{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T13:03:54Z","timestamp":1779714234684,"version":"3.53.1"},"reference-count":22,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Neuroinflammation is a key contributor to the progression of several neurodegenerative disorders, including Alzheimer\u2019s disease, stroke, and small vessel disease. Emerging evidence highlights the role of circulating microRNAs (miRNAs) as non-invasive biomarkers of neuroinflammation and neuronal injury. miR-106a-5p, a member of the miR-17~92 cluster, is known to regulate inflammation, apoptosis, and vascular function. While typically studied in plasma or cerebrospinal fluid, gastric juice miRNAs represent a novel and underexplored source for biomarker discovery within the gut\u2013brain axis. This exploratory study aimed to investigate the association between gastric juice miR-106a-5p expression and markers of neuroinflammation, including C-reactive protein (CRP), lactate dehydrogenase (LDH), and imaging-based evidence of neurodegeneration. Methods: A prospective, observational study was conducted on 38 participants (22 with neurodegenerative pathology and 16 healthy controls). Gastric juice samples were analyzed for miR-106a-5p using RT-qPCR, normalized to U6 snRNA. \u0394Ct values were used to determine relative expression. Statistical analyses included t-tests\/Wilcoxon tests, ROC curve analysis, and correlation testing, with significance set at p &lt; 0.05. Results: Patients with neurodegenerative changes exhibited significantly lower gastric miR-106a-5p expression compared to controls (p = 0.044). Elevated CRP and LDH levels were associated with higher \u0394Ct values (indicating lower expression), with p-values of 0.019 and 0.023, respectively. ROC analysis showed moderate diagnostic accuracy (AUC = 0.701) for miR-106a in identifying neurodegenerative status. miR-106a levels also correlated inversely with carotid intima-media thickness and brain MRI abnormalities, also reduced gastric miR-106a-5p expression is associated with systemic inflammation and neuroimaging evidence of neurodegeneration. Conclusions: While causality cannot be inferred, these findings suggest that gastric miR-106a may serve as a promising non-invasive biomarker within the gut\u2013brain axis framework. Further longitudinal and mechanistic studies are warranted to validate its clinical utility and explore its potential role in monitoring neuroinflammatory conditions.<\/jats:p>","DOI":"10.3390\/diseases14060187","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:57:44Z","timestamp":1779710264000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastric Juice miR-106a-5p as a Non-Invasive Biomarker of Neuroinflammation and Neurodegeneration: A Prospective Observational Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7368-7674","authenticated-orcid":false,"given":"Sabrina","family":"Birsan","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University Lucian Blaga, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulian","family":"Roman-Filip","sequence":"additional","affiliation":[{"name":"Clinical Department, Faculty of Medicine, University of Medicine \u2018George Emil Palade\u2019, 540139 Targu Mure, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Rusu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University Lucian Blaga, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2217-6755","authenticated-orcid":false,"given":"Fratila","family":"Anca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University Lucian Blaga, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-1585","authenticated-orcid":false,"given":"Adrian","family":"Boicean","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University Lucian Blaga, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pogony","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University Lucian Blaga, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grama","family":"Blanca","sequence":"additional","affiliation":[{"name":"Faculty of Psychology; University Lucian Blaga of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Roman-Filip","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University Lucian Blaga, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adamu, A., Li, S., Gao, F., and Xue, G. (2024). The role of neuroinflammation in neurodegenerative diseases: Current understanding and future therapeutic targets. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1347987"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., Di Benedetto, S., and M\u00fcller, V. (2025). The dual nature of neuroinflammation in networked brain. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1659947"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Du, W., Fan, L., and Du, J. (2023). Neuroinflammation-associated miR-106a-5p serves as a biomarker for the diagnosis and prognosis of acute cerebral infarction. BMC Neurol., 23.","DOI":"10.1186\/s12883-023-03241-3"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Muzio, L., Viotti, A., and Martino, G. (2021). Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.742065"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/ame2.12418","article-title":"MiR-106a targets ATG7 to inhibit autophagy and angiogenesis after myocardial infarction","volume":"7","author":"Bai","year":"2024","journal-title":"Anim. Models Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1177\/0271678X241254772","article-title":"Role of miRNAs in neurovascular injury and repair","volume":"44","author":"Sawant","year":"2024","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1002\/cncr.27903","article-title":"Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer","volume":"119","author":"Cui","year":"2013","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1373\/clinchem.2010.147405","article-title":"The MicroRNA Spectrum in 12 Body Fluids","volume":"56","author":"Weber","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.1073\/pnas.1019055108","article-title":"Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma","volume":"108","author":"Arroyo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41392-024-01743-1","article-title":"Microbiota\u2013gut\u2013brain axis and its therapeutic applications in neurodegenerative diseases","volume":"9","author":"Loh","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chen, Q., Yao, Z., Duan, J., Zhang, Y., Cao, X., Zhai, D., Liu, Y., Mou, S., and Zhu, C. (2025). The levels of plasma MiR-9 and MiR-106a are associated with the development of peritoneal carcinomatosis in patients with gastric cancer. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-14427-y"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Daneshpour, M., and Ghadimi-Daresajini, A. (2023). Overview of miR-106a Regulatory Roles: From Cancer to Aging. Bioengineering, 10.","DOI":"10.3390\/bioengineering10080892"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.7150\/ijbs.47203","article-title":"miRNA-based biomarkers, therapies, and resistance in Cancer","volume":"16","author":"He","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, L., Luo, X., Tang, R., Wu, Y., Liang, Z., Liu, J., Pi, J., and Zhang, H. (2024). MiR-106a-5p by Targeting MAP3K2 Promotes Repair of Oxidative Stress Damage to the Intestinal Barrier in Prelaying Ducks. Animals, 14.","DOI":"10.3390\/ani14071037"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, H., Zeng, Y., Wang, D., Li, Y., Xing, J., Zeng, Y., Liu, Z., Zhou, X., and Fan, H. (2024). Neuroinflammation of Microglial Regulation in Alzheimer\u2019s Disease: Therapeutic Approaches. Molecules, 29.","DOI":"10.3390\/molecules29071478"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nikolajevic, J., Ariaee, N., Liew, A., Abbasnia, S., Fazeli, B., and Sabovic, M. (2022). The Role of MicroRNAs in Endothelial Cell Senescence. Cells, 11.","DOI":"10.3390\/cells11071185"},{"key":"ref_17","first-page":"3827","article-title":"miR-106a promotes growth and metastasis of non-small cell lung cancer by targeting PTEN","volume":"8","author":"Xie","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhi, F., Zhou, G., Shao, N., Xia, X., Shi, Y., Wang, Q., Zhang, Y., Wang, R., Xue, L., and Wang, S. (2013). miR-106a-5p Inhibits the Proliferation and Migration of Astrocytoma Cells and Promotes Apoptosis by Targeting FASTK. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072390"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s13238-012-2003-z","article-title":"Horizontal transfer of microRNAs: Molecular mechanisms and clinical applications","volume":"3","author":"Chen","year":"2012","journal-title":"Protein Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eaai7696","DOI":"10.1126\/scisignal.aai7696","article-title":"Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions","volume":"10","author":"Dickens","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_22","first-page":"3421","article-title":"Gut Microbiota-Immune System Interactions in Health and Neurodegenerative Diseases: Insights into Molecular Mechanisms and Therapeutic Applications","volume":"16","author":"Balakrishnan","year":"2024","journal-title":"Aging Dis."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/6\/187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T12:23:32Z","timestamp":1779711812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/6\/187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":22,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["diseases14060187"],"URL":"https:\/\/doi.org\/10.3390\/diseases14060187","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]}}}