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

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.

• Authors: Samuel Connell, Motoko Kawashima, Shigeru Nakamura, Toshihiro Imada, Hiromitsu Yamamoto, Kazuo Tsubota, Shinji Fukuda
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 22 (Nov 17 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34830266 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Cytokines
• DNA, Bacterial
• Fatty Acids, Volatile
• Protective Agents
• Vancomycin
• Lactoferrin

Topics

• Administration, Oral
• Animals
• Anti-Bacterial Agents (administration & dosage)
• Cytokines (metabolism)
• DNA, Bacterial (genetics, isolation & purification)
• Disease Models, Animal
• Dry Eye Syndromes (drug therapy, metabolism)
• Fatty Acids, Volatile (biosynthesis)
• Female
• Gastrointestinal Microbiome (drug effects, genetics)
• Inflammation (drug therapy, metabolism)
• Lactoferrin (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Protective Agents (administration & dosage)
• Signal Transduction (drug effects)
• Tears (metabolism)
• Treatment Outcome
• Vancomycin (administration & dosage)