Biology subjects

Mosig, A. S.

Publications and source records attributed to Mosig, A. S..

4 recordsLinked to original sources

bioRxiv2025

Secondary bile acid lithocholic acid ameliorates colitis-like inflammation in a human intestine-on-chip system

Inflammatory bowel disease (IBD) is a multifactorial disease of the gastrointestinal tract without curative treatment. Previous studies highlighted that altered fecal bile acid levels correlate with intestinal microbiota composition changes and inflammation in IBD. Lithocholic acid (LCA) is a secondary bile acid (SBA) drastically reduced during active IBD but mediates beneficial effects at the mucosal intestinal barrier during intestinal homeostasis. In a dextran sodium sulfate (DSS)-induced colitis-on-chip model, it was investigated whether the administration of LCA has a protective impact on inflammation-mediated tissue damage. Physiological responses were successfully recapitulated in the human colitis model, enabling the dissection of individual cell responses. Treatment with LCA concentrations similar to healthy human intestinal levels efficiently ameliorated the colitis-like phenotype. LCA treatment stimulated epithelial cell proliferation, thereby maintaining villus morphology, intestinal barrier integrity, and reducing inflammation. The protective effects of LCA were mainly mediated by the activation of the farnesoid X receptor (FXR).

cell biology↗

bioRxiv2025

A plug-and-play transepithelial/transendothelial electric resistance (TEER)-upgraded organ-on-chip system to measure barrier dynamics in real-time

The integration of transepithelial/transendothelial electrical resistance (TEER) measurement into organ-on-chip (OoC) platforms provides a unique opportunity to monitor the integrity of biological barriers in real-time. This is particularly important for detecting rapid changes in the temporal dynamics of intercellular junctional complexes in response to drug compounds, changes in host-microbiota interactions, and pathological disease states. Conventional TEER systems usually require special cell culture components or complex measurement technology that must be operated by experienced users. In this work, we present an innovative approach that represents an extension of the existing and well-established Dynamic42 chip platform by integrating semi-transparent TEER electrodes with fixed positions in combination with a measurement device. Remarkably, this system works in a plug-and-play manner and can continuously measure TEER inside the incubator without user intervention or invasive manipulation. Other important features of OoC, such as the microfluidic perfusion, multicellular cell colonization, and the possibility of microscopic examination, are not compromised by the integrated TEER electrodes. To demonstrate the performance of this new TEER system, we leveraged a 3D intestine-on-chip (IoC) model and investigated TEER during model assembly, barrier disruption, and recovery as a proof-of-concept. Moreover, we compared and discussed this with data from a conventional end-point fluorescence permeability assay to demonstrate the benefits of real-time measurements with higher sensitivity.

bioengineering↗

bioRxiv2024

Synergistic cross-kingdom host cell damage between Candida albicans and Enterococcus faecalis

The fungus Candida albicans and the Gram-positive bacterium Enterococcus faecalis share mucosal niches in the human body. As opportunistic pathogens, both are found to expand population size during dysbiosis, and can cause severe systemic infections in susceptible individuals. Here, we show that the presence of C. albicans results in increased host cell damage by E. faecalis. Furthermore, E. faecalis aggravates oropharyngeal candidiasis in mice. Increased damage is mediated by enterococcal cytolysin, and involves both physical interaction and altered glucose availability. Physical interaction promotes accumulation of bacteria on host cells, facilitating contact of cytolysin with host cells. Glucose depletion by the metabolic activity of the fungus sensitized host cells to cytolysin. This work illustrates how a complex interplay between fungi and bacteria can result in detrimental consequences for the host.

microbiology↗

bioRxiv2020

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction

Infections with SARS-CoV-2 lead to mild to severe coronavirus disease-19 (COVID-19) with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses. To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human alveolus-on-a-chip model composed of epithelial, endothelial, and mononuclear cells. Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including the interferon expression. By contrast, the adjacent endothelial layer was no infected and did neither show productive virus replication or interferon release. With prolonged infection, both cell types are damaged, and the barrier function is deteriorated, allowing the viral particles to overbear. In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokine release, which results in the damage of the alveolar barrier function and viral dissemination.

microbiology↗