a,b, Separation of BEVs from body fluids such as stool samples (a), shown in the Procedure, and blood plasma (b), detailed in Box 2, by orthogonal biophysical methods. a, After collection and preparation of the stool sample, a crude extract is prepared by ultrafiltration. BEVs are separated and recovered from this extract using the combination of a bottom-up density gradient and SEC. b, After collection of the blood sample, platelet-depleted plasma is prepared and a crude extract is obtained by SEC. BEVs are separated and recovered from this extract using the combination of a top-down density gradient and SEC. The expected BEV concentration is given per gram of stool sample (with a BSS category of 3 or 4) or milliliter of blood plasma. Steps requiring sample volume reduction are indicated with an asterisk. In addition, we present alongside a color coded scale to show BEV enrichment of stool and blood plasma relative to body fluid–specific contaminants.