Biology subjects

Gennings, C.

Publications and source records attributed to Gennings, C..

3 recordsLinked to original sources

bioRxiv2025

Zinc and Cobalt exposure influence Akkermansia muciniphila growth and short-chain fatty acid metabolism

Akkermansia muciniphila is a probiotic bacterium that has been proposed as a potential intervention for depression. A. muciniphila is a common mucin degrader, producing short fatty chain acids (SCFAs), including acetate, butyrate, and propionate, which can help regulate mood via the gut-brain axis. However, the interplay between A. muciniphila and other neuroactive environmental exposures is unclear. The objective of this study was to assess the effects of Zn and Co exposure, individually and together, on A. muciniphila growth and SCFA production. Minimum Inhibitory Concentration (MIC) was calculated for each metal, and sub-MIC exposure testing at high and low levels was conducted with single and combined metals. Growth curves were measured for each exposure condition, and SCFAs were measured using liquid chromatography-mass spectroscopy. Growth and SCFA production were compared between exposures and controls using paired t-tests and linear regression models. All p-values were corrected using FDR adjustments (q-values). A. muciniphila was tolerant to both metal exposures, with MICs at 750mg/L for Zn and 4,000 mg/L for Co. Growth at 24-and 48-hours was only significantly reduced upon exposure to high levels of Co, alone and in combination with Zn. Production of propionate significantly increased with high and low Zn exposures alone and in combination with low Co exposure (q-values <0.01), and significantly decreased with high Co exposure alone and in combination with Zn (q-values <0.01). Overall, A. muciniphila was metal tolerant, supporting its use as a probiotic in the presence of other neuroactive metal exposures.

microbiology↗

bioRxiv2025

A mixture of endocrine disrupting chemicals linked to lower birth weight induces adipogenesis and transcriptional changes related to birth weight alterations and diabetes

There is increasing evidence that endocrine disrupting chemicals (EDCs) are contributing to the rise in metabolic disorders and obesity. Humans are constantly exposed to numerous EDCs, thus human exposure entails complex EDC mixtures. In this study, we examined the effects of an EDC mixture, mixture G, composed of four phthalate esters, triclosan, and three poly- och perfluorinated alkyl substances. Mixture G had previously been defined based on its association with lower birth weight in a pregnancy cohort, where low birth weight is an early risk factor for metabolic morbidities later in life. Here, we studied its effects on adipogenesis and uncovered their underlying transcriptional changes. Human mesenchymal stem cells (hMSCs) were exposed to mixture G in concentrations and mixing ratios that reflect those measured in human serum. Mixture G induced adipogenesis in hMSCs, as evidenced by a dose-dependent increase in lipid droplet accumulation after 14-21 days. Notably, significant adipogenic effects were observed at concentrations comparable to those detected in humans. RNA-sequencing upon exposure for 48 h revealed dose-dependent transcriptional changes in over 1000 genes. Mixture G-induced differentially expressed genes (DEGs) showed significant overlap with genes involved in osteogenesis, with glucocorticoid-regulated genes, and with genes associated with birth weight alterations and diabetes type II. These results indicate that exposure to an environmentally relevant EDC mixture induces adipogenesis and leads to transcriptional alterations that might change the balance between adipogenic and osteogenic differentiation as well as the functionality of MSCs, possibly via interference with glucocorticoid signalling. Thus our findings underscore the role of EDCs as metabolic disruptors and shed light on the molecular mechanisms underlying their potential contribution to the development of metabolic disorders. HighlightsO_LIAn endocrine disruptor mixture linked to lower birth weight increases adipogenesis C_LIO_LIThe mixture induced transcriptomic changes at low doses C_LIO_LIAffected genes are associated with birth weight and diabetes type II C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/638050v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@12428bforg.highwire.dtl.DTLVardef@ef28b3org.highwire.dtl.DTLVardef@159024corg.highwire.dtl.DTLVardef@a605b7_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2017

From Cohorts to Molecules: Adverse Impacts of Endocrine Disrupting Mixtures

Convergent evidence associates endocrine disrupting chemicals (EDCs) with major, increasingly-prevalent human disorders. Regulation requires elucidation of EDC-triggered molecular events causally linked to adverse health outcomes, but two factors limit their identification. First, experiments frequently use individual chemicals, whereas real life entails simultaneous exposure to multiple EDCs. Second, population-based and experimental studies are seldom integrated. This drawback was exacerbated until recently by lack of physiopathologically meaningful human experimental systems that link epidemiological data with results from model organisms.\n\nWe developed a novel approach, integrating epidemiological with experimental evidence. Starting from 1,874 mother-child pairs we identified mixtures of chemicals, measured during early pregnancy, associated with language delay or low-birth weight in offspring. These mixtures were then tested on multiple complementary in vitro and in vivo models. We demonstrate that each EDC mixture, at levels found in pregnant women, disrupts hormone-regulated and disease-relevant gene regulatory networks at both the cellular and organismal scale.

molecular biology↗