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Over the last four decades, its biological functions have been elucidated and shown to be critically modulated by tyrosine sulfation. Recently, this octapeptide has been identified as a potential biomarker in several tumours. Regrettably, there are no clinical or analytical methods capable of distinguishing between the unsulfated (CCK\u20108) and sulfated (SO\n                    <jats:sub>3<\/jats:sub>\n                    \u2010CCK\u20108) forms in controlled media (e.g., saline) or complex biofluids (e.g., human serum). Here, we use an aerolysin nanopore inserted in a lipid\u2010polymer membrane to discriminate them with high specificity and sensitivity at the single\u2010molecule level in both controlled media and complex biofluids, even at low nanomolar concentrations. We found that sulfated and unsulfated CCK\u20108 generate highly resolutive electrical signatures. Analysis of these signals shows discrimination based on three independent parameters. Using a robust hybrid lipid\u2010coblock membrane, we successfully performed measurements in 20% (v\/v) human serum, thereby enabling the identification of peptides differing by a subtle post\u2010translational modification. These results enable reliable discrimination of these biomarkers for diagnostic evaluation.\n                  <\/jats:p>","DOI":"10.1002\/smll.74968","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:03:38Z","timestamp":1785751418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Discrimination of Sulfated and Unsulfated Gut\u2010Hormone Biomarkers in Human Serum by Nanopore"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4055-7909","authenticated-orcid":false,"given":"Luca","family":"Iesu","sequence":"first","affiliation":[{"name":"CNRS, LAMBE, Universit\u00e9 Paris\u2010Saclay, Univ. d'\u00c9vry CY Cergy Paris Universit\u00e9  Cergy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1763-2456","authenticated-orcid":false,"given":"Laurent","family":"Bacri","sequence":"additional","affiliation":[{"name":"CNRS, LAMBE, Universit\u00e9 Paris\u2010Saclay, Univ. d'\u00c9vry CY Cergy Paris Universit\u00e9  \u00c9vry\u2010Courcouronnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1896-4137","authenticated-orcid":false,"given":"Juan","family":"Pelta","sequence":"additional","affiliation":[{"name":"CNRS, LAMBE, Universit\u00e9 Paris\u2010Saclay, Univ. d'\u00c9vry CY Cergy Paris Universit\u00e9  \u00c9vry\u2010Courcouronnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9319-3152","authenticated-orcid":false,"given":"Benjamin","family":"Cressiot","sequence":"additional","affiliation":[{"name":"CNRS, LAMBE, Universit\u00e9 Paris\u2010Saclay, Univ. d'\u00c9vry CY Cergy Paris Universit\u00e9  Cergy France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889\u2010019\u20107762\u20105"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2018.11"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.166340"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586\u2010018\u201001668\u20100"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010002\u20101309\u20109"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/DNND.S228939"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21854"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2018.1483340"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00825-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.2c01256"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00047"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016\u20105085(99)70227\u20101"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2006.1856"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000055831"},{"key":"e_1_2_8_16_1","first-page":"1","article-title":"Neurobiology of Cholecystokinin","volume":"9","author":"Moran T. 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