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Cited by 327Gut microbiota and healthLiver Disease Diagnosis and TreatmentAlcohol Consumption and Health Effects

Gut–liver axis, nutrition, and non-alcoholic fatty liver disease

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Kirpich, Irina A., Marsano, Luis S., McClain, Craig J.·2015·Clinical Biochemistry
DOI 10.1016/j.clinbiochem.2015.06.023PMC PMC4558208
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Abstract

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called "gut-liver axis", play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host's metabolism contributing to NAFLD development.

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  • The multiple hits theory is supported by rodent models of MASH characterised by excess calorie intake, weight gain and onset of insulin resistance in which increased hepatic lipid accumulation is observed, but additional insults are required to initiate inflammation and fibrosis.

    “The 'multiple hits' theory is supported by rodent models of MASH characterised by excess calorie intake, weight gain and the onset of IR in which increased hepatic lipid accumulation is observed, but additional insults are required to initiate inflammation and fibrosis.”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [222]

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  • Additional insults in MASH include altered gut flora and increased intestinal permeability, circadian rhythm misalignment, epigenetic modifications, and changes to the composition of liver myeloid cell populations.

    “These include altered gut flora and an increase in intestinal permeability(222, 223), circadian rhythm misalignment(224), epigenetic modifications(210, 225) and changes to the composition of liver myeloid cell populations(210, 211, 226).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [222]

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Cited by

Sorted by citations

Authors
Kirpich, I. A., Marsano, L. S., & McClain, C. J.
Affiliations
University of Louisville (US)
Corresponding author
Kirpich, Irina A.
ORCID
Venue
Clinical Biochemistry
Publisher
Elsevier BV
Published
2015-09
Volume
48
Issue
13-14
Pages
923-930
ISSN
0009-9120 (ISSN-L)
DOI
10.1016/j.clinbiochem.2015.06.023
PMC
PMC4558208
OpenAlex
W794483546
Cited by
327
References
20
Citations by year
2026: 17 · 2025: 30 · 2024: 30 · 2023: 35 · 2022: 34 · 2021: 44 · 2020: 35 · 2019: 30 · 2018: 26 · 2017: 21 · 2016: 23 · 2015: 1
FWCI
2.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Biochemistry (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (R01 AA018869, R21 AA020849-01A1, 1UO1AA022489, 1U01AA021901-01, 1U01AA021893-01, R01 AA023681)
  • U.S. Department of Veterans Affairs (BX000350)
  • U.S. Department of Defense (W81XWH-11-1-0595)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
non-alcoholic fatty liver disease, gut-liver axis, gut microbiota, intestinal barrier integrity, endotoxemia, low-grade inflammation, obesity, insulin resistance, diabetes mellitus, prebiotics, probiotics, dietary factors, NAFLD pathogenesis
MeSH terms
Gastrointestinal Microbiome, Humans, Liver, Nutritional Physiological Phenomena, Obesity, Gastrointestinal Tract, Non-alcoholic Fatty Liver Disease

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