Allergic conjunctivitis and gut microbiota

Allergic conjunctivitis has a major impact on the quality of life of all those who suffer from it. But what's new from genetic research.

When spring approaches, even in the altered rhythm of the seasons brought about by climate change, with the first fine days, the nightmare of spring allergies and, in particular, allergic conjunctivitis, appears on the horizon for sufferers.

Allergic conjunctivitis

Allergic conjunctivitis is an inflammatory, autoimmune-based eye disease that affects the conjunctiva, eyelids and cornea.

Among the most frequent forms are seasonal allergic conjunctivitis (SAC) and the Perennial allergic conjunctivitis (CAP).

Seasonal allergic conjunctivitis (SAC)

Seasonal allergic conjunctivitis (SAC) occurs during spring and/or summer and is triggered by the presence of pollen in the air, usually from grasses. SAC is often also associated with significant symptoms affecting the nasal passages, and in this case we speak of rhino-conjunctivitis.

Perennial allergic conjunctivitis (CAP)

Perennial allergic conjunctivitis (CAP) can occur at all times of the year and for this allergic form, the allergens can be different: dust mites, pet dander or the presence of fungal spores and moulds.

The role of the gut microbiota

In recent years, growing evidence has emerged of a decisive role played by the gut microbiota in balancing and modulating the immune response and in the pathogenesis of allergic manifestations.

This finding implies that an imbalance in the gut microbiota could constitute a useful marker to predict the onset of allergic conjunctivitis.

Microbiota and microbiome

These two terms are sometimes used as synonyms even though, on a strictly scientific level, they have different meanings.

Microbiota

The microbiota indicates the population, in the order of a few billion, of micro-organisms (archaea, bacteria, yeasts, viruses, fungi), present throughout our body, on the dermis and in all our cavities.

These micro-organisms, in the right balance between eubionti (micro-organisms with beneficial actions) and pathobionts (disease-causing microorganisms), are necessary for our well-being.

Microbiome

By the term microbiome indicates, on the other hand, the totality of the genetic heritage possessed by the microbiota, i.e. the genes it is able to express.

The functions of the microbiota

The microorganisms of the gut microbiota help us assimilate food and protect us from many diseases. They also produce substances that are very useful for our metabolism, including vitamins, including vitamin D, short-chain fatty acids (SCFA), some hormones and neurotransmitters.

Today, the gut microbiota is an important therapeutic target for many inflammatory, autoimmune, neurodegenerative and many other diseases that scientific studies are progressively identifying.

The composition of the individual microbiota, and of the gut microbiota in particular, is influenced by pregnancy, natural or caesarean birth, breast or formula feeding, weaning, excessive hygiene, stress, exercise, drug therapies, and above all diet.

With reference to drugs, it is very important to emphasise that the antibiotics, while preventing the proliferation of pathogens and the development of infectious diseases, on the other hand compromise the normal bacterial population, which resides mainly in the intestine, where it plays a key role in maintaining the health of the host organism.

Specificity of the ocular microbiome

In the human eye coexist numerous bacterial microhabitats, whose composition reflects levels of exposure to the outdoor environment.

Studies, published in the literature, have shown that the gender most represented on the ocular surface is the Corynebacterium, followed by Staphylococcus, Streptococcus, Acinetobacter e Pseudomonas.

Microbiota and eye diseases

Established scientific data are now available on the correlation between alterations in the composition of the gut microbiota and the pathogenesis of intestinal diseases, including irritable bowel syndrome.

Probably less is known about the correlations between alterations in the microbiota and the onset of certain eye diseases.

The first point to highlight is that this correlation is detectable for eye diseases in which there is an inflammatory component and the specific areas can be summarised as follows:

• Microbiota and age-related macular degeneration
• Microbiota and ocular surface diseases, in particular dry eye
• Microbiota and ocular neurodegenerative diseases, including Glaucoma

Microbiota and ocular surface diseases

In recent years, research has focused on the relationship between the balance of the microbiota and certain ocular surface pathologiessuch as dry eye syndrome, episcleritis, chronic follicular conjunctivitis, pterygium and Thygeson's disease.

All of the aforementioned pathologies are essentially idiopathic in nature, i.e. they are characterised by the absence of an unambiguously identifiable cause, and at the same time are united by the presence of a inflammatory component.

The hypothesis that has guided research in recent years has been that an imbalance in the specific microbiotic community of the ocular surface may determine or contribute to their occurrence, as in the case of the intestinal microbiome and diseases affecting the gut.

Role of the microbiota in the onset of allergic conjunctivitis

In the perspective of predictive, preventive and customised medicine, clarifying the role of the gut microbiota imbalance in the onset of allergic conjunctivitis could offer an opportunity for primary prediction first and then for targeted prevention and, finally, for customised treatment of the disease.

Dysbiosis and inflammatory response

In a study, published in May 2023 in the EPMA Journal, the official organ of Evidence-based Predictive, Preventive & Personalised Medicine, researchers tested the hypothesis that individuals with gut dysbiosis may be more susceptible to allergic conjunctivitis due to an increased inflammatory response.

Genetic variants

For this purpose, genetic variants related to gut microbiota conditions (N= 18,340) and allergic conjunctivitis (4,513 cases, with 649,376 controls) were selected from genome-wide association studies.

Innovative Screening and Targeted Interventions

With the advent of modern sequencing technologies targeting the 16S ribosomal RNA gene (16S rRNA), it is now possible to rapidly and cost-effectively analyse microbial communities in the gut from faecal samples, which can be obtained easily and non-invasively.

Identifying an alteration in the gut microbiota is crucial, not least because allergic conjunctivitis can serve as an early and reliable indicator of systemic disorders such as atopic dermatitis and asthma. Sequencing of the 16S rRNA gene showed that people who are at risk of a reduction in the Ruminococcaceae_UCG_002 , Holdemanella, Catenibacterium, Senegalimassilia and increased levels of the Oscillospira are at increased risk of allergic conjunctivitis.

New treatment options

Individuals identified through genetic sequencing should be given aggressive early treatment to correct the dysbiosis, such as: changing the diet, taking probiotic supplements and prebiotics.

Recent studies confirm that certain probiotic strains are able to alleviate the symptoms of allergic conjunctivitis. Probiotics are naturally occurring micro-organisms that are compatible with those naturally present in the gut and make up, together with prebiotics, the intestinal ecosystem which, between harmless and pathogenic micro-organisms, hosts more than 400 species.

For example, you can raise the level of Ruminococcaceae_UCG_002  with targeted probiotic supplementation, while targeted antibiotics can be administered to suppress the growth of Oscillospira

Future perspectives and prevention strategies

Furthermore, 'high-throughput' 16S rDNA sequencing could become a routine test to identify alterations in the gut microbiota in patients with allergic conjunctivitis, which would be the first step to then delineate the specific probiotic strains for each patient, modify their diet and administer specific antibiotics to improve the inflammatory response and symptoms and improve quality of life from the early stages of allergic conjunctivitis.

This approach is also very useful for secondary prevention of the disease. Remember that primary prevention consists of preventing an individual from becoming allergic, while secondary prevention consists of preventing contact with the allergen.

Read more with:

• Eye allergies: a problem for all seasons - Oculista Italiano
• Ocular allergies - Oculista Italiano
• Ocular allergy: risk factor for dry eye syndrome? - Italian Ophthalmologist

• Liu K, Cai Y, Song K, Yuan R, Zou J. Clarifying the effect of gut microbiota on allergic conjunctivitis risk is instrumental for predictive, preventive, and personalized medicine: a Mendelian randomization analysis. EPMA J. 2023 May 22;14(2):235-248. doi: 10.1007/s13167-023-00321-9. PMID: 37275551; PMCID: PMC10201039.
• Bielory L, Delgado L, Katelaris CH, Leonardi A, Rosario N, Vichyanoud P. ICON: Diagnosis and management of allergic conjunctivitis.  Allergy Asthma Immunol: official publication of the American College of Allergy, Asthma, & Immunology. 2020;124(2):118-134. doi: 10.1016/j.anai.2019.11.014.
• Vazirani J, Shukla S, Chhawchharia R, Sahu S, Gokhale N, Basu S. Allergic conjunctivitis in children: current understanding and future perspectives. Curr Opin Allergy Clin Immunol. 2020;20(5):507-515. doi: 10.1097/aci.0000000000000675.