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Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell \u03b1-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81\u00a0years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age\u2009&gt;\u200970\u00a0years old) was significantly lower than the middle-aged group (age\u2009\u2264\u200970\u00a0years old). Furthermore, individual age was negatively correlated with HD5 concentration (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2009\u2212\u20090.307, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In \u03b2-diversity, the intestinal microbiota of the elderly showed a significantly different composition compared to the middle-aged. At the genus level, relative abundance of <jats:italic>Collinsella<\/jats:italic>, <jats:italic>Alistipes<\/jats:italic>, Peptococcaceae; unassigned, <jats:italic>Lactobacillus<\/jats:italic>, <jats:italic>Lactococcus<\/jats:italic>, <jats:italic>Weissella<\/jats:italic>, <jats:italic>Christensenellaceae R-7 group<\/jats:italic>, <jats:italic>Megasphaera<\/jats:italic>, and <jats:italic>[Eubacterium] eligens group<\/jats:italic> was significantly higher, and Lachnospiraceae; unassigned, <jats:italic>Blautia<\/jats:italic>, <jats:italic>Anaerostipes<\/jats:italic>, <jats:italic>Fusicatenibacter<\/jats:italic>, <jats:italic>Dorea<\/jats:italic>, and <jats:italic>Faecalibacterium<\/jats:italic> was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with <jats:italic>Alistipes<\/jats:italic>, Peptococcaceae; unassigned, and <jats:italic>Christensenellaceae R-7 group<\/jats:italic> and positively correlated with Lachnospiraceae; unassigned and <jats:italic>Dorea<\/jats:italic>. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.<\/jats:p>","DOI":"10.1007\/s11357-021-00398-y","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T16:03:17Z","timestamp":1623168197000},"page":"997-1009","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Lower human defensin 5 in elderly people compared to middle-aged is associated with differences in the intestinal microbiota composition: the DOSANCO Health Study"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-7678","authenticated-orcid":false,"given":"Yu","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2138-1733","authenticated-orcid":false,"given":"Kiminori","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-4873","authenticated-orcid":false,"given":"Mani","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4084-1720","authenticated-orcid":false,"given":"Shigekazu","family":"Ukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-7614","authenticated-orcid":false,"given":"Koshi","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9345-0937","authenticated-orcid":false,"given":"Emiko","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Imae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-7702","authenticated-orcid":false,"given":"Ryodai","family":"Yamamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-3879","authenticated-orcid":false,"given":"Akiko","family":"Tamakoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8631-5593","authenticated-orcid":false,"given":"Tokiyoshi","family":"Ayabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"398_CR1","doi-asserted-by":"publisher","DOI":"10.18356\/13bf5476-en","volume-title":"World Population Prospects 2019: Highlights","author":"United Nations","year":"2019","unstructured":"United Nations. 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