between intestinal permeability (“leaky gut”) and allergic disease, with particular reference to allergic rhinitis, but also within the broader context of atopy.

The gut–immune interface: Central to immune tolerance

The gastrointestinal tract is not simply a digestive organ, but a highly specialised immune interface composed of multiple, interacting barrier layers, including the gut microbiota, mucus layer, epithelial lining, and GALT. Together, these components form a dynamic system that regulates immune surveillance while limiting inappropriate immune activation (Valitutti, 2025).

Commensal bacteria interact continuously with epithelial cells, dendritic cells, and lymphoid tissue to:

• educate immune cells during development
• promote regulatory T cell (Treg) differentiation
• reinforce epithelial tight junctions
• maintain immune tolerance to non‑pathogenic antigens (Wiertsema, 2021)

In addition, microbial signals influence mucus production, secretory IgA release, and epithelial pattern‑recognition receptor signalling, all of which help restrict antigen translocation while allowing controlled immune sampling of the gut lumen. This finely tuned interaction enables the immune system to tolerate dietary antigens and commensal microbes while remaining responsive to pathogens (Valitutti, 2025).

When functioning optimally, this system allows the immune system to distinguish between genuine threats and harmless environmental exposures. However, disruption at any level of the gut barrier, whether through dysbiosis, impaired mucus integrity, epithelial tight‑junction dysfunction, or altered microbial metabolites can increase antigen penetration and skew immune responses toward Th2‑dominant, pro‑allergic pathways. This loss of tolerance is increasingly recognised as a contributing factor in allergic and atopic diseases, including food allergy, eczema, and airway allergy (Niewiem, 2022).

The gut–lung and gut–skin axes in allergic disease

Current research highlights the concept of inter‑organ immune crosstalk, particularly the gut–lung and gut–skin axes. These pathways are especially relevant to allergic conditions affecting the airways and skin (Enaud, 2020).

A balanced gut microbiome produces short‑chain fatty acids (SCFAs), notably acetate, propionate, and butyrate via fermentation of dietary fibre. SCFAs exert multiple immunomodulatory effects:

• enhancement of epithelial barrier integrity
• promotion of Treg activity
• suppression of excessive Th2‑mediated allergic responses
• modulation of airway immune responses via systemic circulation (Parada, 2019)

Reduced SCFA production has been associated with increased allergic inflammation, not only in allergic rhinitis but also in asthma, food allergy, and atopic dermatitis (Niewiem, 2022).

Beyond the airways, gut‑derived microbial metabolites, including SCFAs and tryptophan derivatives, have been shown to influence skin immune homeostasis by promoting Treg activity, IL‑10 signalling, and keratinocyte barrier function, highlighting the relevance of gut dysfunction across multiple atopic phenotypes (Rios-Carlos, 2024).

Individuals with food allergy have also been shown to exhibit lower stool concentrations of butyrate, acetate, and propionate, suggesting that impaired SCFA production may contribute to barrier dysfunction and allergic sensitisation (Szukalska, 2025).

Allergic rhinitis and atopy: A shared immunological framework

Seasonal allergic rhinitis (SAR), or hay fever is a well‑characterised IgE‑mediated condition, but it shares common immunological features with other atopic diseases:

• Th2‑skewed immune responses
• elevated IgE production
• mast cell activation and histamine release
• impaired immune tolerance

While pollen exposure is the obvious trigger in SAR, baseline immune tone and barrier integrity appear to influence symptom severity and chronicity. When gut‑derived signals favour immune regulation (e.g. adequate SCFA signalling), allergic responses may be attenuated. Conversely, dysbiosis and barrier dysfunction may lower the threshold for allergic reactivity (Niewiem 2022).

Intestinal permeability: From barrier dysfunction to systemic immune activation

Drivers of increased intestinal permeability

A number of dietary factors potentially contribute to increased intestinal permeability:

• Poor‑quality dietary patterns, particularly those low in fermentable fibre and high in refined carbohydrates, saturated fats, and ultra‑processed foods (UPFs), impair gut barrier integrity by disrupting microbiota composition, reducing SCFA production and weakening epithelial tight‑junction and mucus‑layer function. This disruption within the GALT environment limits SCFA‑mediated support for Treg differentiation and immune tolerance, increasing antigen translocation and favouring Th2‑skewed immune responses characteristic of allergic and atopic disease. (Dmytriv et al., 2024)
• Exposure to specific emulsifiers (notably carrageenan and carboxymethylcellulose), commonly found in UPFs increases intestinal permeability and reduces SCFA concentrations, even in healthy individuals, supporting a diet‑driven barrier‑disruptive effect. (Wellens 2025)
• Advanced glycation end‑products (AGEs), common in highly processed and high‑temperature‑cooked foods, have also been implicated in disrupting intestinal tight junctions and amplifying Th2‑mediated immune responses, thereby increasing susceptibility to food allergy. (Zhang 2025)

Non-dietary disruptors to intestinal barrier integrity may include:

• Dysbiosis contributes to increased intestinal permeability by reducing SCFA production, impairing mucus synthesis and disrupting the expression and assembly of epithelial tight‑junction proteins. These changes weaken barrier integrity and promote translocation of microbial components such as lipopolysaccharides, driving low‑grade inflammation and immune dysregulation within the GALT (Dmytriv 2025). Dysbiosis‑driven permeability is not disease‑specific but a shared mechanism across food allergy, IBS, and other inflammatory conditions (Valitutti 2025).
• Psychological stress increases intestinal permeability through coordinated effects on the gut–brain–immune axis. Chronic activation of stress pathways, including the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system, alters gut microbiota composition, increases pro‑inflammatory cytokine signalling, and disrupts epithelial tight‑junction and mucus‑layer integrity (Beurel 2024).
• Environmental exposures, including air pollutants can impair intestinal barrier integrity by inducing oxidative stress, disrupting epithelial tight‑junction proteins, and altering gut microbiota composition (Ma 2026). Exposure to microplastics can also induce gut dysbiosis, reduce SCFA production and promote inflammatory signalling pathways associated with impaired barrier integrity (Thin 2025).
• Oxidative stress is a key mediator linking dysbiosis, inflammation, and epithelial damage, with excessive reactive oxygen species (ROS) impairing tight junction integrity and promoting permeability in chronic inflammatory states (Sun 2024).

It is important to bear in mind that intestinal permeability is rarely caused by a single factor but emerges from cumulative dietary, microbial, inflammatory, psychological, and environmental stressors acting on a vulnerable barrier system (Neurath 2025).

How intestinal permeability may exacerbate allergic disease

1. Heightened immune reactivity

Increased permeability allows microbial components and partially digested antigens to cross the epithelial barrier, promoting systemic immune priming. In individuals with atopic predisposition, this may amplify IgE‑mediated responses and perpetuate immune hyper‑reactivity.

Importantly, while the strongest evidence for barrier dysfunction exists in food allergy and eczema, similar mechanisms are increasingly implicated in airway allergic disease, including allergic rhinitis and asthma. (Niewiem 2022)

2. Systemic inflammation and immune priming

Barrier disruption promotes the release of pro‑inflammatory cytokines into circulation. This low‑grade systemic inflammation may further impair epithelial integrity, creating a self‑reinforcing cycle that primes immune responses at distant sites, including the nasal mucosa and airways.

3. Reduced SCFA availability

Dysbiosis and barrier dysfunction reduce SCFA production, with several downstream consequences:

• weakened tight junction integrity
• reduced Treg‑mediated immune tolerance
• increased mucosal and systemic inflammation
• heightened allergic responsiveness (Parada Venegas 2019)

Lower circulating or faecal SCFA levels are consistently associated with increased risk and severity of allergic diseases, including allergic rhinitis, asthma, and food allergy, supporting a central role for microbial metabolites in immune tolerance. (Sasaki 2024)

Histamine metabolism: The gut connection

Histamine is a key mediator across allergic diseases. Under normal conditions, diamine oxidase (DAO) produced by enterocytes in the small intestine degrades dietary and endogenous histamine before systemic absorption. (Comas-Basté 2020)

When intestinal barrier integrity is compromised or low‑grade mucosal inflammation is present, enterocyte function may be impaired and DAO activity reduced. This can result in an increased systemic histamine burden, potentially amplifying histamine‑mediated symptoms such as sneezing, pruritus, rhinorrhoea, flushing, and headache. (Sánchez-Pérez 2022)

Clinically, this mechanism may be particularly relevant in individuals with severe allergic symptoms, multiple atopic comorbidities, or disproportionate symptom severity relative to allergen exposure, where impaired histamine degradation may act as an aggravating factor rather than a primary cause. (Zhao 2022)

Nutritional strategies to support gut and immune function in allergic disease

From a clinical perspective, nutritional interventions aim to restore epithelial integrity, enhance microbial diversity, and support immune tolerance.

Key nutritional considerations

• Fermentable dietary fibre (~30 g/day): plays a crucial role in modulating intestinal SCFAs levels, preserving mucosal homeostasis, enhancing intestinal epithelial integrity, fostering the growth of Tregs, and suppressing the expression of inflammatory cytokines (Facchin 2024)
• Resistant starches are fermented in the colon, where they selectively stimulate SCFA‑producing bacteria (notably butyrate producers), thereby supporting gut barrier integrity, immune regulation, and metabolic health. Key dietary sources include cooked‑and‑cooled potatoes, rice and pasta, green bananas and plantains, legumes and whole grains. (Sankarganesh 2025)
• Polyphenols, found in a wide range of plant foods, including vegetables, fruits, pulses, cereals, grains, nuts, herbs, spices, and teas modulate microbiota composition and epithelial signalling. (Rudrapal 2025)
• Micronutrients (vitamin D, vitamin A, zinc): support epithelial repair and immune regulation (DiGuilio 2022)
• Glutamine: primary fuel for enterocytes; shown to reduce intestinal permeability (Abbasi 2024)
• Collagen peptides supplementation is associated with improvements in gastrointestinal health due to its provision of amino acids such as glycine and glutamine that support enterocyte function, mucosal repair, and intestinal barrier integrity (Abrahams 2022)
• Omega‑3 fatty acids can improve intestinal barrier integrity (Seethaler 2023) as well as modulate inflammatory pathways relevant to allergic airway disease (Tian 2024)

Probiotics, prebiotics, and allergic disease: current evidence

Recent human trials suggest that targeted microbiome modulation may provide adjunctive benefit in allergic rhinitis and related atopic conditions:

• Combined probiotic‑prebiotic intervention over 90 days significantly reduced allergic rhinitis symptoms, improved inflammatory markers, and increased SCFA production. (Hou 2024)
• Symptom reduction and improved quality of life reported in adults with seasonal allergic rhinitis following a multi‑strain probiotic intervention. (Ried 2022)
• A multi-strain formula using Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium breve, and longum demonstrated favourable microbiota shifts and clinical improvement (Lungaro 2024).
• A recent overview concluded that probiotics show therapeutic potential as adjuncts in allergic rhinitis, with good safety and tolerability (Wang 2026).

While strain specificity and individual responsiveness remain important considerations, these findings support a mechanistically plausible role for microbiome‑targeted strategies in allergic disease management.

Practical clinical takeaways

• Allergic disease expression is influenced by gut barrier integrity and microbial signalling, not solely by allergen exposure.
• The gut–associated lymphoid tissue (GALT) plays a central role in immune tolerance, meaning intestinal permeability and dysbiosis can modulate allergic reactivity across the airways, skin, and gut.
• Reduced short‑chain fatty acid (SCFA) production is a recurring feature in atopic disease, contributing to impaired epithelial integrity, reduced Treg activity, and Th2‑skewed immune responses.
• Dietary patterns low in fermentable fibre and high in ultra‑processed foods may undermine gut barrier function, lowering the threshold for allergic sensitisation and symptom flares.
• Dysbiosis, psychological stress, environmental pollutants, and oxidative stress act cumulatively to impair intestinal permeability; progress often requires addressing multiple drivers concurrently.
• Impaired histamine degradation (e.g. reduced DAO activity) may exacerbate allergic symptoms in patients with mucosal inflammation or multisystem atopy.
• Microbiome‑targeted strategies (dietary fibre, resistant starches, selected probiotics) may offer useful adjunctive support in allergic rhinitis and related atopic conditions when applied proactively and in a strain‑specific manner.
• Intestinal permeability should be viewed as a modifiable physiological process, offering a valuable therapeutic target alongside conventional allergy management.

---

References

• Abbasi F, Haghighat, et al. A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adults. Amino Acids. 2024 Oct 13;56(1):60.
• Abrahams M, O’Grady R, et al. Effect of a daily collagen peptide supplement on digestive symptoms in healthy women: 2‑phase mixed methods study. JMIR Form Res. 2022;6(5):e36339
• Beurel E. Stress in the microbiome-immune crosstalk. Gut Microbes. 2024 Jan-Dec;16(1):2327409.
• Comas-Basté O, Sánchez-Pérez S, et al. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020 Aug 14;10(8):1181.
• DiGuilio KM, Rybakovsky E, et al. Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy. Int J Mol Sci. 2022 Mar 10;23(6):2995. 10.3390/ijms23062995. PMID: 35328419; PMCID: PMC8951934.
• Dmytriv TR, Storey KB, et al. Intestinal barrier permeability: the influence of gut microbiota, nutrition, and exercise. Front Physiol. 2024 Jul 8;15:1380713.
• Enaud R, Prevel R, et al. The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks. Front Cell Infect Microbiol. 2020 Feb 19;10:9.
• Facchin S, Bertin L, et al. Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications. Life (Basel). 2024 Apr 26;14(5):559.
• Hou Y, Wang D, et al. Probiotics combined with prebiotics alleviated seasonal allergic rhinitis by altering the composition and metabolic function of intestinal microbiota: a prospective, randomized, double-blind, placebo-controlled clinical trial. Front Immunol. 2024 Nov 1;15:1439830.
• Lungaro L, Malfa P, et al. Clinical Efficacy of Probiotics for Allergic Rhinitis: Results of an Exploratory Randomized Controlled Trial. Nutrients. 2024 Nov 30;16(23):4173.
• Ma W, Xiong X, et al. Environmental pollutants and the gut microbiota: mechanistic links from exposure to systemic disease. Front Microbiol. 2026 Jan 23;17:1737229.
• Neurath MF, Artis D, et al. The intestinal barrier: a pivotal role in health, inflammation, and cancer. Lancet Gastroenterol Hepatol. 2025 Jun;10(6):573-592.
• Niewiem M, Grzybowska-Chlebowczyk U. Intestinal Barrier Permeability in Allergic Diseases. Nutrients. 2022 Apr 30;14(9):1893. doi: 10.3390/nu14091893. PMID: 35565858; PMCID: PMC9101724.
• Parada Venegas D, De la Fuente MK, et al. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019;10:277.
• Ried K, Travica N, et al. Effects of a Probiotic Formulation on Seasonal Allergic Rhinitis in Adults-A Randomized Double-Blind Placebo-Controlled Trial: The Probiotics for Hay Fever Trial. Front Nutr. 2022 May 23;9:887978.
• Rios-Carlos M, Cervantes-García D, et al. Unraveling the gut-skin axis in atopic dermatitis: exploiting insights for therapeutic strategies. Gut Microbes. 2024 Jan-Dec;16(1):2430420.
• Rudrapal M, de Oliveira AM, et al. Dietary polyphenols maintain human health through modulation of gut microbiota. Front Pharmacol. 2026 Jan 5;16:1710088.
• Sánchez-Pérez S, Comas-Basté O, et al. The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study. Front Nutr. 2022 Oct 21;9:1018463. 10.3389/fnut.2022.1018463. PMID: 36337620; PMCID: PMC9633985.
• Sankarganesh P, Bhunia A, et al. Short‑chain fatty acids (SCFAs) in gut health: implications for drug metabolism and therapeutics. Medicine in Microecology. 2025;25:100139.
• Sasaki M, Suaini NHA, et al. Systematic review of the association between short-chain fatty acids and allergic diseases. Allergy. 2024 Jul;79(7):1789-1811.
• Seethaler B, Lehnert K, et al. Omega-3 polyunsaturated fatty acids improve intestinal barrier integrity-albeit to a lesser degree than short-chain fatty acids: an exploratory analysis of the randomized controlled LIBRE trial. Eur J Nutr. 2023 Oct;62(7):2779-2791.
• Sun Y, Wang X, et al. The role of gut microbiota in intestinal disease: from an oxidative stress perspective. Front Microbiol. 2024 Feb 14;15:1328324.
• Szukalska I, Ziętek M, et al. The Association Between Short-Chain Fatty Acids and the Incidence of Food Allergies-Systematic Review. Nutrients. 2025 Sep 30;17(19):3117.
• Thin ZS, Chew J, et al. Impact of microplastics on the human gut microbiome: a systematic review of microbial composition, diversity, and metabolic disruptions. BMC Gastroenterol. 2025 Aug 13;25(1):583.
• Tian Y, Sun J, Jiao D, Zhang W. The potential role of n-3 fatty acids and their lipid mediators on asthmatic airway inflammation. Front Immunol. 2024 Dec 10;15:1488570.
• Valitutti F, Mennini M, et al. Intestinal permeability, food antigens and the microbiome: a multifaceted perspective. Front Allergy. 2025 Jan 9;5:1505834. PMC11754301.
• Wang Z, Song Y, et al. Probiotic therapy as adjuvant for allergic rhinitis: an overview of systematic reviews and meta-analyses. Front Med (Lausanne). 2026 Jan 12;12:1711096.
• Wellens J, Vanderstappen J, et al.Effect of Five Dietary Emulsifiers on Inflammation, Permeability, and the Gut Microbiome: A Placebo-controlled Randomized Trial. Clin Gastroenterol Hepatol. 2025 Aug 13:S1542-3565(25)00698-6.
• Wiertsema SP, van Bergenhenegouwen J, et al. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients. 2021 Mar 9;13(3):886.
• Zhang Q, Yu G, Jiang Y, et al.Dietary advanced glycation end-products promote food allergy by disrupting intestinal barrier and enhancing Th2 immunity. Nat Commun. 2025 May 28;16(1):4960. 10.1038/s41467-025-60235-0. PMID: 40436880; PMCID: PMC12120056.
• Zhao Y, Zhang X, Jin H, et al. Histamine Intolerance-A Kind of Pseudoallergic Reaction. Biomolecules. 2022 Mar 15;12(3):454.

---

All of our blogs are written by our team of expert Nutritional Therapists. If you have questions regarding the topics that have been raised, or any other health matters, please do contact them using the details below:

nutrition@cytoplan.co.uk
01684 310099

Find out what makes Cytoplan different

Last updated on 19th February 2026 by cytoffice