Geçirgen Bağırsağın COVID-19 Kliniği Üzerinde Etkisinin Araştırılması

Abstract

Amaç: COVID-19 pandemisi sürecinde milyonlarca vakada bazı hastaların herhangi bir semptom göstermediği, bazılarının ise ölümcül sonuçla hastaneye kaldırıldığı gözlemlenmiştir. En önemli bulgulardan biri, komorbiditesi olan hastaların aşırı inflamatuvar yanıta bağlı gelişen ciddi klinik durumlara aşırı derecede maruz kalmasıdır. Yani kronik inflamasyonun belirleyici nedeni, bozulmuş bağırsak mukozal bariyerlerinden türetilen bakteriyel translokasyon olabilir. Bu çalışma, bozulmuş bağırsak bariyeri bütünlüğü ile COVID-19 klinik durumlarının şiddeti ile ilişkilendirilebilecek olası ilişkileri araştırmayı amaçlamaktadır. Gereç ve Yöntemler: Klinik ve laboratuvar bulgularına göre hastalar hafif, orta ve şiddetli klinik durumlar olarak üç gruba ayrılmıştır. Tüm hastalardan kan örnekleri hastaneye ilk başvurularında alınmıştır. Lipopolisakkarit bağlayıcı proteinin (LBP) serum konsantrasyonları, bağırsak bariyer fonksiyonunu ve bakteriyel translokasyonu değerlendirmek için analiz edilmiştir. Bulgular: Tüm gruplar arasında yüksek LBP düzeyine sahip olanların oranları önemli ölçüde farklıydı (p <0,001) (Tablo 1). Hafif hasta grubunda (%65,4) yüksek LBP düzeyleri olan hastaların oranı, orta (%100) ve ciddi klinik durumları (%95,2) olanlara göre anlamlı derecede düşük bulunmuştur (her biri için p <0,05). Sonuç: Son yıllarda bağırsakların fonksiyonlarının sindirim fonksiyonundan çok daha fazla olduğu ve ayrıca bağırsak mikrobiyotası ve mukozal bariyer bütünlüğünün bağışıklık sistemi üzerinde çok büyük etkisi olduğu açıkça ortaya konmuştur. Bu sonuçlar, bozulmuş bağırsak bariyeri bütünlüğünün ve bakteriyel translokasyonun şiddetli COVID-19 gelişiminde etkili olabileceğini düşündürmektedir.

Keywords

• Bakteriyel translokasyon
• COVID-19
• doğal bağışıklık
• geçirgen bağırsak
• SARS-CoV-2

Investigation of the Effect of Leaky Gut on COVID-19 Clinic

Abstract

Aim: In the course of the COVID-19 pandemic, in millions of cases were observed those of some patients do not exhibit any symptoms whereas some others are hospitalized with having fatal outcomes. One of the most significant findings is that patients with existing comorbidities are extremely exposed to severe clinical conditions developed due to excessive inflammatory response. That is to say, the indicative cause of chronic inflammation may be bacterial translocation derived from the impaired intestinal mucosal barriers. This study is aimed to investigate the probable relations between the impaired intestinal barrier integrity and which would be associated with severity of COVID-19 clinical conditions. Material and Methods: According to the clinical and laboratory findings, the patients were classified into three groups as mild, moderate, and severe clinical conditions. All patients’ blood samples were collected on the first admission to the hospital. Serum concentrations of lipopolysaccharide-binding protein (LBP), were analyzed to evaluate the intestinal barrier function and bacterial translocation. Results: The proportions of those with high LBP levels among all the groups were significantly different (p<0.001). The proportion of the patients with high LBP levels in the mild patient group (65.4%) was significantly lower than those with moderate (100%) and with severe clinical conditions (95.2%) (p<0.05 for each). Conclusion: In recent years, it has been clearly demonstrated that the functions of the intestines are much more than the digestive function, and that the intestinal microbiota and mucosal barrier integrity have a great impact on the immune system. These results would indicate that the impaired intestinal barrier integrity and bacterial translocation might be effective in severe COVID-19 development.

Keywords

• Bacterial translocation
• COVID-19
• innate immunity
• leaky gut
• SARS-CoV-2

References

1. Chiappetta S, Sharma AM, Bottino V, Stier C. COVID-19 and the role of chronic inflammation in patients with obesity. Int J Obes. 2020; 44: 1790-2.
2. Janda L, Mihalcin M, Stastna M. Is a healthy microbiome responsible for lower mortality in COVID-19? Biologia. 2021; 76: 819-29. https://link.springer.com/article/10.2478/s11756-020-00614-8
3. Fasano A. Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity and cancer. Physiol Rev. 2011; 91: 151-75. https://www.tandfonline.com/doi/full/10.1080/21688370.2016.1251384
4. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009; 9(11):799-809.
5. Ruiz GA, Casafont F, Crespo J, Cayon A, Mayorga M, Estebanez A, et al. Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: Evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes Surg. 2007; 17: 1374-80.
6. Lim PS, Chang YK & Wu TK. Serum Lipopolysaccharide-binding protein is associated with chronic inflammation and metabolic syndrome in hemodialysis patients. Blood Purif. 2019; 47: 28-36.
7. Grossberg AN, Koza LA, Ledreux A, Prusmack C, Krishnamurthy HK, Jayaraman V, et al. A multiplex chemiluminescent immunoassay for serological profiling of COVID-19-positive symptomatic and asymptomatic patients. Nat Commun. 2021; 12: 740.
8. Loconsole D, Passerini F, Ostilio PV, Centrone F, Sallustio A, Pugliese S, et al. Recurrence of COVID-19 after recovery: a case report from Italy. Infection. 2020; 48: 965-7. Abdool Karim SS, de Oliveira T. New SARS-CoV-2 variants - clinical, public health, and vaccine implications. N Engl J Med. 2021; 384(19): 1866-8.

9. Karim SSA. Vaccines and SARS-CoV-2 variants: the urgent need for a correlate of protection. Lancet. 2021; 3: 397.
10. Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus. Cell. 2020; 182: 812-27.
11. Schumann, R. R. Old and new findings on lipopolysaccharide-binding protein: A soluble pattern-recognition molecule. Biochem Soc Trans. 2011; 39: 989-93.
12. Citronberg JS, Wilkens LR, Marchand LL, Lim U, Monroe KR, Hullar MAJ, et al. Plasma lipopolysaccharide-binding protein and colorectal cancer risk: a nested case-control study in the Multiethnic Cohort. Cancer Causes Control. 2018; 29: 115–23.
13. Giron LB, Dweep H, Yin X, Wang H, Damra M, Goldman AR, et al. Severe COVID-19 is fueled by disrupted gut barrier integrity. MedRxiv [Internet]. 2020 Jan 1;2020.11.13.20231209. Available from: http://medrxiv.org/content/early/2020/11/16/2020.11.13.20231209.abstract
14. Ferreira TB, Hygino J, Barros PO, Teixeira B, Kasahara TM, Linhares UC, et al. Endogenous interleukin-6 amplifies interleukin-17 production and corticoid-resistance in peripheral T cells from patients with multiple sclerosis. Immunology. 2014; 143: 560-8.
15. Escribano BM, Medina-Fernandez FJ, Aguilar-Luque M, Agüera E, Feijoo M, Garcia-Maceira FI, et al. Lipopolysaccharide binding protein and oxidative stress in a multiple sclerosis model. Neurotherapeutics. 2017; 14(1): 199-211.
16. Belizario JE, Faintuch J, Garay-Malpartida M. Gut microbiome dysbiosis and immunometabolism: New frontiers for treatment of metabolic diseases. Mediators Inflamm. 2018; 2037838.