Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis
Gut
by Liu, J., MacNaughtan, J., Kerbert, A. J. C., Portlock, T., Martinez Gonzalez, J., Jin, Y., Clasen, F., Habtesion, A., Ji, H., Jin, Q., Phillips, A., De Chiara, F., Ingavle, G., Jimenez, C., Zaccherini, G., Husi, K., Rodriguez Gandia, M. A., Cordero, P., Soeda, J., McConaghy, L., Oben, J., Church, K., Li, J. V., Wu, H., Jalan, A., Gines, P., Sola, E., Eaton, S., Morgan, C., Kowalski, M., Green, D., Gander, A., Edwards, L. A., Cox, I. J., Cortez-Pinto, H., Avery, T., Wiest, R., Durand, F., Caraceni, P., Elosua, R., Vila, J., Pavesi, M., Arroyo, V., Davies, N., Mookerjee, R. P., Vargas, V., Sandeman, S., Mehta, G., Shoaie, S., Marchesi, J., Albillos, A., Andreola, F., Jalan, R.
2w ago
Objective Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. Design Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosi ..read more
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High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT
Gut
by Bu, L., Zhang, Z., Chen, J., Fan, Y., Guo, J., Su, Y., Wang, H., Zhang, X., Wu, X., Jiang, Q., Gao, B., Wang, L., Hu, K., Zhang, X., Xie, W., Wei, W., Kuang, M., Guo, J.
2w ago
Objective Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC. Design Metabolite library screening disclosed that palmitic acid (PA) could activate AKT. In vivo and in vitro palmitoylation assay were employed to detect AKT palmitoylation. Diverse cell and mouse models, including generation of AKT1C77S and AKT1C224S knock-in cells, Zdhhc17 and Zdhhc24 k ..read more
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HBV integrations reshaping genomic structures promote hepatocellular carcinoma
Gut
by Qian, Z., Liang, J., Huang, R., Song, W., Ying, J., Bi, X., Zhao, J., Shi, Z., Liu, W., Liu, J., Li, Z., Zhou, J., Huang, Z., Zhang, Y., Zhao, D., Wu, J., Wang, L., Chen, X., Mao, R., Zhou, Y., Guo, L., Hu, H., Ge, D., Li, X., Luo, Z., Yao, J., Li, T., Chen, Q., Wang, B., Wei, Z., Chen, K., Qu, C., Cai, J., Jiao, Y., Bao, L., Zhao, H.
2w ago
Objective Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. Design Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic r ..read more
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B and T cell responses to the BNT162b2 COVID-19 mRNA vaccine are not impaired in germ-free or antibiotic-treated mice
Gut
by Norton, T., Lynn, M. A., Rossouw, C., Abayasingam, A., Perkins, G., Hissaria, P., Bull, R. A., Lynn, D. J.
2w ago
As reviewed by us recently,1 an increasing number of studies suggest that the gut microbiota is an important regulator of immune responses to vaccination. Consistent with these data, several recent clinical studies,2–4 including three published in Gut,5–7 uncover correlations between the composition of the faecal/gut microbiota and antibody responses to different COVID-19 vaccines. Additionally, recent antibiotic usage has also been associated with a lower seroconversion rate following BNT162b2 vaccination.8 These studies suggest that the gut microbiota plays a significant role in regulating o ..read more
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It is in the matrix: a molecular clue to fibro-stenotic Crohns disease
Gut
by Adolph, T. E.
2w ago
Stricturing Crohn’s disease (CD), a consequence of fibrosis occurring during chronic unresolved gut inflammation, is a common problem in clinical praxis for which we currently lack targeted medical therapy.1 Patients typically present with obstructive bowel symptoms and radiographic signs of a stricture that is commonly (but not exclusively) located in the terminal ileum or at the ileocecal valve.2 Histopathology of the stricture reveals CD features, such as submucosal fibrosis by excess extracellular matrix deposition, fibromuscular hyperplasia, chronic transmural inflammation and epithelioid ..read more
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Clarithromycin-containing triple therapy for Helicobacter pylori eradication is inducing increased long-term resistant bacteria communities in the gut
Gut
by Sjomina, O., Vangravs, R., Leonova, E., Polaka, I., Pupola, D., Civkulis, K., Jeniceka, A., Parsutins, S., Stonans, I., Park, J. Y., Engstrand, L., Leja, M.
2w ago
The current European guidelines (Maastricht VI/Florence consensus report) on the management of Helicobacter pylori infection1 recommend population-based H. pylori screening programmes for asymptomatic individuals in the general population to eradicate the microorganism for gastric cancer prevention. However, this is expected to result in a considerable increase in antibiotic use2 as half of the global population are estimated to be infected.3 Therefore, the guidelines suggest that caution is required in choosing the appropriate antibiotics to minimise antimicrobial resistance.1 The importance ..read more
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Temporal trend of mortality in patients with cirrhosis with primary biliary cholangitis and primary sclerosing cholangitis during the COVID-19 pandemic
Gut
by He, X., Gao, N., Lv, F., Wu, F., Liu, Y., Li, L., Ayoub, W. S., Yeo, Y. H., Ji, F.
2w ago
We read with interest the study by Ampuero et al1 on the vulnerability of primary biliary cholangitis (PBC) patients to SARS-CoV-2. Their study, conducted on patients from 13 referral hospitals, highlighted a heightened risk of infection and hospitalisation compared with the general population. However, we propose that their patient selection may inadvertently over-represent severe cases, thus introducing selection bias. Using the CDC WONDER, a database with deidentified death records that included >99% of decedents in the USA, data associated with cirrhosis among adults aged 25 years and a ..read more
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Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial
Gut
by Zhu, J., Sun, C., Li, M., Hu, G., Zhao, X.-M., Chen, W.-H.
2w ago
Objective We aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis. Design Healthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing. We analysed intervention-induced alterations in the oral and gut microbiome including microbial abundance and growth rates, oral-to-gut transmissions, and compared differences be ..read more
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Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study
Gut
by Xiao, X., Zhang, X., Wang, J., Liu, Y., Yan, H., Xing, X., Yang, J.
2w ago
Background The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation. Methods Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on ..read more
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Novel transcriptomic panel identifies histologically active eosinophilic oesophagitis
Gut
by Gueguen, E., Morsy, Y., Mamie, C., Schoepfer, A., Saner, C., Biedermann, L., Straumann, A., Kreienbühl, A., Swiss EoE Cohort Study Group, Scharl, M., Wawrzyniak, M., Aepli, Biedermann, Biral, Blanchard, Botteselle, Borovicka, Buetikofer, Burri, Diebold, Eckhold, Franke, Frei, Greuter, Hasler, Jochum, Kilchmann, Koller, Kreienbühl, Netzer, Pelzer, Reichhart, Ristorcelli, Rogler, Rossel, Safroneeva, Saner, Senn, Schoepfer, Schreiner, Sempoux, Simon, Simon, Straumann, Trelle, Weber, Willi, Zwahlen
2w ago
Background and aims Eosinophilic oesophagitis (EoE) is characterised by symptoms of esophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a set of 77 genes. Recently, the existence of distinct EoE variants featuring symptoms similar to EoE, such as oesophageal dysfunction but lacking eosinophil infiltration, had been determined. Methods We used oesophageal biopsies from patients with histologically active (n=10) and non-active EoE (n=9) as well as from healthy oesophageal controls (n=5) participating in ..read more
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