The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver Disease
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a multifactorial condition linked to liver injury, insulin resistance, and disrupted gut–liver interactions. A key aspect of MASLD pathogenesis is the dysfunction of intestinal barriers, including mechanical, immunological, and micr...
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MDPI AG
2025-04-01
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| Series: | Livers |
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| Online Access: | https://www.mdpi.com/2673-4389/5/2/17 |
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| author | Carlo Acierno Riccardo Nevola Luca Rinaldi Ferdinando Carlo Sasso Luigi Elio Adinolfi Alfredo Caturano |
| author_facet | Carlo Acierno Riccardo Nevola Luca Rinaldi Ferdinando Carlo Sasso Luigi Elio Adinolfi Alfredo Caturano |
| author_sort | Carlo Acierno |
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| description | Metabolic dysfunction–associated steatotic liver disease (MASLD) is a multifactorial condition linked to liver injury, insulin resistance, and disrupted gut–liver interactions. A key aspect of MASLD pathogenesis is the dysfunction of intestinal barriers, including mechanical, immunological, and microbial alterations that amplify liver damage. The disruption of tight junctions and increased intestinal permeability allow microbial products, such as lipopolysaccharides, to enter the bloodstream, triggering liver inflammation via Kupffer cell activation. In MASLD, the gut vascular barrier is also compromised, marked by increased expression of PV-1. Additionally, dysbiosis, driven by high-fat, high-sugar diets, shifts the gut microbiota toward pro-inflammatory species, exacerbating systemic inflammation and intestinal permeability. This imbalance activates Toll-like receptor signaling, which promotes endotoxin-induced liver injury. Gut dysbiosis further impairs lipid metabolism, contributing to hepatic steatosis and MASLD progression. The gut–liver axis plays a critical role, with factors like altered bile acid metabolism and toxic metabolites such as hydrogen sulfide worsening intestinal barrier function and fueling chronic inflammation. This review aims to explore the complex role of the gut–liver axis in MASLD progression, highlighting the mechanisms of intestinal barrier dysfunction, dysbiosis, and microbial contributions to liver injury. It also discusses therapeutic strategies targeting intestinal barriers, including dietary and microbiota-based interventions, while acknowledging the challenges of personalized treatment approaches. Future research should focus on multi-omics technologies and the safety and efficacy of microbiota-targeted therapies in MASLD management. |
| format | Article |
| id | doaj-art-371ca23219eb49e38ff0bccfcca1a45f |
| institution | Kabale University |
| issn | 2673-4389 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Livers |
| spelling | doaj-art-371ca23219eb49e38ff0bccfcca1a45f2025-08-20T03:27:23ZengMDPI AGLivers2673-43892025-04-01521710.3390/livers5020017The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver DiseaseCarlo Acierno0Riccardo Nevola1Luca Rinaldi2Ferdinando Carlo Sasso3Luigi Elio Adinolfi4Alfredo Caturano5Department of Infectious Diseases, San Carlo Hospital, 85100 Potenza, ItalyLiver Unit, AORN S. G. Moscati, “A. Landolfi” Hospital, 83029 Solofra, ItalyDepartment of Medicine and Health Science “Vincenzo Tiberio”, Università degli Studi del Molise, 86100 Campobasso, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalyMetabolic dysfunction–associated steatotic liver disease (MASLD) is a multifactorial condition linked to liver injury, insulin resistance, and disrupted gut–liver interactions. A key aspect of MASLD pathogenesis is the dysfunction of intestinal barriers, including mechanical, immunological, and microbial alterations that amplify liver damage. The disruption of tight junctions and increased intestinal permeability allow microbial products, such as lipopolysaccharides, to enter the bloodstream, triggering liver inflammation via Kupffer cell activation. In MASLD, the gut vascular barrier is also compromised, marked by increased expression of PV-1. Additionally, dysbiosis, driven by high-fat, high-sugar diets, shifts the gut microbiota toward pro-inflammatory species, exacerbating systemic inflammation and intestinal permeability. This imbalance activates Toll-like receptor signaling, which promotes endotoxin-induced liver injury. Gut dysbiosis further impairs lipid metabolism, contributing to hepatic steatosis and MASLD progression. The gut–liver axis plays a critical role, with factors like altered bile acid metabolism and toxic metabolites such as hydrogen sulfide worsening intestinal barrier function and fueling chronic inflammation. This review aims to explore the complex role of the gut–liver axis in MASLD progression, highlighting the mechanisms of intestinal barrier dysfunction, dysbiosis, and microbial contributions to liver injury. It also discusses therapeutic strategies targeting intestinal barriers, including dietary and microbiota-based interventions, while acknowledging the challenges of personalized treatment approaches. Future research should focus on multi-omics technologies and the safety and efficacy of microbiota-targeted therapies in MASLD management.https://www.mdpi.com/2673-4389/5/2/17gut microbiotagut–liver axisMASLD progressionintestinal permeabilityprecision medicine |
| spellingShingle | Carlo Acierno Riccardo Nevola Luca Rinaldi Ferdinando Carlo Sasso Luigi Elio Adinolfi Alfredo Caturano The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver Disease Livers gut microbiota gut–liver axis MASLD progression intestinal permeability precision medicine |
| title | The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver Disease |
| title_full | The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver Disease |
| title_fullStr | The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver Disease |
| title_full_unstemmed | The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver Disease |
| title_short | The Intestinal Thread of Fate: How the Microbiota Shapes the Story of Liver Disease |
| title_sort | intestinal thread of fate how the microbiota shapes the story of liver disease |
| topic | gut microbiota gut–liver axis MASLD progression intestinal permeability precision medicine |
| url | https://www.mdpi.com/2673-4389/5/2/17 |
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