{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:08:55Z","timestamp":1791824935626,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014Next Generation EU","award":["PNRR-MCNT2-2023-12378074 CUP Master I53C23002680006"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378074 CUP Master I53C23002680006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Eosinophilic esophagitis (EoE) and achalasia are two chronic esophageal disorders, characterized by inflammatory and neuromotor dysfunction, respectively, that share overlapping immune-inflammatory features. Emerging evidence suggests that dysbiosis of the oral and esophageal microbiota may represent a common determinant in their pathophysiology. This review aims to provide a comparative and integrated overview of microbial and immune alterations in EoE and Achalasia, with potential diagnostic and therapeutic implications. Methods: A bibliographic search was conducted on PubMed and Scopus including clinical studies, experimental research, and review articles published between 2015 and 2025. The keywords Eosinophilic Esophagitis, Achalasia, Microbiota, and Dysbiosis were used for article selection. Results: In EoE, several studies demonstrated increased bacterial diversity with predominance of Prevotella and reduction of Streptococcus, findings associated with greater inflammatory severity and epithelial barrier dysfunction. Conversely, Achalasia is characterized by reduced microbial diversity and a shift from Gram-positive commensals to Gram-negative taxa capable of activating pro-inflammatory pathways (TLR4-MYD88-NF-\u03baB), leading to neuronal loss and impaired peristalsis. Conclusions: Both EoE and Achalasia share the hallmark of dysbiosis, although with distinct immune profiles (Th2 vs. Th17). The identification of specific microbial \u201csignatures\u201d suggests promising perspectives for non-invasive biomarkers and microbiota-targeted therapies, including probiotics and glycan-modulating strategies. Further prospective studies are needed to clarify causal mechanisms and validate microbiota manipulation as a complementary therapeutic approach in esophageal diseases.<\/jats:p>","DOI":"10.3390\/jcm14217502","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T09:44:30Z","timestamp":1761212670000},"page":"7502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of the Oral and Esophageal Microbiota in EoE and Achalasia"],"prefix":"10.3390","volume":"14","author":[{"given":"Roberta","family":"Manente","sequence":"first","affiliation":[{"name":"San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84081 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"De Caro","sequence":"additional","affiliation":[{"name":"San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84081 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4526-8353","authenticated-orcid":false,"given":"Debora","family":"Paris","sequence":"additional","affiliation":[{"name":"CNR-Institute of Biomolecular Chemistry, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2425-2670","authenticated-orcid":false,"given":"Annabella","family":"Tramice","sequence":"additional","affiliation":[{"name":"CNR-Institute of Biomolecular Chemistry, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-6855","authenticated-orcid":false,"given":"Giovanni","family":"Boccia","sequence":"additional","affiliation":[{"name":"Health Hygiene Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"},{"name":"Integrated Care Department of Health Hygiene and Evaluative Medicine, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84131 Salerno, Italy"},{"name":"Hospital and Epidemiological Hygiene Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-5925","authenticated-orcid":false,"given":"Pio","family":"Zeppa","sequence":"additional","affiliation":[{"name":"Health Hygiene Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"},{"name":"Pathological Anatomy Unit, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Chiodo","sequence":"additional","affiliation":[{"name":"CNR-Institute of Biomolecular Chemistry, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9568-0680","authenticated-orcid":false,"given":"Paola","family":"Iovino","sequence":"additional","affiliation":[{"name":"Health Hygiene Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"},{"name":"Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ullah, H., Arbab, S., Tian, Y., Chen, Y., Liu, C.Q., Li, Q., and Li, K. (2024). Crosstalk between gut microbiota and host immune system and its response to traumatic injury. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1413485"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2393270","DOI":"10.1080\/19490976.2024.2393270","article-title":"The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease","volume":"16","author":"Hays","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1007\/s10482-020-01474-7","article-title":"Human gut microbiota\/microbiome in health and diseases: A review","volume":"113","author":"Gomaa","year":"2020","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/s41423-021-00661-4","article-title":"Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases","volume":"18","author":"Yang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zuo, T., and Ng, S.C. (2018). The gut microbiota in the pathogenesis and therapeutics of inflammatory bowel disease. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02247"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Quaranta, G., Guarnaccia, A., Fancello, G., Agrillo, C., Iannarelli, F., Sanguinetti, M., and Masucci, L. (2022). Fecal microbiota transplantation and other gut microbiota manipulation strategies. Microorganisms, 10.","DOI":"10.3390\/microorganisms10122424"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, X., Liu, Y., Yang, X., Li, C., and Song, Z. (2022). The oral microbiota: Community composition, influencing factors, pathogenesis, and interventions. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.895537"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Contaldo, M., Fusco, A., Stiuso, P., Lama, S., Gravina, A.G., Itro, A., Federico, A., Dipalma, G., Inchingolo, F., and Serpico, R. (2021). Oral microbiota and salivary levels of oral pathogens in gastrointestinal diseases: Current knowledge and exploratory study. Microorganisms, 9.","DOI":"10.3390\/microorganisms9051064"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hrncir, T. (2022). Gut microbiota dysbiosis: Triggers, consequences, diagnostic and therapeutic options. Microorganisms., 10.","DOI":"10.3390\/microorganisms10030578"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"goae076","DOI":"10.1093\/gastro\/goae076","article-title":"The involvement of oral bacteria in inflammatory bowel disease","volume":"12","author":"Xiang","year":"2024","journal-title":"Gastroenterol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Koliarakis, I., Messaritakis, I., Nikolouzakis, T.K., Hamilos, G., Souglakos, J., and Tsiaoussis, J. (2019). Oral bacteria and intestinal dysbiosis in colorectal cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174146"},{"key":"ref_12","first-page":"51","article-title":"Helicobacter pylori adheres selectively to Fusobacterium spp. Oral Microbiol","volume":"13","author":"Andersen","year":"1998","journal-title":"Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zou, Q., Feng, L., Cai, X., Qian, Y., and Xu, L. (2023). Esophageal microflora in esophageal diseases. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1145791"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/dote\/11.4.248","article-title":"Microbial flora of the normal esophagus","volume":"11","author":"Gagliardi","year":"1998","journal-title":"Dis. Esophagus"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1073\/pnas.0306398101","article-title":"Bacterial biota in the human distal esophagus","volume":"101","author":"Pei","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","first-page":"doab076","article-title":"Esophageal microbiota composition and outcome of esophageal cancer treatment: A systematic review","volume":"35","author":"Plat","year":"2022","journal-title":"Dis. Esophagus"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/0016-5085(78)90710-2","article-title":"Eosinophilic esophagitis in a patient with vigorous achalasia","volume":"74","author":"Landres","year":"1978","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"640","DOI":"10.15537\/smj.2023.44.7.20220812","article-title":"Eosinophilic esophagitis","volume":"44","author":"Alkhowaiter","year":"2023","journal-title":"Saudi Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/cea.14196","article-title":"Eosinophilic esophagitis: Immune mechanisms and therapeutic targets","volume":"52","author":"Khokhar","year":"2022","journal-title":"Clin. Exp. Allergy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1159\/000515520","article-title":"Eosinophilic esophagitis and achalasia: Two distinct nosologic entities or a possible etiopathogenic association?","volume":"39","author":"Schizas","year":"2021","journal-title":"Dig. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/alr.22095","article-title":"Airborne and food sensitization patterns in children and adults with eosinophilic esophagitis","volume":"8","author":"He","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cgh.2023.06.013","article-title":"Achalasia is strongly associated with eosinophilic esophagitis and other allergic disorders","volume":"22","author":"Reddy","year":"2024","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/qjmed\/os-23.92.491","article-title":"Achalasia of the cardia: So-called cardiospasm","volume":"23","author":"Hurst","year":"1930","journal-title":"QJM"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Di Brina, A.L.P., Palmieri, O., Cannarozzi, A.L., Tavano, F., Guerra, M., Bossa, F., Gentile, M., Merla, A., Biscaglia, G., and Cuttitta, A. (2024). Focus on achalasia in the omics era. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810148"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1053\/j.gastro.2013.08.038","article-title":"The spectrum of achalasia: Lessons from studies of pathophysiology and high-resolution manometry","volume":"145","author":"Kahrilas","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.3748\/wjg.v18.i24.3050","article-title":"Pathogenesis of achalasia cardia","volume":"18","author":"Ghoshal","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e14475","DOI":"10.1111\/nmo.14475","article-title":"Association between eosinophilic esophagitis and esophageal dysmotility: A systematic review and meta-analysis","volume":"35","author":"Reddy","year":"2023","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/00365521.2018.1457712","article-title":"The cultivable bacterial flora of the esophagus in subjects with esophagitis","volume":"53","author":"Ruth","year":"2018","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00039","DOI":"10.14309\/ctg.0000000000000039","article-title":"The salivary microbiome is altered in children with eosinophilic esophagitis and correlates with disease activity","volume":"10","author":"Hiremath","year":"2019","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Hitch, T.C.A., Bisdorf, K., Afrizal, A., Riedel, T., Overmann, J., Strowig, T., and Clavel, T. (2022). A taxonomic note on the genus Prevotella: Description of four novel genera and emended description of the genera Hallella and Xylanibacter. Syst. Appl. Microbiol., 45.","DOI":"10.1016\/j.syapm.2022.126354"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sasahira, M., Matsumoto, H., Go, T.T., Yo, S., Monden, S., Ninomiya, T., Oosawa, M., Handa, O., Umegaki, E., and Inoue, R. (2025). The relationship between bacterial flora in saliva and esophageal mucus and endoscopic severity in patients with eosinophilic esophagitis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073026"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Harris, J.K., Fang, R., Wagner, B.D., Choe, H.N., Kelly, C.J., Schroeder, S., Moore, W., Stevens, M.J., Yeckes, A., and Amsden, K. (2015). Esophageal microbiome in eosinophilic esophagitis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128346"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jaci.2024.07.022","article-title":"Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR\/TIGERs symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting","volume":"154","author":"Wright","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/apt.17091","article-title":"Salivary microbiota composition may discriminate between patients with eosinophilic oesophagitis (EoE) and non-EoE subjects","volume":"56","author":"Facchin","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1080\/17474124.2025.2530606","article-title":"Could modulating the esophageal microbiome be the answer for eosinophilic esophagitis treatment?","volume":"19","author":"Facchin","year":"2025","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4211626","DOI":"10.1155\/2022\/4211626","article-title":"The effectiveness of synbiotic on the improvement of clinical symptoms in children with eosinophilic esophagitis","volume":"2022","author":"Amini","year":"2022","journal-title":"Int. J. Pediatr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1111\/all.12951","article-title":"Beneficial effect of Lactococcus lactis NCC 2287 in a murine model of eosinophilic esophagitis","volume":"71","author":"Holvoet","year":"2016","journal-title":"Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Geng, Z.H., Zhu, Y., Chen, W.F., Fu, P.Y., Xu, J.Q., Wang, T.Y., Yao, L., Liu, Z.Q., Li, X.Q., and Zhang, Z.C. (2023). The role of type II esophageal microbiota in achalasia: Activation of macrophages and degeneration of myenteric neurons. Microbiol. Res., 276.","DOI":"10.1016\/j.micres.2023.127470"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15767","DOI":"10.1021\/acs.chemrev.0c01321","article-title":"A journey from structure to function of bacterial lipopolysaccharides","volume":"122","author":"Duda","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Tume, R., El Sherbiny, S., Bono, R., Gautier, T., Pais de Barros, J.P., and Mero\u00f1o, T. (2025). The balance between proinflammatory \u201cbad\u201d and immunomodulatory \u201cgood\u201d lipopolysaccharide for understanding gut-derived systemic inflammation. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1588129"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.5056\/jnm21057","article-title":"Esophageal microbiota and nutritional intakes in patients with achalasia before and after peroral endoscopic myotomy","volume":"28","author":"Jung","year":"2022","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42","DOI":"10.5152\/tjg.2020.19995","article-title":"Comparison of oral and esophageal microbiota in patients with achalasia before and after peroral endoscopic myotomy","volume":"32","author":"Takahashi","year":"2021","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00535-024-02088-w","article-title":"The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia","volume":"59","author":"Ikeda","year":"2024","journal-title":"J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1042\/BCJ20200610","article-title":"Anti-glycan antibodies: Roles in human disease","volume":"478","author":"Temme","year":"2021","journal-title":"Biochem. J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7502\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:04:45Z","timestamp":1761213885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":44,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217502"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217502","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}