Lactococcus lactis delivery of surface layer protein a protects mice from colitis by re-setting host immune repertoire

Ananta Prasad Arukha, Christian Furlan Freguia, Meerambika Mishra, Jyoti K. Jha, Subhashinie Kariyawasam, Neil A. Fanger, Ellen M. Zimmermann, Gary R. Fanger, Bikash Sahay

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation com-prised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease manage-ment, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of Lactobacillus acidophilus that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade Lactococcus lactis to further investigate and characterize the protective mechanisms of the actions of SlpA. Oral administration of SlpA-expressing L. lactis (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in hu-mans.

Original languageEnglish (US)
Article number1098
JournalBiomedicines
Volume9
Issue number9
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
Funding: The research was funded by a grant received from NIH R43DK117726 and R44DK117726, received by G.R.F. and contracted to B.S.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Colitis
  • Lactococcus
  • Microbiome

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