Zonulin, a marker of gut permeability, is associated with mortality in a cohort of hospitalised peruvian COVID-19 patients

Palomino-Kobayashi, Luciano A.; Ymaña, Barbara; Ruiz, Joaquı́m; Mayanga-Herrera, Ana; Ugarte‐Gil, Manuel F.; Pons, María J.

doi:10.3389/fcimb.2022.1000291

Cited by 15 publications

(9 citation statements)

References 50 publications

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“…Zonulin is released in plasma after intestinal barrier disruption and is also considered a diagnostic marker of intestinal dysbiosis. 43 Our finding of elevated plasma zonulin in statins users supports these reports because statins can induce dysbiosis of intestinal microbes in experimental animal models. 44 Interestingly, a mechanistic relation between statins and intestinal barrier dysfunction has also been reported because atorvastatin reduces the expression of tight junction proteins in colonic epithelial cells.…”

Section: Discussionsupporting

confidence: 85%

Statin Therapy Induces Gut Leakage and Neuromuscular Disjunction in Patients With Chronic Heart Failure

Ahmad

Karim

Khan

et al. 2023

Journal of Cardiovascular Pharmacology

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Statins are commonly used to limit the risk of cardiovascular diseases, including ischemic heart attack and stroke. However, treatment often leads to myopathy and muscle weakness. Therefore, a better understanding of underlying pathomechanism is needed to improve the clinical outcomes. Here, we assessed the physical performance, including handgrip strength (HGS), gait speed (GS), and short physical performance battery, in 172 patients diagnosed with chronic heart failure (CHF) treated with (n = 50) or without (n = 122) statin and 59 controls. The plasma biomarkers, including sarcopenia marker C-terminal agrin fragment-22 (CAF22), intestinal barrier integrity marker zonulin, and C-reactive protein (CRP), were measured and correlated with the physical performance of patients. The HGS, short physical performance battery scores, and GS were significantly compromised in patients with CHF versus controls. Irrespective of etiology, significant elevation of plasma CAF22, zonulin, and CRP was observed in patients with CHF. There were strong inverse correlations of CAF22 with HGS (r 2 = 0.34, P , 0.0001), short physical performance battery scores (r 2 = 0.08, P = 0.0001), and GS (r 2 = 0.143, P , 0.0001). Strikingly, CAF22 and zonulin were positively correlated with each other (r 2 = 0.10, P = 0.0002) and with the level of CRP in patients with CHF.Further investigations revealed a significant induction of CAF22, zonulin, and CRP in patients with CHF taking statin versus nonstatin group. Consistently, HGS and GS were significantly lower in the statin versus nonstatin CHF patients' group. Collectively, statin therapy adversely affects the neuromuscular junction and intestinal barrier, which potentially induces systemic inflammation and physical disability in patients with CHF. Further prospective confirmation of the findings is required in a well-controlled study.

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Section: Discussionsupporting

confidence: 85%

Statin Therapy Induces Gut Leakage and Neuromuscular Disjunction in Patients With Chronic Heart Failure

Ahmad

Karim

Khan

et al. 2023

Journal of Cardiovascular Pharmacology

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“…The dysbiosis of gut microbiota directly contributes to increased gut permeability, thereby facilitating the translocation of pathogenic bacteria and allowing the translocation of bacterial products from the gut into circulation ( Chen et al., 2022 ). Zonulin, LBP and sCD14 have been identified as reliable indicators of gut permeability and bacterial translocation ( Kavanagh et al., 2019 ; Palomino-Kobayashi et al., 2022 ). The Zonulin can be detected in plasma and exhibit a strong correlation with bacterial DNAemia, making it a valuable biomarker for assessing impaired gut barrier function ( Veres-Szekely et al., 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury

Yang,

Xi,

Yao

et al. 2024

Front. Cell. Infect. Microbiol.

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ObjectiveThe current study sought to clarify the role of lysozyme-regulated gut microbiota and explored the potential therapeutic effects of lysozyme on ileum injury induced by severe traumatic brain injury (sTBI) and bacterial pneumonia in vivo and in vitro experiments.MethodsMale 6–8-week-old specific pathogen-free (SPF) C57BL/6 mice were randomly divided into Normal group (N), Sham group (S), sTBI group (T), sTBI + or Lysozyme-treated group (L), Normal + Lysozyme group (NL) and Sham group + Lysozyme group (SL). At the day 7 after establishment of the model, mice were anesthetized and the samples were collected. The microbiota in lungs and fresh contents of the ileocecum were analyzed. Lungs and distal ileum were used to detect the degree of injury. The number of Paneth cells and the expression level of lysozyme were assessed. The bacterial translocation was determined. Intestinal organoids culture and co-coculture system was used to test whether lysozyme remodels the intestinal barrier through the gut microbiota.ResultsAfter oral administration of lysozyme, the intestinal microbiota is rebalanced, the composition of lung microbiota is restored, and translocation of intestinal bacteria is mitigated. Lysozyme administration reinstates lysozyme expression in Paneth cells, thereby reducing intestinal permeability, pathological score, apoptosis rate, and inflammation levels. The gut microbiota, including Oscillospira, Ruminococcus, Alistipes, Butyricicoccus, and Lactobacillus, play a crucial role in regulating and improving intestinal barrier damage and modulating Paneth cells in lysozyme-treated mice. A co-culture system comprising intestinal organoids and brain-derived proteins (BP), which demonstrated that the BP effectively downregulated the expression of lysozyme in intestinal organoids. However, supplementation of lysozyme to this co-culture system failed to restore its expression in intestinal organoids.ConclusionThe present study unveiled a virtuous cycle whereby oral administration of lysozyme restores Paneth cell’s function, mitigates intestinal injury and bacterial translocation through the remodeling of gut microbiota.

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“…It has been reported that SARS-CoV-2 spike stimulates the expression of zonulin, leading to the increase of gut permeability ( Llorens et al, 2021 ). Moreover, it was found that levels of zonulin in patients dying of severe COVID-19 are higher than those in patients recovered from the disease ( Giron et al, 2021 ; Palomino-Kobayashi et al, 2022 ). These data suggest that zonulin might be associated with poor outcomes in COVID-19.…”

Section: Long-term Gi Effects Of Long-covidmentioning

confidence: 99%

Development and management of gastrointestinal symptoms in long-term COVID-19

He,

Lei,

Zhang

et al. 2023

Front. Microbiol.

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BackgroundEmerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine.ObjectiveTo provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients.ResultsLong-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms.ConclusionTimely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.

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Zonulin, a marker of gut permeability, is associated with mortality in a cohort of hospitalised peruvian COVID-19 patients

Cited by 15 publications

References 50 publications

Statin Therapy Induces Gut Leakage and Neuromuscular Disjunction in Patients With Chronic Heart Failure

Statin Therapy Induces Gut Leakage and Neuromuscular Disjunction in Patients With Chronic Heart Failure

Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury

Development and management of gastrointestinal symptoms in long-term COVID-19

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