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Article

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

1
Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
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
*
Authors to whom correspondence should be addressed.
Academic Editor: Cintia S. De Paiva
Int. J. Mol. Sci. 2021, 22(22), 12384; https://doi.org/10.3390/ijms222212384
Received: 19 October 2021 / Revised: 1 November 2021 / Accepted: 6 November 2021 / Published: 17 November 2021
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 3.0)
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. View Full-Text
Keywords: lactoferrin; lacrimal gland; dry eye; gut microbiota; short-chain fatty acid lactoferrin; lacrimal gland; dry eye; gut microbiota; short-chain fatty acid
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MDPI and ACS Style

Connell, S.; Kawashima, M.; Nakamura, S.; Imada, T.; Yamamoto, H.; Tsubota, K.; Fukuda, S. Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice. Int. J. Mol. Sci. 2021, 22, 12384. https://doi.org/10.3390/ijms222212384

AMA Style

Connell S, Kawashima M, Nakamura S, Imada T, Yamamoto H, Tsubota K, Fukuda S. Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice. International Journal of Molecular Sciences. 2021; 22(22):12384. https://doi.org/10.3390/ijms222212384

Chicago/Turabian Style

Connell, Samuel, Motoko Kawashima, Shigeru Nakamura, Toshihiro Imada, Hiromitsu Yamamoto, Kazuo Tsubota, and Shinji Fukuda. 2021. "Lactoferrin Ameliorates Dry Eye Disease Potentially through Enhancement of Short-Chain Fatty Acid Production by Gut Microbiota in Mice" International Journal of Molecular Sciences 22, no. 22: 12384. https://doi.org/10.3390/ijms222212384

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