Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice |
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Authors: | Samuel Connell Motoko Kawashima Shigeru Nakamura Toshihiro Imada Hiromitsu Yamamoto Kazuo Tsubota Shinji Fukuda |
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Affiliation: | 1.Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; (S.C.); (M.K.); (S.N.); (T.I.);2.Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Yamagata, Japan;3.Tsubota Laboratory, Inc., Tokyo 160-0016, Japan;4.Transborder Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan;5.Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki 210-0821, Kanagawa, Japan |
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Abstract: | 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. |
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Keywords: | lactoferrin lacrimal gland dry eye gut microbiota short-chain fatty acid |
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