Alterations in the gut microbiome and its metabolites are associated with the immune response to mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 spike epitopes in mice

Front Cell Infect Microbiol. 2023 Aug 29:13:1242681. doi: 10.3389/fcimb.2023.1242681. eCollection 2023.

Abstract

Lactic acid bacteria (LAB) expressing foreign antigens have great potential as mucosal vaccines. Our previous study reported that recombinant Lactiplantibacillus plantarum SK156 displaying SARS-CoV-2 spike S1 epitopes elicited humoral and cell-mediated immune responses in mice. Here, we further examined the effect of the LAB-based mucosal vaccine on gut microbiome composition and function, and gut microbiota-derived metabolites. Forty-nine (49) female BALB/c mice were orally administered L. plantarum SK156-displaying SARS-CoV-2 spike S1 epitopes thrice (at 14-day intervals). Mucosal immunization considerably altered the gut microbiome of mice by enriching the abundance of beneficial gut bacteria, such as Muribaculaceae, Mucispirillum, Ruminococcaceae, Alistipes, Roseburia, and Clostridia vadinBB60. Moreover, the predicted function of the gut microbiome showed increased metabolic pathways for amino acids, energy, carbohydrates, cofactors, and vitamins. The fecal concentration of short-chain fatty acids, especially butyrate, was also altered by mucosal immunization. Notably, alterations in gut microbiome composition, function, and butyrate levels were positively associated with the immune response to the vaccine. Our results suggest that the gut microbiome and its metabolites may have influenced the immunogenicity of the LAB-based SARS-CoV-2 vaccine.

Keywords: COVID-19; SARS-CoV-2; butyrate; gut microbiome; lactic acid bacteria; mucosal vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroidetes
  • Butyrates
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Clostridiales
  • Epitopes
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Immunity
  • Immunization
  • Mice
  • SARS-CoV-2

Substances

  • Epitopes
  • COVID-19 Vaccines
  • Butyrates

Grants and funding

This work was supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A2C1010406 and No. 2020K1A3A1A47110820). It was also supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, and Forestry (IPET) through the High Value-added Food Technology Development Program, funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) (grant no. 321035052HD040). Partial support is also provided by the Swedish Research Council (Vetenskapsrådet Grant No. 2020-06320).