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

Int J Mol Sci. 2021 Nov 17;22(22):12384. doi: 10.3390/ijms222212384.

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.

Keywords: dry eye; gut microbiota; lacrimal gland; lactoferrin; short-chain fatty acid.

MeSH terms

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

Substances

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