Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions
Abstract Human milk extracellular vesicles (EVs) are crucial mother‐to‐baby messengers that transfer biological signals. These EVs are reported to survive digestion and transport across the intestine. The mechanisms of interaction between human milk EVs and the intestinal mucosa, including epithelia...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Journal of Extracellular Biology |
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| Online Access: | https://doi.org/10.1002/jex2.70032 |
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| _version_ | 1832584430869282816 |
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| author | Xiang Luo Yunyue Zhang Ning Ding Jana Javorovic Bahijja Tolulope Raimi‐Abraham Steven Lynham Xiaoping Yang Natalie Shenker Driton Vllasaliu |
| author_facet | Xiang Luo Yunyue Zhang Ning Ding Jana Javorovic Bahijja Tolulope Raimi‐Abraham Steven Lynham Xiaoping Yang Natalie Shenker Driton Vllasaliu |
| author_sort | Xiang Luo |
| collection | DOAJ |
| description | Abstract Human milk extracellular vesicles (EVs) are crucial mother‐to‐baby messengers that transfer biological signals. These EVs are reported to survive digestion and transport across the intestine. The mechanisms of interaction between human milk EVs and the intestinal mucosa, including epithelial uptake remain unclear. Here, we studied the interaction of human milk EVs with the gut barrier components, including intestinal biofluids, enzymes, mucus and epithelium. Additionally, we probed the endocytic mechanisms mediating the EV intestinal uptake. Finally, using proteomic analysis, we determined the existence and identification of proteins enriched in the EV fraction transported across the intestinal epithelium. We show that human milk EVs are largely stable in the biochemical gut barriers and demonstrate high mucus diffusivity. EVs show a high level of epithelial cell uptake (∼70%) and efficient transport across Caco‐2 monolayers. Whilst cell uptake of EVs was mediated by multiple routes, none of the pathway‐specific inhibitors inhibited their epithelial translocation. Proteomic analysis of EVs transported across Caco‐2 monolayers identified 14 enriched EV proteins that may facilitate intestinal transport. These findings significantly expand our understanding of the interactions between human milk EVs and the gut barriers, including their intestinal uptake. |
| format | Article |
| id | doaj-art-13f6ca59b6354d5faa233d13d35762fc |
| institution | Kabale University |
| issn | 2768-2811 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Biology |
| spelling | doaj-art-13f6ca59b6354d5faa233d13d35762fc2025-01-27T13:48:43ZengWileyJournal of Extracellular Biology2768-28112025-01-0141n/an/a10.1002/jex2.70032Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactionsXiang Luo0Yunyue Zhang1Ning Ding2Jana Javorovic3Bahijja Tolulope Raimi‐Abraham4Steven Lynham5Xiaoping Yang6Natalie Shenker7Driton Vllasaliu8Institute of Pharmaceutical Science School of Cancer and Pharmaceutical Science King's College London London UKInstitute of Pharmaceutical Science School of Cancer and Pharmaceutical Science King's College London London UKInstitute of Pharmaceutical Science School of Cancer and Pharmaceutical Science King's College London London UKInstitute of Pharmaceutical Science School of Cancer and Pharmaceutical Science King's College London London UKInstitute of Pharmaceutical Science School of Cancer and Pharmaceutical Science King's College London London UKCentre of Excellence for Mass Spectrometry, The James Black Centre King's College London London UKCentre of Excellence for Mass Spectrometry, The James Black Centre King's College London London UKInstitute of Reproductive and Developmental Biology Imperial College London UKInstitute of Pharmaceutical Science School of Cancer and Pharmaceutical Science King's College London London UKAbstract Human milk extracellular vesicles (EVs) are crucial mother‐to‐baby messengers that transfer biological signals. These EVs are reported to survive digestion and transport across the intestine. The mechanisms of interaction between human milk EVs and the intestinal mucosa, including epithelial uptake remain unclear. Here, we studied the interaction of human milk EVs with the gut barrier components, including intestinal biofluids, enzymes, mucus and epithelium. Additionally, we probed the endocytic mechanisms mediating the EV intestinal uptake. Finally, using proteomic analysis, we determined the existence and identification of proteins enriched in the EV fraction transported across the intestinal epithelium. We show that human milk EVs are largely stable in the biochemical gut barriers and demonstrate high mucus diffusivity. EVs show a high level of epithelial cell uptake (∼70%) and efficient transport across Caco‐2 monolayers. Whilst cell uptake of EVs was mediated by multiple routes, none of the pathway‐specific inhibitors inhibited their epithelial translocation. Proteomic analysis of EVs transported across Caco‐2 monolayers identified 14 enriched EV proteins that may facilitate intestinal transport. These findings significantly expand our understanding of the interactions between human milk EVs and the gut barriers, including their intestinal uptake.https://doi.org/10.1002/jex2.70032EV cell uptakeEV intestinal translocationEV proteomicshuman milk EVs |
| spellingShingle | Xiang Luo Yunyue Zhang Ning Ding Jana Javorovic Bahijja Tolulope Raimi‐Abraham Steven Lynham Xiaoping Yang Natalie Shenker Driton Vllasaliu Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions Journal of Extracellular Biology EV cell uptake EV intestinal translocation EV proteomics human milk EVs |
| title | Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions |
| title_full | Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions |
| title_fullStr | Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions |
| title_full_unstemmed | Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions |
| title_short | Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions |
| title_sort | mechanistic insight into human milk extracellular vesicle intestinal barrier interactions |
| topic | EV cell uptake EV intestinal translocation EV proteomics human milk EVs |
| url | https://doi.org/10.1002/jex2.70032 |
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