O091 : Oral therapy with non-absorbable carbons of controlled porosity (YAQ-001) selectively modulates stool microbiome and its function and this is associated with restoration of immune function and inflammasome activation

Gottardi

Rescigno

2020

Journal of Hepatology

1,263

881

The gut-liver axis refers to the bidirectional relationship between the gut and its microbiota, and the liver, resulting from the integration of signals generated by dietary, genetic and environmental factors. This reciprocal interaction is established by the portal vein which enables transport of gut-derived products directly to the liver, and the liver feedback route of bile and antibody secretion to the intestine. The intestinal mucosal and vascular barrier is the functional and anatomical structure that serves as a playground for the interactions between the gut and the liver, limiting the systemic dissemination of microbes and toxins while allowing nutrients to access the circulation and to reach the liver. The control of microbial communities is critical to maintaining homeostasis of the gut-liver axis, and as part of this bidirectional communication the liver shapes intestinal microbial communities. Alcohol disrupts the gut-liver axis at multiple interconnected levels, including the gut microbiome, mucus barrier, epithelial barrier and at the level of antimicrobial peptide production, which increases microbial exposure and the proinflammatory environment of the liver. Growing evidence indicates the pathogenetic role of microbe-derived metabolites, such as trimethylamine, secondary bile acids, short-chain fatty acids and ethanol, in the pathogenesis of non-alcoholic fatty liver disease. Cirrhosis by itself is associated with profound alterations in gut microbiota and damage at the different levels of defence of the intestinal barrier, including the epithelial, vascular and immune barriers. The relevance of the severe disturbance of the intestinal barrier in cirrhosis has been linked to translocation of live bacteria, bacterial infections and disease progression. The identification of the elements of the gut-liver axis primarily damaged in each chronic liver disease offers possibilities for intervention. Beyond antibiotics, upcoming therapies centred on the gut include new generations of probiotics, bacterial metabolites (postbiotics), faecal microbial transplantation, and carbon nanoparticles. FXR-agonists target both the gut and the liver and are currently being tested in different liver diseases. Finally, synthetic biotic medicines, phages that target specific bacteria or therapies that create physical barriers between the gut and the liver offer new therapeutic approaches.

Section: Key Pointsmentioning

confidence: 91%

The gut-liver axis in liver disease: Pathophysiological basis for therapy

Gottardi

Rescigno

2020

Journal of Hepatology

1,263

881

“…CARBALIVE is an orally administered, non-absorbable, highly engineered, activated charcoal with a wide range of porosities that adsorbs endotoxins and other products of bacterial metabolism, reduces translocation and influences severity of immune dysfunction in a bile-duct ligation model of cirrhosis. The exact mechanism of how modulating the gut environment changes immune function is unknown 206 . This therapy is currently being evaluated in phase 2 clinical trials (NCT03202498).…”

Section: [H1] Gut-associated Lymphoid Tissue In Cirrhosismentioning

confidence: 99%

Cirrhosis-associated immune dysfunction

Nat Rev Gastroenterol Hepatol

Martín-Mateos

Merwe

et al. 2021

214

148

“…Non-absorbable carbons of controlled porosity (Yaq-001) have shown to selectively modulate the composition and function of stool microbiome (82), and thus, safety and tolerability of Yaq-001 is currently under investigation (NCT03962608). Other ongoing study aims to assess the feasibility and safety of endoscopic duodenal mucosal resurfacing in this population (NCT03536650), which can potentially mimic the beneficial metabolic effects on glucose metabolism achieved by surgical upper-intestinal bypass (83).…”

Section: Therapeutic Interventions Targeting the Gut-liver-axis In Pamentioning

confidence: 99%

The Role of the Gut-Liver Axis in Metabolic Dysfunction-Associated Fatty Liver Disease

Martín-Mateos

2021

Front. Immunol.

The complex interplay between the gut microbiota, the intestinal barrier, the immune system and the liver is strongly influenced by environmental and genetic factors that can disrupt the homeostasis leading to disease. Among the modulable factors, diet has been identified as a key regulator of microbiota composition in patients with metabolic syndrome and related diseases, including the metabolic dysfunction-associated fatty liver disease (MAFLD). The altered microbiota disrupts the intestinal barrier at different levels inducing functional and structural changes at the mucus lining, the intercellular junctions on the epithelial layer, or at the recently characterized vascular barrier. Barrier disruption leads to an increased gut permeability to bacteria and derived products which challenge the immune system and promote inflammation. All these alterations contribute to the pathogenesis of MAFLD, and thus, therapeutic approaches targeting the gut-liver-axis are increasingly being explored. In addition, the specific changes induced in the intestinal flora may allow to characterize distinctive microbial signatures for non-invasive diagnosis, severity stratification and disease monitoring.