MAIT cell activation is reduced by direct and microbiota-mediated exposure to bisphenols.

Oral uptake is the primary route of human bisphenol exposure, resulting in an exposure of the intestinal microbiota and intestine-associated immune cells. Therefore, we compared the impact of bisphenol A (BPA), bisphenol F (BPF) and bisphenol S (BPS) on (i) intestinal microbiota, (ii) microbiota-mediated immunomodulatory effects and (iii) direct effects on mucosal-associated invariant T (MAIT) cells in vitro. We acutely exposed human fecal microbiota, Bacteroides thetaiotaomicron and Escherichia coli to BPA and its analogues BPF and BPS referring to the European tolerable daily intake (TDI), i.e. 2.3 µg/mL, 28.3 µg/mL and 354.0 µg/mL. Growth and viability of E. coli was most susceptible to BPF, whereas B.thetaiotaomicron and fecal microbiota were affected by BPA > BPF > BPS. At 354.0 µg/mL bisphenols altered microbial diversity in compound-specific manner and modulated microbial metabolism, with BPA already acting on metabolism at 28.3 µg/mL. Microbiota-mediated effects on MAIT cells were observed for the individual bacteria at 354.0 µg/mL only. However, BPA and BPF directly modulated MAIT cell responses at low concentrations, whereby bisphenols at concentrations equivalent for the current TDI had no modulatory effects for microbiota or for MAIT cells. Our findings indicate that acute bisphenol exposure may alter microbial metabolism and impact directly on immune cells.

Metagenomic insights into the taxonomy, function, and dysbiosis of prokaryotic communities in octocorals.

BACKGROUND: In octocorals (Cnidaria Octocorallia), the functional relationship between host health and its symbiotic consortium has yet to be determined. Here, we employed comparative metagenomics to uncover the distinct functional and phylogenetic features of the microbiomes of healthy Eunicella gazella, Eunicella verrucosa, and Leptogorgia sarmentosa tissues, in contrast with the microbiomes found in seawater and sediments. We further explored how the octocoral microbiome shifts to a pathobiome state in E. gazella. RESULTS: Multivariate analyses based on 16S rRNA genes, Clusters of Orthologous Groups of proteins (COGs), Protein families (Pfams), and secondary metabolite-biosynthetic gene clusters annotated from 20 Illumina-sequenced metagenomes each revealed separate clustering of the prokaryotic communities of healthy tissue samples of the three octocoral species from those of necrotic E. gazella tissue and surrounding environments. While the healthy octocoral microbiome was distinguished by so-far uncultivated Endozoicomonadaceae, Oceanospirillales, and Alteromonadales phylotypes in all host species, a pronounced increase of Flavobacteriaceae and Alphaproteobacteria, originating from seawater, was observed in necrotic E. gazella tissue. Increased abundances of eukaryotic-like proteins, exonucleases, restriction endonucleases, CRISPR/Cas proteins, and genes encoding for heat-shock proteins, inorganic ion transport, and iron storage distinguished the prokaryotic communities of healthy octocoral tissue regardless of the host species. An increase of arginase and nitric oxide reductase genes, observed in necrotic E. gazella tissues, suggests the existence of a mechanism for suppression of nitrite oxide production by which octocoral pathogens may overcome the host's immune system. CONCLUSIONS: This is the first study to employ primer-less, shotgun metagenome sequencing to unveil the taxonomic, functional, and secondary metabolism features of prokaryotic communities in octocorals. Our analyses reveal that the octocoral microbiome is distinct from those of the environmental surroundings, is host genus (but not species) specific, and undergoes large, complex structural changes in the transition to the dysbiotic state. Host-symbiont recognition, abiotic-stress response, micronutrient acquisition, and an antiviral defense arsenal comprising multiple restriction endonucleases, CRISPR/Cas systems, and phage lysogenization regulators are signatures of prokaryotic communities in octocorals. We argue that these features collectively contribute to the stabilization of symbiosis in the octocoral holobiont and constitute beneficial traits that can guide future studies on coral reef conservation and microbiome therapy. Video Abstract.