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Cited by 232Gut microbiota and healthGastrointestinal motility and disordersAnimal Nutrition and Physiology

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Nutritional Keys for Intestinal Barrier Modulation

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De Santis, Stefania, Cavalcanti, Elisabetta, Mastronardi, Mauro, Jirillo, Emilio, Chieppa, Marcello·2015·Frontiers in Immunology
DOI 10.3389/fimmu.2015.00612PMC PMC4670985
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Abstract

The intestinal tract represents the largest interface between the external environment and the human body. Nutrient uptake mostly happens in the intestinal tract, where the epithelial surface is constantly exposed to dietary antigens. Since inflammatory response toward these antigens may be deleterious for the host, a plethora of protective mechanisms take place to avoid or attenuate local damage. For instance, the intestinal barrier is able to elicit a dynamic response that either promotes or impairs luminal antigens adhesion and crossing. Regulation of intestinal barrier is crucial to control intestinal permeability whose increase is associated with chronic inflammatory conditions. The cross talk among bacteria, immune, and dietary factors is able to modulate the mucosal barrier function, as well as the intestinal permeability. Several nutritional products have recently been proposed as regulators of the epithelial barrier, even if their effects are in part contradictory. At the same time, the metabolic function of the microbiota generates new products with different effects based on the dietary content. Besides conventional treatments, novel therapies based on complementary nutrients are now growing. Fecal therapy has been recently used for the clinical treatment of refractory Clostridium difficile infection instead of the classical antibiotic therapy. In the present review, we will outline the epithelial response to nutritional components derived from dietary intake and microbial fermentation focusing on the consequent effects on the integrity of the epithelial barrier.

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Figure 1 Structure of intestinal barrier. The intestinal barrier is a complex entity, which is composed of cellular and extracellular elements. The cellular part is defined by intestinal epithelium (five distinct type of cells, such as stem cells, Paneth cells, enterocytes, goblet cells, and enteroendocrine cells) and the underlying lamina propria, which contains DCs (also intraepithelial DCs, IEDCs), macrophages, intraepithelial lymphocytes (IEL), T regulatory cells (T Regs), TCD4+ lymphocytes (T CD4), B lymphocytes (B), and plasma cells (PCs). The extracellular component consists in a mucus layer produced by Globet cells, AMPs secreted by Paneth cells, and sIgA dimers released by plasma cells. DCs, dendritic cells; AMPs, antimicrobial peptides; sIgA, secretory ImmunoglobulinA.
Figure 1 Structure of intestinal barrier. The intestinal barrier is a complex entity, which is composed of cellular and extracellular elements. The cellular part is defined by intestinal epithelium (five distinct type of cells, such as stem cells, Paneth cells, enterocytes, goblet cells, and enteroendocrine cells) and the underlying lamina propria, which contains DCs (also intraepithelial DCs, IEDCs), macrophages, intraepithelial lymphocytes (IEL), T regulatory cells (T Regs), TCD4+ lymphocytes (T CD4), B lymphocytes (B), and plasma cells (PCs). The extracellular component consists in a mucus layer produced by Globet cells, AMPs secreted by Paneth cells, and sIgA dimers released by plasma cells. DCs, dendritic cells; AMPs, antimicrobial peptides; sIgA, secretory ImmunoglobulinA.CC BY · PubMed Central
Figure 2 Tight Junction regulation by food antigens. (A) TJs are composed of some transmembrane proteins [occludin, claudins, and junctional adhesion molecules (JAMs)] and cytosolic scaffold proteins [zonulae occludens (ZO) and cingulin]. The extracellular domains of transmembrane proteins of adjacent IECs interact to form the selective intestinal barrier, while cytosolic scaffolds anchor the transmembrane proteins to the actomyosin ring. (B) The intake of some food antigens, such as gliadin, fatty acids, or ethanol, can directly increase intestinal permeability by different mechanisms (1–7); (1) alteration in cellular distribution of occludin proteins, (2) reduction in the cellular content of occludins, (3) alteration in cellular distribution of claudin, (4) inhibition of protein tyrosine phosphatase (PTP) activity that induce tyrosine phosphorylation of ZO-1 and occludin and their dissociation from the junctional complex, (5) activation of PKC that leads to polymerization of actin and subsequent displacement of TJ proteins, including ZO-1, (6) displacement of ZO proteins from the junctional complexes, (7) activation of MLCK activity. (C) Other dietary antigens, such as amino acid, milk and cheese peptides, vitamins, and polyphenols, have the ability to decrease intestinal permeability through distinct pathways; (1–3) increase in the cellular content of occludin, claudin, and ZO proteins, respectively, (4) restoration of ZO-1/occludin assembly, (5) inhibition of MLCK activation. PKC, protein kinase C; MLC, myosin light-chain; MLCK, myosin light-chain kinase; TK, tyrosine kinase.
Figure 2 Tight Junction regulation by food antigens. (A) TJs are composed of some transmembrane proteins [occludin, claudins, and junctional adhesion molecules (JAMs)] and cytosolic scaffold proteins [zonulae occludens (ZO) and cingulin]. The extracellular domains of transmembrane proteins of adjacent IECs interact to form the selective intestinal barrier, while cytosolic scaffolds anchor the transmembrane proteins to the actomyosin ring. (B) The intake of some food antigens, such as gliadin, fatty acids, or ethanol, can directly increase intestinal permeability by different mechanisms (1–7); (1) alteration in cellular distribution of occludin proteins, (2) reduction in the cellular content of occludins, (3) alteration in cellular distribution of claudin, (4) inhibition of protein tyrosine phosphatase (PTP) activity that induce tyrosine phosphorylation of ZO-1 and occludin and their dissociation from the junctional complex, (5) activation of PKC that leads to polymerization of actin and subsequent displacement of TJ proteins, including ZO-1, (6) displacement of ZO proteins from the junctional complexes, (7) activation of MLCK activity. (C) Other dietary antigens, such as amino acid, milk and cheese peptides, vitamins, and polyphenols, have the ability to decrease intestinal permeability through distinct pathways; (1–3) increase in the cellular content of occludin, claudin, and ZO proteins, respectively, (4) restoration of ZO-1/occludin assembly, (5) inhibition of MLCK activation. PKC, protein kinase C; MLC, myosin light-chain; MLCK, myosin light-chain kinase; TK, tyrosine kinase.CC BY · PubMed Central

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Metadata

Authors
De Santis, S., Cavalcanti, E., Mastronardi, M., Jirillo, E., & Chieppa, M.
Affiliations
  • Gastroenterology Hospital "Saverio de Bellis" (IT)
  • University of Bari Aldo Moro (IT)
Corresponding author
Chieppa, Marcello
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2015-12-07
Volume
6
Pages
612-612
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2015.00612
PMC
PMC4670985
OpenAlex
W2195104529
Cited by
232
References
182
Citations by year
2026: 16 · 2025: 19 · 2024: 15 · 2023: 31 · 2022: 28 · 2021: 26 · 2020: 33 · 2019: 24 · 2018: 19 · 2017: 17 · 2016: 4
FWCI
1.29
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • AIRUS (submittedVersion)
  • CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, other-oa)
Funders
Ministero della Salute (GR-2011-02347991)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
Keywords
intestinal barrier, intestinal permeability, epithelial barrier integrity, dietary nutrients, gut microbiota, microbial fermentation, mucosal immunity, dietary antigens, Clostridium difficile infection, fecal microbiota transplantation, chronic inflammation, epithelial response

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