Impact of
                    <scp>YAQ001</scp>
                    on the Gut Microbiome, Permeability and Markers of Systemic Inflammation in Patients With Cirrhosis

doi:10.1111/liv.70933

DOI: 10.1111/liv.70933 ISSN: 1478-3223

Impact of YAQ001 on the Gut Microbiome, Permeability and Markers of Systemic Inflammation in Patients With Cirrhosis

Jinxia Liu, Fernando Garcia‐Guevara, Jane Macnaughtan, Yi Jin, Ainhoa Ferret‐Miñana, Frederick Clasen, Nicholas Yuen, Ramón Garcia Maset, Javier Ramón‐Azcón, Annarein J. C. Kerbert, Theo Portlock, Javier Martinez, Abeba Habtesion, Alexandra Phillips, Francesco De Chiara, Ganesh Ingavle, Tom Baldwin, Cesar Jimenez, Giacomo Zaccherini, Katherine Husi, Miguel Rodriguez‐Gandia, Paul Cordero‐Sanchez, Junpei Soeda, Jude A. Oben, Karen Church, Jia V. Li, Aarti Jalan, Adria Juanola, Elsa Sola, Simon Eaton, Carrie Morgan, Thomas Avery, Michal Kowalski, Daniel Green, Amir Gander, Lindsey Ann Edwards, I. Jane Cox, Helena Cortez‐Pinto, Reiner Wiest, Francois Durand, Paolo Caraceni, Roberto Elosua, Joan Vila, Marco Pavesi, Vicente Arroyo, Nathan Davies, Rajeshwar P. Mookerjee, Susan Sandeman, Gautam Mehta, Julian R. Marchesi, Agustin Albillos, Jennifer L. Rohn, Fausto Andreola, Saeed Shoaie, Rajiv Jalan

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ABSTRACT

Background & Aims

YAQ001 is a novel, non‐absorbable, gut‐restricted, multiporous, carbon bead adsorbent. Pre‐clinical studies and a clinical trial suggested its therapeutic potential and safety in patients with cirrhosis. This substudy aimed to explore the effects of YAQ001 on the gut microbiome and their exploratory association with biomarkers of gut permeability and systemic inflammation.

Methods

Twenty‐eight‐patients with cirrhosis were randomized (double‐blind) to receive YAQ001 (4 g once daily) or placebo. Gut microbiome and biomarkers of inflammation and gut permeability were assessed at baseline, after 4 and 12 weeks. Changes in biomarkers and relationship with microbiome composition and gene profiling were assessed. The effect of YAQ001 on Klebsiella pneumoniae biofilms was assessed in vitro.

Results

Overall alpha and beta diversity remained unaltered. YAQ001 increased the abundance of bacteria associated with improved gut health such as Adlercreutzia equolifaciens , a bacterium commonly depleted in liver disease, and decreased the abundance of bacteria associated with infections and poor outcomes such as Klebsiella pneumonia , and Streptococcus mutans . YAQ001 impacted positively on virulence factors such as siderophores, fimbriae structures, and lipopolysaccharides that are associated with inflammation and invasion. Antibiotic resistance genes decreased significantly in the YAQ001 group. These changes were associated with a reduction in markers of gut permeability and systemic inflammation. YAQ001 prevented K. pneumoniae biofilms in vitro.

Conclusion

YAQ001 was associated with favourable compositional shifts and trends towards reduced virulence‐related gene signatures in the gut microbiome, alongside trends towards improved inflammatory biomarkers. The in vitro anti‐biofilm effect of YAQ001 warrants further mechanistic investigation. The findings position YAQ001 as a potential microbiome therapeutic.