https://orcid.org/0000-0003-1779-8832
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ABSTRACT
Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), a growing health concern. The complex progression of MASLD extends beyond the liver, driven by “gut-liver axis,” where diet, genetics, and gut-liver interactions influence disease development. The pathophysiology of MASLD involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, and fibrosis, with subsequent risk of hepatocellular carcinoma (HCC). The gut, a tripartite barrier, with mechanical, immune, and microbial components, engages in a constant communication with the liver. Recent evidence links dysbiosis and disrupted barriers to systemic inflammation and disease progression. Toll-like receptors (TLRs) mediate immunological crosstalk between the gut and liver, recognizing microbial structures and triggering immune responses. The “multiple hit model” of MASLD development involves factors like fat accumulation, insulin resistance, gut dysbiosis, and genetics/environmental elements disrupting the gut-liver axis, leading to impaired intestinal barrier function and increased gut permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, and microbiome modulation approaches through prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). This review underscores the complex interactions between diet, metabolism, microbiome, and their impact on MASLD pathophysiology and therapeutic prospects.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
The authors confirm that the data supporting the findings of this study are available within the article.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2331460
List of Abbreviations
| ALD | = | Alcohol-associated liver disease |
| AMPK | = | AMP-activated protein kinase |
| BA | = | Bile acid |
| BSEP | = | Bile salt export pump |
| CA | = | Cholic acid |
| CDCA | = | Chenodeoxycholic acid |
| CLD | = | Chronic liver disease |
| DAMP | = | Damage-associated molecular pattern |
| ECM | = | Extracellular matrix |
| FGF | = | Fibroblast growth factor |
| FGFR | = | Fibroblast growth factor receptor |
| FL | = | Fatty liver |
| FMT | = | Fecal microbiota transplant |
| FXR | = | Farnesoid X receptor |
| GALT | = | Gut associated lymphoid tissue |
| GF | = | Germ free |
| GI | = | Gastrointestinal |
| GVB | = | Gut vascular barrier |
| HCC | = | Hepatocellular carcinoma |
| H&E | = | Hematoxylin and eosin staining |
| HFD | = | High fat diet |
| HSC | = | Hepatic stellate cell |
| ICAM −1 | = | Intercellular adhesion molecule-1 |
| IEC | = | Intestinal epithelial cell |
| IgA | = | Immunoglobulin A\ |
| ILF | = | Isolated lymphoid follicles |
| IR | = | Insulin resistance |
| KC | = | Kupfer cell |
| LPL | = | Lipoprotein lipase |
| LPS | = | Lipopolysaccharide |
| MAMP | = | Microorganism-associated molecular patterns |
| MASH | = | Metabolic dysfunction associated steatohepatitis |
| MASLD | = | Metabolic dysfunction associated steatotic liver disease |
| MetALD | = | Metabolic associated liver disease and increased alcohol intake |
| MLN | = | Mesenteric lymph nodes |
| MNL | = | Mesenteric lymph nodes lymphocytes |
| MS | = | Metabolic syndrome |
| MUC2 | = | Mucin-2 |
| NAFLD | = | Non-alcoholic fatty liver disease |
| NASH | = | Non-alcoholic steatohepatitis |
| NF-κB | = | Nuclear factor- κB |
| NLR | = | NOD-like receptors |
| NTCP | = | Na+/taurocholate cotransporting polypeptide |
| OST | = | Organic solute transporter |
| PAMP | = | Pathogen-associated molecular patterns |
| PGN | = | Peptidoglycan |
| PPs | = | Peyer Patches |
| PRR | = | Pattern recognition receptors |
| PV-1 | = | Plasmalemma vesicle-associated protein-1 |
| ROS | = | Reactive oxygen species |
| SCFA | = | Short chain fatty acid |
| sIgA | = | Secretory Immunoglobulin A |
| TG | = | Triglyceride |
| TJ | = | Tight junction |
| TLR | = | Toll-like receptor |
| VCAM | = | Vascular cell adhesion molecule |
| VLDL | = | Very low density lipoprotein |
| WAT | = | White adipose tissue |
| WD | = | Western diet |
| ZO | = | Zona occludens. |