microorganisms Review Oral Bacterial Microbiota in Digestive Cancer Patients: A Systematic Review Elisa Reitano 1 , Nicola de’Angelis 2,3 , Paschalis Gavriilidis 4 , Federica Gaiani 5,6 , Riccardo Memeo 7 , Riccardo Inchingolo 8 , Giorgio Bianchi 2 , Gian Luigi de’Angelis 5, * and Maria Clotilde Carra 9   Citation: Reitano, E.; de’Angelis, N.; Gavriilidis, P.; Gaiani, F.; Memeo, R.; Inchingolo, R.; Bianchi, G.; de’Angelis, G.L.; Carra, M.C. Oral Bacterial Microbiota in Digestive Cancer Patients: A Systematic Review. Microorganisms 2021, 9, 2585. https://doi.org/10.3390/ microorganisms9122585 Academic Editors: Iradj Sobhani, Denis Mestivier and Georgios N. Belibasakis Received: 22 November 2021 Accepted: 9 December 2021 Published: 14 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Division of General Surgery, Department of Translational Medicine, Maggiore della Carità Hospital, University of Eastern Piedmont, 28100 Novara, Italy; elisa.reitano@live.it 2 Unit of Digestive and HPB Surgery, CARE Department, Henri Mondor Hospital, AP-HP, 94010 Créteil, France; nic.deangelis@yahoo.it (N.d.); giorgio.bianchi@gmail.com (G.B.) 3 Faculté de Santé, Université Paris Est, UPEC, 94010 Créteil, France 4 Department of HBP Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, UK; pgavrielidis@yahoo.com 5 Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy; federica.gaiani@unipr.it 6 Microbiome Research Hub, University of Parma, 43126 Parma, Italy 7 Unit of HPB Surgery, General Regional University Hospital F. Miulli, Acquaviva delle Fonti, 72021 Bari, Italy; drmemeo@yahoo.it 8 Unit of Interventional Radiology, General Regional Hospital F. Miulli, Acquaviva delle Fonti, 72021 Bari, Italy; riccardoin@hotmail.it 9 Service of Odontology, Department of Periodontology, Rothschild Hospital, AP-HP, Université de Paris, U.F.R. of Odontology-Garanciere, 75006 Paris, France; mclotildecarra@gmail.com * Correspondence: gianluigi.deangelis@unipr.it Abstract: The relation between the gut microbiota and human health is increasingly recognized. Recently, some evidence suggested that dysbiosis of the oral microbiota may be involved in the development of digestive cancers. A systematic review was conducted according to the PRISMA guidelines to investigate the association between the oral microbiota and digestive cancers. Several databases including Medline, Scopus, and Embase were searched by three independent reviewers, without date restriction. Over a total of 1654 records initially identified, 28 studies (2 prospective cohort studies and 26 case-controls) were selected. They investigated oral microbiota composition in patients with esophageal squamous cell carcinoma (n = 5), gastric cancer (n = 5), colorectal cancer (n = 9), liver carcinoma (n = 2), and pancreatic cancer (n = 7). In most of the studies, oral microbiota composition was found to be different between digestive cancer patients and controls. Particularly, oral microbiota dysbiosis and specific bacteria, such as Fusobacterium nucleatum and Porphyromonas gingivalis, appeared to be associated with colorectal cancers. Current evidence suggests that differences exist in oral microbiota composition between patients with and without digestive cancers. Further studies are required to investigate and validate oral–gut microbial transmission patterns and their role in digestive cancer carcinogenesis. Keywords: oral microbiota; carcinogenesis; digestive cancer; systematic review 1. Introduction Digestive cancers include cancers located in the esophagus, stomach, liver, pancreas, colon, and rectum. Their incidence and related mortality are increasing worldwide, but with some characteristic geographical differences [1]. According to the GLOBOCAN, i.e., Cancer Incidence in Five Continents, and the World Health Organization (WHO) mortality databases in 2018, the majority of new cases of digestive cancers (63%) and related deaths (65%) occurred in Asia, followed by Europe and North America. Moreover, esophageal, gastric, and liver cancers appear to be more prevalent in Asia, whereas colorectal and Microorganisms 2021, 9, 2585. https://doi.org/10.3390/microorganisms9122585 https://www.mdpi.com/journal/microorganisms