Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocation
Chemotherapy kills fast-growing cells including gut stem cells. This affects all components of the physical and functional intestinal barrier, i.e., the mucus layer, epithelium, and immune system. This results in an altered intestinal permeability of toxic compounds (e.g., endotoxins) as well as lum...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223004328 |
| _version_ | 1797837160169078784 |
|---|---|
| author | David Dahlgren Hans Lennernäs |
| author_facet | David Dahlgren Hans Lennernäs |
| author_sort | David Dahlgren |
| collection | DOAJ |
| description | Chemotherapy kills fast-growing cells including gut stem cells. This affects all components of the physical and functional intestinal barrier, i.e., the mucus layer, epithelium, and immune system. This results in an altered intestinal permeability of toxic compounds (e.g., endotoxins) as well as luminal bacterial translocation into the mucosa and central circulation. However, there is uncertainty regarding the relative contributions of the different barrier components for the development of chemotherapy-induced gut toxicity. This review present an overview of the intestinal mucosal barrier determined with various types of molecular probes and methods, and how they are affected by chemotherapy based on reported rodent and human data. We conclude that there is overwhelming evidence that chemotherapy increases bacterial translocation, and that it affects the mucosal barrier by rendering the mucosa more permeable to large permeability probes. Chemotherapy also seems to impede the intestinal mucus barrier, even though this has been less clearly evaluated from a functional standpoint but certainly plays a role in bacteria translocation. Combined, it is however difficult to outline a clear temporal or succession between the different gastrointestinal events and barrier functions, especially as chemotherapy-induced neutropenia is also involved in intestinal immunological homeostasis and bacterial translocation. A thorough characterization of this would need to include a time dependent development of neutropenia, intestinal permeability, and bacterial translocation, ideally after a range of chemotherapeutics and dosing regimens. |
| first_indexed | 2024-04-09T15:20:20Z |
| format | Article |
| id | doaj.art-5cfbe65de23048edab0b051859f548cf |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T15:20:20Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-5cfbe65de23048edab0b051859f548cf2023-04-29T14:46:09ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-06-01162114644Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocationDavid Dahlgren0Hans Lennernäs1Department of Pharmaceutical Biosciences Uppsala University, Uppsala, SwedenCorresponding author.; Department of Pharmaceutical Biosciences Uppsala University, Uppsala, SwedenChemotherapy kills fast-growing cells including gut stem cells. This affects all components of the physical and functional intestinal barrier, i.e., the mucus layer, epithelium, and immune system. This results in an altered intestinal permeability of toxic compounds (e.g., endotoxins) as well as luminal bacterial translocation into the mucosa and central circulation. However, there is uncertainty regarding the relative contributions of the different barrier components for the development of chemotherapy-induced gut toxicity. This review present an overview of the intestinal mucosal barrier determined with various types of molecular probes and methods, and how they are affected by chemotherapy based on reported rodent and human data. We conclude that there is overwhelming evidence that chemotherapy increases bacterial translocation, and that it affects the mucosal barrier by rendering the mucosa more permeable to large permeability probes. Chemotherapy also seems to impede the intestinal mucus barrier, even though this has been less clearly evaluated from a functional standpoint but certainly plays a role in bacteria translocation. Combined, it is however difficult to outline a clear temporal or succession between the different gastrointestinal events and barrier functions, especially as chemotherapy-induced neutropenia is also involved in intestinal immunological homeostasis and bacterial translocation. A thorough characterization of this would need to include a time dependent development of neutropenia, intestinal permeability, and bacterial translocation, ideally after a range of chemotherapeutics and dosing regimens.http://www.sciencedirect.com/science/article/pii/S0753332223004328Chemotherapy-induced mucositisIntestinal permeabilityBacterial translocationCancer |
| spellingShingle | David Dahlgren Hans Lennernäs Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocation Biomedicine & Pharmacotherapy Chemotherapy-induced mucositis Intestinal permeability Bacterial translocation Cancer |
| title | Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocation |
| title_full | Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocation |
| title_fullStr | Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocation |
| title_full_unstemmed | Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocation |
| title_short | Review on the effect of chemotherapy on the intestinal barrier: Epithelial permeability, mucus and bacterial translocation |
| title_sort | review on the effect of chemotherapy on the intestinal barrier epithelial permeability mucus and bacterial translocation |
| topic | Chemotherapy-induced mucositis Intestinal permeability Bacterial translocation Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223004328 |
| work_keys_str_mv | AT daviddahlgren reviewontheeffectofchemotherapyontheintestinalbarrierepithelialpermeabilitymucusandbacterialtranslocation AT hanslennernas reviewontheeffectofchemotherapyontheintestinalbarrierepithelialpermeabilitymucusandbacterialtranslocation |