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Cited by 1,498Gut microbiota and healthGastrointestinal motility and disordersInflammatory Bowel Disease

Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review

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Di Vincenzo, Federica, Del Gaudio, Angelo, Petito, Valentina, Lopetuso, Loris Riccardo, Scaldaferri, Franco·2024·Internal and Emergency Medicine
DOI 10.1007/s11739-023-03374-wPMC PMC10954893
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Abstract

The intestine is the largest interface between the internal body and the external environment. The intestinal barrier is a dynamic system influenced by the composition of the intestinal microbiome and the activity of intercellular connections, regulated by hormones, dietary components, inflammatory mediators, and the enteric nervous system (ENS). Over the years, it has become increasingly evident that maintaining a stable intestinal barrier is crucial to prevent various potentially harmful substances and pathogens from entering the internal environment. Disruption of the barrier is referred to as 'leaky gut' or leaky gut wall syndrome and seems to be characterized by the release of bacterial metabolites and endotoxins, such as lipopolysaccharide (LPS), into the circulation. This condition, mainly caused by bacterial infections, oxidative stress, high-fat diet, exposure to alcohol or chronic allergens, and dysbiosis, appear to be highly connected with the development and/or progression of several metabolic and autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, inflammatory bowel disease, and type 1 diabetes mellitus (T1D). In this review, starting from a description of the mechanisms that enable barrier homeostasis and analyzing the relationship between this complex ecosystem and various pathological conditions, we explore the role of the gut barrier in driving systemic inflammation, also shedding light on current and future therapeutic interventions.

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  • Dysbiosis promotes intestinal barrier dysfunction, leading to leaky gut and translocation of bacterial products such as LPS and peptidoglycans into systemic circulation.

    “Mechanistically, dysbiosis promotes intestinal barrier dysfunction, leading to “leaky gut” and translocation of bacterial products such as lipopolysaccharides (LPS) and peptidoglycans into systemic circulation [125].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [125]

    The Introduction (page not available) identifies dysbiosis as a cause of barrier impairment, calls that impairment “leaky gut,” and says it permits bacterial components to pass through the barrier. The review also describes LPS entering the circulation. Its Atherosclerosis and cardiovascular diseases section mentions peptidoglycan in plaques, but does not say that leaky gut causes peptidoglycan to translocate into systemic circulation; the Conclusions also caution that a clear cause–effect relationship has not been fully established. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Di Vincenzo, F., Del Gaudio, A., Petito, V., Lopetuso, L. R., & Scaldaferri, F.
Affiliations
  • Agostino Gemelli University Polyclinic (IT)
  • Università Cattolica del Sacro Cuore (IT)
ORCID
Venue
Internal and Emergency Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-07-28
Volume
19
Issue
2
Pages
275-293
ISSN
  • 1828-0447 (ISSN-L)
  • 1970-9366
DOI
10.1007/s11739-023-03374-w
PMC
PMC10954893
OpenAlex
W4385330162
Cited by
1,498
References
10
Citations by year
2026: 699 · 2025: 589 · 2024: 197 · 2023: 11 · 2022: 1
FWCI
38.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Internal and Emergency Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
Funders
Università Cattolica del Sacro Cuore
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
gut microbiota, intestinal permeability, intestinal barrier, leaky gut, systemic inflammation, dysbiosis, lipopolysaccharide, bacterial metabolites, endotoxemia, obesity, non-alcoholic fatty liver disease, neurodegeneration, cardiovascular disease, inflammatory bowel disease, type 1 diabetes, autoimmune disease, enteric nervous system
MeSH terms
Gastrointestinal Microbiome, Intestinal Barrier Function, Autoimmune Diseases, Humans, Inflammation, Intestinal Mucosa, Non-alcoholic Fatty Liver Disease

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