Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention

Skinner, Charlotte; Thompson, Alexander; Thursz, Mark; Marchesi, Julian; Vergis, Nikhil

doi:10.1177/1756284820942616

Cited by 23 publications

(21 citation statements)

References 127 publications

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“…The gut barrier dysfunction could increase the microbial translocation into blood [ 45 ], which plays a key role in activating the systemic immune response [ 46 ]. We therefore measured the bacterial proteins in blood samples in our COVID-19 patients.…”

Section: Resultsmentioning

confidence: 99%

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients

Sun

Song

Liu

et al. 2022

BMC Med

112

113

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Background COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. Methods To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients. Results Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. Conclusions Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.

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Section: Resultsmentioning

confidence: 99%

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients

Sun

Song

Liu

et al. 2022

BMC Med

112

113

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“…An alteration in intestinal microbiomes, which is the supported mechanism of ACLF, was also observed in patients with non-cirrhosis CLD and alcohol-related liver disease by many recent literatures [ 28 – 30 ]. Increasing evidence of an imbalance of gut microbiota and bacterial translocation was frequently found in alcoholic CLD [ 31 – 33 ]. These might be the possible explanations for why non-cirrhosis had a poorer prognosis in patients with alcoholic CLD.…”

Section: Discussionmentioning

confidence: 99%

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure

et al. 2021

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Background and aims Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. Methods A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. Results Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36–0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43–0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. Conclusions The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

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“…These experimental data provide evidence of long-term antibiotic-induced impairment of intestinal permeability that facilitates the translocation of pathogenic bacteria, antigens, and other microbial products to the systemic circulation leading to chronic inflammation ( Johnson et al, 2015 ; Poole et al, 2017 ; Sharapatov et al, 2021 ). Gut microbiota-derived inflammation, so-called metabolic endotoxemia, has been recently demonstrated to play a key role in the pathogenesis of many diseases such as obesity, type 2 diabetes, pancreatitis, cardiovascular, systemic, kidney, liver, and bone diseases, as well as brain and mental disorders ( Durack and Lynch, 2019 ; Barbosa and Barbosa, 2020 ; Ilchmann-Diounou and Menard, 2020 ; Ren et al, 2020 ; Skinner et al, 2020 ; Zhou et al, 2020 ). Interestingly, endotoxemia and low-level inflammation caused by increased intestinal permeability have also been demonstrated in psychological stress and depression, which often coexist with RUTIs ( de Punder and Pruimboom, 2015 ; Trzeciak and Herbet, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections

Stepanova

2022

Front. Pharmacol.

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A comprehensive understanding of urinary tract infections (UTIs), one of the most common human infections, is required as they are complex and poorly understood diseases. Periurethral and vaginal colonization by rectal flora, with the constant presence of pathogens in the urethra, is the initial step of the recurrent UTIs pathway. Current scientific data describe the genetic, etiological, biological, and behavioral risk factors for recurring UTIs, but they do not include the effect of intestinal barrier function on the disease. Although gut microbiota has been proposed as the main source for UTIs, the cross-talk between intestinal barrier dysfunction and the recurrence of UTIs has not yet been supported by scientific data. In this opinion review, based on published data and the results of our clinical studies, I aimed to outline the possible contribution of intestinal barrier dysfunction to the pathogenesis of recurrent UTIs. I believe that the unanswered questions raised by this review can guide further experimental and controlled studies to clarify the mechanisms underlying the role of intestinal barrier dysfunction in the pathogenesis of recurrent UTIs.

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Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention

Cited by 23 publications

References 127 publications

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure

How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections

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