{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:59:29Z","timestamp":1790675969981,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Diabetic cardiomyopathy (DCM) is an important substrate of diabetes-related heart failure and is increasingly considered within a gut\u2013heart systems framework. Here, we propose a compartment-resolved microbial sulfur\u2013cardiac signaling model rather than a linear pathway in which free gut-derived sulfide species are assumed to reach the myocardium intact. Gut microbes generate sulfide through dissimilatory sulfate reduction, anaerobic sulfite reduction, assimilatory sulfur pathways, and sulfur-amino-acid catabolism, whereas intestinal epithelial cells and liver strongly constrain systemic exposure through mitochondrial sulfide oxidation. Recent work reports that microbial sulfide-associated metabolism can influence enteroendocrine GLP-1 signaling, hepatic PPAR\u03b1-dependent metabolism, and systemic sulfur handling through intestinal SQOR-dependent pathways; however, none of these studies demonstrates direct sulfur transfer from microbial metabolism to the diabetic heart or establishes a sulfur-specific causal pathway leading to myocardial persulfidation. In parallel, diabetic-heart studies report sulfide-donor-responsive persulfidation candidates including MuRF1 Cys44, SYVN1\/Hrd1 Cys115, and SENP1 Cys683, but the evidence is concentrated in an overlapping research program and is methodologically dependent. We therefore separate better-supported local processes, cross-organ supporting evidence, and unresolved DCM-specific links, and outline source-resolved isotope tracing, microbial genetics, host sulfur-enzyme models, and orthogonal site-resolved persulfidation assays needed to test causality.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1966245","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:29:02Z","timestamp":1790674142000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A compartment-resolved framework for microbial sulfur\u2013reactive sulfur signaling in diabetic cardiomyopathy: from gut metabolism to cardiac sulfur responses"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingda","family":"Han","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Sun","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences Guang'anmen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Mu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaile","family":"Ma","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences Guang'anmen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jia","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences Guang'anmen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences Guang'anmen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.3389\/fphys.2018.01514","article-title":"Diabetic cardiomyopathy: current and future therapies. 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