# MASLD Under the Umbrella of the Microbiota: A Narrative Review on Ecological Risk and Functional Transmissibility

## TL;DR

This review explores how gut microbiota may influence the development of liver disease, suggesting it could be functionally transmissible, not contagious.

## Contribution

The paper introduces the concept of MASLD as an eco-biological disease influenced by gut microbiota, not just genetics or environment.

## Key findings

- Gut microbiota can transfer susceptibility to liver disease in gnotobiotic animal models.
- Microbiota-targeted interventions in humans support the modifiable role of gut ecosystems in liver and metabolic health.
- MASLD risk is context-dependent and microbiota-mediated, not genetically inherited or contagious.

## Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide, distinguished by pronounced clinical heterogeneity and a frequent dissociation between metabolic risk factors and the degree of hepatic injury. These observations, together with the limited contribution of genetic heritability, have prompted a re-evaluation of the traditional conceptual framework of the disease. In this context, the question has emerged as to whether MASLD could be, at least in part, a transmissible condition. While there is no evidence to suggest that MASLD is contagious in humans, as no data support person-to-person transmission, gnotobiotic animal studies demonstrate that human gut microbiota can transfer susceptibility to steatosis, inflammation, and systemic metabolic disturbances through immunometabolic mechanisms, independent of host genetics. In parallel, human studies involving microbiota-targeted interventions support the concept that the gut ecosystem is a modifiable determinant of metabolic and hepatic phenotypes. Crucially, these findings do not imply natural transmission of disease, but rather underscore the functional plasticity of microbiota-host interactions. This narrative review integrates epidemiological, experimental, and clinical data to explore the hypothesis that MASLD may be functionally transmissible. MASLD is increasingly recognized as an eco-biological disease, where liver disease risk is not only shaped by host genetics and environment, but also by the ecological configuration and functional outputs of the gut microbiome. This perspective redefines disease susceptibility as, in part, context-dependent and microbiota-mediated, without implying infectiousness in the traditional sense.