{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:32:57Z","timestamp":1791293577561,"version":"4.1.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,6,13]]},"abstract":"<jats:p>\n                    <jats:italic>Shigella<\/jats:italic>\n                    is a major cause of morbidity, mortality, and growth retardation for children in developing countries. Emergence of antibiotic resistance among\n                    <jats:italic>Shigellae<\/jats:italic>\n                    demands the development of effective medicines. Previous studies found that the endogenous antimicrobial peptide LL-37 is down-regulated in the rectal epithelium of patients during shigellosis and that butyrate up-regulates the expression of LL-37 in colonic epithelial cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    and decreases severity of inflammation in experimental shigellosis. In this study,\n                    <jats:italic>Shigella<\/jats:italic>\n                    -infected dysenteric rabbits were treated with butyrate (0.14 mmol\/kg of body weight) twice daily for 3 days, and the expression levels of the rabbit homologue to LL-37, CAP-18, were monitored in the colon. Butyrate treatment resulted in (\n                    <jats:italic>i<\/jats:italic>\n                    ) reduced clinical illness, severity of inflammation in the colon, and bacterial load in the stool, (\n                    <jats:italic>ii<\/jats:italic>\n                    ) significant up-regulation of CAP-18 in the surface epithelium, and (\n                    <jats:italic>iii<\/jats:italic>\n                    ) disappearance of CAP-18-positive cells in lamina propria. The active CAP-18 peptide was released in stool from its proform by butyrate treatment. In healthy controls, CAP-18 expression was localized predominantly to the epithelial surface of the colon. In infected rabbits, CAP-18 expression was localized to immune and inflammatory cells in the colon, whereas the ulcerated epithelium was devoid of CAP-18 expression. The combination of CAP-18 and butyrate was more efficient in killing\n                    <jats:italic>Shigella in vitro<\/jats:italic>\n                    than CAP-18 alone. Our findings indicate that oral butyrate treatment in shigellosis may be of clinical value because of induction of the endogenous cathelicidin CAP-18 in the colonic epithelium, stimulation of the release of the active peptide CAP-18, and promoting elimination of\n                    <jats:italic>Shigella<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.0602888103","type":"journal-article","created":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T20:57:35Z","timestamp":1149195455000},"page":"9178-9183","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":259,"title":["Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic"],"prefix":"10.1073","volume":"103","author":[{"given":"Rubhana","family":"Raqib","sequence":"first","affiliation":[{"name":"*International Centre for Diarrhoeal Disease Research Bangladesh, Centre for Health and Population Research, Dhaka 1212, Bangladesh;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Protim","family":"Sarker","sequence":"additional","affiliation":[{"name":"*International Centre for Diarrhoeal Disease Research Bangladesh, Centre for Health and Population Research, Dhaka 1212, Bangladesh;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bergman","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gul","family":"Ara","sequence":"additional","affiliation":[{"name":"*International Centre for Diarrhoeal Disease Research Bangladesh, Centre for Health and Population Research, Dhaka 1212, Bangladesh;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lindh","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Sack","sequence":"additional","affiliation":[{"name":"*International Centre for Diarrhoeal Disease Research Bangladesh, Centre for Health and Population Research, Dhaka 1212, Bangladesh;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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