{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:38:26Z","timestamp":1780918706337,"version":"3.54.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>Owing to advancements in non-invasive magnetic resonance imaging, many studies have repeatedly showed that diabetes affects the central nervous system in the presence of peripheral neuropathy, suggesting a common or interacting pathological mechanism for both complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We aimed to investigate the role of abnormal gut microbiota in rats with diabetic peripheral neuropathy (DPN) combined with cognitive dysfunction. Glucose-compliant rats with nerve conduction deficits were screened as a successful group of DPN rats. The DPN group was then divided into rats with combined cognitive impairment (CD) and rats with normal cognitive function (NCD) based on the results of the Novel object recognition test. Rat feces were then collected for 16S rRNA gene sequencing of the intestinal flora.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>The results revealed that abnormalities in <jats:italic>Firmicutes<\/jats:italic>, <jats:italic>Ruminococcaceae<\/jats:italic>, <jats:italic>Bacteroidia<\/jats:italic>, and <jats:italic>Actinobacteria-like microorganisms<\/jats:italic> may induce DPN complicated by cognitive dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1156591","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T05:07:20Z","timestamp":1681794440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The role of gut microbiota in diabetic peripheral neuropathy rats with cognitive dysfunction"],"prefix":"10.3389","volume":"14","author":[{"given":"Wei","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JieMin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Manyande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao Feng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxiong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1159\/000522381","article-title":"Is there any link between cognitive impairment and gut microbiota? 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Lipid Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1128\/IAI.01374-15","article-title":"Intestinal epithelial toll-like receptor 4 signaling affects epithelial function and colonic microbiota and promotes a risk for transmissible colitis","volume":"84","author":"Dheer","year":"2016","journal-title":"Infect. Immun."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1002\/ptr.7429","article-title":"Anti-inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K\/Akt\/mTOR signaling pathway and regulating gut microbiota","volume":"36","author":"Dong","year":"2022","journal-title":"Phytother. Res."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3389\/fcimb.2020.00063","article-title":"Gut microbiome profiles are associated with type 2 diabetes in urban Africans","volume":"10","author":"Doumatey","year":"2020","journal-title":"Front. Cell. Infect. 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Psychiatry"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1096\/fj.00-0359fje","article-title":"Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production","volume":"14","author":"S\u00e4emann","year":"2000","journal-title":"FASEB J."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"3461","DOI":"10.3892\/etm.2019.7943","article-title":"Dysbiosis of gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease","volume":"18","author":"Salguero","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1016\/j.cell.2016.11.018","article-title":"Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson\u2019s disease","volume":"167","author":"Sampson","year":"2016","journal-title":"Cells"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1007\/s11892-011-0205-z","article-title":"Central nervous system involvement in diabetic neuropathy","volume":"11","author":"Selvarajah","year":"2011","journal-title":"Curr. Diab. Rep."},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12892","article-title":"Induction of a single-dose of Streptozotocin (50 mg) in rat model causes insulin resistance with type 2 diabetes mellitus","author":"Sharma","year":"2023","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14069","article-title":"Decoding the contributions of gut microbiota and cerebral metabolism in acute liver injury mice with and without cognitive dysfunction","author":"Sun","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.neuropharm.2014.05.023","article-title":"Memantine prevents reference and working memory impairment caused by sleep deprivation in both young and aged Octodon degus","volume":"85","author":"Tarragon","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"16009","DOI":"10.1038\/npjbiofilms.2016.9","article-title":"Oral treatment with Eubacterium hallii improves insulin sensitivity in db\/db mice","volume":"2","author":"Udayappan","year":"2016","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"2834","DOI":"10.3748\/wjg.v27.i21.2834","article-title":"Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation","volume":"27","author":"Wen","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s11892-013-0394-8","article-title":"Magnetic resonance imaging of the central nervous system in diabetic neuropathy","volume":"13","author":"Wilkinson","year":"2013","journal-title":"Curr. Diab. Rep."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"909461","DOI":"10.3389\/fmicb.2022.909461","article-title":"The role of gut microbiota in mice with bile duct ligation-evoked Cholestatic liver disease-related cognitive dysfunction","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.2147\/NSS.S330022","article-title":"Gut microbiota in patients with type 1 narcolepsy","volume":"13","author":"Zhang","year":"2021","journal-title":"Nature Sci. 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