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.

Enteric glia as a player of gut-brain interactions during Parkinson’s disease

“…Bidirectionally, enteric glia is associated with microbial diversity based on structural domains of S100B (EF-hand calcium-binding and S100) and its protein domains. Interestingly, normal S100B condition and inhibition of its active or binding domain produce opposing effects on microbial diversity (Romano et al, 2021;Spica et al, 2023). Surprisingly, this work shows that distinct concentrations of S100B are associated with different microbial clusters.…”

The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker

“…Finally, as above indicated, based on the consideration that a decrease in the abundance and diversity of gut microbiota-specific genera may putatively trigger IBD-initiating events [134], the possible interactions of S100B with microbiota have been recently investigated both in silico [135] and experimentally in vivo in mice [136]. Microbiota proteins putatively interacting with S100B domains were found to be reduced in IBD patients with respect to healthy subjects, also exhibiting differences in the occurrence of interacting domains.…”

“…Interestingly, these in silico inferences were experimentally confirmed in mice. In fact, S100B levels were experimentally shown to correlate with microbiota biodiversity, and the correlation was significantly reduced after treatment with the S100B inhibitor PTM [136].…”

The Multifaceted S100B Protein: A Role in Obesity and Diabetes?

“…In contrast, after the first demonstration of S100B in the extracellular compartment in the late seventies of the last century, when elevated levels of the protein were detected in the cerebrospinal fluid of multiple sclerosis patients in the acute phase, whereas lower levels were found in the stationary phase of the disease [16], growing evidence indicates an increasingly clearer role for S100B when secreted in the extracellular compartment. Extracellular S100B is regarded to interact with target cells mainly, but not only, through the multi-ligand transmembrane Receptor for Advanced Glycation End-products (RAGE) initiating intracellular signaling cascades, which may result in physiological regulation at low nanomolar concentrations ("Jekyll side"), or various pathological conditions, acting as a Danger/Damage Associated Molecular Pattern (DAMP) protein, at higher micromolar concentrations ("Hyde side") [2,3,17]. Interestingly, some characteristics of S100B, such as its binding with RAGE, its non-canonical secretion modality that bypasses the classical Golgi route, and its ability to stimulate microglial migration, are shared with DAMPs [18,19].…”