{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:58:22Z","timestamp":1790287102611,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"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>Background and objective<\/jats:title><jats:p>Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Specific pathogen-free C57BL\/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3\u2009weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30\u2009min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1252795","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T05:19:33Z","timestamp":1700716773000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Gut microbiota from essential tremor patients aggravates tremors in mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Ruo-Xin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Ting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Jie","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Li","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Pei","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ting","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Xiang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/s0304-3940(02)00042-3","article-title":"Effect of acute caffeine on severity of harmaline induced tremor in rats","volume":"325","author":"Al-Deeb","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1442-9993.2001.01070.pp.x","article-title":"A new method for non-parametric multivariate analysis of variance","volume":"26","author":"Anderson","year":"2001","journal-title":"Austral Ecol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1111\/j.1365-2672.2012.05344.x","article-title":"\u03b3-aminobutyric acid production by culturable bacteria from the human intestine","volume":"113","author":"Barrett","year":"2012","journal-title":"J. Appl. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"10719","DOI":"10.1073\/pnas.1711233114","article-title":"Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice","volume":"114","author":"Berer","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1172\/jci118861","article-title":"Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4+ TH1-like responses","volume":"98","author":"Berg","year":"1996","journal-title":"J. Clin. Invest."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s40168-018-0470-z","article-title":"Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2\u2019s q2-feature-classifier plugin","volume":"6","author":"Bokulich","year":"2018","journal-title":"Microbiome"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"16050","DOI":"10.1073\/pnas.1102999108","article-title":"Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve","volume":"108","author":"Bravo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"325","DOI":"10.2307\/1942268","article-title":"An ordination of the upland forest communities of southern Wisconsin","volume":"27","author":"Bray","year":"1957","journal-title":"Ecol. Monogr."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e103","DOI":"10.1093\/nar\/gkz569","article-title":"High-throughput amplicon sequencing of the full-length 16S rRNA gene with single-nucleotide resolution","volume":"47","author":"Callahan","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3354\/MEPS180257","article-title":"Ecological patterns in multivariate assemblages: information and interpretation of negative values in ANOSIM tests","volume":"180","author":"Chapman","year":"1999","journal-title":"Mar. Ecol. Prog. Ser."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1136\/gut.17.11.895","article-title":"Analysis of the effects of food and of digestive secretions on the small intestine of the rat. 1 Mucosal morphology and epithelial replacement","volume":"17","author":"Clarke","year":"1976","journal-title":"Gut"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1101\/gr.112730.110","article-title":"Chimeric 16S rRNA sequence formation and detection in sanger and 454-pyrosequenced PCR amplicons","volume":"21","author":"Haas","year":"2011","journal-title":"Genome Res."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1056\/NEJMcp1707928","article-title":"Essential tremor","volume":"378","author":"Haubenberger","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3389\/fnmol.2019.00171","article-title":"Gut microbiota differs between Parkinson\u2019s disease patients and healthy controls in Northeast China","volume":"12","author":"Li","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"634069","DOI":"10.3389\/fcell.2020.634069","article-title":"Structural and functional dysbiosis of fecal microbiota in Chinese patients with Alzheimer\u2019s disease","volume":"8","author":"Ling","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1111\/psyg.12583","article-title":"Faecal microbiota transplantation simultaneously ameliorated patient\u2019s essential tremor and irritable bowel syndrome","volume":"20","author":"Liu","year":"2020","journal-title":"Psychogeriatrics"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/mds.22838","article-title":"How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor","volume":"25","author":"Louis","year":"2010","journal-title":"Mov. Disord."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1128\/aem.01996-06","article-title":"Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities","volume":"73","author":"Lozupone","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"8228","DOI":"10.1128\/aem.71.12.8228-8235.2005","article-title":"UniFrac: a new phylogenetic method for comparing microbial communities","volume":"71","author":"Lozupone","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/ismej.2010.133","article-title":"UniFrac: an effective distance metric for microbial community comparison","volume":"5","author":"Lozupone","year":"2011","journal-title":"ISME J."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.bbi.2017.06.018","article-title":"Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice","volume":"66","author":"Ma","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1093\/bioinformatics\/btr507","article-title":"FLASH: fast length adjustment of short reads to improve genome assemblies","volume":"27","author":"Mago\u010d","year":"2011","journal-title":"Bioinformatics"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1136\/jnnp.57.8.1012","article-title":"Change in the concentrations of amino acids in cisternal CSF of patients with essential tremor","volume":"57","author":"M\u00e1lly","year":"1994","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"aah3374","DOI":"10.1126\/science.aah3374","article-title":"Pathological \u03b1-synuclein transmission initiated by binding lymphocyte-activation gene 3","volume":"353","author":"Mao","year":"2016","journal-title":"Science"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1890\/0012-9658","article-title":"Fitting multivariate models to community data: a comment on distance-based redundancy analysis","volume":"82","author":"McArdle","year":"2001","journal-title":"Ecology"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/BF00038690","article-title":"An evaluation of the relative robustness of techniques for ecological ordination","volume":"69","author":"Minchin","year":"1987","journal-title":"Vegetatio"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/s41579-020-00460-0","article-title":"The gut microbiota-brain axis in behaviour and brain disorders","volume":"19","author":"Morais","year":"2021","journal-title":"Nat. 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Rep."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"928785","DOI":"10.3389\/fped.2022.928785","article-title":"Beneficial effects of repeated washed microbiota transplantation in children with autism","volume":"10","author":"Pan","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1093\/brain\/awr301","article-title":"Defective dentate nucleus GABA receptors in essential tremor","volume":"135","author":"Paris-Robidas","year":"2012","journal-title":"Brain"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ejphar.2012.08.014","article-title":"Effects of riluzole on harmaline induced tremor and ataxia in rats: biochemical, histological and behavioral studies","volume":"695","author":"Rahimi Shourmasti","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref37","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":"ref38","doi-asserted-by":"publisher","first-page":"e28434","DOI":"10.7554\/eLife.28434","article-title":"The who, where and how of fusobacteria and colon cancer","volume":"7","author":"Sears","year":"2018","journal-title":"eLife"},{"key":"ref39","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":"ref40","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.tibtech.2015.06.011","article-title":"Proteobacteria: microbial signature of dysbiosis in gut microbiota","volume":"33","author":"Shin","year":"2015","journal-title":"Trends Biotechnol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/ece3.556","article-title":"The distribution of the thermally tolerant symbiont lineage (Symbiodinium clade D) in corals from Hawaii: correlations with host and the history of ocean thermal stress","volume":"3","author":"Stat","year":"2013","journal-title":"Ecol. Evol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/s41564-018-0307-3","article-title":"GABA-modulating bacteria of the human gut microbiota","volume":"4","author":"Strandwitz","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.bbi.2018.02.005","article-title":"Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson\u2019s disease mice: gut microbiota, glial reaction and TLR4\/TNF-\u03b1 signaling pathway","volume":"70","author":"Sun","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/s0304-3940(01)02166-8","article-title":"Baclofen attenuates harmaline induced tremors in rats","volume":"312","author":"Tariq","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.neulet.2015.01.078","article-title":"The therapeutic potential of Berberine chloride hydrate against harmaline-induced motor impairments in a rat model of tremor","volume":"590","author":"Vaziri","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/j.2041-210X.2011.00127.x","article-title":"Distance-based multivariate analyses confound location and dispersion effects","volume":"3","author":"Warton","year":"2012","journal-title":"Methods Ecol. Evol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1002\/1531-8257(199907)14:4<557::aid-mds1004>3.0.co;2-g","article-title":"Animal models of tremor","volume":"14","author":"Wilms","year":"1999","journal-title":"Mov. Disord."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1007\/s00415-012-6628-x","article-title":"Treatment of essential tremor: a systematic review of evidence and recommendations from the Italian Movement Disorders Association","volume":"260","author":"Zappia","year":"2013","journal-title":"J. Neurol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1212\/WNL.0b013e318236f0fd","article-title":"Evidence-based guideline update: treatment of essential tremor: report of the quality standards subcommittee of the American Academy of Neurology","volume":"77","author":"Zesiewicz","year":"2011","journal-title":"Neurology"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41531-022-00359-y","article-title":"Specific gut microbiota alterations in essential tremor and its difference from Parkinson\u2019s disease","volume":"8","author":"Zhang","year":"2022","journal-title":"NPJ Parkinsons Dis."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"eaau8317","DOI":"10.1126\/sciadv.aau8317","article-title":"The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice","volume":"5","author":"Zheng","year":"2019","journal-title":"Sci. Adv."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1038\/s41380-019-0475-4","article-title":"Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice","volume":"25","author":"Zhu","year":"2020","journal-title":"Mol. 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