{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:39:41Z","timestamp":1768747181496,"version":"3.49.0"},"reference-count":86,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yunling Scholar of Yunnan Province"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Elucidating the gene regulatory mechanisms underlying the gut\u2013brain axis is critical for uncovering novel gut\u2013brain interaction pathways and developing therapeutic strategies for gut bacteria-associated neurological disorders. Most studies have primarily investigated how gut bacteria modulate host epigenetics and gene expression; their impact on host alternative splicing, particularly in the brain, remains largely unexplored. Here, we investigated the effects of the gut-associated probiotic Lacidofil\u00ae on alternative splicing across 10 regions of the rat brain using published RNA-sequencing data. The Lacidofil\u00ae altogether altered 2941 differential splicing events, predominantly, skipped exon (SE) and mutually exclusive exon (MXE) events. Protein\u2013protein interactions and a KEGG analysis of differentially spliced genes (DSGs) revealed consistent enrichment in the spliceosome and vesicle transport complexes, as well as in pathways related to neurodegenerative diseases, synaptic function and plasticity, and substance addiction across brain regions. Using the PsyGeNET platform, we found that DSGs from the locus coeruleus (LConly), medial preoptic area (mPOA), and ventral dentate gyrus (venDG) were enriched in depression-associated or schizophrenia-associated genes. Notably, we highlight the App gene, where Lacidofil\u00ae precisely regulated the splicing of two exons causally involved in amyloid \u03b2 protein-based neurodegenerative diseases. Although the splicing factors exhibited both splicing plasticity and expression plasticity in response to Lacidofil\u00ae, the overlap between DSGs and differentially expressed genes (DEGs) in most brain regions was rather low. Our study provides novel mechanistic insight into how gut probiotics might influence brain function through the modulation of RNA splicing.<\/jats:p>","DOI":"10.3390\/microorganisms13010165","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T11:28:31Z","timestamp":1736854111000},"page":"165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Changes in RNA Splicing: A New Paradigm of Transcriptional Responses to Probiotic Action in the Mammalian Brain"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiaojie","family":"Yue","sequence":"first","affiliation":[{"name":"State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3602-1281","authenticated-orcid":false,"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liang, S., Wu, X., and Jin, F. (2018). Gut-Brain Psychology: Rethinking Psychology From the Microbiota-Gut-Brain Axis. Front. Integr. Neurosci., 12.","DOI":"10.3389\/fnint.2018.00033"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2174\/1570159X15666170915141036","article-title":"The Microbiota-Gut-Brain Axis in Neuropsychiatric Disorders: Pathophysiological Mechanisms and Novel Treatments","volume":"16","author":"Kim","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.chom.2020.06.013","article-title":"Co-evolution and Co-speciation of Host-Gut Bacteria Systems","volume":"28","author":"Groussin","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00592-023-02088-x","article-title":"Microbiota-gut-brain axis: Relationships among the vagus nerve, gut microbiota, obesity, and diabetes","volume":"60","author":"Longo","year":"2023","journal-title":"Acta Diabetol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chen, Y., Xu, J., and Chen, Y. (2021). Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients, 13.","DOI":"10.3390\/nu13062099"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Holzer, P. (2022). Gut Signals and Gut Feelings: Science at the Interface of Data and Beliefs. Front. Behav. Neurosci., 16.","DOI":"10.3389\/fnbeh.2022.929332"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1089\/jmf.2014.7000","article-title":"The gut microbiome and the brain","volume":"17","author":"Galland","year":"2014","journal-title":"J. Med. Food"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cobeha.2019.01.011","article-title":"Stress, depression, diet, and the gut microbiota: Human-bacteria interactions at the core of psychoneuroimmunology and nutrition","volume":"28","author":"Madison","year":"2019","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, regional, and national burden of neurological disorders, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Collaborators","year":"2019","journal-title":"Lancet Neurol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e274","DOI":"10.1016\/S2666-7568(23)00051-X","article-title":"The role of population-level preventive care for brain health in ageing","volume":"4","author":"Sabayan","year":"2023","journal-title":"Lancet Healthy Longev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"394","DOI":"10.4103\/1673-5374.266045","article-title":"Dietary habits, lifestyle factors and neurodegenerative diseases","volume":"15","author":"Dumitrascu","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1093\/brain\/awab147","article-title":"Classification of neurological diseases using multi-dimensional CSF analysis","volume":"144","author":"Gross","year":"2021","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s41019-016-0011-3","article-title":"Medical Big Data: Neurological Diseases Diagnosis Through Medical Data Analysis","volume":"1","author":"Siuly","year":"2016","journal-title":"Data Sci. Eng."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Person, H., and Keefer, L. (2021). Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis. Prog. Neuropsychopharmacol. Biol. Psychiatry, 107.","DOI":"10.1016\/j.pnpbp.2020.110209"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S2468-1253(20)30363-0","article-title":"Common mental disorders in irritable bowel syndrome: Pathophysiology, management, and considerations for future randomised controlled trials","volume":"6","author":"Staudacher","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Westfall, S., Lomis, N., and Prakash, S. (2018). Longevity extension in Drosophila through gut-brain communication. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-25382-z"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, J.G., Cho, H.J., Jeong, Y.M., and Lee, J.S. (2021). Genetic Approaches Using Zebrafish to Study the Microbiota-Gut-Brain Axis in Neurological Disorders. Cells, 10.","DOI":"10.3390\/cells10030566"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.cell.2019.05.004","article-title":"Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice","volume":"177","author":"Sharon","year":"2019","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Huang, T.T., Lai, J.B., Du, Y.L., Xu, Y., Ruan, L.M., and Hu, S.H. (2019). Current Understanding of Gut Microbiota in Mood Disorders: An Update of Human Studies. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00098"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6869","DOI":"10.1038\/s41467-024-51077-3","article-title":"A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss","volume":"15","author":"Liu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Begum, N., Mandhare, A., Tryphena, K.P., Srivastava, S., Shaikh, M.F., Singh, S.B., and Khatri, D.K. (2022). Epigenetics in depression and gut-brain axis: A molecular crosstalk. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.1048333"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neulet.2016.02.009","article-title":"Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?","volume":"625","author":"Bourassa","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41467-017-02651-5","article-title":"Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases","volume":"9","author":"Fellows","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Shock, T., Badang, L., Ferguson, B., and Martinez-Guryn, K. (2021). The interplay between diet, gut microbes, and host epigenetics in health and disease. J. Nutr. Biochem., 95.","DOI":"10.1016\/j.jnutbio.2021.108631"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1161\/CIRCULATIONAHA.110.956839","article-title":"Epigenetic modifications: Basic mechanisms and role in cardiovascular disease","volume":"123","author":"Handy","year":"2011","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bbr.2017.01.021","article-title":"Effects of gut microbiota on the microRNA and mRNA expression in the hippocampus of mice","volume":"322","author":"Chen","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41392-024-01734-2","article-title":"Alternative splicing and related RNA binding proteins in human health and disease","volume":"9","author":"Tao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1080\/15384101.2021.1889187","article-title":"Splicing regulation in brain and testis: Common themes for highly specialized organs","volume":"20","author":"Naro","year":"2021","journal-title":"Cell Cycle"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41583-023-00717-6","article-title":"Alternative splicing in neurodegenerative disease and the promise of RNA therapies","volume":"24","author":"Nikom","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.neuron.2016.09.050","article-title":"Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System","volume":"92","author":"Martinez","year":"2016","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3727\/096368912X655154","article-title":"Aberrant alternative splicing events in Parkinson\u2019s disease","volume":"22","author":"Fu","year":"2013","journal-title":"Cell Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e02438-21","DOI":"10.1128\/spectrum.02438-21","article-title":"Distinct Roles of Honeybee Gut Bacteria on Host Metabolism and Neurological Processes","volume":"10","author":"Zhang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1038\/s41380-024-02619-0","article-title":"Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain","volume":"29","author":"Rayan","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1038\/nprot.2016.095","article-title":"Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown","volume":"11","author":"Pertea","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","article-title":"rMATS: Robust and flexible detection of differential alternative splicing from replicate RNA-Seq data","volume":"111","author":"Shen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1093\/bioinformatics\/btv301","article-title":"PsyGeNET: A knowledge platform on psychiatric disorders and their genes","volume":"31","author":"Grosdidier","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1093\/bioinformatics\/btx506","article-title":"psygenet2r: A R\/Bioconductor package for the analysis of psychiatric disease genes","volume":"33","author":"Gonzalez","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kiattiweerasak, A., Aumpan, N., Chonprasertsuk, S., Pornthisarn, B., Siramolpiwat, S., Bhanthumkomol, P., Nunanan, P., Issariyakulkarn, N., Mahachai, V., and Yamaoka, Y. (2023). Efficacy and safety of Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 as an adjuvant for Helicobacter pylori eradication: A double-blind, randomized, placebo-controlled study. Front. Gastroenterol., 2.","DOI":"10.3389\/fgstr.2023.1245993"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41467-023-44658-1","article-title":"hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS)","volume":"15","author":"Salapa","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1038\/s41467-023-37815-z","article-title":"Parkinson\u2019s disease-associated ATP13A2\/PARK9 functions as a lysosomal H+,K+-ATPase","volume":"14","author":"Fujii","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8562","DOI":"10.1093\/nar\/gkaa646","article-title":"RNA-tethering assay and eIF4G:eIF4A obligate dimer design uncovers multiple eIF4F functional complexes","volume":"48","author":"Robert","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ajhg.2022.11.011","article-title":"Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy","volume":"110","author":"Paul","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1017\/S0033583508004708","article-title":"Protein-protein interaction and quaternary structure","volume":"41","author":"Janin","year":"2008","journal-title":"Q. Rev. Biophys."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kawamura, N., Sun-Wada, G.H., and Wada, Y. (2015). Loss of G2 subunit of vacuolar-type proton transporting ATPase leads to G1 subunit upregulation in the brain. Sci. Rep., 5.","DOI":"10.1038\/srep14027"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Falace, A., Volpedo, G., Scala, M., Zara, F., Striano, P., and Fassio, A. (2024). V-ATPase Dysfunction in the Brain: Genetic Insights and Therapeutic Opportunities. Cells, 13.","DOI":"10.3390\/cells13171441"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Twine, N.A., Janitz, K., Wilkins, M.R., and Janitz, M. (2011). Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer\u2019s disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016266"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40035-021-00240-7","article-title":"Neurodegenerative diseases: A hotbed for splicing defects and the potential therapies","volume":"10","author":"Li","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Jakubauskiene, E., and Kanopka, A. (2021). Alternative Splicing and Hypoxia Puzzle in Alzheimer\u2019s and Parkinson\u2019s Diseases. Genes, 12.","DOI":"10.3390\/genes12081272"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Montagna, E., Dorostkar, M.M., and Herms, J. (2017). The Role of APP in Structural Spine Plasticity. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00136"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0301-0082(03)00089-3","article-title":"Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory","volume":"70","author":"Turner","year":"2003","journal-title":"Prog. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0169-328X(95)00302-9","article-title":"Two types of amyloid precursor protein (APP) mRNA in rat glioma cell lines: Upregulation via a cyclic AMP-dependent pathway","volume":"37","author":"Gegelashvili","year":"1996","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1749-6632.1996.tb34433.x","article-title":"APP gene family. Alternative splicing generates functionally related isoforms","volume":"777","author":"Sandbrink","year":"1996","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Sawmiller, D., Koyama, N., Fujiwara, M., Segawa, T., Maeda, M., and Mori, T. (2023). Targeting apolipoprotein E and N-terminal amyloid beta-protein precursor interaction improves cognition and reduces amyloid pathology in Alzheimer\u2019s mice. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.104846"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1523\/JNEUROSCI.3253-07.2008","article-title":"Intron-3 retention\/splicing controls neuronal expression of apolipoprotein E in the CNS","volume":"28","author":"Xu","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/s41374-019-0197-x","article-title":"MAPT mutations, tauopathy, and mechanisms of neurodegeneration","volume":"99","author":"Strang","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Shehadeh, L.A., Yu, K., Wang, L., Guevara, A., Singer, C., Vance, J., and Papapetropoulos, S. (2010). SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson\u2019s disease. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009104"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41525-024-00432-w","article-title":"Alternative splicing is coupled to gene expression in a subset of variably expressed genes","volume":"9","author":"Karlebach","year":"2024","journal-title":"NPJ Genom. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"R319","DOI":"10.1016\/S0960-9822(02)00829-1","article-title":"Gene expression: The close coupling of transcription and splicing","volume":"12","author":"Rosonina","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1111\/cns.12185","article-title":"Phosphatidylethanolamine-binding protein 1 (PEBP1) as a potential target for the treatment for depression","volume":"19","author":"Sun","year":"2013","journal-title":"CNS Neurosci. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kaminska, D. (2024). The Role of RNA Splicing in Liver Function and Disease: A Focus on Metabolic Dysfunction-Associated Steatotic Liver Disease. Genes, 15.","DOI":"10.3390\/genes15091181"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1101\/gad.1703108","article-title":"Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2","volume":"22","author":"Zhang","year":"2008","journal-title":"Genes. Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1053\/j.gastro.2011.04.052","article-title":"The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice","volume":"141","author":"Bercik","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"109491","DOI":"10.1016\/j.neuropharm.2023.109491","article-title":"The gut-brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders","volume":"231","author":"Damiani","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1073\/pnas.1010529108","article-title":"Normal gut microbiota modulates brain development and behavior","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Grau-Bove, X., Ruiz-Trillo, I., and Irimia, M. (2018). Origin of exon skipping-rich transcriptomes in animals driven by evolution of gene architecture. Genome Biol., 19.","DOI":"10.1186\/s13059-018-1499-9"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Hatje, K., Rahman, R.U., Vidal, R.O., Simm, D., Hammesfahr, B., Bansal, V., Rajput, A., Mickael, M.E., Sun, T., and Bonn, S. (2017). The landscape of human mutually exclusive splicing. Mol. Syst. Biol., 13.","DOI":"10.15252\/msb.20177728"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lam, S.D., Babu, M.M., Lees, J., and Orengo, C.A. (2021). Biological impact of mutually exclusive exon switching. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1008708"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41398-020-01163-z","article-title":"Alcohol use disorder causes global changes in splicing in the human brain","volume":"11","author":"Mengying","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41398-020-0772-3","article-title":"Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents","volume":"10","author":"Ota","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-\u03b2 Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neuint.2014.08.001","article-title":"Alternative splicing regulation of APP exon 7 by RBFox proteins","volume":"78","author":"Alam","year":"2014","journal-title":"Neurochem. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1111\/mec.15817","article-title":"Alternative splicing and gene expression play contrasting roles in the parallel phenotypic evolution of a salmonid fish","volume":"30","author":"Jacobs","year":"2021","journal-title":"Mol. Ecol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.tree.2021.11.010","article-title":"The role of alternative splicing in adaptation and evolution","volume":"37","author":"Verta","year":"2022","journal-title":"Trends Ecol. Evol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1093\/molbev\/msy095","article-title":"Extensive Differential Splicing Underlies Phenotypically Plastic Aphid Morphs","volume":"35","author":"Grantham","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.molcel.2007.06.016","article-title":"Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1","volume":"27","author":"Spellman","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"110985","DOI":"10.1016\/j.celrep.2022.110985","article-title":"Dynamics and functional roles of splicing factor autoregulation","volume":"39","author":"Ding","year":"2022","journal-title":"Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Anko, M.L., Muller-McNicoll, M., Brandl, H., Curk, T., Gorup, C., Henry, I., Ule, J., and Neugebauer, K.M. (2012). The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes. Genome Biol., 13.","DOI":"10.1186\/gb-2012-13-3-r17"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9223","DOI":"10.1523\/JNEUROSCI.2461-20.2021","article-title":"The Roles of Basolateral Amygdala Parvalbumin Neurons in Fear Learning","volume":"41","author":"Yau","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4997","DOI":"10.1523\/JNEUROSCI.1775-22.2023","article-title":"Basolateral Amygdala Astrocytes Are Engaged by the Acquisition and Expression of a Contextual Fear Memory","volume":"43","author":"Suthard","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e127","DOI":"10.1038\/tp.2012.51","article-title":"Hippocampal subfields predict positive symptoms in schizophrenia: First evidence from brain morphometry","volume":"2","author":"Kuhn","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1017\/S0033291719001144","article-title":"Dentate gyrus volume deficit in schizophrenia","volume":"50","author":"Nakahara","year":"2020","journal-title":"Psychol. Med."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/1\/165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:28:43Z","timestamp":1759919323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/1\/165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,14]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["microorganisms13010165"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13010165","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,14]]}}}