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The main clinical interventions for CKD\u2013SHPT involve calcium supplements to boost absorption, but ineffective for some patients, and the reasons remain unclear. Here, CKD mice are divided into high and low groups based on intact parathyroid hormone (iPTH) levels. The high group exhibits significant changes in gut microbes, including a decrease in <jats:italic>Lactobacillus<\/jats:italic>, an increase in parathyroid hyperplasia, and a decrease in intestinal calcium. Fecal microbiota transplantation and <jats:italic>L. johnsonii<\/jats:italic> colonization indicate a link between gut microbes and CKD\u2013SHPT. Clinically, higher <jats:italic>L. johnsonii<\/jats:italic> levels are correlated with milder hyperparathyroidism CKD\u2013SHPT. The receiver operating characteristic (ROC) curve for <jats:italic>L. johnsonii<\/jats:italic> abundance and surgical risk is 0.81, with the calibration curve confirming predictive accuracy, and decision curve analysis revealing good clinical applicability. In vivo and in vitro experiments show that cyclo(pro\u2010trp) enhance calcium inflow and lower iPTH levels in intestinal epithelial cells via a calcium\u2010sensing receptor and transient receptor potential vanilloid 4 pathways. This study identified the crucial role of <jats:italic>L. johnsonii<\/jats:italic> in CKD\u2013SHPT, unveiling a new mechanism for calcium imbalance and offering novel strategies for SHPT treatment and drug development.<\/jats:p>","DOI":"10.1002\/advs.202414678","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T06:11:07Z","timestamp":1738303867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<i>Lactobacillus johnsonii<\/i> Generates Cyclo(pro\u2010trp) and Promotes Intestinal Ca<sup>2+<\/sup> Absorption to Alleviate CKD\u2013SHPT"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiong","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of General Surgery Xinqiao Hospital Army Medical University (Third Military Medical University)  Chongqing 400037 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