MAIT cell activation is reduced by direct and microbiota-mediated exposure to bisphenols
J L Krause1, B Engelmann2, U Nunes da Rocha3
1Helmholtz-Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; present address: German Rheumatism Research Center Berlin, a Leibniz Institute - DRFZ, Schwiete laboratory for microbiota and inflammation, Berlin, Germany.
Abstract:
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.
Insights
Acute exposure to bisphenols (BPA, BPF, BPS) impacts gut microbiota and immune cells. BPA and BPF directly affect mucosal-associated invariant T (MAIT) cells, even at low concentrations.
Area of Science:
- Environmental Health
- Microbiology
- Immunology
Background:
- Oral bisphenol exposure affects the gut microbiota and immune cells.
- Bisphenol A (BPA) and its analogues, bisphenol F (BPF) and bisphenol S (BPS), are common environmental contaminants.
Purpose of the Study:
- To compare the effects of BPA, BPF, and BPS on human intestinal microbiota and immune cells in vitro.
- To investigate microbiota-mediated and direct effects on mucosal-associated invariant T (MAIT) cells.
Main Methods:
- Exposure of human fecal microbiota, Bacteroides thetaiotaomicron, and Escherichia coli to BPA, BPF, and BPS at concentrations related to the European tolerable daily intake (TDI).
- Assessment of microbial growth, viability, diversity, and metabolism.
- Evaluation of microbiota-mediated and direct effects on MAIT cells.
Main Results:
- E. coli viability was most sensitive to BPF; B. thetaiotaomicron and fecal microbiota were affected by BPA > BPF > BPS.
- Bisphenols altered microbial diversity and metabolism, with BPA affecting metabolism at lower concentrations.
- BPA and BPF directly modulated MAIT cell responses at low concentrations, while effects on microbiota and MAIT cells were minimal at current TDI levels.
Conclusions:
- Acute bisphenol exposure can alter gut microbial metabolism.
- Bisphenols, particularly BPA and BPF, can directly impact immune cell function (MAIT cells).
- Further research is needed to understand the long-term health implications of bisphenol exposure.
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