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Rolof, A.

Publications and source records attributed to Rolof, A..

2 recordsLinked to original sources

A prebiotic-postbiotic combination supports dietary carbohydrate-targeting functional properties in a fiber-deprived microbiota

Dietary fiber deprivation compromises gut mucosal barrier integrity by promoting microbial degradation of host mucus, a process linked to various gut-related auto immune diseases. While postbiotics are considered safer alternatives to fiber for susceptible patients, their mechanistic ef- fects on a fiber-deprived gut remain poorly understood. Here, we demonstrate in a mouse model that a fermented postbiotic, alone or in combination with a prebiotic and aloe vera, counteracted the increase of detrimental properties of the microbiota on a fiber-free diet. The supplement regimen reshaped the gut microbiota, counteracting the expansion of key mucin-degrading bac- teria, including Akkermansia muciniphila and Parabacteroides goldsteinii. Metatranscriptomic analysis revealed this compositional change corresponded to a community-wide functional pivot away from expressing mucinolytic enzymes, such as sialidases, and towards utilizing alternative substrates. These microbial shifts recapitulated the effects of dietary fiber reintroduction and translated to direct host benefits, including sustentation of the colonic mucus layer and attenu- ation of diet-induced type III immune cytokine expression. Our findings provide a mechanistic rationale for using postbiotics to functionally replace dietary fiber, offering a promising strategy to support gut homeostasis in contexts where fiber intake is limited.

microbiology↗

Human internal exposures of bisphenol A and six data-poor analogues predicted by physiologically based kinetic models with multimodal parameterization

BackgroundBisphenols (BP) AF, B, E, F, M, and S have been introduced as substitutes for bisphenol A (BPA) and are increasingly used in consumer products. Despite widespread human exposure and potential adverse health outcomes related to BPF, BPB, BPS, and BPAF, their physiological disposition in humans is poorly characterized, which hinders assessment of associated risks. ObjectivesOur goal was to simulate the kinetic behavior of prevalent bisphenol analogs in organs of toxicological interest. To enable predictions of physiologically relevant internal concentrations of a family of structurally similar compounds with limited available human data, we aim to establish a reproducible framework using multimodal parameterization methods. MethodsHerein we developed physiologically based kinetic (PBK) models, following oral exposure. Their parametrization was primarily based on structural, physiological and experimental values, as well as quantitative structure-activity relationship (QSAR) predictions. Outputs were evaluated against available biomonitoring data for BPA and BPS. Critical parameters were identified by sensitivity analysis and iteratively re-sampled in Monte Carlo (MC) simulations to quantify uncertainties. ResultsAmong human models parametrized for males and females of different ages, we predicted that bisphenols reached the highest concentrations in 5-year-old males. Environmentally relevant exposure levels resulted in maximum concentrations in the blood and testes for BPS, and in the thyroid for BPM. After 96 hours, steady-state concentrations were not yet reached in the breasts for BPA, BPAF, BPB, BPE, BPF and BPM. ConclusionsThe data from this study suggest significant variability in internal concentrations for identical exposures to different bisphenols analogs that further depend on age, sex and organ. This diversity in toxicokinetic behavior should be considered for health risk assessment of these substitutes.

pharmacology and toxicology↗