Adaptation and Resistance: How Bacteroides thetaiotaomicron Copes with the Bisphenol A Substitute Bisphenol F

Abstract

Bisphenols are used in the process of polymerization of polycarbonate plastics and epoxy resins. Bisphenols can easily migrate out of plastic products and enter the gastrointestinal system. By increasing colonic inflammation in mice, disrupting the intestinal bacterial community structure and altering the microbial membrane transport system in zebrafish, bisphenols seem to interfere with the gut microbiome. The highly abundant human commensal bacterium Bacteroides thetaiotaomicron was exposed to bisphenols (Bisphenol A (BPA), Bisphenol F (BPF), Bisphenol S (BPS)), to examine the mode of action, in particular of BPF. All chemicals caused a concentration-dependent growth inhibition and the half-maximal effective concentration (EC50) corresponded to their individual logP values, a measure of their hydrophobicity. B. thetaiotaomicron exposed to BPF decreased membrane fluidity with increasing BPF concentrations. Physiological changes including an increase of acetate concentrations were observed. On the proteome level, a higher abundance of several ATP synthase subunits and multidrug efflux pumps suggested an increased energy demand for adaptive mechanisms after BPF exposure. Defense mechanisms were also implicated by a pathway analysis that identified a higher abundance of members of resistance pathways/strategies to cope with xenobiotics (i.e., antibiotics). Here, we present further insights into the mode of action of bisphenols in a human commensal gut bacterium regarding growth inhibition, and the physiological and functional state of the cell. These results, combined with microbiota-directed effects, could lead to a better understanding of host health disturbances and disease development based on xenobiotic uptake.

High-throughput screening of the effects of 90 xenobiotics on the simplified human gut microbiota model (SIHUMIx): a metaproteomic and metabolomic study

“…Similarly, regarding xenobiotic metabolism, A. caccae showed positive correlation values with pathways involved in the extrusion of compounds outside the bacterial cell ( Figure 5B ). These stress response pathways, which are over-regulated, play a crucial role in the bacterial response to xenobiotics ( Riesbeck et al, 2022 ), enabling bacteria to export effector proteins, promote bacterial attachment, and adapt to changing environments.…”

“…Samples were prepared as previously described ( Riesbeck et al, 2022 ) with some modifications. Briefly, preserved pellets of SIHUMIx were resuspended in a lysis buffer consisting of 8 M urea, 2 M thiourea, and 1 mM phenylmethylsulfonyl fluoride.…”

High-Throughput Screening of the Effects of 90 Xenobiotics on the Simplified Human Gut Microbiota Model (SIHUMIx): A Metaproteomic and Metabolomic Study

“…5B ). These stress response pathways, which are over-regulated, play a crucial role in the bacterial response to xenobiotics (Riesbeck et al, 2022), enabling bacteria to export effector proteins, promote bacterial attachment, and adapt to changing environments.…”

“…Samples were prepared as previously described (Riesbeck et al, 2022) with some modifications. Briefly, preserved pellets of SIHUMIx were resuspended in a lysis buffer consisting of 8M urea, 2M thiourea, and 1 mM phenylmethylsulfonyl fluoride.…”

The Crosstalk between Gut Microbiota and Nervous System: A Bidirectional Interaction between Microorganisms and Metabolome

“…The host benefits of this suppression include the uptake of oligosaccharides to meet the body’s energy needs, suppression of the inflammatory response, immune tolerance to these microorganisms, and protection against allergic responses. The digestive adaptability of B. thetaiotaomicron contributes to the maintenance of intestinal homeostasis by allowing the microbiota to better respond to dietary changes without altering the intestinal microbial composition [ 59 ]. It has been noted that, in some animal studies (mice), the properties of this bacterium are involved in the development of the intestine from the earliest stages of life.…”