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Here, we profiled stool-derived bEVs from healthy individuals using metaproteomic profiling, revealing that vesiculation is widespread across gut bacterial phyla. We selected a subset of vesiculating species, showing that bEVs localize to distinct tissues\n                  <jats:italic>in vivo<\/jats:italic>\n                  , including extraintestinal sites such as lung, liver, kidney, and bone, suggesting roles beyond the gastrointestinal tract. We profiled intestinal epithelial cells and macrophages after endocytosing bEVs from various species, uncovering pronounced, cell-type-specific responses. For example,\n                  <jats:italic>Bacteroides fragilis<\/jats:italic>\n                  bEVs promote anti-inflammatory mitochondrial-telomeric regulation, while a set of commensal-derived bEVs contribute to epithelial survival and structural renewal. By combining proteomic, lipidomic, and metabolomic cargo profiling with transcriptional output, we find that specific Bacteroidota-derived protein cargo activates cytoprotective stress defenses while attenuating inflammatory signaling. Together, these findings establish a multi-layered comparative atlas of bEV composition, uptake, and host response, providing a framework for understanding bEV-mediated microbiome-host communication.\n                <\/jats:p>","DOI":"10.64898\/2026.07.01.732738","type":"posted-content","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:05:44Z","timestamp":1783073144000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated multi-omics profiling of gut bacterial extracellular vesicles links cargo composition to host transcriptional responses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-8619","authenticated-orcid":false,"given":"Adarsh","family":"Singh","sequence":"first","affiliation":[{"name":"Nancy E. and Peter C. 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