Swiss Institute of Allergy and Asthma Research

SIAF performs basic and translational research in the field of allergies and asthma.

25/09/2023

Congratulations to Yagiz Pat, one of our postdocs, for his presentation at the EAACI Summer Symposium on Epithelial Cell Biology at Imperial College, London about the regulation of gut and skin epithelial barrier by microbiome metabolites.

The human body is colonized by a diverse microbial flora that plays an essential role in human health and disease. It is known that a healthy gut microbiota limits pathogen colonization through competition for space and nutrients, and by producing antimicrobial peptides and metabolites that promote epithelial homeostasis. However, the increased exposure to toxic substances such as emulsifiers, detergents and pollutants poses a significant threat to the gastrointestinal epithelial and skin barrier. In this context, the microbiota and their metabolites could be the key to rescuing the damaged gastrointestinal barrier. The researchers screened various gut microbiota-associated metabolites regarding their gut and skin barrier strengthening and anti-inflammatory capacities.

European Academy of Allergy and Clinical Immunology – EAACI

24/09/2023

Congratulations to Cezmi Akdis, our director, for his presentation at the EAACI Summer Symposium on Epithelial Cell Biology at Imperial College, London about the immunological basis and level of evidence for the epithelial barrier theory.

In our daily lives, we are constantly exposed to a multitude of toxins and chemicals. According to the epithelial barrier hypothesis, many of these substances can cause damage to the delicate layer of cells that form the epithelium, which covers our skin, lungs, and intestine. The consequences of compromised epithelial barriers are far-reaching, contributing to the alarming rise of almost two billion cases of allergic, autoimmune, neurodegenerative, and psychiatric diseases. The scientific community recognises this as one of the three major threats to humanity, alongside global warming and climate change, as well as virus infection pandemics like COVID and Ebola.

Local damage to the skin and mucosal barriers can lead to allergic conditions, inflammatory bowel disorders, and celiac disease. It is essential to pursue research in the field of epithelial barriers, where experimental models must be developed and validated to better understand the transportation of environmental antigens. This knowledge will guide us in preventing these conditions, intervening early, and creating innovative therapies.

Website: www.epithelialbarriertheory.com

Recent Barrier Papers to better understand the "Epithelial Barrier Theory": https://www.nature.com/articles/s41577-021-00538-7.
https://www.nature.com/articles/s41577-022-00776-3.
https://onlinelibrary.wiley.com/doi/10.1111/all.15240

A recent webinar on "Epithelial Barrier Theory and Global Health Crisis" https://youtu.be/mSFOkpXbAv4

Cezmi Akdis EAACI

24/09/2023

Congratulations to Duygu Yazici, one of our postdocs, for her insightful presentations at the EAACI Summer Symposium on Epithelial Cell Biology at Imperial College, London.
Disrupted epithelial permeability as a predictor of severe COVID-19 development

An impaired epithelial barrier integrity in the gastrointestinal tract is important in the pathogenesis of many inflammatory diseases. Accordingly, the authors assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID-19. The results demonstrate that biomarkers of intact or defective epithelial barriers are associated with disease severity and can provide early information on the prediction at the time of hospital admission.

Yazici, D., Cagan, E., Tan, G., Li, M., Do, E., Kucukkase, O. C., Simsek, A., Kizmaz, M. A., Bozkurt, T., Aydin, T., Heider, A., Rückert, B., Brüggen, M. C., Dhir, R., O'Mahony, L., Akdis, M., Nadeau, K. C., Budak, F., Akdis, C. A., & Ogulur, I. (2023). Disrupted epithelial permeability as a predictor of severe COVID-19 development. Allergy, 10.1111/all.15800. Advanced publication. https://doi.org/10.1111/all.15800

Epithelitis: barrier disruption and activation of pro-inflammatory pathways in gut epithelial cells by food emulsifiers.

Food emulsifiers are frequently used as food additives, primarily in processed foods, serving as stabilisers for emulsions. The regulations governing their usage in food are primarily based on animal studies, with a limited assessment of their molecular toxicity such as their impact on epithelial cell physiology and tissue inflammation. In this context, researchers elucidated the effects of food emulsifiers on the gut epithelial barrier using a gut-on-a-chip system, employing transcriptomics and proteomics.

European Academy of Allergy and Clinical Immunology – EAACI

Photos from Swiss Institute of Allergy and Asthma Research's post 24/09/2023

Congratulations to Mohamed Shamji, Ioana Agache and Cezmi Akdis for preparing yet another EAACI Summer Symposium on Epithelial Cell Biology at Imperial College, London. It was a delightful experience full of science. We also congratulate all the SIAF members for their attendance and contributions to this wonderful event.

EAACI

Photos from Swiss Institute of Allergy and Asthma Research's post 23/09/2023

in Epithelial Biology Meeting in Imperial College, London organized by on how to detect skin epithelial integrity by Electric Impedancemeter (Navisense) in 2 seconds.

05/08/2023

Congratulations to Ismail Ogulur on their original article entitled "Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80".

Link to the article for further reading (open for free download):
https://lnkd.in/eF_fdV9W

Polysorbate 20 and Polysorbate 80 were shown to damage the gut barrier, leading to cell death and inflammation –– even at doses 10 to 20 times lower than those currently authorized for use

The findings illustrate the urgent need to use fine-scale immunology to evaluate safety and establish a new standard for consumer products

The Swiss Institute of Allergy and Asthma Research (SIAF) today announced the findings of a new study demonstrating the mechanisms of gut epithelial barrier impairment caused by food emulsifiers. Published today in Allergy, the research reveals the detrimental effects of the widely-used emulsifiers Polysorbate 20 (P20) and Polysorbate 80 (P80) on intestinal epithelial integrity and inflammation –– even at significantly lower concentrations than those currently authorized.

The study comes from the research group of epithelial biology at SIAF, associated with the University of Zurich, which has been working on epithelial barriers for more than 20 years.

Polysorbates are a type of nonionic surfactant often used in food preparation to improve the texture and consistency of foods, as well as to act as an emulsifier to help mix ingredients that might not otherwise blend well, such as oil and water. They were first introduced in the mid-20th century as a food additive, and their use has since become widespread globally. Today, they are found in a wide range of processed foods, including ice cream, baked goods, salad dressings, and sauces, at concentrations up to 1%.

The research group investigated the impact of P20 and P80, the most common types of polysorbates used in foods, on epithelial barriers and inflammatory response. Using human models, such as induced pluripotent stem cell-derived human intestinal organoids, colon organoids, organ-on-a-chips, and liquid-liquid interface cultures, the researchers revealed that P20 and P80 damage the gut barrier. This disruption is due to cell death and molecular toxicity, as well as the triggering of numerous genes and proteins that stimulate inflammatory responses in epithelial cells (known as 'epithelitis'). The food emulsifiers also triggered a range of cellular processes, including tissue damage, alterations in cell signaling and communication, and induced inflammation.

The study highlights that these effects occurred even at doses much lower than those approved for public use.

Cezmi Akdis Duygu Yazici Yağız Pat

05/08/2023

Congratulations to Duygu Yazıcı on their original article entitled "Disrupted epithelial permeability as a predictor of severe COVID- 19 development".

Free Access Link to the article for further reading: https://lnkd.in/eFkPY3Z7

This study provides evidence that compromised epithelial barrier function is predicting severe COVID- 19, in line with the epithelial barrier theory. According to the epithelial barrier theory, disruption of epithelial barriers by environmental and toxic agents triggers microbial dysbiosis, bacterial translocation to subepithelial areas and local or systemic immune/inflammatory response to environmental agents, allergens and microbes. Such events have been implicated in the development of chronic conditions like allergic, autoimmune, and metabolic diseases.
The compromised epithelial barrier facilitates the translocation of microbiota and their secreted metabolites, thus initiating or exacerbating inflammatory cascades in many inflammatory diseases. The authors analyzed the amount of bacterial DNA leakage to circulation and showed the link between disrupted epithelial barriers and an excessive inflammatory response. They identified other major inflammatory proteins, which strongly correlated with bacterial translocation. Interestingly, all of these analyses were done at the time of hospital admission even before severe symptoms occurred demonstrating that there is a link between certain protein biomarkers and disease progression from moderate to severe COVID-19 and death.

Duygu Yazici Cezmi Akdis

29/06/2023

Dear WIRM friends and colleagues,
Only a few days until WIRM will start for the 17th time. We are very proud to present an outstanding scientific program and look forward to many interesting talks and fruitful discussions.

We are delighted to announce the plenary program of the 17th WIRM https://www.wirm.ch/program-2/

Your way to Davos ..... by plane
As the official carrier of WIRM, Swiss International Air Lines offers you the best booking flexibility together with Swiss product and service quality. All participants will receive a special rate. You got the promotional code together with your registration confirmation.
... by train
Enjoy a special idyllic landscape. There are hourly train connections to Davos. It takes 2h 40 min. from Zurich Airport to Davos: https://www.wirm.ch/location-travel/

Do not miss our "Meet the expert" Session on Wednesday, 5 July 2023, 15:45h
with Prof. Antonio Lanzavecchia
"Broadly neutralising antibodies, and beyond"

and

the Special Lecture Session on Thursday, 6 July 2023, 16:00h
with Prof. Dr. Maria R. Lukatskaya
“Engineering local chemical environments for sustainable energy technologies”


Quick Links
- Registration: https://www.wirm.ch/registration-abstracts/
- Confirmed Speakers: https://www.wirm.ch/topics-speakers-talk-titles-2/
- Programs: https://www.wirm.ch/program-2/

26/06/2023

Congratulations to Duygu Yazici for her presentation entitled “Novel biomarkers of disrupted gut permeability in severe COVID-19 patients” at EAACI 2023 held in Hamburg.

Their study aimed to investigate the association between gut barrier dysfunction and severe COVID-19. Serum samples from 327 COVID-19 patients and 49 healthy controls were analyzed for markers of gut barrier dysfunction and bacterial DNA. The results showed that all COVID-19 patient groups had significantly increased levels of circulating markers of gut barrier dysfunction compared to healthy controls. Severe COVID-19 patients had significantly elevated levels of circulating bacterial DNA compared to other patient groups. Additionally, certain proteins were identified as potential biomarkers for disease severity and progression. These findings suggest that biomarkers related to gut barrier integrity may offer valuable information for predicting disease severity in COVID-19 patients at the time of hospital admission.

Duygu Yazici

Photos from Swiss Institute of Allergy and Asthma Research's post 23/06/2023

Urszula Radzikowska, Postdoctoral Researcher in the Immune Metabolism Group at SIAF gave two talks during the recent EAACI Annual Congress 2023 in Hamburg.

She presented her first-author original research describing rhinovirus-induced epithelial RIG-I inflammasome activation, which suppressed antiviral immunity and promotes inflammation in asthma and COVID-19 recently published in Nature Communications. There, authors show that i) rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance, and unresolved inflammation in vitro and in vivo; ii) pre-exposure to house dust mites augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses, and iii) prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Additionally, as Secretary of the EAACI Working Group on Genomics and Proteomics, she presented a talk entitled “Omics technologies in allergy and asthma research”. Both talks are available on demand in EAACI Hybrid Congress 2023 app.

For more info about the immune metabolism group at SIAF: https://www.siaf.uzh.ch/immune_metabolism.html

Presented works:
Radzikowska et al. Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19. Nature Communications 2023 Apr 22;14(1):2329. https://doi.org/10.1038/s41467-023-37470-4

Radzikowska, Ding, et al. Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors. Allergy. 2020; 00: 1– 16. https://doi.org/10.1111/all.14429.

Radzikowska, et al. Omics technologies in allergy and asthma research: An EAACI position paper. Allergy. 2022; 77: 2888- 2908. doi: 10.1111/all.15412

-19

22/06/2023

Congratulations to Yagiz Pat for his presentation entitled “Epithelial Barrier Effecting Compounds with Gut-on-a-chip System” at EAACI 2023 held in Hamburg.

He talked about their recent work with gut-on-a-chip system which is a state-of-art, high throughput technique for assessing gut barrier function in a 3D culture model. They screened food additives such as emulsifiers, food colourants and artificial sweeteners. They detected several barrier-disrupting food additive compounds. They have decreased the barrier function and they have a cytotoxic effect on cells.

17/06/2023

Congratulations to Ismail Ogulur, one of our junior group leaders, for his exciting presentation about recent evidence and molecular mechanisms on epithelial barrier theory.

In the last 60 years, human and domestic animal health has been challenged by continuous exposure to toxic substances and pollutants because of uncontrolled growth, modernization, and industrialization. More than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their health effects and toxicity. A plethora of studies shows exposure to these harmful substances during this period with their implications on the skin and mucosal epithelial barrier and increasing prevalence of allergic and autoimmune diseases in the context of the "epithelial barrier theory". Exposure to these substances causes an epithelial injury with peri-epithelial inflammation, microbial dysbiosis, and bacterial translocation to sub-epithelial areas and immune response to dysbiotic bacteria.

For more information about epithelial barrier theory: Akdis C. A. (2021). Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?. Nature reviews. Immunology, 21(11), 739–751.
https://doi.org/10.1038/s41577-021-00538-7

17/06/2023

The editors of EAACI journals side by side!
EAACI has three official Journals published by Wiley: Allergy Journal which is currently the leading journal in the field of Allergy; Pediatric Allergy and Immunology and Clinical and Translational Allergy, a fully open-access journal.

Quick links:
Allergy: https://journalallergy.com/

Pediatric Allergy and Immunology (PAI): https://onlinelibrary.wiley.com/journal/13993038

Clinical and Translational Allergy (CTA): https://onlinelibrary.wiley.com/journal/20457022

Cezmi Akdis

15/06/2023

Congratulations to Milena Sokolowska, our group head of Immune metabolism, for her outstanding presentation about the Crosstalk of innate immunity and immune metabolism in allergic disease.

Their recent study investigated the response to viral infections in patients with asthma, specifically focusing on rhinovirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They found that rhinovirus infection in asthmatic patients led to excessive activation of the RIG-I inflammasome, impairing the type I/III interferon responses. This resulted in a delayed resolution of inflammation, prolonged viral clearance, and unresolved inflammation both in vitro and in vivo. Additionally, pre-exposure to house dust mites further enhanced this effect by priming the inflammasome and inhibiting early interferon responses. Their study suggests that timely inhibition of the epithelial RIG-I inflammasome could improve viral clearance and reduce the burden of rhinovirus and SARS-CoV-2 infections.

For more info about the immune metabolism group at SIAF: https://www.siaf.uzh.ch/immune_metabolism.html

Their recent work:
Radzikowska, Urszula et al. “Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.” Nature communications vol. 14,1 2329. 22 Apr. 2023, doi:10.1038/s41467-023-37470-4
https://doi.org/10.1038/s41467-023-37470-4

15/06/2023

We had an amazing time at EAACI 2023, representing SIAF and actively engaging in the congress. It was an enriching experience filled with insightful discussions and valuable connections. As SIAF, we felt privileged to have been part of this fantastic event. Looking forward to more exciting collaborations and advancements in the field of allergology and immunology!

More about us: https://www.siaf.uzh.ch/

03/06/2023

We have a new member!

Ozge Ardicli earned her Bachelor’s degree in the Faculty of Veterinary Medicine at Bursa Uludag University, Turkiye. Ozge received her Ph.D. degree in the Department of Microbiology at the same institution in 2021. Her primary research interests are the molecular diagnosis of diseases and bacterial and viral pathogens of livestock. Ozge has joined SIAF in the B cell and Immune Regulation Research Group led by Dr. Willem Van de Veen and Prof. Dr. Mübeccel Akdis. She will study the effects of cow’s milk proteins on eosinophilic esophagitis organoid models.

25/05/2023

We have a new member!

Carina Keßler is a current Master student of Molecular Biotechnology at Heidelberg University, Germany, where she earned her beachelor's degree last year. She is joining the Molecular Allergology group at SIAF for a lab rotation. Her focus will be on identifying and validating previously unknown prenylation states of various proteins. Therefore, she will be establishing immunoprecipitation assays, and join the course "Biomedical Data Mining" in the group of Katja Baerenfaller.

22/05/2023

An original article entitled “Skin Distress Screening: Validation of an Efficient One-question Tool” with the contributions of members.

Blom, T., Fieten, K. B., Kemperman, P. M. J. H., Spillekom-van Koulil, S., & Dikmans, R. E. G. (2023). Skin Distress Screening: Validation of an Efficient One-question Tool. Acta dermato-venereologica, 103, adv4590.

https://doi.org/10.2340/actadv.v103.4590

Skin diseases are often accompanied by physical, emotional and social problems, which may negatively impact health-related quality of life and result in skin-related distress. It is essential to identify patients with skin-related distress within the short time-window of an outpatient dermatological visit. Therefore the one-question screening tool, the Distress Thermometer adjusted for skin conditions, was validated in a cross-sectional questionnaire study. In 2 medical centres in Amsterdam, 214 patients with a chronic skin disease were invited to complete the Distress Thermometer and additional health-related quality of life questionnaires. To validate the Distress Thermometer, the Skindex29 was used as gold standard. To test test–retest reliability, the questionnaires were answered at 2 different time-points. Severely impaired health-related quality of life was present in 30% of respondents according to the Skindex29 using a cut-off score of 44. Receiver operating characteristic curve analyses yielded an area under the curve of 0.813 (standard error 0.04, 95% confidence interval 0.74–0.89). A cut-off score ≥ 4 on the Distress Thermometer provided the optimal ratio of sensitivity (90.7%) to specificity (56.1%). Therefore, for general practice, a cut-off score of ≥ 4 on the Distress Thermometer is advised. The Distress Thermometer seems to be a rapid, valid and reliable screening tool for identifying skin-related distress in patients with a chronic skin disease in the outpatient dermatology setting.

12/05/2023

Do not miss the chance to register for WIRM XVII 2023.

Only a few days are left for the Late Breaking Abstract Submission, open until 16 May 2023! There are still some slots for short talks, workshops, and posters.

If you have new and exciting research results in the field of Immune Regulation, grab the opportunity to be part of this year’s conference and join the experts from all over the world.

Quick Links
- Registration: https://lnkd.in/eDUM4BDF
- Abstract Submission: https://lnkd.in/eDUM4BDF
- Confirmed Speakers: https://lnkd.in/eDHPqDYB
- Prizes & Grants: https://lnkd.in/ewg23msH

11/05/2023

We have a new member!
Sena Ardicli earned his Bachelor’s degree in the Faculty of Veterinary Medicine at Bursa Uludag University, Turkiye. He received his Ph.D. degree in 2015 at the same institution. He is an associate professor at the Bursa Uludag University, Faculty of Veterinary Medicine, Department of Genetics in Turkiye. His primary research fields are genetic markers related to quantitative traits, genomic selection, and gene regulation in livestock species. He has joined SIAF in the Immunology Research Group led by Prof. Dr. Cezmi Akdis. He will study the effects of cow milk on epithelial cells via organoids and organ-on-chips.

Photos from Swiss Institute of Allergy and Asthma Research's post 03/05/2023

SIAF had the pleasure of welcoming distinguished guests, namely the President of the European Academy of Allergy and Clinical Immunology (EAACI), Prof. Dr. Stefano Del Giacco, Cagliari University, the Secretary General of the EAACI, Prof. Dr. Maria Jose Torres from Malaga University, EAACI Vice-President Congresses, Prof. Dr. Mohamed Shamji from Imperial College, London, and the Scientific Programme Committee Co-Chair of the EAACI congresses, Prof. Dr. André Moreira from Porto University. A scientific symposia was organized in addition to many bilateral meetings. Immunomodulation in allergic patients and novel diagnosis, biologics in Asthma, artificial intelligence for biomarker discovery and role of environmental factors in allergy development were discussed. EAACI is the world's biggest society in allergology and clinical immunology with 15'000 members. It's journal Allergy is being developed inside the SIAF since 2018. Allergy is the number one journal of the specialty in the world and one of the highest impact factor scientific journal developed inside Switzerland. Prof. Mübeccel Akdis from SIAF, the EAACI Scientific Programme Committee Co-Chair of the EAACI hosted the esteemed guests and organized the symposium.

29/04/2023

We have a new member!

Inés Jardón Parages earned her Bachelors and Master degree in Biochemistry at the University of St Andrews, Scotland. As part of her degree, she spent a year working at GSK’s Biopharmaceutical Process Development department, where she used metabolomics to find biomarkers that would allow earlier selection of their cell lines. During her Masters she worked in the field of Innate Immunity against Viral infections, paramyxoviruses in particular. She has joined SIAF as a PhD student in the Immunometabolism group led by Milena Sokolowska. For her project, she will be studying the metabolism of airway epithelium from patients with asthma at baseline and during viral infections.

23/04/2023

Join the discussion with Cezmi Akdis, editor of the journal Allergy and director of the Swiss Institute of Allergy and Asthma Research, University Zurich as we discuss the role of microplastics, household chemicals, and processed foods in allergic diseases.

https://www.parentsforeczemaresearch.com/podcast

Research discussed in this podcast:

Boston Globe: Scrubbing away our collective health

Nature Reviews Immunology: Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?

J Allergy Cininical Immunlogy: Gut epithelial barrier damage caused by dishwasher detergents and rinse aids

Allergy: Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease


Cezmi Akdis

22/04/2023

A letter to the editor entitled “How Can Allergen Immunotherapy Protect Against COVID-19?” from members.

https://doi.org/10.1164/rccm.202302-0317LE

Sokolowska M, Radzikowska U. How Can Allergen Immunotherapy Protect Against COVID-19? Am J Respir Crit Care Med. 2023 Mar 29. doi: 10.1164/rccm.202302-0317LE. Epub ahead of print. PMID: 36989503.

20/04/2023

Late-breaking abstracts are open now!
Thank you all for already submitting so many interesting abstracts. Your enthusiasm to share your latest research gives us great pleasure.

We received one of the highest numbers of abstracts again this year. 22 Short Talks in the plenary session and 78 Workshop Talks have been selected. In addition, we will have 12-15 Poster Walks in Dip & Discuss Evening Sessions.

We are ready for a great scientific program and to welcome you on the 5th of July. To bring in the most recent science, we will accept late-breaking abstracts until the 16th of May.

Quick Links
- Registration: https://www.wirm.ch/registration-abstracts/
- Abstract Submission: https://www.wirm.ch/registration-abstracts/
- Confirmed Speakers: https://www.wirm.ch/topics-speakers-talk-titles/
- Prizes & Grants: https://www.wirm.ch/prizes-grants/

17/04/2023

An original article entitled “Spermidine ameliorates colitis via induction of anti-inflammatory macrophages and prevention of intestinal dysbiosis” with the contributions of members.

Niechcial A, Schwarzfischer M, Wawrzyniak M, Atrott K, Laimbacher A, Morsy Y, Katkeviciute E, Häfliger J, Westermann P, Akdis CA, Scharl M, Spalinger MR. Spermidine ameliorates colitis via induction of anti-inflammatory macrophages and prevention of intestinal dysbiosis. J Crohns Colitis. 2023 Mar 30:jjad058. doi: 10.1093/ecco-jcc/jjad058. Epub ahead of print. PMID: 36995738.

https://doi.org/10.1093/ecco-jcc/jjad058

Exacerbated immune activation, intestinal dysbiosis, and a disrupted intestinal barrier are common features among inflammatory bowel disease (IBD) patients. The polyamine spermidine, which is naturally present in all living organisms, is an integral component of the human diet, and exerts beneficial effects in human diseases. Here, the authors investigated whether spermidine treatment ameliorates intestinal inflammation and offers therapeutic potential for IBD treatment.
Spermidine administration protected mice from intestinal inflammation in a dose-dependent manner. While T helper cell subsets remained unaffected, spermidine promoted anti-inflammatory macrophages and prevented the microbiome shift from Firmicutes and Bacteroides to Proteobacteria, maintaining a healthy gut microbiome. Consistent with spermidine as a potent activator of the anti-inflammatory molecule protein tyrosine phosphatase non-receptor type 2 (PTPN2), its colitis-protective effect was dependent on PTPN2 in intestinal epithelial cells and in myeloid cells. The loss of PTPN2 in epithelial and myeloid cells, but not in T cells, abrogated the barrier-protective, anti-inflammatory effect of spermidine and prevented the anti-inflammatory polarization of macrophages.
Spermidine reduces intestinal inflammation by promoting anti-inflammatory macrophages, maintaining a healthy microbiome, and preserving epithelial barrier integrity in a PTPN2-dependent manner.

Patrick Westermann Cezmi Akdis

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