S100B Affects Gut Microbiota Biodiversity

Abstract

This in vivo study in mice addresses the relationship between the biodiversity of the microbiota and the levels of S100B, a protein present in enteroglial cells, but also in foods such as milk. A positive significant correlation was observed between S100B levels and Shannon values, which was reduced after treatment with Pentamidine, an inhibitor of S100B function, indicating that the correlation was influenced by the modulation of S100B activity. Using the bootstrap average method based on the distribution of the S100B concentration, three groups were identified, exhibiting a significant difference between the microbial profiles. Operational taxonomic units, when analyzed by SIMPER analysis, showed that genera regarded to be eubiotic were mainly concentrated in the intermediate group, while genera potentially harboring pathobionts often appeared to be more concentrated in groups where the S100B amounts were very low or high. Finally, in a pilot experiment, S100B was administered orally, and the microbial profiles appeared to be modified accordingly. These data may open novel perspectives involving the possibility of S100B-mediated regulation in the intestinal microbiota.

Keywords: 16S amplicon sequencing; IBD; NGS; Pentamidine; S100B; eubiosis; gut–brain axis; mfDNA; microbiome; milk; protein-binding domain.

Figure 1

Relationship between concentration of S100B and Shannon alpha-biodiversity index. The scatterplot shows a positive correlation between S100B concentration (ng/mL) and Shannon values. The regression equation was Y = 0.15X + 2.59 without the 0 values (intercept 2.4–2.8).

Figure 2

Relationship between S100B concentration and Shannon index in mice treated (n = 25) with PTM (red line) and without (n = 28) PTM treatment (blue line). The diagram shows a positive correlation between S100B concentration (ng/mL) and Shannon values without treatment (R² = 0.95) that is reduced after PTM treatment (R² = 0.75).

Figure 3

(A) Correlation between S100B levels and the microbiota biodiversity clusters samples into 3 groups. Bootstrap average analysis of the microbiota composition in relationship with levels of S100B (A = lower than 1.75 ng/mL, B = between 1.76 and 2.4 ng/mL, C = higher than 2.5 ng/mL). (B) Shannon index values with respect to S100B clusters. Box plots represent the distribution of calculated Shannon index for microbiota samples based on the different levels of S100B (A = lower than 1.75 ng/mL, B = between 1.76 and 2.4 ng/mL, C = higher than 2.5 ng mL).

Figure 4

Hierarchical clustering dendrogram on 16S amplicon sequencing data. Dendrogram shows hierarchical clustering of samples based on genus-level classifications. The bar chart under each sample summarizes the relative abundance of its genus-level classifications, as measured in number of reads. Samples are divided based on the different levels of S100B (A = lower than 1.75 ng/mL, B = between 1.76 and 2.4 ng/mL, C = higher than 2.5 ng/mL).