<b>Análisis in silico del potencial de los probióticos <i>Bacillus subtilis</i> CW14 y <i>Propionibacterium freudenreichii</i> ITG P9 como moduladores en las patologías del eje microbiotaintestino- cerebro</b>
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Palabras clave

Enriquecimiento funcional
Probióticos
Microbiota
Bioinformática
Transcriptoma

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Buitrago-Roldán, N., García-Zea, J. A., & Sierra-Zapata, L. (2026). Análisis in silico del potencial de los probióticos Bacillus subtilis CW14 y Propionibacterium freudenreichii ITG P9 como moduladores en las patologías del eje microbiotaintestino- cerebro. Revista De La Academia Colombiana De Ciencias Exactas, Físicas Y Naturales. https://doi.org/10.18257/raccefyn.4034

Societal impact


Resumen

La microbiota intestinal comprende más de 100 billones de microorganismos y desempeña funciones críticas en la inmunidad, el metabolismo y la homeostasis. Su desequilibrio (disbiosis) se ha asociado con trastornos gastrointestinales, metabólicos, autoinmunes y neurológicos. Por otra parte, los probióticos, microorganismos vivos con efectos beneficiosos, han surgido como una estrategia terapéutica prometedora. Analizamos aquí el impacto de los probióticos Bacillus subtilis CW14 y Propionibacterium freudenreichii ITG P9 en células epiteliales intestinales de las líneas celulares Caco-2 y HT-29, respectivamente. Mediante un enfoque integrador basado en herramientas bioinformáticas, se examinaron genes expresados diferencialmente e interacciones proteína-proteína (IPP) para establecer el impacto de estos probióticos en la modulación génica y su relación con diversas patologías humanas. Los resultados mostraron efectos específicos para cada probiótico: B. subtilis CW14 moduló principalmente una respuesta inmunitaria coordinada y controlada que involucró quimiocinas y factores inflamatorios, en tanto que P. freudenreichii ITG P9 provocó una respuesta transcripcional caracterizada por la modulación de genes asociados al control del ciclo celular y el estrés. Se estableció el efecto pleiotrópico de ambos probióticos en genes vinculados a enfermedades metabólicas, neurológicas y autoinmunes, regulando en muchos casos genes con propiedades inmunomoduladoras, neuroprotectoras o antitumorales. De los resultados emergieron, además, mecanismos moleculares claves relacionados con la inmunomodulación, incluidos receptores innatos como el TLR y el NOD, y vías de señalización como la NF-κB y la MAPK, lo que respalda la relevancia de la conexión del eje intestino-cerebro a partir de los datos transcriptómicos como marco de futuras investigaciones.

       
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Referencias

Anderson, G. (2023). Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Cancer. Current Topics in Medicinal Chemistry, 23(28), 2699-2719. https://doi.org/10.2174/0115680266253465230920114223

Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Adesina, A., Ahmad, S., Bowler-Barnett, E. H., Bye-A-Jee, H., Carpentier, D., Denny, P., Fan, J., Garmiri, P., Gonzáles, L. J. da C., Hussein, A., Ignatchenko, A., Insana, G., Ishtiaq, R., Joshi, V., Jyothi, D., … Zhang, J. (2025). UniProt: the Universal Protein Knowledgebase in 2025. Nucleic Acids Research, 53(D1), D609-D617. https://doi.org/10.1093/nar/gkae1010

Bhuvaneshwar, K. & Gusev, Y. (2024). Translational bioinformatics and data science for biomarker discovery in mental health: an analytical review. Briefings in Bioinformatics, 25(2), bbae098. https://doi.org/10.1093/bib/bbae098

Biggs, K. E., Fikse, E. N., Anderson, F. L., Kettenbach, A. N., Havrda, M. C. (2025). Coronin1A Regulates the Trafficking of Alpha Synuclein in Microglia. The Journal of Neuroscience, 45(11), e1337242025. https://doi.org/10.1523/JNEUROSCI.1337-24.2025

Bueno-Fortes, S., Muenzner, J. K., Berral-Gonzalez, A., Hampel, C., Lindner, P., Berninger, A., Huebner, K., Kunze, P., Bäuerle, T., Erlenbach-Wuensch, K., Sánchez-Santos, J. M., Hartmann, A., De Las Rivas, J., Schneider-Stock, R. (2021). A Gene Signature Derived from the Loss of CDKN1A (p21) Is Associated with CMS4 Colorectal Cancer. Cancers, 14(1), 136. https://doi.org/10.3390/cancers14010136

Chandiok, T. (2024). ERK 1/2 Pathways: Discoveries in Disease Causation and Developments in Their Treatment. International Journal of Research and Review, 11(6), 808-817. https://doi.org/10.52403/ijrr.20240687

Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., Ma’ayan, A. (2013). Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics, 14(1), 128. https://doi.org/10.1186/1471-2105-14-128

Chen, R., Ma, L., Jiang, C., Zhang, S. (2022). Expression and potential role of CCL4 in CD8+T cells in NSCLC. Clinical and Translational Oncology, 24(12), 2420-2431. https://doi.org/10.1007/s12094-022-02913-9

Chen, Z., Tang, M., Wang, N., Liu, J., Tan, X., Ma, H., Luo, J., Xie, K. (2025). Genetic variation reveals the therapeutic potential of BRSK2 in idiopathic pulmonary fibrosis. BMC Medicine, 23(1), 22. https://doi.org/10.1186/s12916-025-03848-y

Ciccacci, C., Latini, A., Perricone, C., Conigliaro, P., Colafrancesco, S., Ceccarelli, F., Priori, R., Conti, F., Perricone, R., Novelli, G., Borgiani, P. (2019). TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome—Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients. Journal of Immunology Research, 2019, 1-6. https://doi.org/10.1155/2019/6728694

Clough, E. & Barrett, T. (2016). The Gene Expression Omnibus Database. In: Mathé, E., Davis, S. (eds) Statistical Genomics. Methods in Molecular Biology, 1418. Humana Press. https://doi.org/10.1007/978-1-4939-3578-9_5

Cousin, F. J., Jouan-Lanhouet, S., Théret, N., Brenner, C., Jouan, E., Le Moigne-Muller, G., Dimanche-Boitrel, M.-T., Jan, G. (2016). The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer. Oncotarget, 7(6), 7161-7178. https://doi.org/10.18632/oncotarget.6881

Cremon, C., Barbaro, M. R., Ventura, M., Barbara, G. (2018). Pre- and probiotic overview. Current Opinion in Pharmacology, 43, 87-92. https://doi.org/10.1016/j.coph.2018.08.010

Cryan, J. F., O’Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., Guzzetta, K. E., Jaggar, M., Long-Smith, C. M., Lyte, J. M., Martin, J. A., Molinero-Perez, A., Moloney, G., Morelli, E., Morillas, E., … Dinan, T. G. (2019). The Microbiota-Gut-Brain Axis. Physiological Reviews, 99(4), 1877-2013. https://doi.org/10.1152/physrev.00018.2018

Dekaboruah, E., Suryavanshi, M. V., Chettri, D., Verma, A. K. (2020). Human microbiome: an academic update on human body site specific surveillance and its possible role. Archives of Microbiology, 202(8), 2147-2167. https://doi.org/10.1007/s00203-020-01931-x

del Toro, N., Shrivastava, A., Ragueneau, E., Meldal, B., Combe, C., Barrera, E., Perfetto, L., How, K., Ratan, P., Shirodkar, G., Lu, O., Mészáros, B., Watkins, X., Pundir, S., Licata, L., Iannuccelli, M., Pellegrini, M., Martin, M. J., Panni, S., … Hermjakob, H. (2022). The IntAct database: efficient access to fine-grained molecular interaction data. Nucleic Acids Research, 50(D1), D648-D653. https://doi.org/10.1093/nar/gkab1006

Dicks, L. M. T. (2022). Gut Bacteria and Neurotransmitters. Microorganisms, 10(9), 1838. https://doi.org/10.3390/microorganisms10091838

do Carmo, F. L. R., Rabah, H., Huang, S., Gaucher, F., Deplanche, M., Dutertre, S., Jardin, J., Le Loir, Y., Azevedo, V., Jan, G. (2017). Propionibacterium freudenreichii Surface Protein SlpB Is Involved in Adhesion to Intestinal HT-29 Cells. Frontiers in Microbiology, 8, 1033. https://doi.org/10.3389/fmicb.2017.01033

Feng, Y., Chen, Z., Xu, Y., Han, Y., Jia, X., Wang, Z., Zhang, N., Lv, W. (2023). The central inflammatory regulator IκBζ: induction, regulation and physiological functions. Frontiers in Immunology, 14, 1188253. https://doi.org/10.3389/fimmu.2023.1188253

Hashemi, B., Abdollahi, M., Abbaspour-Aghdam, S., Hazrati, A., Malekpour, K., meshgi, S., Kafil, H. S., ghazi, F., Yousefi, M., Roshangar, L., Ahmadi, M. (2023). The effect of probiotics on immune responses and their therapeutic application: A new treatment option for multiple sclerosis. Biomedicine & Pharmacotherapy, 159, 114195. https://doi.org/10.1016/j.biopha.2022.114195

Hou, K., Wu, Z.-X., Chen, X.-Y., Wang, J.-Q., Zhang, D., Xiao, C., Zhu, D., Koya, J. B., Wei, L., Li, J., Chen, Z.-S. (2022). Microbiota in health and diseases. Signal Transduction and Targeted Therapy, 7(1), 135. https://doi.org/10.1038/s41392-022-00974-4

Hu, M. & Shao, Z. (2022). Lactobacillus pentosus Alleviates Lipopolysaccharide-Induced Neuronal Pyroptosis via Promoting BIRC3-Mediated Inactivation of NLRC4. Evidence-Based Complementary and Alternative Medicine, 2022, 1-9. https://doi.org/10.1155/2022/2124876

Jung-Rodríguez, E., Barbault, F., Bignon, E., Monari, A. (2024). Molecular bases and specificity behind the activation of the immune system OAS/RNAse L pathway by viral RNA. bioRxiv, 2024.07.08.602453 https://doi.org/10.1101/2024.07.08.602453

Karin, N. & Razon, H. (2018). Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. Cytokine, 109, 24-28. https://doi.org/10.1016/j.cyto.2018.02.012

Kim, H., Jo, J.-H., Lee, H.-G., Park, W., Lee, H.-K., Park, J.-E., Shin, D. (2024). Inflammatory response in dairy cows caused by heat stress and biological mechanisms for maintaining homeostasis. PLOS ONE, 19(3), e0300719. https://doi.org/10.1371/journal.pone.0300719

Kou, Y., Liu, Q., Liu, W., Sun, H., Liang, M., Kong, F., Zhang, B., Wei, Y., Liu, Z., Wang, Y. (2019). LIGHT/TNFSF14 signaling attenuates beige fat biogenesis. The FASEB Journal, 33(2), 1595-1604. https://doi.org/10.1096/fj.201800792R

Krause, P., Zahner, S. P., Kim, G., Shaikh, R. B., Steinberg, M. W., Kronenberg, M. (2014). The Tumor Necrosis Factor Family Member TNFSF14 (LIGHT) Is Required for Resolution of Intestinal Inflammation in Mice. Gastroenterology, 146(7), 1752-1762.e4. https://doi.org/10.1053/j.gastro.2014.02.010

Lasso, G., Mayer, S. V., Winkelmann, E. R., Chu, T., Elliot, O., Patino-Galindo, J. A., Park, K., Rabadan, R., Honig, B., Shapira, S. D. (2019). A Structure-Informed Atlas of Human-Virus Interactions. Cell, 178(6), 1526-1541.e16. https://doi.org/10.1016/j.cell.2019.08.005

Liu, Z., Zhao, J., Sun, R., Wang, M., Wang, K., Li, Y., Shang, H., Hou, J., Jiang, Z. (2022). Lactobacillus plantarum 23-1 improves intestinal inflammation and barrier function through the TLR4/NF-κB signaling pathway in obese mice. Food & Function, 13(11), 5971-5986. https://doi.org/10.1039/D1FO04316A

Love, M. I., Huber, W., Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15(12), 550. https://doi.org/10.1186/s13059-014-0550-8

Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F., Tillisch, K. (2014). Gut Microbes and the Brain: Paradigm Shift in Neuroscience. The Journal of Neuroscience, 34(46), 15490-15496. https://doi.org/10.1523/JNEUROSCI.3299-14.2014

McFarland, L. V., Evans, C. T., Goldstein, E. J. C. (2018). Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis. Frontiers in Medicine, 5, 124. https://doi.org/10.3389/fmed.2018.00124

Nesterova, A.P., Klimov, E.A., Zharkova, M., Sozin, S., Sobolev, V. Ivanikova, N.V., Shkrob, M., Yuryev, A. (2020). Disease Pathways. Elsevier. https://doi.org/10.1016/C2018-0-00586-1

Neurath, M. F. (2014). Cytokines in inflammatory bowel disease. Nature Reviews Immunology, 14(5), 329-342. https://doi.org/10.1038/nri3661

Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., Kanehisa, M. (1999). KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research, 27(1), 29-34. https://doi.org/10.1093/nar/27.1.29

Oughtred, R., Rust, J., Chang, C., Breitkreutz, B., Stark, C., Willems, A., Boucher, L., Leung, G., Kolas, N., Zhang, F., Dolma, S., Coulombe‐Huntington, J., Chatr‐aryamontri, A., Dolinski, K., Tyers, M. (2021). The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions. Protein Science, 30(1), 187-200. https://doi.org/10.1002/pro.3978

Pauletto, M., Elgendy, R., Ianni, A., Marone, E., Giantin, M., Grotta, L., Ramazzotti, S., Bennato, F., Dacasto, M., Martino, G. (2020). Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows. Animals, 10(4), 714. https://doi.org/10.3390/ani10040714

Peng, M., Liu, J., Liang, Z. (2019). Probiotic Bacillus subtilis CW14 reduces disruption of the epithelial barrier and toxicity of ochratoxin A to Caco-2 cells. Food and Chemical Toxicology, 126, 25-33. https://doi.org/10.1016/j.fct.2019.02.009

Piñero, J., Ramírez-Anguita, J. M., Saüch-Pitarch, J., Ronzano, F., Centeno, E., Sanz, F., Furlong, L. I. (2019). The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Research, 48, D845-D855. https://doi.org/10.1093/nar/gkz1021

Qumsiyeh, E., Showe, L., Yousef, M. (2022). GediNET for discovering gene associations across diseases using knowledge based machine learning approach. Scientific Reports, 12(1), 19955. https://doi.org/10.1038/s41598-022-24421-0

Rath, A., Olry, A., Dhombres, F., Brandt, M. M., Urbero, B., Ayme, S. (2012). Representation of rare diseases in health information systems: The orphanet approach to serve a wide range of end users. Human Mutation, 33(5), 803-808. https://doi.org/10.1002/humu.22078

Richard, M. L. & Sokol, H. (2019). The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases. Nature Reviews Gastroenterology & Hepatology, 16, 331-345. https://doi.org/10.1038/s41575-019-0121-2

Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., Smyth, G. K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research, 43(7), e47-e47. https://doi.org/10.1093/nar/gkv007

Saiyin, H., Na, N., Han, X., Fang, Y., Wu, Y., Lou, W., Yang, X. (2017). BRSK2 induced by nutrient deprivation promotes Akt activity in pancreatic cancer via downregulation of mTOR activity. Oncotarget, 8(27), 44669-44681. https://doi.org/10.18632/oncotarget.17965

Sarkar, A., Lehto, S. M., Harty, S., Dinan, T. G., Cryan, J. F., Burnet, P. W. J. (2016). Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals. Trends in Neurosciences, 39(11), 763-781. https://doi.org/10.1016/j.tins.2016.09.002

Shah, B. R., Xu, W., Mraz, J. (2019). Cytochrome P450 1B1: role in health and disease and effect of nutrition on its expression. RSC Advances, 9(36), 21050-21062. https://doi.org/10.1039/C9RA03674A

Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., Ideker, T. (2003). Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Research, 13(11), 2498-2504. https://doi.org/10.1101/gr.1239303

Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., Gable, A. L., Fang, T., Doncheva, N. T., Pyysalo, S., Bork, P., Jensen, L. J., von Mering, C. (2023). The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Research, 51(D1), D638-D646. https://doi.org/10.1093/nar/gkac1000

Trejo, F. & Sanz, Y. (2013). Intestinal bacteria and probiotics: effects on the immune system and impacts on human health. In: Philip C. Calder, Parveen Yaqoob (Eds.). Diet, Immunity and Inflammation (pp. 267–291). Woodhead Publishing. https://doi.org/10.1533/9780857095749.3.267

Vida, H., Sahar, M., Nikdouz, A., Arezoo, H. (2025). Chemokines in neurodegenerative diseases. Immunology & Cell Biology, 103(3), 275-292. https://doi.org/10.1111/imcb.12843

Wang, C., Wang, J., Zhu, Z., Hu, J., Lin, Y. (2024). Spotlight on pro-inflammatory chemokines: regulators of cellular communication in cognitive impairment. Frontiers in Immunology, 15, 1421076. https://doi.org/10.3389/fimmu.2024.1421076

Wang, Q., Wu, H., Hu, J., Fu, H., Qu, Y., Yang, Y., Cai, K. Q., Efimov, A., Wu, M., Yen, T., Wang, Y., Yang, Z.-J. (2021). Nestin Is Required for Spindle Assembly and Cell-Cycle Progression in Glioblastoma Cells. Molecular Cancer Research, 19(10), 1651-1665. https://doi.org/10.1158/1541-7786.MCR-20-0994

Weiss, S. R. (2020). Activation and Antagonism of the OAS–RNase L Pathway. Proceedings, 50(1), 14. https://doi.org/10.3390/proceedings2020050014

Yamazaki, S., Inohara, N., Ohmuraya, M., Tsuneoka, Y., Yagita, H., Katagiri, T., Nishina, T., Mikami, T., Funato, H., Araki, K., Nakano, H. (2022). IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies. Mucosal Immunology, 15(6), 1321-1337. https://doi.org/10.1038/s41385-022-00554-3

Yang, R.-Y., Tan, J.-Y., Liu, Z., Shen, X.-L., Hu, Y.-J. (2023). Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells. Pharmaceutical Biology, 61(1), 337-344. https://doi.org/10.1080/13880209.2023.2172048

Yates, A., Akanni, W., Amode, M. R., Barrell, D., Billis, K., Carvalho-Silva, D., Cummins, C., Clapham, P., Fitzgerald, S., Gil, L., Girón, C. G., Gordon, L., Hourlier, T., Hunt, S. E., Janacek, S. H., Johnson, N., Juettemann, T., Keenan, S., Lavidas, I., … Flicek, P. (2016). Ensembl 2016. Nucleic Acids Research, 44(D1), D710-D716. https://doi.org/10.1093/nar/gkv1157

Ygberg, S. & Nilsson, A. (2012). The developing immune system – from foetus to toddler. Acta Paediatrica, 101(2), 120-127. https://doi.org/10.1111/j.1651-2227.2011.02494.x

Yu, M., Ma, X., Jiang, D., Wang, L., Zhan, Q., Zhao, J. (2021). CXC chemokine ligand 5 (CXCL5) disrupted the permeability of human brain microvascular endothelial cells via regulating p38 signal. Microbiology and Immunology, 65(1), 40-47. https://doi.org/10.1111/1348-0421.12854

Zhang, W., Yi, Z., Wei, C., Keung, K. L., Sun, Z., Xi, C., Woytovich, C., Farouk, S., Gallon, L., Menon, M. C., Magee, C., Najafian, N., Samaniego, M. D., Djamali, A., Alexander, S. I., Rosales, I. A., Smith, R. N., O’Connell, P. J., Colvin, R., … Murphy, B. (2019). Pretransplant transcriptomic signature in peripheral blood predicts early acute rejection. JCI Insight, 4(11): e127543. https://doi.org/10.1172/jci.insight.127543

Zhu, Y., Yang, S., Zhao, N., Liu, C., Zhang, F., Guo, Y., Liu, H. (2021). CXCL8 chemokine in ulcerative colitis. Biomedicine & Pharmacotherapy, 138, 111427. https://doi.org/10.1016/j.biopha.2021.111427

Zmora, N., Suez, J., Elinav, E. (2019). You are what you eat: diet, health and the gut microbiota. Nature Reviews Gastroenterology & Hepatology, 16(1), 35-56. https://doi.org/10.1038/s41575-018-0061-2

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