Abstract
Extracellular vesicles (EVs) derived from the gut microbiota are largely uncharacterized and their impacts on host intestinal physiology remain unresolved. Here, we isolated EVs from F. nucleatum for detailed characterization. Our analyses highlight the presence of the outer membrane protein porin FomA on EVs. Besides, we evaluated the impact of EVs on human intestinal epithelial cells (IECs) in a non-inflammatory context. Our results show no detrimental impact on the epithelial barrier. No internalization of EVs was observed. Moreover, we demonstrate that F. nucleatum EVs trigger innate immunity of IECs by promoting NF-κB activation via the dynamin-mediated endocytosis. The NF-κB activation was found to be TLR2-dependent yet, TLR4 was dispensable. Using competitive binding assays, we establish that FomA is involved in the NF-κB response. Taken together, our data indicate that EVs induce effects similar to those observed with whole F. nucleatum bacteria on IECs. In particular, our study highlights the role of TLR2 and FomA as major modulators of the gut epithelium immune responses to F. nucleatum.
Highlights
The gut microbiota and its human host are constantly exchanging a panoply of distinct molecules, resulting in a complex and dynamic interrelationship
In Transmission Electron Microscopy (TEM), Extracellular vesicles (EVs) were mostly present in fractions 2 to 8, which is in accordance with our SDSPAGE assay results
It is worth noting that FomA, as well as other contaminant proteins and vesicles were found in the “crude” EV preparations before density gradient separation by far-western blot and TEM observation
Summary
The gut microbiota and its human host are constantly exchanging a panoply of distinct molecules, resulting in a complex and dynamic interrelationship This molecular dialogue is dependent on the microbial composition at the strain level and functions at gene level, and shifts in the microbial community can have profound effects on the host’s health status. Alterations of community composition are context- and disease-specific, and rarely homogenous across patients leading to unsolved questions over causality [1, 2]. Despite these heterogeneities, the over-growth of species expressing a high “pathogenic potential”, previously referred to as pathobionts, is one feature repeatedly associated with alterations of the gut microbiota composition [3]. What triggers Fusobacterium expansion in these individuals is undetermined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
