The Gut–Skin Axis in Atopic Eczema: From Immune Education to Microbiome Modulation

Atopic eczema is one of the most common chronic inflammatory skin conditions in the UK, affecting up to 20% of schoolchildren and up to 10% of adults.¹ Yet its visible manifestations — redness, swelling, dryness, itching and damaged skin — represent only one part of a much more interconnected biological picture.

An unusual real-world observation during the COVID-19 pandemic has added further interest to this question. 

Researchers at the Faculty of Medicine, The Chinese University of Hong Kong (CU Medicine) analysed data from 1,152 children born before and during the pandemic. They reported a 46% higher incidence of allergy among infants born during the pandemic. Analysis of 700 infant stool samples also found reduced gut microbial diversity and richness, together with lower levels of beneficial bacteria associated with immune development.²

The researchers linked these observations to the “hygiene hypothesis”: reduced exposure to a diverse range of microorganisms during early life may interfere with the normal development and education of the immune system.² During the pandemic, increased sanitation and reduced environmental microbial exposure created a particularly relevant setting in which to examine this relationship.

These findings raise a broader question that has become increasingly important in eczema research:

Could changes in the gut microbiome influence the way the immune system responds — and, ultimately, how inflammation is expressed in the skin?

Recognising Atopic Eczema — and How Severity Is Measured

Atopic eczema can present differently between individuals and across different skin tones, but several characteristic clinical signs are commonly assessed:

• Erythema — visible inflammatory colour change, often appearing red on lighter skin but potentially purple, grey or darker on deeper skin tones.
• Oedema or papulation — swelling or raised inflammatory lesions.
• Excoriation — scratch marks and skin damage caused by repeated itching.
• Lichenification — thickening and increased prominence of skin markings caused by chronic rubbing or scratching.
  

These are not simply descriptive terms. They form the four principal clinical signs assessed in the Eczema Area and Severity Index (EASI), one of the most widely used tools for evaluating eczema severity in clinical research.³

EASI assesses the intensity of these four signs across four body regions and combines this with the proportion of skin affected.³ Understanding EASI is particularly useful when interpreting clinical eczema studies, as changes in the score provide a standardised way of following changes in disease severity over time.

Eczema Is More Than Skin Inflammation

The symptoms of eczema appear on the skin, but research increasingly points to several interconnected biological features beyond the visible inflammation. These include immune dysregulation, altered gut microbial diversity and broader disturbances of the gut microbiome, often referred to as gut dysbiosis.⁴

But how does an altered immune response actually translate into red, inflamed and itchy skin?

One important pathway involves type 2 inflammation. In atopic eczema, immune signalling can become disproportionately biased towards type 2 responses. Cytokines — signalling proteins used by immune cells to communicate — including interleukin-4 (IL-4) and interleukin-13 (IL-13) can act on keratinocytes, the predominant cells of the epidermis. These cytokines can reduce the expression of barrier proteins including filaggrin, which plays an important role in maintaining epidermal structure and hydration.⁵

As barrier function deteriorates, transepidermal water loss increases and the skin becomes more permeable to irritants, allergens and microbial products. These external signals can then stimulate further inflammatory responses.

At the same time, another type 2 cytokine, IL-31, is strongly associated with pruritus. It can stimulate sensory nerve pathways involved in itching, while IL-4 and IL-13 can amplify this signalling.⁵

This can establish a self-reinforcing cycle:

In other words, the immune system does not simply “attack the skin”. Rather, dysregulated inflammatory signalling alters how skin cells function, weakens barrier integrity and increases the skin’s susceptibility to further inflammatory triggers.

The next question is therefore important: what helps regulate these immune responses in the first place?

Increasingly, attention has turned upstream — towards the gut microbiome.

The Gut–Skin Axis: How the Gut, Immune System and Skin Communicate

The gut contains a vast microbial ecosystem that interacts continuously with the intestinal barrier and immune system. These microorganisms do far more than participate in digestion. They generate metabolites, interact with immune cells and contribute to the development and regulation of immune responses.

Research into atopic eczema has identified differences in both skin and gut microbial communities compared with healthy controls, including reduced microbial diversity and altered proportions of particular bacterial groups.⁴

The importance of these observations lies in the close relationship between the gut microbiome and immune regulation.

Microorganisms in the intestine provide a continuous stream of molecular signals to the immune system. Microbial metabolites can also circulate beyond the gut and influence immune activity elsewhere in the body. When this microbial ecosystem becomes disrupted, the signals presented to the immune system may also change. Conversely, a more balanced and diverse microbial community can provide signals associated with immune regulation and tolerance.

This relationship provides the biological basis for the gut–skin axis — the interconnected communication between the gut microbiome, immune system and skin.⁶

The concept helps explain why disturbances originating in the gut may potentially be reflected in a distant organ such as the skin.

A less favourable gut microbial environment may contribute to altered immune signalling and a greater tendency towards inflammatory or hypersensitivity responses. Through this pathway, the skin may respond more intensely to environmental stimuli that would otherwise be tolerated.

The opposite direction is equally important. A gut environment rich in appropriate commensal microorganisms can provide repeated microbial and metabolic signals that help the immune system develop tolerance — the ability to recognise when an aggressive immune response is unnecessary. This is sometimes described informally as microbes helping to “train” the immune system.

But what does that actually mean?

How Beneficial Microbes Help “Train” the Immune System

The immune system has a difficult task. It must react rapidly to genuine threats such as pathogens while remaining tolerant of food components, harmless environmental antigens and the enormous number of microorganisms that normally live within the human body.

A healthy immune response therefore depends not simply on being “strong”, but on being well regulated. The interaction between gut microorganisms and immune cells is one of the mechanisms through which this regulation develops.

Recognising microbial signals

Microorganisms contain characteristic molecular structures known as microbe-associated molecular patterns (MAMPs). These are molecular signatures that allow the immune system to recognise the presence of microbes.

Immune cells detect these signals using pattern-recognition receptors (PRRs) — receptors designed to recognise common molecular features of microorganisms. One important family of PRRs is the Toll-like receptors (TLRs).

In simple terms:

MAMPs are the microbial signals; PRRs, including TLRs, are part of the immune system’s detection system.

Recognition does not automatically mean inflammation. The biological context in which a microbial signal is encountered helps determine what kind of immune response follows.

Dendritic cells: interpreting the signal

Among the cells involved are dendritic cells, specialised antigen-presenting cells that collect information from their environment and help instruct T cells about how to respond. They can be thought of as part of the immune system’s decision-making network.

Depending on the signals they encounter, dendritic cells can encourage inflammatory responses when genuine threats are present, or support more regulatory responses when aggressive immunity is unnecessary.

Cytokines: the immune system’s signalling language

Immune cells communicate using cytokines — small signalling proteins that influence how other immune cells behave.

Two cytokines particularly relevant to immune regulation are:

• IL-10, which helps limit excessive inflammatory responses; and
• transforming growth factor beta (TGF-β), which has important roles in immune regulation and tolerance.
  

These regulatory signals can help create an environment that favours the development and activity of regulatory T cells, commonly abbreviated to Treg cells.⁴˒⁶

Treg cells: the regulatory brakes

Under a regulatory cytokine environment, naïve CD4+ T cells (Th0) can be guided towards regulatory T-cell (Treg) development. Treg cells act as one of the immune system’s important regulatory mechanisms. Rather than initiating an attack, they help restrain unnecessary or excessive immune responses and contribute to immune tolerance. This distinction is particularly relevant to allergic and atopic conditions.

A properly regulated immune system still reacts to pathogens and genuine danger, but it is less likely to mount a disproportionate response against harmless antigens or innocuous environmental stimuli.

This is the essence of what is meant when beneficial microbes are described as helping to “train” the immune system.

This does not mean that beneficial microorganisms simply “boost” or “suppress” immunity. Rather, they participate in immune education: helping the immune system become better regulated, maintain tolerance towards non-threatening stimuli and reserve aggressive responses for situations in which they are actually required. This relationship also provides a plausible biological link between an altered gut microbiome and hypersensitivity at the skin. If the microbial signals involved in immune regulation change, the balance of immune responses may change with them.

Everyday Factors Can Shape the Gut Microbiome

If the gut microbiome contributes to immune education and regulation, then factors that alter the microbiome may also alter the signals being presented to the immune system. Many aspects of everyday life can influence gut microbial composition, diversity and function.

These include:

• early-life microbial exposure;
• mode of birth and infant feeding;
• diet and dietary fibre intake;
• medications;
• antibiotic exposure;
• illness;
• psychological and physiological stress; and
• wider environmental and lifestyle factors.⁷
  

Antibiotics provide a particularly clear example. While indispensable for treating bacterial infections, they can also alter commensal microbial communities. The resulting disruption of the gut microbiome — sometimes referred to as microbiome perturbation — can differ considerably depending on the antibiotic used, duration of treatment, age, diet and underlying health status.⁸

The gut microbiome therefore sits relatively far upstream in this chain — which naturally raises interest in whether it can be deliberately modulated.

Modulating the Gut Microbiome: Where Can We Intervene?

Microbiome research has explored multiple ways of influencing microbial ecosystems.
Tamburini and colleagues proposed a conceptual framework in which different microbiome-directed interventions may be considered at different stages of health and disease. These range from early bacterial inoculation and dietary intervention to antibiotics and, in selected clinical settings, microbiota transplantation.⁹

These approaches do not represent a simple sequence of treatments, nor do the arrows in the framework indicate that one direction is necessarily “good” and the other “bad”. Rather, they illustrate different potential windows during which microbial ecosystems may be modified.

For the gut–skin axis, one part of this framework is particularly relevant: dietary intervention.

Tamburini and colleagues highlighted several approaches that may help create a more tolerogenic environment — an environment that supports appropriate immune tolerance rather than unnecessary immune activation.⁹ These include:

• dietary fibres;
• prebiotics, probiotics and synbiotics; and
• human milk oligosaccharides, particularly in early life.
  

Dietary fibre and prebiotics: related, but not identical

Dietary fibre and prebiotics overlap, but they are not interchangeable terms.
Dietary fibre is a broad nutritional category comprising carbohydrates that are not fully digested and absorbed in the small intestine. Different fibres have very different physiological and microbial effects.

A prebiotic, by contrast, is a substrate that is selectively utilised by host microorganisms and confers a health benefit.¹⁰

Many recognised prebiotics are therefore fibres, but not every dietary fibre meets the definition of a prebiotic.

Examples include Inulin and Fructooligosaccharides (FOS), which can be selectively fermented by particular gut microorganisms.

A probiotic introduces specific live microorganisms, while a synbiotic combines microorganisms with substrates designed to support beneficial microbial activity.

Human milk oligosaccharides provide another naturally occurring example of how diet can influence microbial ecology. They are poorly digested by the infant itself but can be utilised by selected intestinal bacteria, contributing to the development of the early-life microbiome.⁹

The relevance of these approaches is straightforward:

If microbial communities help educate the immune system, and diet can influence those microbial communities, then dietary microbiome modulation provides one route through which immune regulation may potentially be influenced.

This idea has now begun to move from mechanistic theory into human clinical investigation in atopic eczema.

A Synbiotic Approach: Clinical Findings From CUHK Adult Research

A clinical example of this approach comes from research conducted by the Faculty of Medicine at The Chinese University of Hong Kong.

The researchers developed a synbiotic microbiome formulation known as SIM05, combining three probiotic strains — Lactobacillus salivarius LS01, Bifidobacterium breve and Bifidobacterium bifidum — with the prebiotic fibres inulin and fructooligosaccharides. Of particular interest, L. salivarius LS01 is itself a strain with an independent research history in atopic eczema, which is explored in the next section.

In an adult pilot study involving 22 participants with atopic eczema, clinical outcomes were assessed over four months.¹¹

Reduction in EASI score

The mean Final EASI Score decreased from 5.99 at baseline to 5.05 at Month 2 and 4.60 at Month 4, corresponding to a 23.2% reduction from baseline.¹¹

Region-specific analysis also showed:

• 31.7% reduction in the upper-extremity score, and
• 31.1% reduction in the lower-extremity score.¹¹
  

Because EASI incorporates both the extent of affected skin and the intensity of erythema, oedema/papulation, excoriation and lichenification, these changes reflect an overall reduction in measured eczema area and severity.

 

Improvement in dermatology-related quality of life

Clinical severity is only part of the burden of eczema.

The Dermatology Life Quality Index (DLQI) assesses the impact of a dermatological condition on areas including daily activities, clothing, social and leisure activities and personal relationships.
In the same pilot study, mean DLQI decreased from 8 at baseline to 7 at Month 2 and 5 at Month 4, representing a 37.5% improvement in the impact of eczema on quality of life.¹¹

Taken together, the findings provide clinical evidence consistent with the concept developed throughout this article: modifying the gut microbial environment through a targeted synbiotic intervention may influence outcomes at the skin.

The findings are particularly relevant when considered alongside the gut–skin axis.

The intervention begins in the gut. The measured clinical outcomes — EASI and DLQI — are expressed through the skin and through the daily burden of eczema.

Between these two points lies the microbiome–immune interaction that has become an increasingly important area of research.

 

Research Spotlight: Lactobacillus salivarius LS01

Research involving Lactobacillus salivarius LS01 (DSM 22775) has examined clinical outcomes, intestinal microbiota and gut–immune markers in adults with atopic dermatitis.
Clinical research in adults with atopic dermatitis

A randomised, double-blind, placebo-controlled study investigated LS01 in 38 adults with moderate-to-severe atopic dermatitis, with 19 participants receiving LS01 and 19 receiving placebo for 16 weeks.¹² Clinical improvements were substantial. Mean SCORAD, another established eczema severity measure, decreased from 27.57 at baseline to 13.14 after 16 weeks, representing an approximately 52% reduction, while no statistically significant change was observed in the placebo group.¹² Dermatology-related quality of life also improved, with mean DLQI decreasing from 8.28 to 4.42 at Week 16 — an approximately 47% reduction in score. Improvement was evident from Week 8 and remained detectable four weeks after supplementation had ended.¹²

Changes were also observed in the intestinal microbiota. Faecal staphylococcal counts decreased significantly after 16 weeks of LS01 supplementation and remained significantly reduced one month after supplementation had stopped.¹² Staphylococci are a group of bacteria that have been reported at higher levels in the gut microbiota of people with atopic dermatitis than in healthy controls. In this study, the reduction was interpreted as a shift towards rebalancing the altered intestinal microbiota rather than simply a change in skin symptoms.¹²

A related publication from the same clinical research programme extended the analysis beyond clinical outcomes to examine gut-barrier and immune markers.¹³

The researchers measured plasma lipopolysaccharide (LPS), a structural component of the outer membrane of Gram-negative bacteria. When bacterial products such as LPS cross the intestinal barrier and enter the circulation, this is referred to as microbial translocation. Plasma LPS can therefore be used as an indicator of how much bacterial material is crossing from the gut into the bloodstream. In the probiotic group, plasma LPS concentrations decreased and were significantly lower than in the placebo group at the end of the study period.¹³ In this context, the finding was consistent with reduced microbial translocation across the intestinal barrier.

The researchers also examined Th1- and Th2-associated cytokines. Earlier in this article, naïve CD4+ T cells were described as Th0 cells before differentiation. Th1 and Th2 represent two different patterns of T-helper immune response that these cells can develop into. Th2 signalling is particularly relevant to allergic and atopic inflammation, whereas Th1 represents a different immune-response pathway.

Importantly, the findings did not suggest that LS01 simply “boosted” Th1 activity. Instead, the probiotic group maintained a more stable cytokine profile, while the placebo group showed changes consistent with a greater shift towards Th2 activity during the study period.¹²˒¹³ The authors therefore interpreted the findings as regulation of the Th1/Th2 balance, rather than stimulation of one arm of immunity.

This again returns to the concept developed earlier in this article: beneficial microbes may contribute to immune regulation not by making the immune response stronger, but by helping it remain appropriately balanced.

When probiotics are investigated for targeted health applications, evidence attached to the individual strain — including its immunological profile, human clinical findings and microbial interactions — becomes particularly important.

 

What This Tells Us About the Gut–Skin Axis: Key Takeaways

Atopic eczema is most visible at the skin, but the biological pathways influencing that response can extend much further.

The evidence reviewed here follows a progressively connected pathway.

Environmental, dietary and medical factors can shape the gut microbiome.

Gut microorganisms and their metabolites interact continuously with the immune system.
These microbial signals contribute to immune education and tolerance — helping the immune system distinguish genuine threats from harmless antigens and ordinary environmental stimuli.

When this regulatory balance is disturbed, inflammatory responses may become disproportionate. In atopic eczema, type 2 inflammatory signalling can weaken epidermal barrier function, increase susceptibility to irritants and allergens, amplify pruritus and perpetuate the itch–scratch inflammatory cycle.

This interconnected communication between the gut microbiome, immune system and skin is the basis of the gut–skin axis.

Several key points emerge:

• Atopic eczema extends beyond local skin inflammation. Immune dysregulation, altered gut microbial diversity and gut dysbiosis are increasingly investigated as interconnected features of the condition.⁴˒⁶
• Gut microbes participate in immune education. Microbial signals interact with PRRs, dendritic cells, cytokines and regulatory T cells, helping maintain tolerance towards harmless stimuli while preserving responses to genuine threats.⁴˒⁶
• The gut microbiome can be shaped by everyday exposures. Diet, medications, antibiotics, stress, illness and environmental factors can influence microbial diversity, composition and function.⁷˒⁸
• Diet provides one route for microbiome modulation. Dietary fibres, prebiotics, probiotics and synbiotics have been investigated as approaches for supporting microbial environments associated with immune tolerance.⁹˒¹⁰
• Human intervention data are beginning to support this biological framework. In the CUHK adult pilot study, a targeted synbiotic intervention was associated with reductions in EASI scores and improvement in dermatology-related quality of life.¹¹
• Independent clinical research involving LS01 in adults with atopic dermatitis reported improvements in clinical severity and dermatology-related quality of life, alongside changes in the gut microbiota and markers related to microbial translocation and immune regulation.¹²˒¹³
  

Taken together, these observations support continued investigation of microbiome modulation as an additional biological dimension in atopic eczema research.

Eczema is visible on the skin, but part of the biology shaping that response may begin much further away — in the gut.

 

References

1. National Eczema Society. Eczema and its management: a guide for healthcare professionals [Internet]. London: National Eczema Society; 2024 [cited 2026 Aug 27]. Available from: https://eczema.org/wp-content/uploads/NES_Eczema_Guide_for_HCPs_2024.pdf

2. Faculty of Medicine, The Chinese University of Hong Kong. CUHK study finds vigorous disinfection linked to increased risk of eczema and atopic diseases [Internet]. Hong Kong: The Chinese University of Hong Kong; 2025 Feb 3 [cited 2026 Aug 27]. Available from: https://www.med.cuhk.edu.hk/press-releases/cuhk-study-finds-vigorous-disinfection-linked-to-increased-risk-of-eczema-and-atopic-diseases

3. Hanifin JM, Baghoomian W, Grinich E, Leshem YA, Jacobson M, Simpson EL. The Eczema Area and Severity Index-A Practical Guide. Dermatitis. 2022;33(3):187-192. doi:10.1097/DER.0000000000000895.

4. Kim JE, Kim HS. Microbiome of the skin and gut in atopic dermatitis (AD): understanding the pathophysiology and finding novel management strategies. J Clin Med. 2019;8(4):444. doi:10.3390/jcm8040444.

5. Furue M, Ulzii D, Vu YH, Tsuji G, Kido-Nakahara M, Nakahara T. Pathogenesis of atopic dermatitis: current paradigm. Iran J Immunol. 2019;16(2):97-107. doi:10.22034/IJI.2019.80253.

6. Mahmud MR, Akter S, Tamanna SK, Mazumder L, Esti IZ, Banerjee S, et al. Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases. Gut Microbes. 2022;14(1):2096995. doi:10.1080/19490976.2022.2096995.

7. Dong TS, Gupta A. Influence of early life, diet, and the environment on the microbiome. Clin Gastroenterol Hepatol. 2019;17(2):231-242. doi:10.1016/j.cgh.2018.08.067.

8. Schwartz DJ, Langdon AE, Dantas G. Understanding the impact of antibiotic perturbation on the human microbiome. Genome Med. 2020;12(1):82. doi:10.1186/s13073-020-00782-x.

9. Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016;22(7):713-722. doi:10.1038/nm.4142.

10. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502. doi:10.1038/nrgastro.2017.75.

11. Faculty of Medicine, The Chinese University of Hong Kong. A pilot study of efficacy and safety of a microbiome immunity formula in adults with atopic eczema. Hong Kong: The Chinese University of Hong Kong; 2024. Data on file.

12. Drago L, Iemoli E, Rodighiero V, Nicola L, De Vecchi E, Piconi S. Effects of Lactobacillus salivarius LS01 (DSM 22775) treatment on adult atopic dermatitis: a randomized placebo-controlled study. Int J Immunopathol Pharmacol. 2011;24(4):1037-1048. doi:10.1177/039463201102400421.

13. Drago L, Toscano M, De Vecchi E, Piconi S, Iemoli E. Changing of fecal flora and clinical effect of L. salivarius LS01 in adults with atopic dermatitis. J Clin Gastroenterol. 2012;46 Suppl:S56-S63. doi:10.1097/MCG.0b013e318265ef38.