Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice

Lactoferrin is a glycoprotein found at high concentrations within exocrine secretions, including tears. Low levels of lactoferrin have been implicated in the loss of tear secretion and ageing. Furthermore, lactoferrin possesses a range of functionalities, including anti-inflammatory properties and t...

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Autores principales: Samuel Connell, Motoko Kawashima, Shigeru Nakamura, Toshihiro Imada, Hiromitsu Yamamoto, Kazuo Tsubota, Shinji Fukuda
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:0ee2aa4aeab44ddb888832970177a2fd2021-11-25T17:56:06ZLactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice10.3390/ijms2222123841422-00671661-6596https://doaj.org/article/0ee2aa4aeab44ddb888832970177a2fd2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12384https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Lactoferrin is a glycoprotein found at high concentrations within exocrine secretions, including tears. Low levels of lactoferrin have been implicated in the loss of tear secretion and ageing. Furthermore, lactoferrin possesses a range of functionalities, including anti-inflammatory properties and the ability to modulate the gut microbiota. Expanding evidence demonstrates a crucial role of the gut microbiota in immune regulation and development. The specific composition of bacterial species of the gut has a profound influence on local and systemic inflammation, leading to a protective capacity against a number of inflammatory diseases, potentially by the induction of regulatory immune cells. In this study, we demonstrated that oral administration of lactoferrin maintains tear secretion in a restraint and desiccating stress induced mouse model of dry eye disease. Furthermore, we revealed that lactoferrin induces the reduction of inflammatory cytokines, modulates gut microbiota, and induces short-chain fatty acid production. Whereas, the antibiotic vancomycin abrogates the effects of lactoferrin on dry eye disease and significantly reduces short-chain fatty acid concentrations. Therefore, this protective effect of LF against a mice model of DED may be explained by our observations of an altered gut microbiota and an enhanced production of immunomodulatory short-chain fatty acids.Samuel ConnellMotoko KawashimaShigeru NakamuraToshihiro ImadaHiromitsu YamamotoKazuo TsubotaShinji FukudaMDPI AGarticlelactoferrinlacrimal glanddry eyegut microbiotashort-chain fatty acidBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12384, p 12384 (2021)
institution DOAJ
collection DOAJ
language EN
topic lactoferrin
lacrimal gland
dry eye
gut microbiota
short-chain fatty acid
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle lactoferrin
lacrimal gland
dry eye
gut microbiota
short-chain fatty acid
Biology (General)
QH301-705.5
Chemistry
QD1-999
Samuel Connell
Motoko Kawashima
Shigeru Nakamura
Toshihiro Imada
Hiromitsu Yamamoto
Kazuo Tsubota
Shinji Fukuda
Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice
description Lactoferrin is a glycoprotein found at high concentrations within exocrine secretions, including tears. Low levels of lactoferrin have been implicated in the loss of tear secretion and ageing. Furthermore, lactoferrin possesses a range of functionalities, including anti-inflammatory properties and the ability to modulate the gut microbiota. Expanding evidence demonstrates a crucial role of the gut microbiota in immune regulation and development. The specific composition of bacterial species of the gut has a profound influence on local and systemic inflammation, leading to a protective capacity against a number of inflammatory diseases, potentially by the induction of regulatory immune cells. In this study, we demonstrated that oral administration of lactoferrin maintains tear secretion in a restraint and desiccating stress induced mouse model of dry eye disease. Furthermore, we revealed that lactoferrin induces the reduction of inflammatory cytokines, modulates gut microbiota, and induces short-chain fatty acid production. Whereas, the antibiotic vancomycin abrogates the effects of lactoferrin on dry eye disease and significantly reduces short-chain fatty acid concentrations. Therefore, this protective effect of LF against a mice model of DED may be explained by our observations of an altered gut microbiota and an enhanced production of immunomodulatory short-chain fatty acids.
format article
author Samuel Connell
Motoko Kawashima
Shigeru Nakamura
Toshihiro Imada
Hiromitsu Yamamoto
Kazuo Tsubota
Shinji Fukuda
author_facet Samuel Connell
Motoko Kawashima
Shigeru Nakamura
Toshihiro Imada
Hiromitsu Yamamoto
Kazuo Tsubota
Shinji Fukuda
author_sort Samuel Connell
title Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice
title_short Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice
title_full Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice
title_fullStr Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice
title_full_unstemmed Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice
title_sort lactoferrin ameliorates dry eye disease potentially through enhancement of short-chain fatty acid production by gut microbiota in mice
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0ee2aa4aeab44ddb888832970177a2fd
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