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Lee JG. Microbiota, Gut Health, and Laryngopharyngeal Reflux Disease. Otolaryngol Clin North Am 2025; 58:433-440. [PMID: 39472179 DOI: 10.1016/j.otc.2024.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Recent advances in technology have allowed examination of microbial communities in efforts to classify microbiomes of "healthy" individuals. The gut and the oral cavity have been extensively researched but the upper airway (including the pharynx and larynx) has not received the same attention. This review details the emergence of microbiota as a field of interest and reviews existing evidence supporting a relationship between microbiome alterations and laryngopharyngeal reflux symptoms, as well as potential therapeutic interventions.
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Affiliation(s)
- Jessica G Lee
- Charleston ENT and Allergy, 2295 Henry Tecklenburg Drive, Charleston, SC 29414, USA.
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2
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Marasco G, Colecchia L, Salvi D, Bruni A, Capelli C, Dajti E, Barbaro MR, Cremon C, Stanghellini V, Barbara G. The Role of Microbiota in Upper Gastrointestinal Cancers. Cancers (Basel) 2025; 17:1719. [PMID: 40427216 DOI: 10.3390/cancers17101719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2025] [Revised: 05/19/2025] [Accepted: 05/19/2025] [Indexed: 05/29/2025] Open
Abstract
The gut microbiota significantly impacts the development and progression of upper gastrointestinal (GI) cancers, including esophageal and gastric cancers. Microbial dysbiosis contributes to carcinogenesis through mechanisms such as inflammation, immune modulation, and direct DNA damage. Techniques for sampling oral, esophageal, and gastric microbiota vary, with standardization being essential for reliable results. Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) are associated with an enrichment of Gram-negative bacteria, promoting inflammation and cancer progression. Esophageal squamous cell carcinoma (ESCC) also shows distinct microbial patterns, with reduced diversity and increased harmful bacteria like Porphyromonas gingivalis and Fusobacterium nucleatum. In gastric cancer (GC), Helicobacter pylori (HP) and non-HP gastric microbiota play significant roles, with diverse microbial communities contributing to cancer development through nitrate reduction, immune modulation, and inflammation. Emerging evidence highlights the role of non-HP bacteria in promoting carcinogenesis, with specific taxa like Fusobacterium nucleatum and Lactobacillus influencing tumor growth and immune evasion. Further research is needed to elucidate the complex interactions between gut microbiota and upper GI cancers, paving the way for novel diagnostic and therapeutic approaches. Understanding these microbial dynamics offers potential for microbiota-based interventions, improving the early detection, prognosis, and treatment of upper GI cancers. This comprehensive review summarizes the available evidence on the role of microbiota in upper GI oncology and the need for continued exploration in this field.
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Affiliation(s)
- Giovanni Marasco
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Luigi Colecchia
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Daniele Salvi
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Gastroenterology and Endoscopy, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy
| | - Angelo Bruni
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Cecilia Capelli
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Elton Dajti
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | | | - Cesare Cremon
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
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Liu S, Lin Z, Huang Z, Yu M, Lin Z, Hu Z. Unique Microbial Characterisation of Oesophageal Squamous Cell Carcinoma Patients with Different Dietary Habits Based on Light Gradient Boosting Machine Learning Classifier. Nutrients 2025; 17:1340. [PMID: 40284204 PMCID: PMC12030675 DOI: 10.3390/nu17081340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 04/29/2025] Open
Abstract
Objectives: The microbiome plays an important role in cancer, but the relationship between dietary habits and the microbiota in oesophageal squamous cell carcinoma (ESCC) is not clear. The aim of this study is to explore the complex relationship between the microbiota in oesophagal tissue and dietary habits in ESCC patients. Methods: 173 ESCC patients were included. The method of 16S rRNA sequencing was used to analyze microbial composition and diversity. The LEfSe and Boruta methods were used to screen important microbes, and the LightGBM algorithm distinguished microbes associated with different dietary habits. PICRUST2 and DESeq2 predicted microbial function and screened differential functions. The Pearson test was used to analyze correlations between microbes and functions, and SPARCC microbial symbiotic networks and Cytoscape were used to determine microbial interactions. Results: Significant differences in microbial composition were observed among ESCC patients with different dietary habits. LEfSe and Boruta identified three, six, and two significantly different bacteria in the FF/FP, FF/PF, and FF/PP groups, respectively, with AUC values of 0.683, 0.830, and 0.715. PICRUST2 and DESeq2 analysis revealed 3, 11, and 5 significantly different metabolic pathways in each group. Eubacterium_B sulci was positively correlated with PWY-6285, PWY-3801, and PWY-5823. PWY-6397 was positively correlated with undefinded (Fusobacterium_C). Microbial network analysis confirmed unique microbial characteristics in different diet groups. Conclusions: Different dietary habits lead to alterations in Eubacterium_B sulci and undefinded (Fusobacterium_C) and related functional pathways.
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Affiliation(s)
- Shun Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zhifeng Lin
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zhimin Huang
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Menglin Yu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zheng Lin
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350122, China
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Guan Y, Cheng H, Zhang N, Cai Y, Zhang Q, Jiang X, Wang A, Zeng H, Jia B. The role of the esophageal and intestinal microbiome in gastroesophageal reflux disease: past, present, and future. Front Immunol 2025; 16:1558414. [PMID: 40061946 PMCID: PMC11885504 DOI: 10.3389/fimmu.2025.1558414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 02/04/2025] [Indexed: 05/13/2025] Open
Abstract
Gastroesophageal reflux disease (GERD) is one of the common diseases of the digestive system, and its incidence is increasing year by year, in addition to its typical symptoms of acid reflux and heartburn affecting the quality of patients' survival. The pathogenesis of GERD has not yet been clarified. With the development of detection technology, microbiome have been studied in depth. Normal microbiome are symbiotic with the host and can assist the host to fulfill the roles of digestion and absorption, and promote the development of the host. Dysbiosis of the microbiome forms a new internal environment, under which it may affect the development of GERD from the perspectives of molecular mechanisms: microbial activation of Toll-like receptors, microbial stimulation of cyclooxygenase-2 expression, microbial stimulation of inducible nitrous oxide synthase, and activation of the NLRP3 inflammatory vesicle; immune mechanisms; and impact on the dynamics of the lower gastrointestinal tract. This review will explore the esophageal microbiome and intestinal microbiome characteristics of GERD and the mechanisms by which dysbiotic microbiome induces GERD.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Boyi Jia
- Department of Spleen and Stomach Diseases, Fangshan Traditional Medical Hospital of Beijing, Beijing, China
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Barchi A, Massimino L, Mandarino FV, Vespa E, Sinagra E, Almolla O, Passaretti S, Fasulo E, Parigi TL, Cagliani S, Spanò S, Ungaro F, Danese S. Microbiota profiling in esophageal diseases: Novel insights into molecular staining and clinical outcomes. Comput Struct Biotechnol J 2024; 23:626-637. [PMID: 38274997 PMCID: PMC10808859 DOI: 10.1016/j.csbj.2023.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 12/22/2023] [Accepted: 12/23/2023] [Indexed: 01/27/2024] Open
Abstract
Gut microbiota is recognized nowadays as one of the key players in the development of several gastro-intestinal diseases. The first studies focused mainly on healthy subjects with staining of main bacterial species via culture-based techniques. Subsequently, lots of studies tried to focus on principal esophageal disease enlarged the knowledge on esophageal microbial environment and its role in pathogenesis. Gastro Esophageal Reflux Disease (GERD), the most widespread esophageal condition, seems related to a certain degree of mucosal inflammation, via interleukin (IL) 8 potentially enhanced by bacterial components, lipopolysaccharide (LPS) above all. Gram- bacteria, producing LPS), such as Campylobacter genus, have been found associated with GERD. Barrett esophagus (BE) seems characterized by a Gram- and microaerophils-shaped microbiota. Esophageal cancer (EC) development leads to an overturn in the esophageal environment with the shift from an oral-like microbiome to a prevalently low-abundant and low-diverse Gram--shaped microbiome. Although underinvestigated, also changes in the esophageal microbiome are associated with rare chronic inflammatory or neuropathic disease pathogenesis. The paucity of knowledge about the microbiota-driven mechanisms in esophageal disease pathogenesis is mainly due to the scarce sensitivity of sequencing technology and culture methods applied so far to study commensals in the esophagus. However, the recent advances in molecular techniques, especially with the advent of non-culture-based genomic sequencing tools and the implementation of multi-omics approaches, have revolutionized the microbiome field, with promises of implementing the current knowledge, discovering more mechanisms underneath, and giving insights into the development of novel therapies aimed to re-establish the microbial equilibrium for ameliorating esophageal diseases..
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Affiliation(s)
- Alberto Barchi
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Luca Massimino
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | | | - Edoardo Vespa
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Cefalù, Italy
| | - Omar Almolla
- Università Vita-Salute San Raffaele, Faculty of Medicine, Milan, Italy
| | - Sandro Passaretti
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Ernesto Fasulo
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Faculty of Medicine, Milan, Italy
| | - Stefania Cagliani
- Università Vita-Salute San Raffaele, Faculty of Medicine, Milan, Italy
| | - Salvatore Spanò
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Federica Ungaro
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Silvio Danese
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Faculty of Medicine, Milan, Italy
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Patel NM, Patel PH, Bhogal RH, Harrington KJ, Singanayagam A, Kumar S. Altered Microbiome Promotes Pro-Inflammatory Pathways in Oesophago-Gastric Tumourigenesis. Cancers (Basel) 2024; 16:3426. [PMID: 39410045 PMCID: PMC11476036 DOI: 10.3390/cancers16193426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/27/2024] [Accepted: 10/04/2024] [Indexed: 10/20/2024] Open
Abstract
INTRODUCTION The upper gastrointestinal microbiome is a dynamic entity that is involved in numerous processes including digestion, production of vitamins and protection against pathogens. Many external and intrinsic factors may cause changes in the proportions of bacteria within the microbial community, termed 'dysbiosis'. A number of these have been identified as risk factors for a range of diseases, including oesophago-gastric carcinoma. MATERIALS AND METHODS A narrative review was conducted to elucidate the current evidence on the role of the microbiome in promoting oesophago-gastric tumourigenesis. Significant causes of dysbiosis including age, medications and GORD were examined and key pro-inflammatory pathways implicated in tumourigenesis and their interaction with the microbiome were described. RESULTS AND DISCUSSION An association between microbial dysbiosis and development of oesophago-gastric cancer may be mediated via activation of pro-inflammatory pathways, the inflammasome and the innate immune system. Advances in sequencing technology allow microbial communities to be fingerprinted by sequencing the 16S rRNA gene, enabling a deeper understanding of the genera that may be implicated in driving tumourigenesis. CONCLUSIONS Developing a greater understanding of the influence of the microbiota on oesophago-gastric tumourigenesis may enable advances to be made in the early detection of malignancy and in the development of novel systemic therapies, leading to improved rates of survival.
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Affiliation(s)
- Nikhil Manish Patel
- Department of Upper GI Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; (N.M.P.)
- The Upper Gastrointestinal Surgical Oncology Research Group, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London SW7 3RP, UK
| | - Pranav Harshad Patel
- Department of Upper GI Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; (N.M.P.)
- The Upper Gastrointestinal Surgical Oncology Research Group, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London SW7 3RP, UK
| | - Ricky Harminder Bhogal
- Department of Upper GI Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; (N.M.P.)
- The Upper Gastrointestinal Surgical Oncology Research Group, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London SW7 3RP, UK
| | - Kevin Joseph Harrington
- Targeted Therapy Group, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London SW7 3RP, UK
| | - Aran Singanayagam
- Centre for Bacterial Resistance Biology, Department of Infectious Disease, Imperial College London, London SW7 2AZ, UK
| | - Sacheen Kumar
- Department of Upper GI Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; (N.M.P.)
- The Upper Gastrointestinal Surgical Oncology Research Group, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London SW7 3RP, UK
- Department of Upper Gastrointestinal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic London Hospital, London SW1X 7HY, UK
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Moe KT, Tan KSW. Mechanistic Insights on Microbiota-Mediated Development and Progression of Esophageal Cancer. Cancers (Basel) 2024; 16:3305. [PMID: 39409925 PMCID: PMC11475040 DOI: 10.3390/cancers16193305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/18/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research has highlighted the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between the microbiome and esophageal carcinogenesis, focusing on the following eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target the microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.
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Affiliation(s)
- Kyaw Thu Moe
- Biomedical Sciences, Newcastle University Medicine Malaysia, Iskandar Puteri 79200, Johor, Malaysia
| | - Kevin Shyong-Wei Tan
- Laboratory of Molecular and Cellular Parasitology, Health Longevity Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive, Singapore 117545, Singapore
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Luo J, Xiao S, Ma D, Xiang J, Wang B, Cai Y, Wang J. Investigating the Impact of Pineapple-Whey Protein Fermentation Products on Cefixime-Induced Intestinal Flora Dysbiosis in Mice Using 16S Sequencing and Untargeted Metabolomics Techniques. Foods 2024; 13:1927. [PMID: 38928868 PMCID: PMC11202880 DOI: 10.3390/foods13121927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 05/21/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
In our previous study, a new fermented food (PWF) created by utilizing pineapple by-products and whey proteins as a matrix via co-fermentation with lactic acid bacteria and yeast was developed, and, in the current study, we examined the impact of a pineapple-whey protein fermentation product on a cefixime-induced dysbiosis model in mice using 16S sequencing and untargeted metabolomics techniques. The results indicated that the pineapple-whey protein fermentation product played a positive role in restoring the intestinal flora. In this study, cefixime reduced the overall abundance of intestinal flora and decreased the relative abundance of probiotics in the gut, while also inhibiting amino acid metabolism. The addition of PWF normalized the intestinal flora to a steady state, significantly increasing the populations of Weissella, Lactococcus, Faecalibaculum, and Bacteroides acidophilus, while decreasing the numbers of Akkermansia and Escherichia-Shigella. Additionally, PWF modulated microbial metabolites, such as L-glutamate and L-threonine, and upregulated amino-acid-related metabolic pathways, including those involving glycine, serine, and threonine. In conclusion, PWF can alleviate intestinal flora dysbiosis and metabolic disturbances induced by antibiotic interventions. It is suggested that PWF could be a potential dietary strategy for patients with antibiotic-associated diarrhea.
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Affiliation(s)
- Jiawei Luo
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China; (J.L.); (D.M.); (J.X.); (B.W.); (Y.C.); (J.W.)
- Dongguan Prefabricated Food Innovation Development and Quality Control Key Laboratory, Dongguan 523808, China
| | - Shan Xiao
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China; (J.L.); (D.M.); (J.X.); (B.W.); (Y.C.); (J.W.)
- Dongguan Prefabricated Food Innovation Development and Quality Control Key Laboratory, Dongguan 523808, China
| | - Da Ma
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China; (J.L.); (D.M.); (J.X.); (B.W.); (Y.C.); (J.W.)
- Dongguan Prefabricated Food Innovation Development and Quality Control Key Laboratory, Dongguan 523808, China
| | - Junhan Xiang
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China; (J.L.); (D.M.); (J.X.); (B.W.); (Y.C.); (J.W.)
- Dongguan Prefabricated Food Innovation Development and Quality Control Key Laboratory, Dongguan 523808, China
| | - Bo Wang
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China; (J.L.); (D.M.); (J.X.); (B.W.); (Y.C.); (J.W.)
- Dongguan Prefabricated Food Innovation Development and Quality Control Key Laboratory, Dongguan 523808, China
| | - Yanxue Cai
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China; (J.L.); (D.M.); (J.X.); (B.W.); (Y.C.); (J.W.)
- Dongguan Prefabricated Food Innovation Development and Quality Control Key Laboratory, Dongguan 523808, China
| | - Jihui Wang
- School of Life and Health Technology, Dongguan University of Technology, Dongguan 523808, China; (J.L.); (D.M.); (J.X.); (B.W.); (Y.C.); (J.W.)
- Dongguan Prefabricated Food Innovation Development and Quality Control Key Laboratory, Dongguan 523808, China
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Mishra Y, Ranjan A, Mishra V, Chattaraj A, Aljabali AAA, El-Tanani M, Hromić-Jahjefendić A, Uversky VN, Tambuwala MM. The role of the gut microbiome in gastrointestinal cancers. Cell Signal 2024; 115:111013. [PMID: 38113978 DOI: 10.1016/j.cellsig.2023.111013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 12/06/2023] [Accepted: 12/13/2023] [Indexed: 12/21/2023]
Abstract
The gut microbiota present in the human digestive system is incredibly varied and is home to trillions of microorganisms. The gut microbiome is shaped at birth, while numerous genetic, dietary, and environmental variables primarily influence the microbiome composition. The importance of gut microbiota on host health is becoming more widely acknowledged. Digestion, intestinal permeability, and immunological and metabolism responses can all be affected by changes in the composition and function of the gut microbiota. There is mounting evidence that the microbial population's complex traits are important biomarkers and indicators of patient outcomes in cancer and its therapies. Numerous studies have demonstrated that changed commensal gut microorganisms contribute to the development and spread of cancer through various routes. Despite the ongoing controversy surrounding the gut microbiome and gastrointestinal cancer, accumulating evidence points to a potentially far more intricate connection than a simple cause-and-effect relationship. SIMPLE SUMMARY: Due to their high frequency and fatality rate, gastrointestinal cancers are regarded as a severe public health issue with complex medical and economic burdens. The gut microbiota may directly or indirectly interact with existing therapies like immunotherapy and chemotherapy, affecting how well a treatment works. The gut microbiome influences the immune response's activity, function, and development. Generally, certain gut bacteria impact the antitumor actions during cancer by creating particular metabolites or triggering T-cell responses. Yet, certain bacterial species have been found to promote cellular proliferation and metastasis in cancer, and comprehending these interactions in the context of cancer may help identify possible treatment targets. Notwithstanding the improvements in the field, additional research is still required to comprehend the underlying processes, examine the effects on existing therapies, and pinpoint certain bacteria and immune cells that can cause this interaction.
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Affiliation(s)
- Yachana Mishra
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Abhigyan Ranjan
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Aditi Chattaraj
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Alaa A A Aljabali
- Department of Pharmaceutical Sciences, Yarmouk University, Irbid, Jordan
| | - Mohamed El-Tanani
- College of Pharmacy, Ras Alkhama Medical and Health Sciences University, United Arab Emirates
| | - Altijana Hromić-Jahjefendić
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnicka cesta 15, Sarajevo 71000, Bosnia and Herzegovina
| | - Vladimir N Uversky
- Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Murtaza M Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool, Lincoln LN6 7TS, England, United Kingdom.
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10
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Li Y, Wei B, Xue X, Li H, Li J. Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis. Cancer Biol Med 2023; 21:j.issn.2095-3941.2023.0177. [PMID: 37817487 PMCID: PMC10884538 DOI: 10.20892/j.issn.2095-3941.2023.0177] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 09/06/2023] [Indexed: 10/12/2023] Open
Abstract
Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. Various factors, including dietary habits, and antacid and antibiotic use, have been shown to influence the esophageal microbiome. Conversely, enrichment and diversity of the esophageal microbiome can also impact its function. Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. Additionally, distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy, indicating the role of the esophageal microbiome in modulating treatment outcomes. In this review, we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases, with a focus on identifying microbial communities associated with EC pathogenesis and prognosis. Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients.
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Affiliation(s)
- Yi Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
| | - Bing Wei
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou 450003, China
| | - Xia Xue
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Hongle Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou 450003, China
| | - Jun Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou 450003, China
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11
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Chiang H, Hughes M, Chang W. The role of microbiota in esophageal squamous cell carcinoma: A review of the literature. Thorac Cancer 2023; 14:2821-2829. [PMID: 37675608 PMCID: PMC10542467 DOI: 10.1111/1759-7714.15096] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 08/23/2023] [Indexed: 09/08/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well-known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF-κB and IL-6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug-resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.
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Affiliation(s)
- Hsueh‐Chien Chiang
- Department of Internal MedicineNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan
- Institute of Clinical Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan
| | - Michael Hughes
- Institute of Clinical Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan
- International Center for Wound Repair and Regeneration (iWRR), College of MedicineNational Cheng Kung UniversityTainanTaiwan
- Department of Life SciencesNational Cheng Kung UniversityTainanTaiwan
| | - Wei‐Lun Chang
- Department of Internal MedicineNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan
- Institute of Clinical Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan
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12
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Zaramella A, Arcidiacono D, Nucci D, Fabris F, Benna C, Pucciarelli S, Fassan M, Fantin A, De Re V, Cannizzaro R, Realdon S. Resident Esophageal Microbiota Dysbiosis Correlates with Cancer Risk in Barrett's Esophagus Patients and Is Linked to Low Adherence to WCRF/AICR Lifestyle Recommendations. Nutrients 2023; 15:2885. [PMID: 37447211 PMCID: PMC10343580 DOI: 10.3390/nu15132885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/19/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is the consequence of longstanding gastroesophageal reflux, which leads to inflammation and could cause Barrett's esophagus (BE), the main risk factor for EAC development. The 5 year survival rate of EAC is poor since the diagnosis occurs at the late stage of the disease. To improve patient management, a better comprehension of the mechanism undergoing the evolution through to adenocarcinoma is needed. Within this scenario, the resident microbiome investigation was studied. This study aimed to explore the esophageal microbial profile in patients affected by non-dysplastic BE, low- and high-grade dysplastic BE, and EAC to identify parameters characterizing cancer progression and to develop a score suitable for clinical practice to stratify cancer risk. The microbiota was investigated through the 16S rRNA gene sequencing of esophageal biopsies. The microbial composition was evaluated at each different taxonomic level along the disease progression. To further investigate bacteria potentially associated with cancer development, non-dysplastic and dysplastic/cancer patients were compared. The presence of the six significant microbial features with multivariate analysis was used to develop a multiparametric score (Resident Esophageal Microbial Dysbiosis Test) to predict the risk of progression toward EAC. Finally, the diagnostic ability of the test and its discrimination threshold for its ability to identify dysplastic/cancer patients were demonstrated. Since EAC has been related to obesity, the relationship between these microbial parameters and patients' diet/lifestyle habits was also investigated. Developing microbiome-based risk prediction models for esophageal adenocarcinoma onset could open new research avenues, demonstrating that the resident microbiome may be a valid cancer risk biomarker.
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Affiliation(s)
- Alice Zaramella
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (C.B.); (S.P.)
- Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy; (D.A.); (A.F.)
| | - Diletta Arcidiacono
- Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy; (D.A.); (A.F.)
| | - Daniele Nucci
- Dietetics and Clinical Nutrition Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy;
| | - Federico Fabris
- Department of Biomedical Sciences, University of Padua, Viale Colombo 3, 35121 Padua, Italy;
| | - Clara Benna
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (C.B.); (S.P.)
| | - Salvatore Pucciarelli
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (C.B.); (S.P.)
| | - Matteo Fassan
- Department of Medicine (DIMED), University of Padua, Via Gabelli 61, 35121 Padua, Italy;
- Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
| | - Alberto Fantin
- Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy; (D.A.); (A.F.)
| | - Vallì De Re
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy;
| | - Renato Cannizzaro
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy; (R.C.); (S.R.)
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy
| | - Stefano Realdon
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy; (R.C.); (S.R.)
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13
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Moreira C, Figueiredo C, Ferreira RM. The Role of the Microbiota in Esophageal Cancer. Cancers (Basel) 2023; 15:cancers15092576. [PMID: 37174041 PMCID: PMC10177416 DOI: 10.3390/cancers15092576] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 04/28/2023] [Accepted: 04/29/2023] [Indexed: 05/15/2023] Open
Abstract
Esophageal cancer is a major health problem, being the seventh most incidence cancer worldwide. Due to the often-late diagnosis and lack of efficient treatments, the overall 5-year survival is as low as 10%. Therefore, understanding the etiology and the mechanisms that drive the development of this type of cancer could improve the management of patients, increasing the chance of achieving a better clinical outcome. Recently, the microbiome has been studied as a putative etiological factor for esophageal cancer. Nevertheless, the number of studies tackling this issue is low, and the heterogeneity in the study design and data analysis has hindered consistent findings. In this work, we reviewed the current literature on the evaluation of the role of microbiota in the development of esophageal cancer. We analyzed the composition of the normal microbiota and the alterations found in precursor lesions, namely Barrett's esophagus and dysplasia, as well as in esophageal cancer. Additionally, we explored how other environmental factors can modify microbiota and contribute to the development of this neoplasia. Finally, we identify critical aspects to be improved in future studies, with the aim of refining the interpretation of the relationship between the microbiome and esophageal cancer.
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Affiliation(s)
- Clara Moreira
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal
- Department of Pathology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal
| | - Ceu Figueiredo
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal
- Department of Pathology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal
| | - Rui Manuel Ferreira
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal
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14
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Wang SE, Hodge A, Dashti SG, Dixon-Suen SC, Castaño-Rodríguez N, Thomas R, Giles G, Boussioutas A, Kendall B, English DR. Diet and risk of Barrett's oesophagus: Melbourne collaborative cohort study. Br J Nutr 2023; 129:1232-1241. [PMID: 35837679 PMCID: PMC10011587 DOI: 10.1017/s0007114522002112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 06/29/2022] [Accepted: 07/04/2022] [Indexed: 11/08/2022]
Abstract
Barrett's oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case-control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20 000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990-1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007-2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile: OR = 0·59; CI: 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI: 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI: 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI: 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.
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Affiliation(s)
- Sabrina E. Wang
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
| | - Allison Hodge
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
| | - S Ghazaleh Dashti
- Clinical Epidemiology and Biostatistics Unit, Murdoch Children’s Research Institute, Melbourne, VIC, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
| | - Suzanne C. Dixon-Suen
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, VIC, Australia
| | - Natalia Castaño-Rodríguez
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, Australia
| | - Robert Thomas
- Department of Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia
| | - Graham Giles
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
| | - Alex Boussioutas
- Department of Gastroenterology, The Alfred, Melbourne, VIC, Australia
- Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Bradley Kendall
- Department of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Dallas R. English
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
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15
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Rashidi A, Koyama M, Dey N, McLean JS, Hill GR. Colonization resistance is dispensable for segregation of oral and gut microbiota. BMC Med Genomics 2023; 16:31. [PMID: 36814251 PMCID: PMC9948407 DOI: 10.1186/s12920-023-01449-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND The oral and colonic microbiota are distinct in healthy individuals. However, this distinction is diminished in common diseases such as colon cancer and inflammatory bowel disease, suggesting a potential pathogenic role for oral bacteria when ectopically colonized in the gut. A key mechanism for the segregation of oral and colonic microbiota niches is thought to be microbiota-mediated colonization resistance whereby the commensal gut microbiota outcompete and eliminate the ingested oral bacteria. METHODS We tested this theory by analyzing exact amplicon sequence variants generated from concurrent fecal and oral samples from healthy volunteers exposed to a brief course of a single antibiotic (cohort 1), acute leukemia patients (cohort 2), and stem cell transplant recipients (cohort 3). Cohorts 2 and 3 represent extreme clinical scenarios with respect to antibiotic pressure and severity of gut microbiota injury. RESULTS While mild antibiotic exposure in cohort 1 was not sufficient for colonization of any oral bacteria in the gut, even with extreme antibiotic pressure and severe gut microbiota disruptions in cohorts 2 and 3, only one oral species in each cohort colonized the gut. CONCLUSIONS Colonization resistance is dispensable for segregation of oral and colonic microbiota in humans. This finding implies that the presence of oral bacteria in the distal gut in diseases such as colon cancer and inflammatory bowel disease is not driven by impaired colonization resistance.
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Affiliation(s)
- Armin Rashidi
- Fred Hutchinson Cancer Center, 1100 Fairview Ave N, D1-100, Seattle, WA, 98109, USA. .,Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
| | - Motoko Koyama
- grid.270240.30000 0001 2180 1622Fred Hutchinson Cancer Center, 1100 Fairview Ave N, D1-100, Seattle, WA 98109 USA
| | - Neelendu Dey
- grid.270240.30000 0001 2180 1622Fred Hutchinson Cancer Center, 1100 Fairview Ave N, D1-100, Seattle, WA 98109 USA ,grid.34477.330000000122986657Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA USA
| | - Jeffrey S. McLean
- grid.34477.330000000122986657School of Dentistry, University of Washington, Seattle, WA USA
| | - Geoffrey R. Hill
- grid.270240.30000 0001 2180 1622Fred Hutchinson Cancer Center, 1100 Fairview Ave N, D1-100, Seattle, WA 98109 USA ,grid.34477.330000000122986657Division of Oncology, Department of Medicine, University of Washington, Seattle, WA USA
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16
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Higashiyama M, Miura S, Hokari R. Modulation by luminal factors on the functions and migration of intestinal innate immunity. Front Immunol 2023; 14:1113467. [PMID: 36860849 PMCID: PMC9968923 DOI: 10.3389/fimmu.2023.1113467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 01/25/2023] [Indexed: 02/15/2023] Open
Abstract
Luminal antigens, nutrients, metabolites from commensal bacteria, bile acids, or neuropeptides influence the function and trafficking of immune cells in the intestine. Among the immune cells in the gut, innate lymphoid cells, including macrophages, neutrophils, dendritic cells, mast cells, and innate lymphoid cells, play an important role for the maintenance of intestinal homeostasis through a rapid immune response to luminal pathogens. These innate cells are influenced by several luminal factors, possibly leading to dysregulated gut immunity and intestinal disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and intestinal allergy. Luminal factors are sensed by distinct neuro-immune cell units, which also have a strong impact on immunoregulation of the gut. Immune cell trafficking from the blood stream through the lymphatic organ to lymphatics, an essential function for immune responses, is also modulated by luminal factors. This mini-review examines knowledge of luminal and neural factors that regulate and modulate response and migration of leukocytes including innate immune cells, some of which are clinically associated with pathological intestinal inflammation.
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Affiliation(s)
- Masaaki Higashiyama
- Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan,*Correspondence: Masaaki Higashiyama,
| | - Soichiro Miura
- International University of Health and Welfare, Tokyo, Japan
| | - Ryota Hokari
- Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan
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17
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Mahmood R, Voisin A, Olof H, Khorasaniha R, Lawal SA, Armstrong HK. Host Microbiomes Influence the Effects of Diet on Inflammation and Cancer. Cancers (Basel) 2023; 15:521. [PMID: 36672469 PMCID: PMC9857231 DOI: 10.3390/cancers15020521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/12/2023] [Accepted: 01/13/2023] [Indexed: 01/19/2023] Open
Abstract
Cancer is the second leading cause of death globally, and there is a growing appreciation for the complex involvement of diet, microbiomes, and inflammatory processes culminating in tumorigenesis. Although research has significantly improved our understanding of the various factors involved in different cancers, the underlying mechanisms through which these factors influence tumor cells and their microenvironment remain to be completely understood. In particular, interactions between the different microbiomes, specific dietary factors, and host cells mediate both local and systemic immune responses, thereby influencing inflammation and tumorigenesis. Developing an improved understanding of how different microbiomes, beyond just the colonic microbiome, can interact with dietary factors to influence inflammatory processes and tumorigenesis will support our ability to better understand the potential for microbe-altering and dietary interventions for these patients in future.
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Affiliation(s)
- Ramsha Mahmood
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Athalia Voisin
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Hana Olof
- Department of Immunology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Reihane Khorasaniha
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Samuel A. Lawal
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Heather K. Armstrong
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
- Department of Immunology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
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18
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Sharma T, Gupta A, Chauhan R, Bhat AA, Nisar S, Hashem S, Akhtar S, Ahmad A, Haris M, Singh M, Uddin S. Cross-talk between the microbiome and chronic inflammation in esophageal cancer: potential driver of oncogenesis. Cancer Metastasis Rev 2022; 41:281-299. [PMID: 35511379 PMCID: PMC9363391 DOI: 10.1007/s10555-022-10026-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 03/12/2022] [Indexed: 12/11/2022]
Abstract
Esophageal cancer (EC) is frequently considered a lethal malignancy and is often identified at a later stage. It is one of the major causes of cancer-related deaths globally. The conventional treatment methods like chemotherapy, radiotherapy, and surgery offer limited efficacy and poor clinical outcome with a less than 25% 5-year survival rate. The poor prognosis of EC persists despite the growth in the development of diagnostic and therapeutic modalities to treat EC. This underlines the need to elucidate the complex molecular mechanisms that drive esophageal oncogenesis. Apart from the role of the tumor microenvironment and its structural and cellular components in tumorigenesis, mounting evidence points towards the involvement of the esophageal microbiome, inflammation, and their cross-talk in promoting esophageal cancer. The current review summarizes recent research that delineates the underlying molecular mechanisms by which the microbiota and inflammation promote the pathophysiology of esophageal cancer, thus unraveling targets for potential therapeutic intervention.
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Affiliation(s)
- Tarang Sharma
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India
| | - Ashna Gupta
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Chauhan
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India
| | - Ajaz A Bhat
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Sabah Nisar
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Sheema Hashem
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Sabah Akhtar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Aamir Ahmad
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Mohammad Haris
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
- Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, PA, Philadelphia, USA
- Laboratory Animal Research Center, Qatar University, Doha, Qatar
| | - Mayank Singh
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India.
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
- Laboratory Animal Research Center, Qatar University, Doha, Qatar.
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19
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Li X, Wang X, Wang Z, Zhang M, Wang S, Xiang Z, Pan H, Li M. The Relationship Between Gut Microbiome and Bile Acids in Primates With Diverse Diets. Front Microbiol 2022; 13:899102. [PMID: 35633689 PMCID: PMC9130754 DOI: 10.3389/fmicb.2022.899102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/06/2022] [Indexed: 11/25/2022] Open
Abstract
Primates have evolved a variety of feeding habits and intestinal physiological structure. Gut microbiome act as metabolic organs in many biological processes and play a vital role in adaptation to dietary niches. Gut microbiome also convert primary bile acids (BAs) to secondary. BAs profile and gut microbiome are together influenced by diets and play a significant role in nutrient absorption. The regulation between gut microbiome and BAs metabolism is bidirectional although the relationship in primates consuming diverse diets is still unclear. Here, we investigated gut microbiome structures, fecal BAs profile, and their relationship in primates preferring three distinct diets. We found that gut microbiome communities are well differentiated among dietary groups. Folivorous primates had higher Firmicutes abundance and lower Prevotella to Bacaeroides ratios, possibly related to fiber consumption. Frugivorous primates are colonized predominantly by Prevotella and Bacteroides, pointing to an increased adaptation to high-sugar and simple carbohydrate diets. Likewise, BA profiles differ according to diet in a manner predictable from the known effects of BAs on metabolism. Folivorous primates have high conjugated bile acid levels and low unconjugated to conjugated BA ratios, consistent with their fiber-rich leaf-eating diet. Much of the differentiation in secondary and unconjugated BAs is associated with microbiome composition shifts and individual bile acid concentrations are correlated with the abundance of distinct bacterial taxonomic groups. Omnivores have higher concentrations of secondary BAs, mainly lithocholic acid (LCA). These levels are significantly positively correlated with the presence of Clostrida species, showing that the digestion requirements of omnivores are different from plant-eating primates. In conclusion, gut microbiome and BAs can respond to changes in diet and are associated with nutrient component consumption in each diet primate group. Our study is the first to demonstrate BA profile differentiation among primates preferring diverse diets. BAs thus appear to work with gut microbiome to help primates adapt to their diet.
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Affiliation(s)
- Xinyue Li
- School of Ecology and Nature Conservation, Beijing Forestry University, Beijing, China.,CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Beijing, China
| | - Xiaochen Wang
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Beijing, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Ziming Wang
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Beijing, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Mingyi Zhang
- School of Ecology and Nature Conservation, Beijing Forestry University, Beijing, China
| | | | - Zuofu Xiang
- College of Life Sciences and Technology, Central South University of Forestry and Technology, Changsha, China
| | - Huijuan Pan
- School of Ecology and Nature Conservation, Beijing Forestry University, Beijing, China
| | - Ming Li
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Beijing, China.,Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
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20
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Kleuskens MT, Haasnoot ML, Herpers BM, Ampting MTJV, Bredenoord AJ, Garssen J, Redegeld FA, van Esch BC. Butyrate and propionate restore interleukin 13-compromised esophageal epithelial barrier function. Allergy 2022; 77:1510-1521. [PMID: 34458999 PMCID: PMC9293003 DOI: 10.1111/all.15069] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 08/15/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a food allergen driven disease that is accompanied by interleukin (IL) 13 overexpression and esophageal barrier dysfunction allowing transepithelial food allergen permeation. Nutraceuticals, such as short-chain fatty acids (SCFAs) that restore barrier function and increase immune fitness may be a promising tool in the management of EoE. Here, we investigated the effects of the SCFAs acetate, propionate, and butyrate on an IL-13-compromised human esophageal epithelial barrier, including the mechanisms involved. METHODS An air-liquid interface culture model of differentiated human EPC2-hTERT (EPC2) was used to study whether SCFAs could restore barrier function after IL-13-induced impairment. Esophageal epithelial barrier function was monitored by transepithelial electrical resistance (TEER) and FITC-dextran paracellular flux, and was further examined by qPCR and immunohistochemical analysis. G protein-coupled receptor (GPR) GPR41, GPR43, GPR109a, or histone deacetylase (HDAC) (ant)agonists were used to assess mechanisms of action of SCFAs. RESULTS IL-13 stimulation decreased TEER and increased FITC flux, which was counteracted by butyrate and propionate, but not acetate treatment. Barrier proteins FLG and DSG1 mRNA expression was upregulated following butyrate and propionate treatment, whereas expression of eosinophil chemoattractant CCL26 and protease CAPN14 was downregulated. Similarly, butyrate and propionate restored FLG and DSG1 protein expression. Similar effects were observed with an HDAC antagonist but not with GPR agonists. CONCLUSION Nutraceuticals butyrate and propionate restore the barrier function of esophageal epithelial cells after an inflammatory insult and may be of therapeutic benefit in the management of EoE.
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Affiliation(s)
- Mirelle T.A. Kleuskens
- Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Faculty of Science Utrecht University Utrecht The Netherlands
| | - Maria L. Haasnoot
- Department of Gastroenterology & Hepatology Amsterdam UMC, location AMC Amsterdam The Netherlands
| | - Bart M. Herpers
- Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Faculty of Science Utrecht University Utrecht The Netherlands
| | | | - Albert J. Bredenoord
- Department of Gastroenterology & Hepatology Amsterdam UMC, location AMC Amsterdam The Netherlands
| | - Johan Garssen
- Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Faculty of Science Utrecht University Utrecht The Netherlands
- Danone Nutricia Research Utrecht The Netherlands
| | - Frank A. Redegeld
- Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Faculty of Science Utrecht University Utrecht The Netherlands
| | - Betty C.A.M. van Esch
- Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Faculty of Science Utrecht University Utrecht The Netherlands
- Danone Nutricia Research Utrecht The Netherlands
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21
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Jung DH, Youn YH, Kim DH, Lim CH, Lim HS, Moon HS, Lee JY, Park H, Hong SJ. Esophageal Microbiota and Nutritional Intakes in Patients With Achalasia Before and After Peroral Endoscopic Myotomy. J Neurogastroenterol Motil 2022; 28:237-246. [PMID: 35362450 PMCID: PMC8978113 DOI: 10.5056/jnm21057] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 06/22/2021] [Accepted: 08/10/2021] [Indexed: 12/18/2022] Open
Abstract
Background/Aims The composition of the microbiota in the esophagus is only partially understood, especially in patients with achalasia. We aim to investigate the esophageal microbial community and nutritional intakes in patients with achalasia before and after peroral endoscopic myotomies (POEM). Methods Twenty-nine patients were prospectively enrolled from 4 referral institutions across Korea. We collected esophageal samples (mucosal biopsies and retention fluid) and conducted dietary surveys for nutritional intake before and 8 weeks after POEM. The esophageal microbiota was analyzed by 16S rRNA gene sequencing targeting the V3-V4 region. Results Out of the 105 samples from 29 patients, 99 samples were subjected to microbial bioinformatic analysis after quality control, which excluded samples with no amplification or low-quality sequence data. The overall esophageal microbial compositions of patients with achalasia showed that Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria were the dominant phyla, representing over 95% of the total phyla in all groups. At the genus level, Streptococcus was the most abundant in all groups. The observed operational taxonomic unit number was significantly higher in the retention fluid than in the tissue biopsies. However, the esophageal microbial composition showed no significant changes 8 weeks post POEM. The dietary survey analysis showed that nutritional intake significantly improved post POEM. Conclusion This study determined the unique esophageal microbial composition of patients with achalasia, and also found that the microbial composition did not significantly change after POEM in the short-term, despite a significant improvement in the nutritional intake.
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Affiliation(s)
- Da Hyun Jung
- Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Hoon Youn
- Department of Gastroenterology, Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Chul-Hyun Lim
- Division of Gastroenterology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee-Sook Lim
- Department of Food and Nutrition, Yeonsung University, Anyang, Gyeonggi-do, Korea.,Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Korea (Current address)
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Ju Yup Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hyojin Park
- Department of Gastroenterology, Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Gyeonggi-do, Korea
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22
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Shen W, Tang D, Wan P, Peng Z, Sun M, Guo X, Liu R. Identification of tissue-specific microbial profile of esophageal squamous cell carcinoma by full-length 16S rDNA sequencing. Appl Microbiol Biotechnol 2022; 106:3215-3229. [PMID: 35435458 DOI: 10.1007/s00253-022-11921-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 04/05/2022] [Accepted: 04/08/2022] [Indexed: 11/25/2022]
Abstract
It was previously believed that the microbial community in the esophagus was relatively stable, but it has been reported that different esophageal diseases have different microbial community characteristics. In this study, we recruited patients with esophageal squamous cell carcinoma (ESCC) and collected 51 pairs of tumor and adjacent non-tumor tissues for full-length 16S rDNAsequencing and qPCR to compare the differences in microbial community structure. The results of sequencing in 19 pairs of tissues showed that Proteobacteria, Firmicutes, Bacteroidetes, Deinococcus-Thermus, and Actinobacteria were the main bacteria in tumor and adjacent non-tumor tissues. At the genus level, the bacteria with the highest relative proportion in tumor and adjacent non-tumor tissues were Streptococcus and Labrys, respectively. At the same time, it was observed that the complexity of microbial interactions in tumor tissues was weaker than that of adjacent non-tumor tissues. The results also found that the relative abundance of 24 taxa was statistically different between tumor and adjacent non-tumor tissues. The findings of qPCR in 32 pairs of tissues further evidence that the relative proportions of Blautia, Treponema, Lactobacillus murinus, Peptoanaerobacter stomatis, and Fusobacteria periodonticum were statistically different in tumor and adjacent non-tumor tissues. The findings of PIRCUSt2 indicated the lipopolysaccharide biosynthesis and biotin metabolism in the microbiome of cancer tissues are more significant. This study supplements the existing information on the structure, function, and interaction of microorganisms in the esophagus in situ and provides a direction for the further exploration of the relationship between esophageal in situ microorganisms and esophageal squamous cell carcinoma. KEY POINTS: • The structure of the microbial community in esophageal cancer tissue and adjacent non-tumor tissues at the phylum level is similar • Streptococcus and Labrys are the most important bacteria in esophageal tumor tissues and adjacent non-tumor tissues, respectively • Microbial interactions in tumor tissues are stronger than in adjacent non-tumor tissues.
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Affiliation(s)
- Weitao Shen
- Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Derong Tang
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, Jiangsu, China
| | - Ping Wan
- Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Zhenyan Peng
- Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Mingjun Sun
- Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Xinxin Guo
- Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Ran Liu
- Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
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23
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Wu C, Wang M, Zhou Q, Shi H. Associations of Changes in Intestinal Flora and Inflammatory Factors with Prognosis of Patients with Esophageal Cancer. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:2426301. [PMID: 35388334 PMCID: PMC8977330 DOI: 10.1155/2022/2426301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 11/29/2022]
Abstract
This study aims to explore the associations of changes in intestinal flora and inflammatory factors with the prognosis of patients with esophageal cancer (EC). A total of 40 EC patients treated and 40 normal people who underwent gastroscopy and CT examination for gastrointestinal discomfort during the same period were selected as the participants of the study. The endotoxin level, colonization ability of intestinal flora, and distribution of intestinal flora (Bifidobacterium, Lactobacillus, Escherichia coli, and Enterococcus) were compared between the two groups. The levels of inflammatory factors interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) were also compared between the two groups. All participants were followed up for 3 years, and the associations of survival time with colonization ability of intestinal flora and changes in hs-CRP were analyzed. Finally, the univariate and multivariate logistic regression analyses were performed for related factors affecting the survival time of EC patients. In the observation group, the endotoxin level was significantly higher (P < 0.05), the colonization ability of intestinal flora was significantly weaker (P < 0.05), the levels of Bifidobacterium and Lactobacillus were obviously lower (P < 0.05), and the levels of Escherichia coli and Enterococcus were obviously higher than those in the normal group (P < 0.05). Besides, the observation group had abnormal and evidently higher levels of IL-6, hs-CRP, and TNF-α than the normal group (P < 0.05). The survival time was positively correlated with the colonization ability of intestinal flora (P < 0.05), but negatively correlated with the changes in hs-CRP (P < 0.05). Moreover, the increased level of endotoxin, weakened colonization ability of intestinal flora, abnormal distribution of intestinal flora, and elevated levels of inflammatory factors were all related and independent risk factors affecting the survival time of EC patients. In EC patients, the endotoxin level markedly rises, the colonization ability of intestinal flora declines, and there are intestinal flora disorders and enhanced inflammatory response. With the decline in colonization ability of intestinal flora and the increase of inflammatory response, the survival time of EC patients will be shortened.
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Affiliation(s)
- Cheng Wu
- Department of Gastroenterology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Ming Wang
- Department of Gastroenterology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Qing Zhou
- Department of Gastroenterology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Hui Shi
- Department of Gastroenterology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
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24
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Dan W, Peng L, Yan B, Li Z, Pan F. Human Microbiota in Esophageal Adenocarcinoma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Implications. Front Microbiol 2022; 12:791274. [PMID: 35126331 PMCID: PMC8815000 DOI: 10.3389/fmicb.2021.791274] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/23/2021] [Indexed: 11/29/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) is one of the main subtypes of esophageal cancer. The incidence rate of EAC increased progressively while the 5-year relative survival rates were poor in the past two decades. The mechanism of EAC has been studied extensively in relation to genetic factors, but less so with respect to human microbiota. Currently, researches about the relationship between EAC and the human microbiota is a newly emerging field of study. Herein, we present the current state of knowledge linking human microbiota to esophageal adenocarcinoma and its precursor lesion—gastroesophageal reflux disease and Barrett’s esophagus. There are specific human bacterial alternations in the process of esophageal carcinogenesis. And bacterial dysbiosis plays an important role in the process of esophageal carcinogenesis via inflammation, microbial metabolism and genotoxicity. Based on the human microbiota alternation in the EAC cascade, it provides potential microbiome-based clinical application. This review is focused on novel targets in prevention, diagnosis, prognosis, and therapy for esophageal adenocarcinoma.
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Affiliation(s)
- Wanyue Dan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- Medical School of Nankai University, Tianjin, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bin Yan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhengpeng Li
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- *Correspondence: Fei Pan,
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25
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Wang X, Wang Z, Pan H, Qi J, Li D, Zhang L, Shen Y, Xiang Z, Li M. Captivity Influences the Gut Microbiome of Rhinopithecus roxellana. Front Microbiol 2021; 12:763022. [PMID: 34950117 PMCID: PMC8689068 DOI: 10.3389/fmicb.2021.763022] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 11/18/2021] [Indexed: 11/20/2022] Open
Abstract
Ex situ (captivity in zoos) is regarded as an important form of conservation for endangered animals. Many studies have compared differences in the gut microbiome between captive and wild animals, but few have explained those differences at the functional level due to the limited amount of 16S rRNA data. Here, we compared the gut microbiome of captive and wild Rhinopithecus roxellana, whose high degree of dietary specificity makes it a good subject to observe the effects of the captive environment on their gut microbiome, by performing a metagenome-wide association study (MWAS). The Chao1 index was significantly higher in the captive R. roxellana cohort than in the wild cohort, and the Shannon index of captive R. roxellana was higher than that of the wild cohort but the difference was not significant. A significantly increased ratio of Prevotella/Bacteroides, which revealed an increased ability to digest simple carbohydrates, was found in the captive cohort. A significant decrease in the abundance of Firmicutes and enrichment of genes related to the pentose phosphate pathway were noted in the captive cohort, indicating a decreased ability of captive monkeys to digest fiber. Additionally, genes required for glutamate biosynthesis were also significantly more abundant in the captive cohort than in the wild cohort. These changes in the gut microbiome correspond to changes in the composition of the diet in captive animals, which has more simple carbohydrates and less crude fiber and protein than the diet of the wild animals. In addition, more unique bacteria in captive R. roxellana were involved in antibiotic resistance (Acinetobacter) and diarrhea (Desulfovibrio piger), and in the prevention of diarrhea (Phascolarctobacterium succinatutens) caused by Clostridioides difficile. Accordingly, our data reveal the cause-and-effect relationships between changes in the exact dietary composition and changes in the gut microbiome on both the structural and functional levels by comparing of captive and wild R. roxellana.
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Affiliation(s)
- Xiaochen Wang
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Ziming Wang
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Huijuan Pan
- School of Ecology and Nature Conservation, Beijing Forestry University, Beijing, China
| | - Jiwei Qi
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Dayong Li
- Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong, China
| | - Liye Zhang
- Primate Genetics Laboratory, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany
| | - Ying Shen
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Zuofu Xiang
- College of Life Sciences and Technology, Central South University of Forestry and Technology, Changsha, China
| | - Ming Li
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
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26
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Plat VD, van Rossen TM, Daams F, de Boer NK, de Meij TGJ, Budding AE, Vandenbroucke-Grauls CMJE, van der Peet DL. Esophageal microbiota composition and outcome of esophageal cancer treatment: a systematic review. Dis Esophagus 2021; 35:6425236. [PMID: 34761269 PMCID: PMC9376764 DOI: 10.1093/dote/doab076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/24/2021] [Accepted: 10/10/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The role of esophageal microbiota in esophageal cancer treatment is gaining renewed interest, largely driven by novel DNA-based microbiota analysis techniques. The aim of this systematic review is to provide an overview of current literature on the possible association between esophageal microbiota and outcome of esophageal cancer treatment, including tumor response to (neo)adjuvant chemo(radio)therapy, short-term surgery-related complications, and long-term oncological outcome. METHODS A systematic review of literature was performed, bibliographic databases were searched and relevant articles were selected by two independent researchers. The Newcastle-Ottawa scale was used to estimate the quality of included studies. RESULTS The search yielded 1303 articles, after selection and cross-referencing, five articles were included for qualitative synthesis and four studies were considered of good quality. Two articles addressed tumor response to neoadjuvant chemotherapy and described a correlation between high intratumoral Fusobacterium nucleatum levels and a poor response. One study assessed surgery-related complications, in which no direct association between esophageal microbiota and occurrence of complications was observed. Three studies described a correlation between shortened survival and high levels of intratumoral F. nucleatum, a low abundance of Proteobacteria and high abundances of Prevotella and Streptococcus species. CONCLUSIONS Current evidence points towards an association between esophageal microbiota and outcome of esophageal cancer treatment and justifies further research. Whether screening of the individual esophageal microbiota can be used to identify and select patients with a predisposition for adverse outcome needs to be further investigated. This could lead to the development of microbiota-based interventions to optimize esophageal microbiota composition, thereby improving outcome of patients with esophageal cancer.
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Affiliation(s)
- Victor D Plat
- Address correspondence to: Mr Victor Dirk Plat, MD, Department of Gastrointestinal Surgery, Amsterdam UMC, VU University Medical Center, De Boelelaan 1117, ZH 7F020, 1081 HV Amsterdam, The Netherlands.
| | - Tessel M van Rossen
- Department of Medical Microbiology and Infection Control, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Freek Daams
- Department of Gastrointestinal Surgery, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Nanne K de Boer
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam UMC, VU University Medical Center Amsterdam, The Netherlands
| | - Tim G J de Meij
- Department of Pediatric Gastroenterology and Hepatology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | | | - Christina M J E Vandenbroucke-Grauls
- Department of Medical Microbiology and Infection Control, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Donald L van der Peet
- Department of Gastrointestinal Surgery, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
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Zhou J, Sun S, Luan S, Xiao X, Yang Y, Mao C, Chen L, Zeng X, Zhang Y, Yuan Y. Gut Microbiota for Esophageal Cancer: Role in Carcinogenesis and Clinical Implications. Front Oncol 2021; 11:717242. [PMID: 34733778 PMCID: PMC8558403 DOI: 10.3389/fonc.2021.717242] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 09/24/2021] [Indexed: 02/05/2023] Open
Abstract
Esophageal cancer (EC) is a common malignant tumor of the upper digestive tract. The microbiota in the digestive tract epithelium comprises a large number of microorganisms that adapt to the immune defense and interact with the host to form symbiotic networks, which affect many physiological processes such as metabolism, tissue development, and immune response. Reports indicate that there are microbial compositional changes in patients with EC, which provides an important opportunity to advance clinical applications based on findings on the gut microbiota. For example, microbiota detection can be used as a biomarker for screening and prognosis, and microorganism levels can be adjusted to treat cancer and decrease the adverse effects of treatment. This review aims to provide an outline of the gut microbiota in esophageal neoplasia, including the mechanisms involved in microbiota-related carcinogenesis and the prospect of utilizing the microbiota as EC biomarkers and treatment targets. These findings have important implications for translating the use of gut microbiota in clinical applications.
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Affiliation(s)
- Jianfeng Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Shangwei Sun
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Luan
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Xiao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yushang Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chengyi Mao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Longqi Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoxi Zeng
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yonggang Zhang
- Department of Periodical Press, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.,Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Yuan
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
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Nucci D, Marino A, Realdon S, Nardi M, Fatigoni C, Gianfredi V. Lifestyle, WCRF/AICR Recommendations, and Esophageal Adenocarcinoma Risk: A Systematic Review of the Literature. Nutrients 2021; 13:3525. [PMID: 34684526 PMCID: PMC8538904 DOI: 10.3390/nu13103525] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/30/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
One of the most notable changes in the epidemiology of esophageal cancer (EC) is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet, and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations, and EAC risk; published in English; without a time filter. The Newcastle-Ottawa Scale was used to assess risk of bias. The results are stratified by risk factor. A total of 106 publications were included. Half of the case-control studies were judged as high quality, whilst practically all cohort studies were judged as high quality. Body mass index and waist circumference were associated with increased EAC risk. Physical activity did not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a Western diet. Alcohol does not seem to be related to EAC, whereas smokers, particularly heavy smokers, have an increased risk of EAC. Prevention remains the best option to avert EAC. Comprehensible and easy to follow recommendations should be provided to all subjects. Protocol ID number: CRD-42021228762, no funds received.
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Affiliation(s)
- Daniele Nucci
- Nutritional Support Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
| | - Alessio Marino
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy
| | - Stefano Realdon
- Digestive Endoscopy Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
| | - Mariateresa Nardi
- Nutritional Support Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
| | - Cristina Fatigoni
- Department of Pharmaceutical Science, University of Perugia, Via del Giochetto 2, 06123 Perugia, Italy
| | - Vincenza Gianfredi
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy
- CAPHRI Care and Public Health Research Institute, Maastricht University, 6211 Maastricht, The Netherlands
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29
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Yano Y, Etemadi A, Abnet CC. Microbiome and Cancers of the Esophagus: A Review. Microorganisms 2021; 9:1764. [PMID: 34442842 PMCID: PMC8398938 DOI: 10.3390/microorganisms9081764] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/11/2021] [Accepted: 08/14/2021] [Indexed: 01/04/2023] Open
Abstract
Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions.
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Affiliation(s)
- Yukiko Yano
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (A.E.); (C.C.A.)
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D'Souza SM, Houston K, Keenan L, Yoo BS, Parekh PJ, Johnson DA. Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria? World J Gastroenterol 2021; 27:2054-2072. [PMID: 34025064 PMCID: PMC8117736 DOI: 10.3748/wjg.v27.i18.2054] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/06/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
Genomic sequencing, bioinformatics, and initial speciation (e.g., relative abundance) of the commensal microbiome have revolutionized the way we think about the "human" body in health and disease. The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases, including those impacting the esophagus. Although relatively stable, there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome (EM) and the host. These changes are thought to be a product of age, diet, antibiotic and other medication use, oral hygiene, smoking, and/or expression of antibiotic products (bacteriocins) by other flora. These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation, systemic inflammation, and ultimately disease progression. Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is, therefore, not merely the result of esophageal mucosal exposure to corrosives (i.e., acid). Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade. Here, we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief (i.e., acid suppression).
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Affiliation(s)
- Steve M D'Souza
- Department of Internal Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA 23502, United States
| | - Kevin Houston
- Department of Internal Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA 23502, United States
| | - Lauren Keenan
- Department of Internal Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA 23502, United States
| | - Byung Soo Yoo
- Department of Internal Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA 23502, United States
| | - Parth J Parekh
- Department of Internal Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA 23502, United States
| | - David A Johnson
- Department of Internal Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA 23502, United States
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Role of Short Chain Fatty Acids and Apolipoproteins in the Regulation of Eosinophilia-Associated Diseases. Int J Mol Sci 2021; 22:ijms22094377. [PMID: 33922158 PMCID: PMC8122716 DOI: 10.3390/ijms22094377] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/17/2021] [Accepted: 04/19/2021] [Indexed: 02/06/2023] Open
Abstract
Eosinophils are key components of our host defense and potent effectors in allergic and inflammatory diseases. Once recruited to the inflammatory site, eosinophils release their cytotoxic granule proteins as well as cytokines and lipid mediators, contributing to parasite clearance but also to exacerbation of inflammation and tissue damage. However, eosinophils have recently been shown to play an important homeostatic role in different tissues under steady state. Despite the tremendous progress in the treatment of eosinophilic disorders with the implementation of biologics, there is an unmet need for novel therapies that specifically target the cytotoxic effector functions of eosinophils without completely depleting this multifunctional immune cell type. Recent studies have uncovered several endogenous molecules that decrease eosinophil migration and activation. These include short chain fatty acids (SCFAs) such as butyrate, which are produced in large quantities in the gastrointestinal tract by commensal bacteria and enter the systemic circulation. In addition, high-density lipoprotein-associated anti-inflammatory apolipoproteins have recently been shown to attenuate eosinophil migration and activation. Here, we focus on the anti-pathogenic properties of SCFAs and apolipoproteins on eosinophil effector function and provide insights into the potential use of SCFAs and apolipoproteins (and their mimetics) as effective agents to combat eosinophilic inflammation.
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Mennini M, Tambucci R, Riccardi C, Rea F, De Angelis P, Fiocchi A, Assa'ad A. Eosinophilic Esophagitis and Microbiota: State of the Art. Front Immunol 2021; 12:595762. [PMID: 33679739 PMCID: PMC7933523 DOI: 10.3389/fimmu.2021.595762] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lamina propria cells with the capacity to distinguish between pathogen and commensal microbes. As TLRs in the different intestinal epithelia represent the primary mechanism of epithelial recognition of bacteria, this evidence underlines that oesophagal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. The oesophagal mucosa hosts a resident microbiota, although in a smaller population as compared with other districts of the gastrointestinal tract. Few studies have focused on the composition of the microbiota of the normal oesophagus alone. Still, additional information has come from studies investigating the oesophagal microbiota in disease and including healthy patients as controls. Our review aims to describe all the evidence on the oesophagal and intestinal microbiota in patients with EoE to identify the specific features of dysbiosis in this condition.
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Affiliation(s)
- Maurizio Mennini
- Division of Allergy, Bambino Gesù Children's Hospital-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Renato Tambucci
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Carla Riccardi
- Division of Allergy, Bambino Gesù Children's Hospital-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Francesca Rea
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Paola De Angelis
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Alessandro Fiocchi
- Division of Allergy, Bambino Gesù Children's Hospital-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Amal Assa'ad
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
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Yang W, Chen CH, Jia M, Xing X, Gao L, Tsai HT, Zhang Z, Liu Z, Zeng B, Yeung SCJ, Lee MH, Cheng C. Tumor-Associated Microbiota in Esophageal Squamous Cell Carcinoma. Front Cell Dev Biol 2021; 9:641270. [PMID: 33681225 PMCID: PMC7930383 DOI: 10.3389/fcell.2021.641270] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/26/2021] [Indexed: 12/24/2022] Open
Abstract
Important evidence indicates the microbiota plays a key role in esophageal squamous cell carcinoma (ESCC). The esophageal microbiota was prospectively investigated in 18 patients with ESCC and 11 patients with physiological normal (PN) esophagus by 16S rRNA gene profiling, using next-generation sequencing. The microbiota composition in tumor tissues of ESCC patients were significantly different from that of patients with PN tissues. The ESCC microbiota was characterized by reduced microbial diversity, by decreased abundance of Bacteroidetes, Fusobacteria, and Spirochaetes. Employing these taxa into a microbial dysbiosis index demonstrated that dysbiosis microbiota had good capacity to discriminate between ESCC and PN esophagus. Functional analysis characterized that ESCC microbiota had altered nitrate reductase and nitrite reductase functions compared with PN group. These results suggest that specific microbes and the microbiota may drive or mitigate ESCC carcinogenesis, and this study will facilitate assigning causal roles in ESCC development to certain microbes and microbiota.
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Affiliation(s)
- Weixiong Yang
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chang-Han Chen
- Department of Applied Chemistry, and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou County, Taiwan
| | - Minghan Jia
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xiangbin Xing
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lu Gao
- BGI Genomics, BGI-Shenzhen, Shenzhen, China
| | - Hsin-Ting Tsai
- Department of Applied Chemistry, and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou County, Taiwan
| | - Zhanfei Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhenguo Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bo Zeng
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sai-Ching Jim Yeung
- Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Mong-Hong Lee
- Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chao Cheng
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Tullio V, Gasperi V, Catani MV, Savini I. The Impact of Whole Grain Intake on Gastrointestinal Tumors: A Focus on Colorectal, Gastric, and Esophageal Cancers. Nutrients 2020; 13:E81. [PMID: 33383776 PMCID: PMC7824588 DOI: 10.3390/nu13010081] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/22/2020] [Accepted: 12/25/2020] [Indexed: 02/08/2023] Open
Abstract
Cereals are one of staple foods in human diet, mainly consumed as refined grains. Nonetheless, epidemiological data indicate that whole grain (WG) intake is inversely related to risk of type 2 diabetes, cardiovascular disease, and several cancer types, as well as to all-cause mortality. Particularly responsive to WG positive action is the gastrointestinal tract, daily exposed to bioactive food components. Herein, we shall provide an up-to-date overview on relationship between WG intake and prevention of gastrointestinal tumors, with a particular focus on colorectal, stomach, and esophagus cancers. Unlike refined counterparts, WG consumption is inversely associated with risk of these gastrointestinal cancers, most consistently with the risk of colorectal tumor. Some WG effects may be mediated by beneficial constituents (such as fiber and polyphenols) that are reduced/lost during milling process. Beside health-promoting action, WGs are still under-consumed in most countries; therefore, World Health Organization and other public/private stakeholders should cooperate to implement WG consumption in the whole population, in order to reach nutritionally effective intakes.
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Gyawali CP, Sonu I, Becker L, Sarosiek J. The esophageal mucosal barrier in health and disease: mucosal pathophysiology and protective mechanisms. Ann N Y Acad Sci 2020; 1482:49-60. [PMID: 33128243 DOI: 10.1111/nyas.14521] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 10/09/2020] [Accepted: 10/10/2020] [Indexed: 12/13/2022]
Abstract
Diseases of the esophagus, such as gastroesophageal reflux (GER), can result in changes to mucosal integrity, neurological function, and the microbiome. Although poorly understood, both age and GER can lead to changes to the enteric nervous system. In addition, the esophagus has a distinct microbiome that can be altered in GER. Mucosal integrity is also at risk due to persistent damage from acid. Diagnostic tools, such as ambulatory pH/impedance testing and esophageal mucosal impedance, can assess short-term and longitudinal GER burden, which can also assess the risk for mucosal compromise. The quality of the mucosal barrier is determined by its intercellular spaces, tight junctions, and tight junction proteins, which are represented by claudins, occludins, and adhesion molecules. Fortunately, there are protective factors for mucosal integrity that are secreted by the esophageal submucosal mucous glands and within saliva that are augmented by mastication. These protective factors have potential as therapeutic targets for GER. In this article, we aim to review diagnostic tools used to predict mucosal integrity, aging, and microbiome changes to the esophagus and esophageal mucosal defense mechanisms.
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Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology and Hepatology, Washington University School of Medicine, St. Louis, Missouri
| | - Irene Sonu
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Laren Becker
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Jerzy Sarosiek
- Division of Gastroenterology and Hepatology, Molecular Medicine Research Laboratory, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas
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Wen T, Rothenberg ME. Cell-by-cell deciphering of T cells in allergic inflammation. J Allergy Clin Immunol 2020; 144:1143-1148. [PMID: 31703761 DOI: 10.1016/j.jaci.2019.10.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 09/30/2019] [Accepted: 10/01/2019] [Indexed: 12/28/2022]
Abstract
Technical advances in single-cell RNA sequencing (scRNA-seq) render it possible to examine the transcriptomes of single cells in patients with allergic inflammation with high resolution in the context of their specific microenvironment, treatment, and disease status. Using a recently published scRNA-seq study of tissue T cells as an example, we introduce the major pipeline steps, illustrate the options of scRNA-seq platforms, summarize new knowledge gained from this study, and provide directions for future research. The presented scRNA-seq study elucidated the T-cell heterogeneity present in an allergic inflammatory tissue focused on eosinophilic esophagitis, a prototypic, chronic, allergic disease, which provided a unique opportunity to probe the pathogenesis of allergic inflammation at the tissue level through readily available endoscopically procured biopsy specimens. scRNA-seq analysis identified 8 populations of CD3+ T cells and defined 2 disease-specific populations of CD3+CD4+ T cells, including a markedly activated type 2 cytokine-producing pathogenic cell population distinguished by expression of the short-chain fatty acid receptor free fatty acid receptor 3 and a population of regulatory T cells. In addition to presenting and interpreting new findings within the prior literature, we postulate about future single-cell next-generation sequencing platforms in this burgeoning field.
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Affiliation(s)
- Ting Wen
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati
| | - Marc E Rothenberg
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati.
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37
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Jung HK, Hong SJ, Lee OY, Pandolfino J, Park H, Miwa H, Ghoshal UC, Mahadeva S, Oshima T, Chen M, Chua ASB, Cho YK, Lee TH, Min YW, Park CH, Kwon JG, Park MI, Jung K, Park JK, Jung KW, Lim HC, Jung DH, Kim DH, Lim CH, Moon HS, Park JH, Choi SC, Suzuki H, Patcharatrakul T, Wu JCY, Lee KJ, Tanaka S, Siah KTH, Park KS, Kim SE. 2019 Seoul Consensus on Esophageal Achalasia Guidelines. J Neurogastroenterol Motil 2020; 26:180-203. [PMID: 32235027 PMCID: PMC7176504 DOI: 10.5056/jnm20014] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 03/08/2020] [Indexed: 12/13/2022] Open
Abstract
Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the "2019 Seoul Consensus on Esophageal Achalasia Guidelines") were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - John Pandolfino
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Hyojin Park
- Division of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sanjiv Mahadeva
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Yu Kyung Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Tae Hee Lee
- Department of Internal Medicine, College of Medicine, Soonchunhyang University Hospital, Seoul, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Kyoungwon Jung
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Jong Kyu Park
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Hyun Lim
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Suck Chei Choi
- Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Korea
| | - Hidekazu Suzuki
- Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Tanisa Patcharatrakul
- Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
| | - Shinwa Tanaka
- Department of Gastroenterology, Kobe University Hospital, Hyogo, Japan
| | - Kewin T H Siah
- Division of Gastroenterology and Hepatology, National University Health System, Singapore City, Singapore
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
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Park CH, Lee SK. Exploring Esophageal Microbiomes in Esophageal Diseases: A Systematic Review. J Neurogastroenterol Motil 2020; 26:171-179. [PMID: 32235026 PMCID: PMC7176507 DOI: 10.5056/jnm19240] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 02/11/2020] [Accepted: 02/27/2020] [Indexed: 12/12/2022] Open
Abstract
Studies that investigated esophageal microbiomes are limited when compared to those on intestinal microbiomes. Nevertheless, several studies have investigated the relationship between esophageal microbiomes and various esophageal diseases, owing to the advancement of next-generation sequencing techniques. Streptococcus is the most common bacterial taxon in a normal esophagus. Additionally, Haemophilus, Neisseria, Prevotella, and Veillonella are also found. However, gram-negative bacteria, including Prevotella, are more abundant in a diseased esophagus, such as in gastroesophageal reflux disease and Barrett's esophagus. This systematic review aims to summarize current evidences on esophageal microbiomes in various esophageal diseases.
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Affiliation(s)
- Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Korea
| | - Sang Kil Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Martinez-Guryn K, Leone V, Chang EB. Regional Diversity of the Gastrointestinal Microbiome. Cell Host Microbe 2020; 26:314-324. [PMID: 31513770 DOI: 10.1016/j.chom.2019.08.011] [Citation(s) in RCA: 251] [Impact Index Per Article: 50.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The role of gut microbes in health and disease has often been surmised from stool, which is easily sampled and rich in microbial diversity, density, and abundance. Microbial analyses of stool have been accepted as measures to determine the relationship of gut microbiomes with host health and disease, based on the belief that it represents all microbial populations throughout the gut. However, functional heterogeneity of each gastrointestinal tract (GIT) segment gives rise to regional differences in gut microbial populations. Herein, we summarize the literature regarding the microbial landscape along the rostral to caudal, i.e., horizontal mouth to anus, axis of the GIT. We aim to identify gaps in the literature, particularly regarding small intestinal microbiota abundance and diversity, highlight the importance of regional microbiota on host health and disease, as well as discuss opportunities to advance this line of research.
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Affiliation(s)
- Kristina Martinez-Guryn
- Biomedical Sciences Department, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA
| | - Vanessa Leone
- Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Eugene B Chang
- Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
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Li M, Shao D, Zhou J, Gu J, Qin J, Chen W, Wei W. Signatures within esophageal microbiota with progression of esophageal squamous cell carcinoma. Chin J Cancer Res 2020; 32:755-767. [PMID: 33446998 PMCID: PMC7797230 DOI: 10.21147/j.issn.1000-9604.2020.06.09] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective Esophageal squamous cell carcinoma (ESCC) is one of the dominant malignances worldwide, but currently there is less focus on the microbiota with ESCC and its precancerous lesions. Methods Paired esophageal biopsy and swab specimens were obtained from 236 participants in Linzhou, China. Data from 16S ribosomal RNA gene sequencing were processed using quantitative insights into microbial ecology (QIIME2) and R Studio to evaluate differences. The Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to compare diversity and characteristic genera by specimens and participant groups. Ordinal logistic regression model was used to build microbiol prediction model. Results Microbial diversity was similar between biopsy and swab specimens, including operational taxonomic unit (OTU) numbers and Shannon index. There were variations and similarities of esophageal microbiota among different pathological characteristics of ESCC. Top 10 relative abundance genera in all groups include Streptococcus, Prevotella, Veillonella, Actinobacillus, Haemophilus, Neisseria, Alloprevotella, Rothia, Gemella and Porphyromonas. Genus Streptococcus, Haemophilus, Neisseria and Porphyromonas showed significantly difference in disease groups when compared to normal control, whereas Streptococcus showed an increasing tendency with the progression of ESCC and others showed a decreasing tendency. About models based on all combinations of characteristic genera, only taken Streptococcus and Neisseria into model, the prediction performance was the ideal one, of which the area under the curve (AUC) was 0.738.
Conclusions Esophageal biopsy and swab specimens could yield similar microbial characterization. The combination of Streptococcus and Neisseria has the potential to predict the progression of ESCC, which is needed to confirm by large-scale, prospective cohort studies.
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Affiliation(s)
- Minjuan Li
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dantong Shao
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jiachen Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jianhua Gu
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Junjie Qin
- Promegene Translational Research Institute, Shenzhen 518000, China
| | - Wen Chen
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wenqiang Wei
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Snider EJ, Compres G, Freedberg DE, Khiabanian H, Nobel YR, Stump S, Uhlemann AC, Lightdale CJ, Abrams JA. Alterations to the Esophageal Microbiome Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2019; 28:1687-1693. [PMID: 31466948 DOI: 10.1158/1055-9965.epi-19-0008] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 04/17/2019] [Accepted: 07/10/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The incidence of esophageal adenocarcinoma has risen dramatically over the past half century, and the underlying reasons are incompletely understood. Broad shifts to the upper gastrointestinal microbiome may be partly responsible. The goal of this study was to describe alterations in the esophageal microbiome that occur with progression from Barrett's esophagus to esophageal adenocarcinoma. METHODS A case-control study was performed of patients with and without Barrett's esophagus who were scheduled to undergo upper endoscopy. Demographic, clinical, and dietary intake data were collected, and esophageal brushings were collected during the endoscopy. 16S rRNA gene sequencing was performed to characterize the microbiome. RESULTS A total of 45 patients were enrolled and included in the analyses [16 controls; 14 Barrett's esophagus without dysplasia (NDBE); 6 low-grade dysplasia (LGD); 5 high-grade dysplasia (HGD); and 4 esophageal adenocarcinoma]. There was no difference in alpha diversity between non-Barrett's esophagus and Barrett's esophagus, but there was evidence of decreased diversity in patients with esophageal adenocarcinoma as assessed by Simpson index. There was an apparent shift in composition at the transition from LGD to HGD, and patients with HGD and esophageal adenocarcinoma had decreased Firmicutes and increased Proteobacteria. In addition, patients with HGD or esophageal adenocarcinoma had increased Enterobacteriaceae and Akkermansia muciniphila and reduced Veillonella. In the study population, patients taking proton pump inhibitors had increased Streptococcus and decreased Gram-negative bacteria overall. CONCLUSIONS Shifts in the Barrett's esophagus-associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria. IMPACT The microbiome may play a role in esophageal carcinogenesis.
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Affiliation(s)
- Erik J Snider
- Department of Medicine, University of Washington School of Medicine, Seattle, Washington
| | - Griselda Compres
- Department of Medicine, Columbia University Irving Medical Center, New York, New York
| | - Daniel E Freedberg
- Department of Medicine, Columbia University Irving Medical Center, New York, New York
| | - Hossein Khiabanian
- Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey
| | - Yael R Nobel
- Department of Medicine, Columbia University Irving Medical Center, New York, New York
| | - Stephania Stump
- Department of Medicine, Columbia University Irving Medical Center, New York, New York.,Microbiome Core Facility, Columbia University Irving Medical Center, New York, New York
| | - Anne-Catrin Uhlemann
- Department of Medicine, Columbia University Irving Medical Center, New York, New York.,Microbiome Core Facility, Columbia University Irving Medical Center, New York, New York
| | - Charles J Lightdale
- Department of Medicine, Columbia University Irving Medical Center, New York, New York
| | - Julian A Abrams
- Department of Medicine, Columbia University Irving Medical Center, New York, New York.
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Ma S, Wang SY, Zhu LP, Chen X, Wang BM. Esophageal microbiota and esophageal diseases. Shijie Huaren Xiaohua Zazhi 2019; 27:767-772. [DOI: 10.11569/wcjd.v27.i12.767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The microbiota of the esophagus has been the least systematically studied among the organs of the gastrointestinal tract. Esophageal microbiota has been proved to be complex with a high diversity until recently. Alterations of its composition are associated with the development and progression of esophageal diseases. Immunoinflammatory responses caused by dysbiosis may play a role in the pathogenesis of esophageal disorders. This review addresses the characteristics of esophageal microbiota in physiological and pathological conditions, aiming to provide new insights into esophageal microecology-based intervention strategies for esophageal diseases.
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Affiliation(s)
- Shuang Ma
- Department of Gastroenterology and Hepatology, General Hospital of Tianjin Medical University, Tianjin 300052, China
| | - Sai-Yu Wang
- Department of Gastroenterology and Hepatology, General Hospital of Tianjin Medical University, Tianjin 300052, China
| | - Lan-Ping Zhu
- Department of Gastroenterology and Hepatology, General Hospital of Tianjin Medical University, Tianjin 300052, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, General Hospital of Tianjin Medical University, Tianjin 300052, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, General Hospital of Tianjin Medical University, Tianjin 300052, China
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Wen T, Aronow BJ, Rochman Y, Rochman M, Kc K, Dexheimer PJ, Putnam P, Mukkada V, Foote H, Rehn K, Darko S, Douek D, Rothenberg ME. Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis. J Clin Invest 2019; 129:2014-2028. [PMID: 30958799 DOI: 10.1172/jci125917] [Citation(s) in RCA: 143] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 02/21/2019] [Indexed: 12/26/2022] Open
Abstract
T cell heterogeneity is highly relevant to allergic disorders. We resolved the heterogeneity of human tissue CD3+ T cells during allergic inflammation, focusing on a tissue-specific allergic disease, eosinophilic esophagitis (EoE). We investigated 1088 single T cells derived from patients with a spectrum of disease activity. Eight disparate tissue T cell subtypes (designated T1-T8) were identified, with T7 and T8 enriched in the diseased tissue. The phenotypes of T7 and T8 resemble putative Treg (FOXP3+) and effector Th2-like (GATA3+) cells, respectively. Prodigious levels of IL-5 and IL-13 were confined to HPGDS+ CRTH2+IL-17RB+FFAR3+CD4+ T8 effector Th2 cells. EoE severity closely paralleled a lipid/fatty acid-induced activation node highlighted by the expression of the short-chain fatty acid receptor FFAR3. Ligands for FFAR3 induced Th2 cytokine production from human and murine T cells, including in an in vivo allergy model. Therefore, we elucidated the defining characteristics of tissue-residing CD3+ T cells in EoE, a specific enrichment of CD4+ Treg and effector Th2 cells, confinement of type 2 cytokine production to the CD4+ effector population, a highly likely role for FFAR3 in amplifying local Th2 responses in EoE, and a resource to further dissect tissue lymphocytes and allergic responses.
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Affiliation(s)
- Ting Wen
- Division of Allergy and Immunology
| | | | | | | | - Kiran Kc
- Division of Allergy and Immunology
| | | | - Philip Putnam
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
| | - Vincent Mukkada
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
| | | | | | - Sam Darko
- Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Daniel Douek
- Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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