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

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.

Unraveling intestinal microbiota’s dominance in polycystic ovary syndrome pathogenesis over vaginal microbiota

“…Limosilactobacillu and Lactobacillus are a group of Gram-positive bacteria under the family Lactobacillaceae of the thick-walled phylum. Their ability to enhance the physical barrier of the mucus layer to improve immunity, their ability to produce lactic acid to maintain a weakly acidic environment as a major metabolic end product of carbohydrate fermentation ( Petrova et al., 2015 ; Li C. et al., 2023 ), and modulation of Muribaculaceae abundance may ameliorate metabolic disorders by altering metabolism and butyrate production, and modulation of antibody and anti-inflammatory cytokine production to ameliorate inflammation ( Hwang et al., 2023 ). In the present study, we found that the intestinal microbiota of Muribaculaceae , Limosilactobacillus and Lactobacillus were reduced in the CP group of mice.…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…Metabolites produced by some bacteria can target the S protein of coronaviruses, thereby improving dysbiosis. 110 , 111 The reduced diversity of intestinal flora in patients with COVID can be accompanied by changes in circulating and intestinal SCFAs and an imbalance in circulating immune cell subsets. The proportions of CD19 + B, CD4 + T, CD8 + T, and NK cells of patients with COVID‐19 were significantly decreased, and the IL‐6 and IL‐10 levels were significantly increased, all of which were more prominent in critically ill patients.…”

“…In turn, the gut microbiome and its metabolites may influence the immunogenicity of SARS‐CoV‐2 vaccines. 111 , 136 Although the mechanism of this vaccine‐induced change in the microbiota and the bidirectional regulation of metabolites and inflammatory immune response caused by the changes in the microbiota has not been elucidated, exploring the relevant mechanisms provides new ideas for the optimization of vaccines and the selection of adjuvants. Vaccine‐associated microbiota changes and the potential bidirectional regulation are shown in Figure 5 .…”