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Dietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome-rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as lipids, by intestinal epithelial cells. However, whether protein absorption is also affected by the gut microbiome is poorly understood. Here, we investigate connections between protein absorption and microbes in the zebrafish gut. Using live microscopy-based quantitative assays, we find that microbes slow the pace of protein uptake and degradation in LREs. While microbes do not affect the number of absorbing LRE cells, microbes lower the expression of endocytic and protein digestion machinery in LREs. Using transgene-assisted cell isolation and single cell RNA-sequencing, we characterize all intestinal cells that take up dietary protein. We find that microbes affect expression of bacteria-sensing and metabolic pathways in LREs, and that some secretory cell types also take up protein and share components of protein uptake and digestion machinery with LREs. Using custom-formulated diets, we investigated the influence of diet and LRE activity on the gut microbiome. Impaired protein uptake activity in LREs, along with a protein-deficient diet, alters the microbial community and leads to an increased abundance of bacterial genera that have the capacity to reduce protein uptake in LREs. Together, these results reveal that diet-dependent reciprocal interactions between LREs and the gut microbiome regulate protein absorption.
Pubmed ID: 40080061
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Database of biological data related to a single initiative, originating from a single organization or from a consortium. A BioProject record provides users a single place to find links to the diverse data types generated for that project. It is a searchable collection of complete and incomplete (in-progress) large-scale sequencing, assembly, annotation, and mapping projects for cellular organisms. Submissions are supported by a web-based Submission Portal. The database facilitates organization and classification of project data submitted to NCBI, EBI and DDBJ databases that captures descriptive information about research projects that result in high volume submissions to archival databases, ties together related data across multiple archives and serves as a central portal by which to inform users of data availability. BioProject records link to corresponding data stored in archival repositories. The BioProject resource is a redesigned, expanded, replacement of the NCBI Genome Project resource. The redesign adds tracking of several data elements including more precise information about a project''''s scope, material, and objectives. Genome Project identifiers are retained in the BioProject as the ID value for a record, and an Accession number has been added. Database content is exchanged with other members of the International Nucleotide Sequence Database Collaboration (INSDC). BioProject is accessible via FTP.
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