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In this study, we employed an AAV-mPCSK9-induced murine atherosclerotic model to investigate the effects of daily\n                      <jats:italic>B. subtilis<\/jats:italic>\n                      natto NTU-18 administration over 16\u00a0weeks. High-dimensional flow cytometry using two 13-marker panels enabled longitudinal profiling of 18 peripheral immune cell subsets across lymphoid and myeloid compartments. While no significant changes in serum cholesterol and mild decrease of body weight were observed,\n                      <jats:italic>B. subtilis<\/jats:italic>\n                      natto NTU-18-treated mice presented a significant reduction in aortic lesion area compared to PBS-treated controls. Immune profiling revealed a transient expansion of peripheral myeloid cells and CD44\u207a trained CD8\u207a T cells, followed by increased frequencies of na\u00efve CD8\u207a T cells and reduced central\/effector memory subsets at longer time point treatment. In the CD4\u207a T cell compartment, a transient increase in trained cells was accompanied by a sustained enrichment of CD25\u207aCD4\u207a Tregs throughout the daily\n                      <jats:italic>B. subtilis<\/jats:italic>\n                      natto NTU-18 treatment. In contrast, no significant differences were observed in Ly6C\u207b or Ly6C\u207a monocytes, neutrophils, or eosinophils. These findings suggest that\n                      <jats:italic>B. subtilis<\/jats:italic>\n                      natto NTU-18 attenuates atherosclerosis progression not through lipid lowering or broad myeloid modulation, but via targeted reprogramming of peripheral T cell responses. This work provides mechanistic insight into the immunotherapeutic potential of\n                      <jats:italic>B. subtilis<\/jats:italic>\n                      natto NTU-18 in atherosclerosis prevention and treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:italic>\u2022 B. subtilis natto NTU-18 significantly reduces aortic plaque burden in atherosclerotic mice without affecting serum cholesterol levels<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>\u2022\u00a0B. subtilis natto NTU-18 induces transient immune remodeling, marked by early expansion of trained CD8\u207a and CD4\u207a T cells, followed by increased na\u00efve and regulatory T cells<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>\u2022\u00a0The atheroprotective effect is primarily mediated through adaptive immunity as myeloid subsets remain unchanged throughout B. subtilis natto NTU-18 treatment<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-025-13604-0","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:57:44Z","timestamp":1760680664000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacillus subtilis natto NTU-18 attenuates atherosclerosis progression by modulating peripheral immune cell alterations"],"prefix":"10.1007","volume":"109","author":[{"given":"Jian-Da","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Zhen","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sin-Ren","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Yi","family":"Kao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kung-Ta","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"issue":"4","key":"13604_CR1","doi-asserted-by":"publisher","first-page":"434","DOI":"10.18502\/ijm.v16i4.16301","volume":"16","author":"P Abedi Elkhichi","year":"2024","unstructured":"Abedi Elkhichi P, Aslanimehr M, Javadi A, Yadegar A (2024) Immunomodulatory effects of live and UV-killed Bacillus subtilis natto on inflammatory response in human colorectal adenocarcinoma cell line in vitro. 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This article does not contain any studies with human participants performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"229"}}