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Li Y, Huang M, Cardinale S, Su Y, Peters DE, Slusher BS, Zhu X. Dectin-1 as a therapeutic target for inflammatory bowel disease. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2024; 101:237-264. [PMID: 39521602 PMCID: PMC11733682 DOI: 10.1016/bs.apha.2024.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Inflammatory bowel disease (IBD) encompasses chronic inflammatory conditions of the distal gastrointestinal tract, including Crohn's disease and ulcerative colitis. This chapter explores the potential of Dendritic cell-associated C-type lectin-1 (Dectin-1), a pattern recognition receptor, as a therapeutic target for IBD. We delve into the multifaceted roles of Dectin-1 in immune response modulation, focusing on its interactions with the gut microbiota and immune system. Key sections include an examination of intestinal dysbiosis and its impact on IBD, highlighting the critical role of fungal dysbiosis and immune responses mediated by Dectin-1. The chapter discusses the dual functions of Dectin-1 in maintaining gut homeostasis and its contribution to disease pathogenesis through interactions with the gut's fungal community. Furthermore, the genetic and molecular mechanisms underpinning Dectin-1's role in IBD susceptibility are explored, alongside its signaling pathways and their effects on immune modulation. We also present therapeutic strategies targeting Dectin-1, including innovative drug delivery systems that leverage its natural binding affinity for β-glucans, enhancing targeted delivery to inflamed tissues. The chapter underscores the potential of dietary modulation of Dectin-1 pathways to restore gut microbiota balance and suggests future research directions to fully exploit Dectin-1's therapeutic potential in managing IBD. By elucidating the complex interplay between Dectin-1 and the gut microbiota, this chapter provides insights into novel therapeutic approaches aimed at mitigating IBD symptoms and improving patient outcomes.
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Affiliation(s)
- Yannan Li
- Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Meixiang Huang
- Johns Hopkins Drug Discovery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Santiago Cardinale
- Department of Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Yu Su
- Johns Hopkins Drug Discovery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Diane E Peters
- Johns Hopkins Drug Discovery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Barbara S Slusher
- Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Johns Hopkins Drug Discovery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Xiaolei Zhu
- Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Johns Hopkins Drug Discovery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
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Józefczuk P, Biliński J, Minkowska A, Łaguna P. Gut microbiome in children undergoing hematopoietic stem cell transplantation. Best Pract Res Clin Gastroenterol 2024; 72:101955. [PMID: 39645282 DOI: 10.1016/j.bpg.2024.101955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 10/10/2024] [Accepted: 10/22/2024] [Indexed: 12/09/2024]
Abstract
Hematopoietic stem cell transplantation (HSCT) is used in children as a treatment for various cancers, e.g. acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or other diseases, e.g. severe congenital immunodeficiency, metabolic disorders, hence the patient population is quite diverse. There is an increasing interest on the role of the microbiome in peri-transplant period. In this review, concepts of HSCT with the focus on the importance of microbiome composition, its changes during treatment and possible microbiota oriented interventions will be discussed. This paper analyzes data in pediatric population, but in view of interesting results and absence of analogous data for pediatric patients, it also looks at studies performed on adult population and pre-clinical trials on animals discussing possible translation to children.
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Affiliation(s)
- Paweł Józefczuk
- Department of Oncology, Pediatric Hematology, Clinical Transplantology and Pediatrics, Medical University of Warsaw, Poland.
| | - Jarosław Biliński
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Poland; Human Biome Institute, Gdansk, Warsaw, Poland
| | - Aleksandra Minkowska
- Department of Oncology, Pediatric Hematology, Clinical Transplantology and Pediatrics, Medical University of Warsaw, Poland
| | - Paweł Łaguna
- Department of Oncology, Pediatric Hematology, Clinical Transplantology and Pediatrics, Medical University of Warsaw, Poland
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Imbrea AM, Balta I, Dumitrescu G, McCleery D, Pet I, Iancu T, Stef L, Corcionivoschi N, Liliana PC. Exploring the Contribution of Campylobacter jejuni to Post-Infectious Irritable Bowel Syndrome: A Literature Review. APPLIED SCIENCES 2024; 14:3373. [DOI: 10.3390/app14083373] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
This comprehensive review investigates the specific impact of the foodborne pathogen Campylobacter jejuni (C. jejuni) on gastrointestinal health, focusing on its connection to post-infectious irritable bowel syndrome (PI-IBS). This review examines the pathogen’s pathophysiology, clinical implications and epidemiological trends using recent research and data to highlight its prevalence and association with PI-IBS. A detailed literature analysis synthesizes current research to illuminate Campylobacter’s long-lasting effects on gut microbiota and intestinal function. It provides a detailed analysis of the literature to shed light on C. jejuni’s long-term impact on gut microbiota and intestinal function. The findings suggest the need for multifaceted prevention and treatment approaches considering individual, microbial and epidemiological factors, thus contributing to a more nuanced understanding of PI-IBS following C. jejuni infection.
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Affiliation(s)
- Ana-Maria Imbrea
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Igori Balta
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Gabi Dumitrescu
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - David McCleery
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, UK
| | - Ioan Pet
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Tiberiu Iancu
- Faculty of Management and Rural Tourism, University of Life Sciences King Mihai I from Timisoara, 300645 Timisoara, Romania
| | - Lavinia Stef
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Nicolae Corcionivoschi
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, UK
- Academy of Romanian Scientists, Ilfov Street, No. 3, 050044 Bucharest, Romania
| | - Petculescu-Ciochina Liliana
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
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4
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Ron R, Moreno E, Rosas Cancio-Suárez M, Serrano-Villar S. The microbiome as a biomarker of anal precancerous lesions in people with HIV. Curr Opin Infect Dis 2024; 37:17-25. [PMID: 37889583 DOI: 10.1097/qco.0000000000000985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2023]
Abstract
PURPOSE OF REVIEW Early detection and treatment of human papillomavirus (HPV)-related anal dysplasia in some high-risk groups can help anal cancer prevention, but new tools to improve diagnostic and risk assessment are needed. Here, we aim to discuss the evidence on the role of the microbiome as a potential biomarker for anal high-grade squamous intraepithelial lesions (HSILs) in people with HIV (PWH). RECENT FINDINGS This review covers relevant studies on the links between the microbiome and HPV infection, cervical dysplasia/cancer, and anal HPV disease. It focuses on anal samples and precancerous lesions. SUMMARY The review highlights the promising potential of the anal microbiome as a novel biomarker for precancerous lesions in people with HIV, while also discussing limitations and future research needs.
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Affiliation(s)
- Raquel Ron
- Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain, CIBERINFEC
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Elahi Z, Shariati A, Bostanghadiri N, Dadgar-Zankbar L, Razavi S, Norzaee S, Vazirbani Arasi S, Darban-Sarokhalil D. Association of Lactobacillus, Firmicutes, Bifidobacterium, Clostridium, and Enterococcus with colorectal cancer in Iranian patients. Heliyon 2023; 9:e22602. [PMID: 38089982 PMCID: PMC10711133 DOI: 10.1016/j.heliyon.2023.e22602] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 11/08/2023] [Accepted: 11/15/2023] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the primary causes of cancer-associated deaths worldwide, and growing evidence shows that alteration in the gut microbiota may be a contributing factor to the development and progression of the disease. This study investigates the correlation between CRC and specific intestinal microbiota abundance, including Firmicutes, Lactobacillus, Enterococcus, Clostridium, and Bifidobacterium. MATERIAL AND METHODS In this study, 100 CRC samples and adjacent normal tissues were obtained from Iranian patients. Afterward, we assessed the abundance of the mentioned bacteria in matched tumor and normal tissue samples from 100 CRC patients, by TaqMan quantitative real-time polymerase chain reaction (qPCR). RESULTS Most of the patients (55 %) had grade II cancer (moderately differentiated), followed by grade III (poorly Differentiated) in 19 %, and the distribution of the tumor location was 65 % in the colon and 35 % in the rectum. Our research showed a substantial difference in the relative abundance of specific bacteria in tumors and healthy tissues. To this end, four genera of bacteria, including Bifidobacterium, Lactobacillus, Clostridium, and Firmicutes, exhibited statistically significant reductions in tumor tissues compared to adjacent normal tissue (p < 0.05). Conversely, Enterococcus demonstrated a statistically significant increase in tumor tissue samples (p < 0.05). Noteworthy, statistical analysis revealed a significant relationship between Enterococcus and prior cancer (p < 0.05). CONCLUSIONS These findings provide significant insight into the complex association between the gut microbiota and CRC and may pave the way for future research on novel screening methods, preventive measures, and therapeutic strategies targeting the gut microbiota in CRC patients.
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Affiliation(s)
- Zahra Elahi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Aref Shariati
- Student Research Committee, Khomein University of Medical Sciences, Khomein, Iran
- Molecular and Medicine Research Centre, Khomein University of Medical Sciences, Khomein, Iran
| | - Narjess Bostanghadiri
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Leila Dadgar-Zankbar
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Samira Norzaee
- Research Center for Environmental Health Technology, Iran University of Medical Sciences, Tehran, Iran
- Department of Environmental Health Engineering, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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6
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Xiao J, Zhang JY, Luo W, He PC, Skondra D. The Emerging Role of Gut Microbiota in Age-Related Macular Degeneration. THE AMERICAN JOURNAL OF PATHOLOGY 2023; 193:1627-1637. [PMID: 37156326 DOI: 10.1016/j.ajpath.2023.04.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/14/2023] [Accepted: 04/11/2023] [Indexed: 05/10/2023]
Abstract
Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy. More recently, the gut microbiome has emerged as an influential player in various ocular pathologies. As mediators of metabolism and immune regulation, perturbations in gut microbiota may impart significant effects distally on the neuroretina and its adjacent tissues, termed the gut-retina axis. In this review, key studies over the past several decades are summarized, both in humans and in animal models, which shed insight on the relationships between the gut microbiome and retinal biology and their implications for AMD. The literature linking gut dysbiosis with AMD is examined, along with preclinical animal models and techniques apt for studying the role of gut microbiota in AMD pathogenesis, which include interactions with systemic inflammation, immune regulation, chorioretinal gene expression, and diet. As understanding of the gut-retina axis continues to advance, so too will the possibility for more accessible and effective prevention and therapy of this vision-threatening condition.
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Affiliation(s)
- Jason Xiao
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | - Jason Y Zhang
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | - Wendy Luo
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | - P Cody He
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | - Dimitra Skondra
- Department of Ophthalmology and Visual Science, University of Chicago, Chicago, Illinois.
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7
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Khattab RH, Abo-Hammam RH, Salah M, Hanora AM, Shabayek S, Zakeer S. Multi-omics analysis of fecal samples in colorectal cancer Egyptians patients: a pilot study. BMC Microbiol 2023; 23:238. [PMID: 37644393 PMCID: PMC10464353 DOI: 10.1186/s12866-023-02991-x] [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: 10/11/2022] [Accepted: 08/21/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a public health concern and the second most common disease worldwide. This is due to genetic coding and is influenced by environmental aspects, in which the gut microbiota plays a significant role. The purpose of this study was to compare the microbiota makeup of CRC patients with that of healthy control and to identify upregulated and downregulated proteins and metabolites in CRC patients. Using a next-generation sequencing approach, fecal samples of five females (4 CRC patients and one healthy control) were analyzed by BGI DNBSEQ-T7, Hong Kong, China. Furthermore, proteomics and metabolomics analysis were performed using LC-MS/MS technique. RESULTS Dysbiosis of gut microbiota has been observed in patients with CRC, with an increase in microbiota diversity at all taxonomic levels relative to healthy control. Where, at the functional level the bacterial species participate in many different pathways among them de novo nucleotide synthesis and amino acids pathways were aberrantly upregulated in CRC patients. Proteomics and metabolomics profiles of CRC patients showed different proteins and metabolites, a total of 360 and 158 proteins and metabolites, respectively were highly expressed compared to healthy control with fold change ≥ 1.2. Among the highly expressed proteins were transketolase, sushi domain-containing protein, sulfide quinone oxidoreductase protein, AAA family ATPase protein, carbonic anhydrase, IgG Fc-binding protein, nucleoside diphosphate kinase protein, arylsulfatase, alkaline phosphatase protein, phosphoglycerate kinase, protein kinase domain-containing protein, non-specific serine/threonine protein kinase, Acyl-CoA synthetase and EF-hand domain-containing protein. Some of the differential metabolites, Taurine, Taurocholic acid, 7-ketodeoxycholic acid, Glycochenodeoxycholic acid, Glycocholic acid, and Taurochenodeoxycholic acid that belong to bile acids metabolites. CONCLUSIONS Some bacterial species, proteins, and metabolites could be used as diagnostic biomarkers for CRC. Our study paves an insight into using multi-omics technology to address the relationship between gut microbiota and CRC.
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Affiliation(s)
- Randa H Khattab
- Department of Microbiology and Immunology, Al-Salam University, Tanta, Egypt
| | - Rana H Abo-Hammam
- Forensic toxicologist and narcotics expert, Ministry of Justice, Tanta, Egypt
| | - Mohammed Salah
- Department of Microbiology and Immunology, Faculty of pharmacy, Port-Said University, Port-Said, Egypt
| | - Amro M Hanora
- Department of Microbiology and Immunology, Faculty of pharmacy, Suez Canal University, Ismailia, Egypt.
| | - Sarah Shabayek
- Department of Microbiology and Immunology, Faculty of pharmacy, Suez Canal University, Ismailia, Egypt
| | - Samira Zakeer
- Department of Microbiology and Immunology, Faculty of pharmacy, Suez Canal University, Ismailia, Egypt
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Iyer K, Erkert L, Becker C. Know your neighbors: microbial recognition at the intestinal barrier and its implications for gut homeostasis and inflammatory bowel disease. Front Cell Dev Biol 2023; 11:1228283. [PMID: 37519301 PMCID: PMC10375050 DOI: 10.3389/fcell.2023.1228283] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/07/2023] [Indexed: 08/01/2023] Open
Abstract
Intestinal epithelial cells (IECs) perform several physiological and metabolic functions at the epithelial barrier. IECs also play an important role in defining the overall immune functions at the mucosal region. Pattern recognition receptors (PRRs) on the cell surface and in other cellular compartments enable them to sense the presence of microbes and microbial products in the intestinal lumen. IECs are thus at the crossroads of mediating a bidirectional interaction between the microbial population and the immune cells present at the intestinal mucosa. This communication between the microbial population, the IECs and the underlying immune cells has a profound impact on the overall health of the host. In this review, we focus on the various PRRs present in different cellular compartments of IECs and discuss the recent developments in the understanding of their role in microbial recognition. Microbial recognition and signaling at the epithelial barrier have implications in the maintenance of intestinal homeostasis, epithelial barrier function, maintenance of commensals, and the overall tolerogenic function of PRRs in the gut mucosa. We also highlight the role of an aberrant microbial sensing at the epithelial barrier in the pathogenesis of inflammatory bowel disease (IBD) and the development of colorectal cancer.
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Affiliation(s)
- Krishna Iyer
- Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, United States
| | - Lena Erkert
- Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Christoph Becker
- Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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Sarkar P, Kandimalla R, Bhattacharya A, Wahengbam R, Dehingia M, Kalita MC, Talukdar NC, Talukdar R, Khan MR. Multi-Omics Analysis Demonstrates the Critical Role of Non-Ethanolic Components of Alcoholic Beverages in the Host Microbiome and Metabolome: A Human- and Animal-Based Study. Microorganisms 2023; 11:1501. [PMID: 37375003 DOI: 10.3390/microorganisms11061501] [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: 03/30/2023] [Revised: 05/26/2023] [Accepted: 05/30/2023] [Indexed: 06/29/2023] Open
Abstract
It is known that alcoholic beverages alter the human gut microbiome. This study focused on the potential impact of non-ethanolic ingredients in whisky on the gut bacteriome. A pilot study was carried out on 15 whisky drinkers, 5 rice beer drinkers, and 9 non-drinkers to determine the effect of alcoholic beverages on the host microbiome and metabolome. Additionally, a mouse model was used to assess the differential impact of three whisky brands (each with an equal ethanol concentration). The results indicate that the non-ethanolic components have an impact on the gut microbiome, as well as on the metabolites in blood and feces. The amount of Prevotella copri, a typical core Indian gut bacterium, decreased in both the human and mouse groups of whisky type 1, but an increase in abundance of Helicobacteriaceae (p = 0.01) was noticed in both groups. Additionally, the alcohol-treated cohorts had lower levels of short-chain fatty acids (SCFAs), specifically butyric acid, and higher amounts of lipids and stress marker IL1-ß than the untreated groups (p = 0.04-0.01). Furthermore, two compounds, ethanal/acetaldehyde (found in all the whisky samples) and arabitol (unique to whisky type 1), were tested in the mice. Similar to the human subjects, the whisky type 1 treated mouse cohort and the arabitol-treated group showed decreased levels of Prevotella copri (p = 0.01) in their gut. The results showed that non-ethanolic compounds have a significant impact on host gut bacterial diversity and metabolite composition, which has a further vital impact on host health. Our work further emphasizes the need to study the impact of non-ethanolic ingredients of alcoholic beverages on host health.
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Affiliation(s)
- Priyanka Sarkar
- Molecular Biology and Microbial Biotechnology Laboratory, Life Science Division, Institute of Advanced Study in Science and Technology (IASST), Department of Science and Technology, Government of India, Paschim Boragaon, Garchuk, Guwahati 781035, Assam, India
- Wellcome/DBT (Indian Alliance) Lab, Institute of Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad 500032, Telangana, India
| | | | - Anupam Bhattacharya
- Molecular Biology and Microbial Biotechnology Laboratory, Life Science Division, Institute of Advanced Study in Science and Technology (IASST), Department of Science and Technology, Government of India, Paschim Boragaon, Garchuk, Guwahati 781035, Assam, India
| | - Romi Wahengbam
- Centre for Infectious Diseases, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India
| | - Madhusmita Dehingia
- Molecular Biology and Microbial Biotechnology Laboratory, Life Science Division, Institute of Advanced Study in Science and Technology (IASST), Department of Science and Technology, Government of India, Paschim Boragaon, Garchuk, Guwahati 781035, Assam, India
| | | | - Narayan Chandra Talukdar
- Molecular Biology and Microbial Biotechnology Laboratory, Life Science Division, Institute of Advanced Study in Science and Technology (IASST), Department of Science and Technology, Government of India, Paschim Boragaon, Garchuk, Guwahati 781035, Assam, India
- Faculty of Science, Assam Down Town University, Panikhaiti, Guwahati 781026, Assam, India
| | - Rupjyoti Talukdar
- Wellcome/DBT (Indian Alliance) Lab, Institute of Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad 500032, Telangana, India
| | - Mojibur R Khan
- Molecular Biology and Microbial Biotechnology Laboratory, Life Science Division, Institute of Advanced Study in Science and Technology (IASST), Department of Science and Technology, Government of India, Paschim Boragaon, Garchuk, Guwahati 781035, Assam, India
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10
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Zhang S, Chen A, Deng H, Jiang L, Liu X, Chai L. Intestinal response of Rana chensinensis larvae exposed to Cr and Pb, alone and in combination. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 255:114774. [PMID: 36931087 DOI: 10.1016/j.ecoenv.2023.114774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 03/06/2023] [Accepted: 03/11/2023] [Indexed: 06/18/2023]
Abstract
Although numerous investigations on the adverse impact of Cr and Pb have been performed, studies on intestinal homeostasis in amphibians are limited. Here, single and combined effects of Cr (104 μg/L) and Pb (50 μg/L) on morphological and histological features, bacterial community, digestive enzymes activities, as well as transcriptomic profile of intestines in Rana chensinensis tadpoles were assessed. Significant decrease in the relative intestine length (intestine length/snout-to-vent length, IL/SVL) was observed after exposure to Pb and Cr/Pb mixture. Intestinal histology and digestive enzymes activities were altered in metal treatment groups. In addition, treatment groups showed significantly increased bacterial richness and diversity. Tadpoles in treatment groups were observed to have differential gut bacterial composition from controls, especially for the abundance of phylum Proteobacteria, Firmicutes, Verrucomicrobia, Actinobacteria, and Fusobacteria as well as genus Citrobacter, Anaerotruncus, Akkermansia, and Alpinimonas. Moreover, transcriptomic analysis showed that the transcript expression profiles of GPx and SOD isoforms responded differently to Cr and/or Pb exposure. Besides, transcriptional activation of pro-apoptotic and glycolysis-related genes, such as Bax, Apaf 1, Caspase 3, PK, PGK, TPI, and GPI were detected in all treatment groups but downregulation of Bcl2 in Pb and Cr/Pb mixture groups. Collectively, these results suggested that Cr and Pb exposure at environmental relevant concentration, alone and in combination, could disrupt intestinal homeostasis of R. chensinensis tadpoles.
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Affiliation(s)
- Siliang Zhang
- School of Water and Environment, Chang'an University, Xi'an 710054, China; Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an 710054, China
| | - Aixia Chen
- School of Water and Environment, Chang'an University, Xi'an 710054, China
| | - Hongzhang Deng
- School of Water and Environment, Chang'an University, Xi'an 710054, China; Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an 710054, China
| | - Ling Jiang
- School of Water and Environment, Chang'an University, Xi'an 710054, China; Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an 710054, China
| | - Xiaoli Liu
- School of Water and Environment, Chang'an University, Xi'an 710054, China; Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an 710054, China
| | - Lihong Chai
- School of Water and Environment, Chang'an University, Xi'an 710054, China; Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Chang'an University, Xi'an 710054, China.
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11
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de Nies L, Galata V, Martin-Gallausiaux C, Despotovic M, Busi SB, Snoeck CJ, Delacour L, Budagavi DP, Laczny CC, Habier J, Lupu PC, Halder R, Fritz JV, Marques T, Sandt E, O'Sullivan MP, Ghosh S, Satagopam V, Krüger R, Fagherazzi G, Ollert M, Hefeng FQ, May P, Wilmes P. Altered infective competence of the human gut microbiome in COVID-19. MICROBIOME 2023; 11:46. [PMID: 36894986 PMCID: PMC9995755 DOI: 10.1186/s40168-023-01472-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/24/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Infections with SARS-CoV-2 have a pronounced impact on the gastrointestinal tract and its resident microbiome. Clear differences between severe cases of infection and healthy individuals have been reported, including the loss of commensal taxa. We aimed to understand if microbiome alterations including functional shifts are unique to severe cases or a common effect of COVID-19. We used high-resolution systematic multi-omic analyses to profile the gut microbiome in asymptomatic-to-moderate COVID-19 individuals compared to a control group. RESULTS We found a striking increase in the overall abundance and expression of both virulence factors and antimicrobial resistance genes in COVID-19. Importantly, these genes are encoded and expressed by commensal taxa from families such as Acidaminococcaceae and Erysipelatoclostridiaceae, which we found to be enriched in COVID-19-positive individuals. We also found an enrichment in the expression of a betaherpesvirus and rotavirus C genes in COVID-19-positive individuals compared to healthy controls. CONCLUSIONS Our analyses identified an altered and increased infective competence of the gut microbiome in COVID-19 patients. Video Abstract.
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Affiliation(s)
- Laura de Nies
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Valentina Galata
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Camille Martin-Gallausiaux
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Milena Despotovic
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Susheel Bhanu Busi
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Chantal J Snoeck
- Clinical and Applied Virology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Lea Delacour
- Luxembourg Centre for Systems Biomedicine, LCSB Operations, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Deepthi Poornima Budagavi
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Cédric Christian Laczny
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Janine Habier
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Paula-Cristina Lupu
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Rashi Halder
- Scientific Central Services, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Joëlle V Fritz
- Transversal Translation Medicine, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Taina Marques
- Translational Neuroscience Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Estelle Sandt
- Translational Medicine Operations Hub, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Marc Paul O'Sullivan
- Translational Medicine Operations Hub, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Soumyabrata Ghosh
- Bioinformatics Core, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Venkata Satagopam
- Bioinformatics Core, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Rejko Krüger
- Transversal Translation Medicine, Luxembourg Institute of Health, Strassen, Luxembourg
- Translational Neuroscience Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Guy Fagherazzi
- Deep Digital Phenotyping Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Markus Ollert
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-Sur-Alzette, Luxembourg
- Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark
| | - Feng Q Hefeng
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-Sur-Alzette, Luxembourg
| | - Patrick May
- Bioinformatics Core, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Paul Wilmes
- Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, 6, Avenue du Swing, L-4367, Belvaux, Luxembourg.
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12
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A Taxonomy-Agnostic Approach to Targeted Microbiome Therapeutics-Leveraging Principles of Systems Biology. Pathogens 2023; 12:pathogens12020238. [PMID: 36839510 PMCID: PMC9959781 DOI: 10.3390/pathogens12020238] [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: 12/15/2022] [Revised: 01/18/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
The study of human microbiomes has yielded insights into basic science, and applied therapeutics are emerging. However, conflicting definitions of what microbiomes are and how they affect the health of the "host" are less understood. A major impediment towards systematic design, discovery, and implementation of targeted microbiome therapeutics is the continued reliance on taxonomic indicators to define microbiomes in health and disease. Such reliance often confounds analyses, potentially suggesting associations where there are none, and conversely failing to identify significant, causal relationships. This review article discusses recent discoveries pointing towards a molecular understanding of microbiome "dysbiosis" and away from a purely taxonomic approach. We highlight the growing role of systems biological principles in the complex interrelationships between the gut microbiome and host cells, and review current approaches commonly used in targeted microbiome therapeutics, including fecal microbial transplant, bacteriophage therapies, and the use of metabolic toxins to selectively eliminate specific taxa from dysbiotic microbiomes. These approaches, however, remain wholly or partially dependent on the bacterial taxa involved in dysbiosis, and therefore may not capitalize fully on many therapeutic opportunities presented at the bioactive molecular level. New technologies capable of addressing microbiome-associated diseases as molecular problems, if solved, will open possibilities of new classes and categories of targeted microbiome therapeutics aimed, in principle, at all dysbiosis-driven disorders.
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13
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Gastric bacteria as potential biomarkers for the diagnosis of atrophic gastritis. Mol Biol Rep 2023; 50:655-664. [PMID: 36371556 DOI: 10.1007/s11033-022-08001-z] [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: 07/17/2022] [Accepted: 10/03/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Identification of the risk factors for atrophic gastritis (AG) and prevention of further deterioration of the gastritis are effective approaches to reduce the incidence of gastric cancer. Previous studies found that dysbiosis has been implicated in a wide range of diseases, while the role of gastric bacteria as a biomarker for AG has not been explored. METHODS AND RESULTS Gastric juices from cases with non-atrophic gastritis (NAG) and AG were collected for investigation of bacterial composition and function. The β-diversity of microbiota exhibited a significant reduction in AG samples compared with that in NAG samples. Differential abundance analysis revealed that a total of 23 predicted species changed their distributions; meanwhile, all obligate anaerobic bacteria with a relatively high abundance lowered their contents in AG samples. Additionally, the correlation analysis indicated a clear shift in bacterial correlation pattern between the two groups. Functional interrogation of the gastric microbiota showed that bacterial metabolisms associated with enzyme families, digestive system, and endocrine system were downregulated in AG samples. The compositional dissection of "core microbiota" exhibited that oral pathogens, including Porphyromonas gingivalis, Campylobacter gracilis, and Granulicatella elegans, were magnified in AG samples, suggesting that oral diseases may be a trigger factor for early exacerbation of gastritis. Then, the differentially expressed bacteria were used as diagnostic biomarkers for the random forest classifier model for group prediction. CONCLUSIONS The results showed that bacterial biomarkers could distinguish AG patients from NAG cases with an accuracy of 90% at the genus level.
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14
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Almeida HM, Sardeli AV, Conway J, Duggal NA, Cavaglieri CR. Comparison between frail and non-frail older adults' gut microbiota: A systematic review and meta-analysis. Ageing Res Rev 2022; 82:101773. [PMID: 36349647 DOI: 10.1016/j.arr.2022.101773] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Emerging evidence suggests that the intestinal microbiota (IM) undergoes remodelling as we age, and this impacts the ageing trajectory and mortality in older adults. The aim was to investigate IM diversity differences between frail and non-frail older adults by meta-analysing previous studies. METHODS The protocol of this systematic review with meta-analysis was registered on PROSPERO (CRD42021276733). We searched for studies comparing IM diversity of frail and non-frail older adults indexed on PubMed, Embase, Cochrane, and Web of Science in November 2021. RESULTS We included 11 studies with 1239 participants, of which 340 were meta-analysed. Frailty was defined by a variety of criteria (i.e. Fried Scale, European Consensus on Sarcopenia). There were no differences in the meta-analyses between the frail and non-frail groups for species richness index (SMD = -0.147; 95% CI = -0.394, 0.100; p = 0.243) and species diversity index (SMD = -0.033; 95% CI = -0.315, 0.250; p = 0.820). However, we identified almost 50 differences between frail and non-frail within the relative abundance of bacteria phyla, families, genera, and species in the primary studies. CONCLUSIONS The evidence to prove that there are differences between frail and non-frail IM diversity by meta-analysis is still lacking. The present results suggest that further investigation into the role of specific bacteria, their function, and their influence on the physiopathology of frailty is needed.
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Affiliation(s)
- Helena Maia Almeida
- Gerontology Program - Faculty of Medical Sciences, UNICAMP, Campinas, SP, Brazil; Laboratory of Exercise Physiology (FISEX), University of Campinas, Campinas, Brazil
| | - Amanda V Sardeli
- Gerontology Program - Faculty of Medical Sciences, UNICAMP, Campinas, SP, Brazil; Laboratory of Exercise Physiology (FISEX), University of Campinas, Campinas, Brazil; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
| | - Jessica Conway
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | | | - Cláudia Regina Cavaglieri
- Gerontology Program - Faculty of Medical Sciences, UNICAMP, Campinas, SP, Brazil; Laboratory of Exercise Physiology (FISEX), University of Campinas, Campinas, Brazil
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15
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Obón-Santacana M, Mas-Lloret J, Bars-Cortina D, Criado-Mesas L, Carreras-Torres R, Díez-Villanueva A, Moratalla-Navarro F, Guinó E, Ibáñez-Sanz G, Rodríguez-Alonso L, Mulet-Margalef N, Mata A, García-Rodríguez A, Duell EJ, Pimenoff VN, Moreno V. Meta-Analysis and Validation of a Colorectal Cancer Risk Prediction Model Using Deep Sequenced Fecal Metagenomes. Cancers (Basel) 2022; 14:cancers14174214. [PMID: 36077748 PMCID: PMC9454621 DOI: 10.3390/cancers14174214] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/26/2022] [Accepted: 08/28/2022] [Indexed: 11/16/2022] Open
Abstract
The gut microbiome is a potential modifiable risk factor for colorectal cancer (CRC). We re-analyzed all eight previously published stool sequencing data and conducted an MWAS meta-analysis. We used cross-validated LASSO predictive models to identify a microbiome signature for predicting the risk of CRC and precancerous lesions. These models were validated in a new study, Colorectal Cancer Screening (COLSCREEN), including 156 participants that were recruited in a CRC screening context. The MWAS meta-analysis identified 95 bacterial species that were statistically significantly associated with CRC (FDR < 0.05). The LASSO CRC predictive model obtained an area under the receiver operating characteristic curve (aROC) of 0.81 (95%CI: 0.78−0.83) and the validation in the COLSCREEN dataset was 0.75 (95%CI: 0.66−0.84). This model selected a total of 32 species. The aROC of this CRC-trained model to predict precancerous lesions was 0.52 (95%CI: 0.41−0.63). We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions, suggesting that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. Further studies should focus on CRC as well as precancerous lesions with the intent to implement a microbiome signature in CRC screening programs.
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Affiliation(s)
- Mireia Obón-Santacana
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Joan Mas-Lloret
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - David Bars-Cortina
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
| | - Lourdes Criado-Mesas
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
| | - Robert Carreras-Torres
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, 17190 Girona, Spain
| | - Anna Díez-Villanueva
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Ferran Moratalla-Navarro
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain
| | - Elisabet Guinó
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Gemma Ibáñez-Sanz
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Gastroenterology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Lorena Rodríguez-Alonso
- Gastroenterology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Núria Mulet-Margalef
- Medical Oncology Department, Catalan Institute of Oncology (ICO), 08916 Badalona, Spain
- Badalona-Applied Research Group in Oncology, Catalan Institute of Oncology (ICO), 08916 Badalona, Spain
| | - Alfredo Mata
- Digestive System Service, Moisés Broggi Hospital, 08970 Sant Joan Despí, Spain
| | - Ana García-Rodríguez
- Endoscopy Unit, Digestive System Service, Viladecans Hospital-IDIBELL, 08840 Viladecans, Spain
| | - Eric J. Duell
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Ville Nikolai Pimenoff
- Department of Laboratory Medicine, Karolinska Institutet, 14186 Stockholm, Sweden
- Correspondence: (V.N.P.); (V.M.)
| | - Victor Moreno
- Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain
- ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain
- Correspondence: (V.N.P.); (V.M.)
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Malesza IJ, Bartkowiak-Wieczorek J, Winkler-Galicki J, Nowicka A, Dzięciołowska D, Błaszczyk M, Gajniak P, Słowińska K, Niepolski L, Walkowiak J, Mądry E. The Dark Side of Iron: The Relationship between Iron, Inflammation and Gut Microbiota in Selected Diseases Associated with Iron Deficiency Anaemia—A Narrative Review. Nutrients 2022; 14:nu14173478. [PMID: 36079734 PMCID: PMC9458173 DOI: 10.3390/nu14173478] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/18/2022] [Accepted: 08/19/2022] [Indexed: 12/21/2022] Open
Abstract
Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.
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Affiliation(s)
- Ida J. Malesza
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | | | - Jakub Winkler-Galicki
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Aleksandra Nowicka
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | | | - Marta Błaszczyk
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Paulina Gajniak
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Karolina Słowińska
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Leszek Niepolski
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Edyta Mądry
- Department of Physiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
- Correspondence:
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17
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Gubatan J, Boye TL, Temby M, Sojwal RS, Holman DR, Sinha SR, Rogalla SR, Nielsen OH. Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer. Microorganisms 2022; 10:1371. [PMID: 35889090 PMCID: PMC9316834 DOI: 10.3390/microorganisms10071371] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/03/2022] [Accepted: 07/05/2022] [Indexed: 12/11/2022] Open
Abstract
The gut microbiome has increasingly been recognized as a critical and central factor in inflammatory bowel disease (IBD). Here, we review specific microorganisms that have been suggested to play a role in the pathogenesis of IBD and the current state of fecal microbial transplants as a therapeutic strategy in IBD. We discuss specific nutritional and dietary interventions in IBD and their effects on gut microbiota composition. Finally, we examine the role and mechanisms of the gut microbiome in mediating colitis-associated colon cancer.
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Affiliation(s)
- John Gubatan
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Theresa Louise Boye
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Copenhagen, Denmark; (T.L.B.); or (O.H.N.)
| | - Michelle Temby
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Raoul S. Sojwal
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Derek R. Holman
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Sidhartha R. Sinha
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Stephan R. Rogalla
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Ole Haagen Nielsen
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Copenhagen, Denmark; (T.L.B.); or (O.H.N.)
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18
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Meta-Analysis of Altered Gut Microbiota Reveals Microbial and Metabolic Biomarkers for Colorectal Cancer. Microbiol Spectr 2022; 10:e0001322. [PMID: 35766483 PMCID: PMC9431300 DOI: 10.1128/spectrum.00013-22] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. The dysbiotic gut microbiota and its metabolite secretions play a significant role in CRC development and progression. In this study, we identified microbial and metabolic biomarkers applicable to CRC using a meta-analysis of metagenomic datasets from diverse geographical regions. We used LEfSe, random forest (RF), and co-occurrence network methods to identify microbial biomarkers. Geographic dataset-specific markers were identified and evaluated using area under the ROC curve (AUC) scores and random effect size. Co-occurrence networks analysis showed a reduction in the overall microbial associations and the presence of oral pathogenic microbial clusters in CRC networks. Analysis of predicted metabolites from CRC datasets showed the enrichment of amino acids, cadaverine, and creatine in CRC, which were positively correlated with CRC-associated microbes (Peptostreptococcus stomatis, Gemella morbillorum, Bacteroides fragilis, Parvimonas spp., Fusobacterium nucleatum, Solobacterium moorei, and Clostridium symbiosum), and negatively correlated with control-associated microbes. Conversely, butyrate, nicotinamide, choline, tryptophan, and 2-hydroxybutanoic acid showed positive correlations with control-associated microbes (P < 0.05). Overall, our study identified a set of global CRC biomarkers that are reproducible across geographic regions. We also reported significant differential metabolites and microbe-metabolite interactions associated with CRC. This study provided significant insights for further investigations leading to the development of noninvasive CRC diagnostic tools and therapeutic interventions. IMPORTANCE Several studies showed associations between gut dysbiosis and CRC. Yet, the results are not conclusive due to cohort-specific associations that are influenced by genomic, dietary, and environmental stimuli and associated reproducibility issues with various analysis approaches. Emerging evidence suggests the role of microbial metabolites in modulating host inflammation and DNA damage in CRC. However, the experimental validations have been hindered by cost, resources, and cumbersome technical expertise required for metabolomic investigations. In this study, we performed a meta-analysis of CRC microbiota data from diverse geographical regions using multiple methods to achieve reproducible results. We used a computational approach to predict the metabolomic profiles using existing CRC metagenomic datasets. We identified a reliable set of CRC-specific biomarkers from this analysis, including microbial and metabolite markers. In addition, we revealed significant microbe-metabolite associations through correlation analysis and microbial gene families associated with dysregulated metabolic pathways in CRC, which are essential in understanding the vastly sporadic nature of CRC development and progression.
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19
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Li Z, Liu Y, Zhang L. Role of the microbiome in oral cancer occurrence, progression and therapy. Microb Pathog 2022; 169:105638. [PMID: 35718272 DOI: 10.1016/j.micpath.2022.105638] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 06/07/2022] [Accepted: 06/10/2022] [Indexed: 02/07/2023]
Abstract
The oral cavity, like other digestive or mucosal sites, contains a site-specific microbiome that plays a significant role in maintaining health and homeostasis. Strictly speaking, the gastrointestinal tract starts from the oral cavity, with special attention paid to the specific flora of the oral cavity. In healthy people, the microbiome of the oral microenvironment is governed by beneficial bacteria, that benefit the host by symbiosis. When a microecological imbalance occurs, changes in immune and metabolic signals affect the characteristics of cancer, as well as chronic inflammation, disruption of the epithelial barrier, changes in cell proliferation and cell apoptosis, genomic instability, angiogenesis, and epithelial barrier destruction and metabolic regulation. These pathophysiological changes could result in oral cancer. Rising evidence suggests that oral dysbacteriosis and particular microbes may play a positive role in the evolution, development, progression, and metastasis of oral cancer, for instance, oral squamous cell carcinoma (OSCC) through direct or indirect action.
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Affiliation(s)
- Zhengrui Li
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China.
| | - Yuan Liu
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China.
| | - Ling Zhang
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China.
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20
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Tosti E, Almeida AS, Tran TTT, Barbachan E Silva M, Broin PÓ, Dubin R, Chen K, Beck AP, Mclellan AS, Vilar E, Golden A, O'Toole PW, Edelmann W. Loss of MMR and TGFBR2 Increases the Susceptibility to Microbiota-Dependent Inflammation-Associated Colon Cancer. Cell Mol Gastroenterol Hepatol 2022; 14:693-717. [PMID: 35688320 PMCID: PMC9421583 DOI: 10.1016/j.jcmgh.2022.05.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 04/29/2022] [Accepted: 05/18/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota. METHODS We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are inactivated by Villin-Cre recombinase in the intestinal epithelium. VCMsh2/Tgfbr2 mice were analyzed for their rate of intestinal cancer development and for the mutational spectra and gene expression profiles of tumors. In addition, we assessed the impact of chemically induced chronic inflammation and gut microbiota composition on colorectal tumorigenesis. RESULTS VCMsh2/Tgfbr2 mice developed small intestinal adenocarcinomas and CRCs with histopathological features highly similar to CRCs in Lynch syndrome patients. The CRCs in VCMsh2/Tgfbr2 mice were associated with the presence of colitis and displayed genetic and histological features that resembled inflammation-associated CRCs in human patients. The development of CRCs in VCMsh2/Tgfbr2 mice was strongly modulated by the gut microbiota composition, which in turn was impacted by the TGFBR2 status of the tumors. CONCLUSIONS Our results demonstrate a synergistic interaction between MMR and TGFBR2 inactivation in inflammation-associated colon tumorigenesis and highlight the crucial impact of the gut microbiota on modulating the incidence of inflammation-associated CRCs.
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Affiliation(s)
- Elena Tosti
- Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York.
| | - Ana S Almeida
- APC Microbiome Ireland and School of Microbiology, University College Cork, Cork, Ireland
| | - Tam T T Tran
- University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam
| | - Mariel Barbachan E Silva
- School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland
| | - Pilib Ó Broin
- School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland
| | - Robert Dubin
- Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
| | - Ken Chen
- Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
| | - Amanda P Beck
- Department of Pathology, Albert Einstein College of Medicine, Bronx, New York
| | - Andrew S Mclellan
- Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
| | - Eduardo Vilar
- Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Aaron Golden
- School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland
| | - Paul W O'Toole
- APC Microbiome Ireland and School of Microbiology, University College Cork, Cork, Ireland
| | - Winfried Edelmann
- Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York.
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21
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Tu P, Chi L, Bian X, Gao B, Ru H, Lu K. A Black Raspberry-Rich Diet Protects From Dextran Sulfate Sodium-Induced Intestinal Inflammation and Host Metabolic Perturbation in Association With Increased Aryl Hydrocarbon Receptor Ligands in the Gut Microbiota of Mice. Front Nutr 2022; 9:842298. [PMID: 35734371 PMCID: PMC9208328 DOI: 10.3389/fnut.2022.842298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 04/21/2022] [Indexed: 11/13/2022] Open
Abstract
Dietary modulation of the gut microbiota recently received considerable attention, and ligand activation of aryl hydrocarbon receptor (AHR) plays a pivotal role in intestinal immunity. Importantly, black raspberry (BRB, Rubus occidentalis) is associated with a variety of beneficial health effects. We aim to investigate effects of a BRB-rich diet on dextran sulfate sodium (DSS)-induced intestinal inflammation and to determine whether its consequent anti-inflammatory effects are relevant to modulation of the gut microbiota, especially its production of AHR ligands. A mouse model of DSS-induced intestinal inflammation was used in the present study. C57BL/6J mice were fed either AIN-76A or BRB diet. Composition and functions of the gut microbiota were assessed by 16S rRNA sequencing and comparative metagenome analysis. Metabolic profiles of host and the gut microbiome were assessed by serum and fecal metabolomic profiling and identification. BRB diet was found to ameliorate DSS-induced intestinal inflammation and host metabolic perturbation. BRB diet also protected from DSS-induced perturbation in diversity and composition in the gut microbiota. BRB diet promoted AHR ligand production by the gut microbiota, as revealed by increased levels of fecal AHR activity in addition to increased levels of two known AHR ligands, hemin and biliverdin. Accordingly, enrichment of bacterial genes and pathways responsible for production of hemin and biliverdin were found, specific gut bacteria that are highly correlated with abundances of hemin and biliverdin were also identified. BRB dietary intervention ameliorated intestinal inflammation in mice in association with promotion of AHR ligand production by the gut microbiota.
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Affiliation(s)
- Pengcheng Tu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Liang Chi
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Xiaoming Bian
- Department of Environmental Health Sciences, University of Georgia, Athens, GA, United States
| | - Bei Gao
- Department of Environmental Health Sciences, University of Georgia, Athens, GA, United States
| | - Hongyu Ru
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Kun Lu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
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22
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Ravegnini G, Fosso B, Ricci R, Gorini F, Turroni S, Serrano C, Pilco-Janeta DF, Zhang Q, Zanotti F, De Robertis M, Nannini M, Pantaleo MA, Hrelia P, Angelini S. Analysis of microbiome in GISTs: looking for different players in tumorigenesis and novel therapeutic options. Cancer Sci 2022; 113:2590-2599. [PMID: 35633186 PMCID: PMC9357631 DOI: 10.1111/cas.15441] [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: 01/18/2022] [Revised: 04/20/2022] [Accepted: 05/23/2022] [Indexed: 12/02/2022] Open
Abstract
Preclinical forms of gastrointestinal stromal tumor (GIST), small asymptomatic lesions, called microGIST, are detected in approximately 30% of the general population. Gastrointestinal stromal tumor driver mutation can be already detected in microGISTs, even if they do not progress into malignant cancer; these mutations are necessary, but insufficient events to foster tumor progression. Here we profiled the tissue microbiota of 60 gastrointestinal specimens in three different patient cohorts—micro, low‐risk, and high‐risk or metastatic GIST—exploring the compositional structure, predicted function, and microbial networks, with the aim of providing a complete overview of microbial ecology in GIST and its preclinical form. Comparing microGISTs and GISTs, both weighted and unweighted UniFrac and Bray–Curtis dissimilarities showed significant community‐level separation between them and a pronounced difference in Proteobacteria, Firmicutes, and Bacteroidota was observed. Through the LEfSe tool, potential microbial biomarkers associated with a specific type of lesion were identified. In particular, GIST samples were significantly enriched in the phylum Proteobacteria compared to microGISTs. Several pathways involved in sugar metabolism were also highlighted in GISTs; this was expected as cancer usually displays high aerobic glycolysis in place of oxidative phosphorylation and rise of glucose flux to promote anabolic request. Our results highlight that specific differences do exist in the tissue microbiome community between GIST and benign lesions and that microbiome restructuration can drive the carcinogenesis process.
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Affiliation(s)
- Gloria Ravegnini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Bruno Fosso
- National Research Council, Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), Bari, Italy.,Department of Biosciences, Biotechnology and Biopharmaceutics (DBBB), University of Bari "A. Moro", Bari, Italy
| | - Riccardo Ricci
- UOC di Anatomia Patologica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Francesca Gorini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Cesar Serrano
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Daniel F Pilco-Janeta
- Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.,Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Qianqian Zhang
- UOC di Anatomia Patologica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Federica Zanotti
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Mariangela De Robertis
- Department of Biosciences, Biotechnology and Biopharmaceutics (DBBB), University of Bari "A. Moro", Bari, Italy
| | - Margherita Nannini
- Department of Experimental, Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy.,Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Abbondanza Pantaleo
- Department of Experimental, Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy.,Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Patrizia Hrelia
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Sabrina Angelini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
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23
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He J, Bosch TCG. Hydra's Lasting Partnership with Microbes: The Key for Escaping Senescence? Microorganisms 2022; 10:774. [PMID: 35456824 PMCID: PMC9028494 DOI: 10.3390/microorganisms10040774] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/25/2022] [Accepted: 04/02/2022] [Indexed: 02/04/2023] Open
Abstract
Aging results from a complex interplay between genetic endowment and environmental exposures during lifetime. As our understanding of the aging process progresses, so does the need for experimental animal models that allow a mechanistic understanding of the genetic and environmental factors involved. One such well-studied animal model is the freshwater polyp Hydra. Hydra are remarkable because they are non-senescent. Much of this non-senescence can be ascribed to a tissue consisting of stem cells with continuous self-renewal capacity. Another important fact is that Hydra's ectodermal epithelial surface is densely colonized by a stable multispecies bacterial community. The symbiotic partnership is driven by interactions among the microbiota and the host. Here, we review key advances over the last decade that are deepening our understanding of the genetic and environmental factors contributing to Hydra's non-senescent lifestyle. We conclude that the microbiome prevents pathobiont invasion (colonization resistance) and stabilizes the patterning mechanisms, and that microbiome malfunction negatively affects Hydra's continuous self-renewal capacity.
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Affiliation(s)
| | - Thomas C. G. Bosch
- Zoological Institute, Christian-Albrechts-University Kiel, 24118 Kiel, Germany;
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24
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Nouri R, Hasani A, Asgharzadeh M, Sefidan FY, Hemmati F, Rezaee MA. Roles of gut microbiota in colorectal carcinogenesis providing a perspective for early diagnosis and treatment. Curr Pharm Biotechnol 2022; 23:1569-1580. [PMID: 35255786 DOI: 10.2174/1389201023666220307112413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/29/2021] [Accepted: 01/03/2022] [Indexed: 12/02/2022]
Abstract
Colorectal cancer (CRC) is the third most prevalent malignant neoplasm in the world. CRC is influenced by both environmental and genetic factors. Through toxin-mediated DNA damage and promotion of persistent dysregulated inflammation, the gut microbiota plays a crucial role in the development of CRC. In this review, we discussed the correlation between the bacterial microbiota and CRC carcinogenesis as well as the mechanism by which Streptococcus bovis/gallolyticus, Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli can cause CRC.
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Affiliation(s)
- Roghayeh Nouri
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alka Hasani
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Asgharzadeh
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Yeganeh Sefidan
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Hemmati
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Ahangarzadeh Rezaee
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Clinical Research Development Unit of Children Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
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25
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Lee SY, Lee BH, Park JH, Park MS, Ji GE, Sung MK. Bifidobacterium bifidum BGN4 Paraprobiotic Supplementation Alleviates Experimental Colitis by Maintaining Gut Barrier and Suppressing Nuclear Factor Kappa B Activation Signaling Molecules. J Med Food 2022; 25:146-157. [PMID: 35148194 DOI: 10.1089/jmf.2021.k.0150] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are characterized by chronic gastrointestinal inflammation with continuous relapse-remission cycles. This study aimed to evaluate the protective effect of Bifidobacterium bifidum BGN4 as a probiotic or paraprobiotic against dextran sulfate sodium (DSS)-induced colitis in mice. Ten-week-old female BALB/c mice were randomly divided into five groups. The control (CON) and DSS groups received oral gavage of PBS, whereas the live B. bifidum (LIVE), heat-killed B. bifidum BGN4 (HEAT), and lysozyme-treated B. bifidum BGN4 (LYSOZYME) groups received live B. bifidum BGN4, heat-killed B. bifidum BGN4, and lysozyme-treated B. bifidum BGN4, respectively, for 10 days, followed by DSS supply to induce colitis. The paraprobiotic (HEAT and LYSOZYME) groups had less body weight loss and colon length shortening than the DSS or LIVE groups. The LYSOZYME group exhibited better preserved intestinal barrier integrity than the LIVE group by upregulating gap junction protein expression possibly through activating NOD-like receptor family pyrin domain containing 6/caspase-1/interleukin (IL)-18 signaling. The LYSOZYME group showed downregulated proinflammatory molecules, including p-inhibitor of kappa B proteins alpha (IκBα), cycloxygenase 2 (COX2), IL-1β, and T-bet, whereas the expression of the regulatory T cell transcription factor, forkhead box P3 expression, was increased. The paraprobiotic groups showed distinct separation of microbiota distribution and improved inflammation-associated dysbiosis. These results suggest that B. bifidum BGN4 paraprobiotics, especially lysozyme-treated BGN4, have a preventive effect against DSS-induced colitis, impacting intestinal barrier integrity, inflammation, and dysbiosis.
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Affiliation(s)
- So-Young Lee
- Department of Food and Nutrition, College of Human Ecology, Sookmyung Women's University, Seoul, Korea
| | - Byung-Hoo Lee
- Department of Food Science and Biotechnology, College of BioNano Technology, Gachon University, Seongnam, Korea
| | - Jong-Hyun Park
- Department of Food Science and Biotechnology, College of BioNano Technology, Gachon University, Seongnam, Korea
| | | | - Geun-Eog Ji
- Research Center, BIFIDO Co., Ltd., Hongcheon, Korea
- Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul, Korea
| | - Mi-Kyung Sung
- Department of Food and Nutrition, College of Human Ecology, Sookmyung Women's University, Seoul, Korea
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26
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D'Amico F, Barone M, Tavella T, Rampelli S, Brigidi P, Turroni S. Host microbiomes in tumor precision medicine: how far are we? Curr Med Chem 2022; 29:3202-3230. [PMID: 34986765 DOI: 10.2174/0929867329666220105121754] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/13/2021] [Accepted: 11/22/2021] [Indexed: 11/22/2022]
Abstract
The human gut microbiome has received a crescendo of attention in recent years, due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.
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Affiliation(s)
- Federica D'Amico
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Monica Barone
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Teresa Tavella
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Simone Rampelli
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Patrizia Brigidi
- Microbiome Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
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27
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Li B, Zhang H, Shi L, Li R, Luo Y, Deng Y, Li S, Li R, Liu Z. Saccharomyces boulardii alleviates DSS-induced intestinal barrier dysfunction and inflammation in humanized mice. Food Funct 2022; 13:102-112. [PMID: 34878454 DOI: 10.1039/d1fo02752b] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Recent clinical studies have demonstrated a beneficial effect of Saccharomyces boulardii (S. boulardii) in inflammatory bowel disease (IBD). However, the underlying mechanisms remain poorly defined. In this study, we investigated the modulating effect of S. boulardii on the intestinal microbiota in humanized mice with dextran sulfate sodium (DSS)-induced colitis. The mice were fed an S. boulardii-supplement diet for 16 days before DSS treatment. The results showed that feeding S. boulardii significantly ameliorated the colon damage and regulated inflammatory responses by modulating the cytokine profile. These changes were found to be associated with an altered microbiome composition and short-chain fatty acid (SCFA) metabolism. Further analysis demonstrated that S. boulardii-derived polysaccharides and polypeptides promoted the growth of certain probiotics and increased the microbial metabolite SCFAs levels. Overall, these findings demonstrated the role of S. boulardii as a potential gut microbiota modulator to prevent and treat IBD.
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Affiliation(s)
- Bei Li
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P. R. China.
| | - Haibo Zhang
- Hubei Provincial Key Laboratory of Yeast Function, Yichang, P. R. China
| | - Linlin Shi
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital (College of Clinical Medicine) of Henan University of Science and Technology, Luoyang, P. R. China
| | - Rong Li
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P. R. China.
| | - Yanan Luo
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P. R. China.
| | - Yun Deng
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P. R. China.
| | - Shihan Li
- Department of Children Healthcare, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, P. R. China.
| | - Ruizhen Li
- Department of Children Healthcare, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, P. R. China.
| | - Zhi Liu
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P. R. China.
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28
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Biswas P, Pal S, Das M, Dam S. Microbe-Induced Oxidative Stress in Cancer Development and Efficacy of Probiotics as Therapeutics in Preventing Its Onset and Progression. HANDBOOK OF OXIDATIVE STRESS IN CANCER: THERAPEUTIC ASPECTS 2022:3513-3542. [DOI: 10.1007/978-981-16-5422-0_159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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29
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Detection of Fusobacterium nucleatum subspecies in the saliva of pre-colorectal cancer patients, using tandem mass spectrometry. Arch Oral Biol 2021; 134:105337. [PMID: 34929558 DOI: 10.1016/j.archoralbio.2021.105337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 11/25/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Rising evidence links Fusobacterium nucleatum (F. nucleatum) with its four subspecies; nucleatum, polymorphum, animalis, and vincentii, with the development of colorectal cancer (CRC) and its precursor colorectal adenoma (CRA). This study aims to optimize a technique for and explore the capability of matrix-assisted laser-desorption ionization-tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to detect F. nucleatum subspecies directly from the saliva samples of CRA patients and controls without preculturing. DESIGN Saliva samples were collected from four CRA patients and eight controls. Proteins were extracted and subjected to solid-phase extraction fractionation, enzymatically digested, and analyzed by MALDI-TOF/TOF MS. F. nucleatum subspecies strains were cultured and used as a positive control. RESULTS A proteomics approach was developed to identify F. nucleatum subspecies directly from saliva samples. With this approach, the bacterial culturing step, which could take up to seven days, was bypassed. Overall, 157 F. nucleatum subspecies proteins were detected in the saliva samples. F. nucleatum subsp. nucleatum was absent in the patients while detected in half of the controls. CONCLUSION This study presents a novel technique for detecting F. nucleatum subspecies from saliva specimens that could later be employed to better understand a potential role of those subspecies in CRC development.
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30
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Fu MM, Chien WC, Chung CH, Lee WC, Tu HP, Fu E. Is periodontitis a risk factor of benign or malignant colorectal tumor? A population-based cohort study. J Periodontal Res 2021; 57:284-293. [PMID: 34854493 DOI: 10.1111/jre.12955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 11/07/2021] [Accepted: 11/08/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To examine the risk of developing benign or malignant colorectal tumors in patients with periodontitis within 15 years using Taiwan's National Health Insurance Database. BACKGROUND Studies have shown that colorectal carcinoma often develops under inflammatory conditions and changes of microbiota in the gut. Recently, a link between Fusobacterium nucleatum, a periodontal pathogen, and colorectal carcinoma has been proposed. However, whether periodontitis is a risk of developing colorectal tumor remains uncertain. METHODS In total, 35 124 participants were enrolled from 2000 to 2015 to examine the development risk of benign colorectal tumors, including 11 708 patients with periodontitis who received therapy (group 1), 11 708 patients with periodontitis not receiving periodontal treatment (group 2), and 11 708 non-periodontitis controls after matching for gender, age, and index year. To examine the risk of developing colorectal malignancy, 11 720 participants were assigned to each of the three groups. Cox proportional hazards model and Kaplan-Meier methods were used to compare the risks. Sensitivity analysis was performed, excluding the diagnoses during the first 1 or 5 years. RESULTS After the follow-up, 177, 154, and 63 participants in group 1, group 2, and control group had benign colorectal tumors. Patients with periodontitis tended to be associated with a greater rate of having a benign colorectal tumor. The adjusted hazard ratios (aHRs) were 3.77 (95% confidence interval [CI] 2.01-4.82, p < .001) and 2.85 (95% CI 1.62-3.74, p < .001) for groups 1 and 2, respectively. Regarding the risk of malignant colorectal tumor, 20, 18, and 14 participants who developed malignant tumors were included in group 1, group 2, and control group; however, no significant increase in malignancy was observed in periodontitis groups (aHR1.92, 95% CI 0.74-2.36, p = .482; aHR 1.50, 95% CI 0.68-1.97, p = .529, for the two periodontitis groups, respectively). CONCLUSIONS The results of this study suggest that patients with periodontitis may have an increased risk of developing benign, but not malignant, colorectal tumors.
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Affiliation(s)
- Martin M Fu
- Department of Periodontology, School of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wu-Chien Chien
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.,School of Public Health, National Defense Medical Center, Taipei, Taiwan.,Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Hsiang Chung
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.,School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Cheng Lee
- Department of Orthodontics, School of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Hsiao-Pei Tu
- Department of Oral hygiene, Hsin-Sheng Junior College of Medical Care and Management, Taoyuan City, Taiwan
| | - Earl Fu
- Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
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31
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Marongiu L, Landry JJM, Rausch T, Abba ML, Delecluse S, Delecluse H, Allgayer H. Metagenomic analysis of primary colorectal carcinomas and their metastases identifies potential microbial risk factors. Mol Oncol 2021; 15:3363-3384. [PMID: 34328665 PMCID: PMC8637581 DOI: 10.1002/1878-0261.13070] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 07/09/2021] [Accepted: 07/29/2021] [Indexed: 12/18/2022] Open
Abstract
The paucity of microbiome studies at intestinal tissues has contributed to a yet limited understanding of potential viral and bacterial cofactors of colorectal cancer (CRC) carcinogenesis or progression. We analysed whole-genome sequences of CRC primary tumours, their corresponding metastases and matched normal tissue for sequences of viral, phage and bacterial species. Bacteriome analysis showed Fusobacterium nucleatum, Streptococcus sanguinis, F. Hwasookii, Anaerococcus mediterraneensis and further species enriched in primary CRCs. The primary CRC of one patient was enriched for F. alocis, S. anginosus, Parvimonas micra and Gemella sp. 948. Enrichment of Escherichia coli strains IAI1, SE11, K-12 and M8 was observed in metastases together with coliphages enterobacteria phage φ80 and Escherichia phage VT2φ_272. Virome analysis showed that phages were the most preponderant viral species (46%), the main families being Myoviridae, Siphoviridae and Podoviridae. Primary CRCs were enriched for bacteriophages, showing five phages (Enterobacteria, Bacillus, Proteus, Streptococcus phages) together with their pathogenic hosts in contrast to normal tissues. The most frequently detected, and Blast-confirmed, viruses included human endogenous retrovirus K113, human herpesviruses 7 and 6B, Megavirus chilensis, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), with one patient showing EBV enrichment in primary tumour and metastases. EBV was PCR-validated in 80 pairs of CRC primary tumour and their corresponding normal tissues; in 21 of these pairs (26.3%), it was detectable in primary tumours only. The number of viral species was increased and bacterial species decreased in CRCs compared with normal tissues, and we could discriminate primary CRCs from metastases and normal tissues by applying the Hutcheson t-test on the Shannon indices based on viral and bacterial species. Taken together, our results descriptively support hypotheses on microorganisms as potential (co)risk factors of CRC and extend putative suggestions on critical microbiome species in CRC metastasis.
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Affiliation(s)
- Luigi Marongiu
- Department of Experimental Surgery – Cancer MetastasisMedical Faculty MannheimRuprecht‐Karls University of HeidelbergMannheimGermany
| | | | - Tobias Rausch
- Genomics Core FacilityEuropean Molecular Biology Laboratory (EMBL)HeidelbergGermany
| | - Mohammed L. Abba
- Department of Experimental Surgery – Cancer MetastasisMedical Faculty MannheimRuprecht‐Karls University of HeidelbergMannheimGermany
| | | | | | - Heike Allgayer
- Department of Experimental Surgery – Cancer MetastasisMedical Faculty MannheimRuprecht‐Karls University of HeidelbergMannheimGermany
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32
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Roslund MI, Puhakka R, Nurminen N, Oikarinen S, Siter N, Grönroos M, Cinek O, Kramná L, Jumpponen A, Laitinen OH, Rajaniemi J, Hyöty H, Sinkkonen A. Long-term biodiversity intervention shapes health-associated commensal microbiota among urban day-care children. ENVIRONMENT INTERNATIONAL 2021; 157:106811. [PMID: 34403882 DOI: 10.1016/j.envint.2021.106811] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 07/17/2021] [Accepted: 07/30/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND In modern urban environments children have a high incidence of inflammatory disorders, including allergies, asthma, and type1 diabetes. The underlying cause of these disorders, according to the biodiversity hypothesis, is an imbalance in immune regulation caused by a weak interaction with environmental microbes. In this 2-year study, we analyzed bacterial community shifts in the soil surface in day-care centers and commensal bacteria inhabiting the mouth, skin, and gut of children. We compared two different day-care environments: standard urban day-care centers and intervention day-care centers. Yards in the latter were amended with biodiverse forest floor vegetation and sod at the beginning of the study. RESULTS Intervention caused a long-standing increase in the relative abundance of nonpathogenic environmental mycobacteria in the surface soils. Treatment-specific shifts became evident in the community composition of Gammaproteobacteria, Negativicutes, and Bacilli, which jointly accounted for almost 40 and 50% of the taxa on the intervention day-care children's skin and in saliva, respectively. In the year-one skin swabs, richness of Alpha-, Beta-, and Gammaproteobacteria was higher, and the relative abundance of potentially pathogenic bacteria, including Haemophilus parainfluenzae, Streptococcus sp., and Veillonella sp., was lower among children in intervention day-care centers compared with children in standard day-care centers. In the gut, the relative abundance of Clostridium sensu stricto decreased, particularly among the intervention children. CONCLUSIONS This study shows that a 2-year biodiversity intervention shapes human commensal microbiota, including taxa that have been associated with immune regulation. Results indicate that intervention enriched commensal microbiota and suppressed the potentially pathogenic bacteria on the skin. We recommend future studies that expand intervention strategies to immune response and eventually the incidence of immune-mediated diseases.
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Affiliation(s)
- Marja I Roslund
- Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Niemenkatu 73, FI-15140 Lahti, Finland
| | - Riikka Puhakka
- Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Niemenkatu 73, FI-15140 Lahti, Finland
| | - Noora Nurminen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, FI-33520 Tampere, Finland
| | - Sami Oikarinen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, FI-33520 Tampere, Finland
| | - Nathan Siter
- Faculty of Built Environment, Tampere University, Korkeakoulunkatu 5, FI-33720 Tampere, Finland
| | - Mira Grönroos
- Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Niemenkatu 73, FI-15140 Lahti, Finland
| | - Ondřej Cinek
- Department of Pediatrics, Second Faculty of Medicine, Charles University, V Úvalu 84, Praha 5, 150 06 Prague, Czech Republic
| | - Lenka Kramná
- Department of Pediatrics, Second Faculty of Medicine, Charles University, V Úvalu 84, Praha 5, 150 06 Prague, Czech Republic
| | - Ari Jumpponen
- Division of Biology, Kansas State University, Manhattan KS66506, KS, United States of America
| | - Olli H Laitinen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, FI-33520 Tampere, Finland
| | - Juho Rajaniemi
- Faculty of Built Environment, Tampere University, Korkeakoulunkatu 5, FI-33720 Tampere, Finland
| | - Heikki Hyöty
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, FI-33520 Tampere, Finland
| | - Aki Sinkkonen
- Natural Resources Institute Finland, Turku, Finland.
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33
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Kudo H, Sugiura T, Higashi S, Oka K, Takahashi M, Kamiya S, Tamura Y, Usui M. Characterization of Reproductive Microbiota of Primiparous Cows During Early Postpartum Periods in the Presence and Absence of Endometritis. Front Vet Sci 2021; 8:736996. [PMID: 34733902 PMCID: PMC8558311 DOI: 10.3389/fvets.2021.736996] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 09/21/2021] [Indexed: 12/30/2022] Open
Abstract
Endometritis has a major impact on fertility in postpartum dairy cows. Since previous studies showed an association between reproductive microbiota and perinatal disease, we monitored both bovine uterine and vaginal microbiota in primiparous cows to elucidate the effect of early postpartum microbiota on endometritis. Uterine and vaginal samples were collected at time points from pre-calving to 35 days postpartum (DPP), and analyzed by 16S rRNA sequencing, combined with ancillary bacterial culture. A total of seven healthy cows and seven cows diagnosed with endometritis on 35 DPP were used in the current study. The uterine and vaginal microbiota showed a maximum of 20.1% shared amplicon sequence variants (ASVs) at linked time points. 16S rRNA based analysis and traditional culture methods revealed that Trueperella showed a higher abundance in both uterus and vagina of the endometritis group compared to the healthy group on 21 DPP (U-test p < 0.05). Differential abundance analysis of the uterine microbiota showed that Enterococcus and six bacterial genera including Bifidobacterium were unique to the healthy group on the day of calving (0 DPP) and 28 DPP, respectively. In contrast, Histophilus and Mogibacteriaceae were characteristic bacteria in the vagina pre-calving in cows that later developed endometritis, suggesting that these bacteria could be valuable to predict clinical outcomes. Comparing the abundances of bacterial genera in the uterine microbiota, a negative correlation was observed between Trueperella and several bacteria including Lactobacillus. These results suggest that building an environment where there is an increase in bacteria that are generally recognized as beneficial, such as Lactobacillus, may be one possible solution to reduce the abundance of Trueperella and control endometritis.
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Affiliation(s)
- Hayami Kudo
- Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.,Research Department, R&D Division, Miyarisan Pharmaceutical Co., Ltd., Saitama, Japan
| | - Tomochika Sugiura
- Department of Large Animal Clinical Science, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan
| | - Seiya Higashi
- Research Department, R&D Division, Miyarisan Pharmaceutical Co., Ltd., Saitama, Japan
| | - Kentaro Oka
- Research Department, R&D Division, Miyarisan Pharmaceutical Co., Ltd., Saitama, Japan
| | - Motomichi Takahashi
- Research Department, R&D Division, Miyarisan Pharmaceutical Co., Ltd., Saitama, Japan
| | - Shigeru Kamiya
- Research Department, R&D Division, Miyarisan Pharmaceutical Co., Ltd., Saitama, Japan
| | - Yutaka Tamura
- Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan
| | - Masaru Usui
- Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan
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Stamps BW, Kuroiwa J, Isidean SD, Schilling MA, Harro C, Talaat KR, Sack DA, Tribble DR, Maue AC, Rimmer JE, Laird RM, Porter CK, Goodson MS, Poly F. Exploring Changes in the Host Gut Microbiota During a Controlled Human Infection Model for Campylobacter jejuni. Front Cell Infect Microbiol 2021; 11:702047. [PMID: 34532299 PMCID: PMC8439579 DOI: 10.3389/fcimb.2021.702047] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 08/13/2021] [Indexed: 01/02/2023] Open
Abstract
Campylobacter jejuni infection is a leading cause of foodborne disease, common to children, adult travelers, and military populations in low- to middle-income countries. In the absence of a licensed vaccine, efforts to evaluate prophylactic agents are underway. The prophylactic efficacy of a twice-daily, 550 mg dose of the antibiotic rifaximin demonstrated no efficacy against campylobacteriosis in a controlled human infection model (CHIM); however, samples from the CHIM study were utilized to assess how the human gut microbiome responds to C. jejuni infection, and if a ‘protective’ microbiota exists in study participants not developing campylobacteriosis. Statistically significant, but minor, differences in study participant beta diversity were identified during the challenge period (p = 0.002, R2 = 0.042), but no significant differences were otherwise observed. Pre-challenge alpha diversity was elevated in study participants who did not develop campylobacteriosis compared to those who did (p < 0.001), but alpha diversity declined in all study participants from the pre-challenge period to post-discharge. Our work provides insight into gut microbiome shifts observed during a C. jejuni CHIM and following antibiotic treatment. This study utilized a high dose of 1.7 x 105 colony-forming units of C. jejuni; future work could include CHIM studies performed with inocula more closely mimicking natural exposure as well as field studies involving naturally-occurring enteric infections.
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Affiliation(s)
- Blake W Stamps
- 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, United States.,Integrative Health and Performance Sciences Division, UES, Inc., Dayton, OH, United States
| | - Janelle Kuroiwa
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States
| | - Sandra D Isidean
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States
| | - Megan A Schilling
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States
| | - Clayton Harro
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Kawsar R Talaat
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - David A Sack
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - David R Tribble
- Infectious Disease Clinical Research Program, Preventive Medicine and Biostatistics Department, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
| | - Alexander C Maue
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States
| | - Joanna E Rimmer
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States.,Academic Department of Military Medicine, Royal Centre for Defence Medicine, Medical Directorate, Joint Medical Command, Information and Communications Technology Centre, Birmingham, United Kingdom
| | - Renee M Laird
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States
| | - Chad K Porter
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States
| | - Michael S Goodson
- 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, United States
| | - Frédéric Poly
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States
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35
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D’Amico F, Perrone AM, Rampelli S, Coluccelli S, Barone M, Ravegnini G, Fabbrini M, Brigidi P, De Iaco P, Turroni S. Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome. Cancers (Basel) 2021; 13:cancers13163999. [PMID: 34439153 PMCID: PMC8393652 DOI: 10.3390/cancers13163999] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/23/2021] [Accepted: 08/05/2021] [Indexed: 12/18/2022] Open
Abstract
Simple Summary This pilot study on the trajectory of the gut microbiota (GM) in patients with epithelial ovarian cancer undergoing neoadjuvant and adjuvant chemotherapy highlighted peculiar dynamics associated with the therapeutic outcome. In particular, platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of lactate-producing microorganisms compared to those sensitive to platinum. These potential GM signatures of therapeutic failure are detectable within the first half of chemotherapy cycles, suggesting that early integrated treatments also aimed at modulating GM could influence therapeutic outcome. Further studies in larger cohorts combining multiple omics and possibly animal models are urgently needed for in-depth mechanistic understanding. Abstract Epithelial ovarian cancer (EOC) is one of the most lethal and silent gynecological tumors. Despite appropriate surgery and chemotherapy, relapse occurs in over half of patients with a poor prognosis. Recently, the gut microbiota (GM) was hypothesized to influence the efficacy of anticancer therapies, but no data are available in EOC. Here, by 16S rRNA gene sequencing and inferred metagenomics, we profiled the GM of EOC patients at diagnosis and reconstructed its trajectory along the course of neoadjuvant or adjuvant chemotherapy up to follow-up. Compared to healthy subjects, the GM of EOC patients appeared unbalanced and severely affected by chemotherapy. Strikingly, discriminating patterns were identified in relation to the therapeutic response. Platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of Coriobacteriaceae and Bifidobacterium. Notably, most of these microorganisms are lactate producers, suggesting increased lactate production as supported by inferred metagenomics. In contrast, the GM of platinum-sensitive patients appeared overall more diverse and stable and enriched in lactate utilizers from the Veillonellaceae family. In conclusion, we identified potential GM signatures of therapeutic outcome in EOC patients, which could open up new opportunities for cancer prognosis and treatment.
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Affiliation(s)
- Federica D’Amico
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.M.P.); (S.C.); (M.B.); (P.B.); (P.D.I.)
- Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy; (S.R.); (G.R.); (M.F.); (S.T.)
- Correspondence: ; Tel.: +39-051-2099727
| | - Anna Myriam Perrone
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.M.P.); (S.C.); (M.B.); (P.B.); (P.D.I.)
- Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero, University of Bologna, 40138 Bologna, Italy
- Centro di Studio e Ricerca delle Neoplasie Ginecologiche (CSR), University of Bologna, 40138 Bologna, Italy
| | - Simone Rampelli
- Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy; (S.R.); (G.R.); (M.F.); (S.T.)
| | - Sara Coluccelli
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.M.P.); (S.C.); (M.B.); (P.B.); (P.D.I.)
- Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero, University of Bologna, 40138 Bologna, Italy
| | - Monica Barone
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.M.P.); (S.C.); (M.B.); (P.B.); (P.D.I.)
- Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy; (S.R.); (G.R.); (M.F.); (S.T.)
| | - Gloria Ravegnini
- Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy; (S.R.); (G.R.); (M.F.); (S.T.)
| | - Marco Fabbrini
- Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy; (S.R.); (G.R.); (M.F.); (S.T.)
| | - Patrizia Brigidi
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.M.P.); (S.C.); (M.B.); (P.B.); (P.D.I.)
- Centro di Studio e Ricerca delle Neoplasie Ginecologiche (CSR), University of Bologna, 40138 Bologna, Italy
| | - Pierandrea De Iaco
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (A.M.P.); (S.C.); (M.B.); (P.B.); (P.D.I.)
- Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero, University of Bologna, 40138 Bologna, Italy
- Centro di Studio e Ricerca delle Neoplasie Ginecologiche (CSR), University of Bologna, 40138 Bologna, Italy
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy; (S.R.); (G.R.); (M.F.); (S.T.)
- Centro di Studio e Ricerca delle Neoplasie Ginecologiche (CSR), University of Bologna, 40138 Bologna, Italy
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Lee MH. Harness the functions of gut microbiome in tumorigenesis for cancer treatment. Cancer Commun (Lond) 2021; 41:937-967. [PMID: 34355542 PMCID: PMC8504147 DOI: 10.1002/cac2.12200] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 07/16/2021] [Indexed: 11/08/2022] Open
Abstract
It has been shown that gut microbiota dysbiosis leads to physiological changes and links to a number of diseases, including cancers. Thus, many cancer categories and treatment regimens should be investigated in the context of the microbiome. Owing to the availability of metagenome sequencing and multiomics studies, analyses of species characterization, host genetic changes, and metabolic profile of gut microbiota have become feasible, which has facilitated an exponential knowledge gain about microbiota composition, taxonomic alterations, and host interactions during tumorigenesis. However, the complexity of the gut microbiota, with a plethora of uncharacterized host‐microbe, microbe‐microbe, and environmental interactions, still contributes to the challenge of advancing our knowledge of the microbiota‐cancer interactions. These interactions manifest in signaling relay, metabolism, immunity, tumor development, genetic instability, sensitivity to cancer chemotherapy and immunotherapy. This review summarizes current studies/molecular mechanisms regarding the association between the gut microbiota and the development of cancers, which provides insights into the therapeutic strategies that could be harnessed for cancer diagnosis, treatment, or prevention.
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Affiliation(s)
- Mong-Hong Lee
- Research Institute of Gastroenterology, Sun Yat-sen University, Guangzhou, Guangdong, 510020, P. R. China.,Guangdong Provincial Key laboratory of Colorectal and Pelvic Floor Disease, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510020, P. R. China
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37
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Chadha S, Kumar A, Srivastava SA, Behl T, Ranjan R. Inulin as a Delivery Vehicle for Targeting Colon-Specific Cancer. Curr Drug Deliv 2021; 17:651-674. [PMID: 32459607 DOI: 10.2174/1567201817666200527133719] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 03/11/2020] [Accepted: 04/01/2020] [Indexed: 12/12/2022]
Abstract
Natural polysaccharides, as well as biopolymers, are now days widely developed for targeting colon cancer using various drug delivery systems. Currently, healing conformations are being explored that can efficiently play a multipurpose role. Owing to the capability of extravagance colonic diseases with the least adverse effects, biopolymers for site specific colon delivery have developed an increased curiosity over the past decades. Inulin (INU) was explored for its probable application as an entrapment material concerning its degradation by enzymes in the colonic microflora and its drug release behavior in a sustained and controlled manner. INU is a polysaccharide and it consists of 2 to 1 linkage having an extensive array of beneficial uses such as a carrier for delivery of therapeutic agents as an indicative/investigative utensil or as a dietary fiber with added well-being aids. In the main, limited research, as well as information, is available on the delivery of therapeutic agents using inulin specifically for colon cancer because of its capability to subsist in the stomach's acidic medium. This exceptional steadiness and robustness properties are exploited in numerous patterns to target drugs securely for the management of colonic cancer, where they effectively act and kills colonic tumor cells easily. In this review article, recent efforts and inulin-based nano-technological approaches for colon cancer targeting are presented and discussed.
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Affiliation(s)
- Swati Chadha
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Arun Kumar
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | | | - Tapan Behl
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Rishu Ranjan
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
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38
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Fang CY, Chen JS, Hsu BM, Hussain B, Rathod J, Lee KH. Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers. Microorganisms 2021; 9:microorganisms9081548. [PMID: 34442626 PMCID: PMC8401100 DOI: 10.3390/microorganisms9081548] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 12/12/2022] Open
Abstract
Despite advances in the characterization of colorectal cancer (CRC), it still faces a poor prognosis. There is growing evidence that gut microbiota and their metabolites potentially contribute to the development of CRC. Thus, microbial dysbiosis and their metabolites associated with CRC, based on stool samples, may be used to advantage to provide an excellent opportunity to find possible biomarkers for the screening, early detection, prevention, and treatment of CRC. Using 16S rRNA amplicon sequencing coupled with statistical analysis, this study analyzed the cause–effect shift of the microbial taxa and their metabolites that was associated with the fecal gut microbiota of 17 healthy controls, 21 polyps patients, and 21 cancer patients. The microbial taxonomic shift analysis revealed striking differences among the healthy control, polyps and cancer groups. At the phylum level, Synergistetes was reduced significantly in the polyps group compared to the healthy control and cancer group. Additionally, at the genus level and in association with the cancer group, a total of 12 genera were highly enriched in abundance. In contrast, only Oscillosprira was significantly higher in abundance in the healthy control group. Comparisons of the polyps and cancer groups showed a total of 18 significantly enriched genera. Among them, 78% of the genera associated with the cancer group were in higher abundance, whereas the remaining genera showed a higher abundance in the polyps group. Additionally, the comparison of healthy control and polyp groups showed six significantly abundant genera. More than 66% of these genera showed a reduced abundance in the polyps group than in healthy controls, whereas the remaining genera were highly abundant in the polyps group. Based on tumor presence and absence, the abundance of Olsenella and Lactobacillus at the genus level was significantly reduced in the patient group compared to healthy controls. The significant microbial function prediction revealed an increase in the abundance of metabolites in the polyps and cancer groups compared to healthy controls. A correlation analysis revealed a higher contribution of Dorea in the predicted functions. This study showed dysbiosis of gut microbiota at the taxonomic level and their metabolic functions among healthy subjects and in two stages of colorectal cancer, including adenoma and adenocarcinoma, which might serve as potential biomarkers for the early diagnosis and treatment of CRC.
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Affiliation(s)
- Chuan-Yin Fang
- Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 621, Taiwan;
| | - Jung-Sheng Chen
- Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan;
| | - Bing-Mu Hsu
- Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi 621, Taiwan;
- Center for Innovative on Aging Society (CIRAS), National Chung Cheng University, Chiayi 621, Taiwan
- Correspondence: ; Tel.: +886-52720411 (ext. 66218)
| | - Bashir Hussain
- Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi 621, Taiwan;
- Department of Biomedical Sciences, National Chung Cheng University, Chiayi 621, Taiwan
| | - Jagat Rathod
- Department of Earth Sciences, National Cheng Kung University, Tainan 701, Taiwan;
| | - Kuo-Hsin Lee
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan;
- School of Medicine, I-Shou University, Kaohsiung 824, Taiwan
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39
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Kumar R, Harilal S, Carradori S, Mathew B. A Comprehensive Overview of Colon Cancer- A Grim Reaper of the 21st Century. Curr Med Chem 2021; 28:2657-2696. [PMID: 33106132 DOI: 10.2174/0929867327666201026143757] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 09/18/2020] [Accepted: 09/18/2020] [Indexed: 12/09/2022]
Abstract
A few decades ago, the incidence of colorectal cancer (CRC) was low and is now the fourth in the list of deadly cancers producing nearly a million deaths annually. A population that is aging along with risk factors such as smoking, obesity, sedentary lifestyle with little or no physical activity, and non-healthy food habits of developed countries can increase the risk of colorectal cancer. The balance in gut microbiota and the metabolites produced during bacterial fermentation within the host plays a significant role in regulating intestinal diseases as well as colorectal cancer development. Recent progress in the understanding of illness resulted in multiple treatment options such as surgery, radiation, and chemotherapy, including targeted therapy and multitherapies. The treatment plan for CRC depends on the location, stage and grade of cancer as well as genomic biomarker tests. Despite all the advancements made in the genetic and molecular aspects of the disease, the knowledge seems inadequate as the drug action as well as the wide variation in drug response did not appear strongly correlated with the individual molecular and genetic characteristics, which suggests the requirement of comprehensive molecular understanding of this complex heterogeneous disease. Furthermore, multitherapies or a broad spectrum approach, which is an amalgamation of the various promising as well as effective therapeutic strategies that can tackle heterogeneity and act on several targets of the disease, need to be validated in clinical studies. The latest treatment options have significantly increased the survival of up to three years in the case of advanced disease. The fact that colorectal cancer is developed from a polypoid precursor, as well as the symptoms of the disease that occur at an advanced stage, underlines how screening programs can help early detection and decrease mortality as well as morbidity from CRC.
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Affiliation(s)
- Rajesh Kumar
- Department of Pharmacy, Kerala University of Health Sciences, Thrissur, Kerala, India
| | - Seetha Harilal
- Department of Pharmacy, Kerala University of Health Sciences, Thrissur, Kerala, India
| | - Simone Carradori
- Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, Italy
| | - Bijo Mathew
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi-682 041, India
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Imai J, Kitamoto S, Kamada N. The pathogenic oral-gut-liver axis: new understandings and clinical implications. Expert Rev Clin Immunol 2021; 17:727-736. [PMID: 34057877 DOI: 10.1080/1744666x.2021.1935877] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Oral health is closely related to extra-oral disease status, as may be represented by the manifestations of gastrointestinal and liver diseases. AREAS COVERED This review focuses on the roles that the oral-gut or the oral-gut-liver axis play in the pathogenesis of inflammatory bowel disease, colorectal cancer, metabolic fatty liver disease, and nonalcoholic steatohepatitis. The discussion will begin with clinical data, including data from preclinical animal models, to elucidate mechanisms. We will also discuss ways to target oral dysbiosis and oral inflammation to treat gastrointestinal and liver diseases. EXPERT OPINION Several studies have demonstrated that oral pathobionts can translocate to the gastrointestinal tract where they contribute to inflammation and tumorigenesis. Furthermore, oral bacteria that migrate to the gastrointestinal tract can disseminate to the liver and cause hepatic disease. Thus, oral bacteria that ectopically colonize the intestine may serve as biomarkers for gastrointestinal and liver diseases. Also, understanding the characteristics of the oral-gut and oral-gut-liver microbial and immune axes will provide new insights into the pathogenesis of these diseases.
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Affiliation(s)
- Jin Imai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Sho Kitamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Nobuhiko Kamada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
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Actin-Binding Proteins as Potential Biomarkers for Chronic Inflammation-Induced Cancer Diagnosis and Therapy. ACTA ACUST UNITED AC 2021; 2021:6692811. [PMID: 34194957 PMCID: PMC8203385 DOI: 10.1155/2021/6692811] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 04/13/2021] [Accepted: 05/18/2021] [Indexed: 12/15/2022]
Abstract
Actin-binding proteins (ABPs), by interacting with actin, regulate the polymerization, depolymerization, bundling, and cross-linking of actin filaments, directly or indirectly, thereby mediating the maintenance of cell morphology, cell movement, and many other biological functions. Consequently, these functions of ABPs help regulate cancer cell invasion and metastasis when cancer occurs. In recent years, a variety of ABPs have been found to be abnormally expressed in various cancers, indicating that the detection and interventions of unusual ABP expression to alter this are available for the treatment of cancer. The early stages of most cancer development involve long-term chronic inflammation or repeated stimulation. This is the case for breast cancer, gastric cancer, lung cancer, prostate cancer, liver cancer, esophageal cancer, pancreatic cancer, melanoma, and colorectal cancer. This article discusses the relationship between chronic inflammation and the above-mentioned cancers, emphatically introduces relevant research on the abnormal expression of ABPs in chronic inflammatory diseases, and reviews research on the expression of different ABPs in the above-mentioned cancers. Furthermore, there is a close relationship between ABP-induced inflammation and cancer. In simple terms, abnormal expression of ABPs contributes to the chronic inflammation developing into cancer. Finally, we provide our viewpoint regarding these unusual ABPs serving as potential biomarkers for chronic inflammation-induced cancer diagnosis and therapy, and interventions to reverse the abnormal expression of ABPs represent a potential approach to preventing or treating the corresponding cancers.
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Olvera-Rosales LB, Cruz-Guerrero AE, Ramírez-Moreno E, Quintero-Lira A, Contreras-López E, Jaimez-Ordaz J, Castañeda-Ovando A, Añorve-Morga J, Calderón-Ramos ZG, Arias-Rico J, González-Olivares LG. Impact of the Gut Microbiota Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics. Foods 2021; 10:1261. [PMID: 34199351 PMCID: PMC8230287 DOI: 10.3390/foods10061261] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/25/2021] [Accepted: 05/29/2021] [Indexed: 02/07/2023] Open
Abstract
Gut microbiota is a group of microorganisms that are deposited throughout the entire gastrointestinal tract. Currently, thanks to genomic tools, studies of gut microbiota have pointed towards the understanding of the metabolism of important bacteria that are not cultivable and their relationship with human homeostasis. Alterations in the composition of gut microbiota could explain, at least in part, some epidemics, such as diabetes and obesity. Likewise, dysbiosis has been associated with gastrointestinal disorders, neurodegenerative diseases, and even cancer. That is why several studies have recently been focused on the direct relationship that these types of conditions have with the specific composition of gut microbiota, as in the case of the microbiota-intestine-brain axis. In the same way, the control of microbiota is related to the diet. Therefore, this review highlights the importance of gut microbiota, from its composition to its relationship with the human health-disease condition, as well as emphasizes the effect of probiotic and prebiotic consumption on the balance of its composition.
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Affiliation(s)
- Laura-Berenice Olvera-Rosales
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Alma-Elizabeth Cruz-Guerrero
- Departamento de Biotecnología, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Iztapalapa, Av. San Rafael Atlixco 186, Ciudad de Mexico 09340, Mexico
| | - Esther Ramírez-Moreno
- Área Académica de Nutrición, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Ex Hacienda, La Concepción S/N, Carretera Pachuca Actopan, San Agustín Tlaxiaca 42060, Hidalgo, Mexico; (E.R.-M.); (Z.-G.C.-R.)
| | - Aurora Quintero-Lira
- Área Académica de Ingeniería Agroindustrial e Ingeniería en alimentos, Instituto de Ciencias Agropecuarias, Universidad Autónoma del Estado de Hidalgo, Av. Universidad km. 1, Ex-Hacienda de Aquetzalpa, Tulancingo 43600, Hidalgo, Mexico;
| | - Elizabeth Contreras-López
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Judith Jaimez-Ordaz
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Araceli Castañeda-Ovando
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Javier Añorve-Morga
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Zuli-Guadalupe Calderón-Ramos
- Área Académica de Nutrición, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Ex Hacienda, La Concepción S/N, Carretera Pachuca Actopan, San Agustín Tlaxiaca 42060, Hidalgo, Mexico; (E.R.-M.); (Z.-G.C.-R.)
| | - José Arias-Rico
- Área Académica de Enfermería, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Ex Hacienda, La Concepción S/N, Carretera Pachuca Actopan, San Agustín Tlaxiaca 42060, Hidalgo, Mexico;
| | - Luis-Guillermo González-Olivares
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
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Fathi M, Pustokhina I, Kuznetsov SV, Khayrullin M, Hojjat-Farsangi M, Karpisheh V, Jalili A, Jadidi-Niaragh F. T-cell immunoglobulin and ITIM domain, as a potential immune checkpoint target for immunotherapy of colorectal cancer. IUBMB Life 2021; 73:726-738. [PMID: 33686787 DOI: 10.1002/iub.2461] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/31/2021] [Accepted: 03/02/2021] [Indexed: 12/24/2022]
Abstract
The importance of the tumor microenvironment in cancer progression has been well studied for many years. Immune checkpoint inhibitors (ICIs) are regarded as potential strategies in enhancing the immune responses in patients with cancer, particularly colorectal cancer (CRC). Notably, CRCs are extraordinarily heterogeneous and mostly are microsatellite-stable (MSS) or cold tumors, which means that the immune response is not usually as strong as that of foreign cells. T-cell immunoglobulin and ITIM domain (TIGIT) is a new immune checkpoint receptor overexpressed inside the CRC tumor-immune microenvironments. Moreover, several studies have shown that TIGIT in combination with other ICIs and/or conventional treatments, can lead to a robust anti-tumor response in CRC. This review looks deep inside TIGIT expression patterns, their various functions, and possible immunotherapy strategies to increase survival rates and decrease immune-related adverse events.
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Affiliation(s)
- Mehrdad Fathi
- Cancer and Immunology Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | | | - Sergey V Kuznetsov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Mars Khayrullin
- Department of Research Management, K.G. Razumovsky Moscow State, University of Technologies and Management (The First Cossack University), Moscow, Russian Federation
| | | | - Vahid Karpisheh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Jalili
- Cancer and Immunology Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Farhad Jadidi-Niaragh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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The Western Dietary Pattern Combined with Vancomycin-Mediated Changes to the Gut Microbiome Exacerbates Colitis Severity and Colon Tumorigenesis. Nutrients 2021; 13:nu13030881. [PMID: 33803094 PMCID: PMC8000903 DOI: 10.3390/nu13030881] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/01/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023] Open
Abstract
Previous work by our group using a mouse model of inflammation-associated colorectal cancer (CAC) showed that the total Western diet (TWD) promoted colon tumor development. Others have also shown that vancomycin-mediated changes to the gut microbiome increased colorectal cancer (CRC). Therefore, the objective of this study was to determine the impact of vancomycin on colon tumorigenesis in the context of a standard mouse diet or the TWD. A 2 × 2 factorial design was used, in which C57Bl/6J mice were fed either the standard AIN93G diet or TWD and with vancomycin in the drinking water or not. While both the TWD and vancomycin treatments independently increased parameters associated with gut inflammation and tumorigenesis compared to AIN93G and plain water controls, mice fed the TWD and treated with vancomycin had significantly increased tumor multiplicity and burden relative to all other treatments. Vancomycin treatment significantly decreased alpha diversity and changed the abundance of several taxa at the phylum, family, and genus levels. Conversely, basal diet had relatively minor effects on the gut microbiome composition. These results support our previous research that the TWD promotes colon tumorigenesis and suggest that vancomycin-induced changes to the gut microbiome are associated with higher tumor rates.
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Na E, Moon KH, Lim SY. The Effect of Stachy sieboldii MIQ. Supplementation on Modulating Gut Microflora and Cytokine Expression in Mice. Comb Chem High Throughput Screen 2021; 24:177-186. [PMID: 32538719 DOI: 10.2174/1386207323666200615143627] [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: 09/19/2019] [Revised: 04/07/2020] [Accepted: 04/19/2020] [Indexed: 11/22/2022]
Abstract
AIMS AND OBJECTIVES The intake of Stachys sieboldii MIQ. has been associated with relieving inflammation and maintaining optimal gut health function. We investigated the diversity and composition of microflora in feces of S. sieboldii MIQ.-fed mice. In addition, we evaluated the production of major cytokines (Interleukin-6 and -10) related to inflammation and fatty acid composition of several tissues. MATERIALS AND METHODS 16S ribosomal DNA sequencing-based microbiome taxonomic profiling analysis was performed using EzBioCloud data base. The total RNA from the mesenteric lymph node was isolated and then synthesized with prime script 1st strand cDNA synthesis kit. Quantitative real-time PCR was performed on cDNA samples using the SYBR™ Green PCR Master Mix. RESULTS Mice fed on S. sieboldii MIQ. showed significantly reduced counts of aerobic and coliform in the feces compared with control. 16S rDNA sequencing analysis of fecal samples showed that supplementation with S. sieboldii MIQ. increased beneficial intestinal microflora (Ruminococcaceae and Akkermansia muciniphila) and decreased the community of harmful microflora (Enterobacteriaceae, including Escherichia coli and Bacteroides sp.) in feces compared with that in the control (P<0.05 for all). Mice showed a significantly lower mRNA expression of cytokines IL-6 and IL-10 in mesenteric lymph node compared with that in control (P<0.05). The fecal fatty acid composition in the S. sieboldii MIQ. group showed a higher percentage of 6:0 and 18:2n-6 compared with that in the control group (P<0.05). The percentages of 6:0 and 20:3n-6 fatty acids were also significantly higher in the intestines of S. sieboldii MIQ. group (P<0.05). No differences were revealed between the two groups in terms of the percentages of total saturated, monounsaturated, n-6 and n-3 polyunsaturated fatty acids found in feces and tissues. CONCLUSION The present results showed that supplementation of mice with S. sieboldii MIQ. increased beneficial gut microflora and decreased harmful microflora. Moreover, lower mRNA expression of pro-inflammatory cytokine IL-6, and anti-inflammatory cytokine IL-10 in the mesenteric lymph node of supplemented mice might be associated with the lower abundances of harmful fecal microflora.
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Affiliation(s)
- Eun Na
- Ocean Science and Technology School, Korea Maritime & Ocean University, Busan, 49112, Korea
| | - Ki Hwan Moon
- Division of Marine Bioscience, Korea Maritime & Ocean University, Busan, 49112, Korea
| | - Sun Young Lim
- Division of Marine Bioscience, Korea Maritime & Ocean University, Busan, 49112, Korea
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Wu G, Zhao N, Zhang C, Lam YY, Zhao L. Guild-based analysis for understanding gut microbiome in human health and diseases. Genome Med 2021; 13:22. [PMID: 33563315 PMCID: PMC7874449 DOI: 10.1186/s13073-021-00840-y] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 01/26/2021] [Indexed: 12/14/2022] Open
Abstract
To demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem's higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same "guild" if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of "guild" to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.
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Affiliation(s)
- Guojun Wu
- Center for Nutrition, Microbiome and Health, New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ, USA
- Rutgers-Jiaotong Joint Laboratory for Microbiome and Human Health, New Brunswick, NJ, USA
| | - Naisi Zhao
- Center for Nutrition, Microbiome and Health, New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA
- Department of Public Health and Community Medicine, School of Medicine, Tufts University, Medford, MA, USA
| | - Chenhong Zhang
- Rutgers-Jiaotong Joint Laboratory for Microbiome and Human Health, New Brunswick, NJ, USA
- State Key Laboratory of Microbial Metabolism, Ministry of Education Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Y Lam
- Center for Nutrition, Microbiome and Health, New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ, USA
- Rutgers-Jiaotong Joint Laboratory for Microbiome and Human Health, New Brunswick, NJ, USA
| | - Liping Zhao
- Center for Nutrition, Microbiome and Health, New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA.
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ, USA.
- Rutgers-Jiaotong Joint Laboratory for Microbiome and Human Health, New Brunswick, NJ, USA.
- State Key Laboratory of Microbial Metabolism, Ministry of Education Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
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Liu K, Yang X, Zeng M, Yuan Y, Sun J, He P, Sun J, Xie Q, Chang X, Zhang S, Chen X, Cai L, Xie Y, Jiao X. The Role of Fecal Fusobacterium nucleatum and pks+ Escherichia coli as Early Diagnostic Markers of Colorectal Cancer. DISEASE MARKERS 2021; 2021:1171239. [PMID: 34853619 PMCID: PMC8629656 DOI: 10.1155/2021/1171239] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/21/2021] [Accepted: 11/02/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Accurate analysis of intestinal microbiota will facilitate establishment of an evaluating system for assessing colorectal cancer (CRC) risk and prognosis. This study evaluates the potential role of Fusobacterium nucleatum (F. nucleatum) and Escherichia coli with a pks gene (pks+ E. coli) in early CRC diagnosis. METHODS We recruited 139 patients, including CRC (n = 60), colorectal adenomatous polyposis (CAP) (n = 37), and healthy individuals (n = 42) based on their colonoscopy examinations. We collected stool and serum samples from the participants and measured the relative abundance of F. nucleatum and pks+ E. coli in fecal samples by quantitative PCR. Receiver operating characteristic curve (ROC) analyses were used to analyze the diagnostic value of single or combined biomarkers. RESULTS Fecal F. nucleatum and pks+ E. coli levels were higher in the CRC group in either the CAP group or healthy controls (P = 0.02; 0.01). There was no statistical difference in the distribution of F. nucleatum and pks+ E. coli in patients with different tumor sites (P > 0.05). The combination of F. nucleatum+pks+ E. coli+CEA+CA19-9+FOBT was chosen as the optimal panel in differentiating both CRC and CAP from the controls. The combination of F. nucleatum, pks+ E. coli, and FOBT improved diagnostic efficiency. However, there was difficulty in differentiating CRC from CAP. CONCLUSION Our results suggested that combining bacterial markers with conventional tumor markers improves the diagnostic efficiency for noninvasive diagnosis of CRC.
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Affiliation(s)
- Kaixi Liu
- Departments of Clinical Laboratory, Shantou Central Hospital, Shantou, China
| | - Xinran Yang
- Departments of Clinical Laboratory, The First Affiliated Hospital of Shantou University Medical College, China
| | - Mi Zeng
- Medical College of Shantou University, Shantou, China
| | - Yumeng Yuan
- Medical College of Shantou University, Shantou, China
| | - Jianhong Sun
- Departments of Clinical Pathology, Shantou Central Hospital, Shantou, China
| | - Ping He
- Medical College of Shantou University, Shantou, China
| | - Jiayu Sun
- Medical College of Shantou University, Shantou, China
| | - Qingdong Xie
- Medical College of Shantou University, Shantou, China
| | - Xiaolan Chang
- Medical College of Shantou University, Shantou, China
| | - Suwei Zhang
- Departments of Clinical Laboratory, Shantou Central Hospital, Shantou, China
| | - Xiang Chen
- Departments of Health Care Center, The First Affiliated Hospital of Shantou University Medical College, China
| | - Leshan Cai
- Departments of Clinical Laboratory, The First Affiliated Hospital of Shantou University Medical College, China
| | - Yanxuan Xie
- Departments of Clinical Laboratory, The First Affiliated Hospital of Shantou University Medical College, China
| | - Xiaoyang Jiao
- Medical College of Shantou University, Shantou, China
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The Protective Role of Probiotics against Colorectal Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:8884583. [PMID: 33488940 PMCID: PMC7803265 DOI: 10.1155/2020/8884583] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/02/2020] [Accepted: 11/26/2020] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide and a major global public health problem. With the rapid development of the economy, the incidence of CRC has increased linearly. Accumulating evidence indicates that changes in the gut microenvironment, such as undesirable changes in the microbiota composition, provide favorable conditions for intestinal inflammation and shaping the tumor growth environment, whereas administration of certain probiotics can reverse this situation to a certain extent. This review summarizes the roles of probiotics in the regulation of CRC, such as enhancing the immune barrier, regulating the intestinal immune state, inhibiting pathogenic enzyme activity, regulating CRC cell proliferation and apoptosis, regulating redox homeostasis, and reprograming intestinal microbial composition. Abundant studies have provided a theoretical foundation for the roles of probiotics in CRC prevention and treatment, but their mechanisms of action remain to be investigated, and further clinical trials are warranted for the application of probiotics in the target population.
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Zhang X, Hoffman KL, Wei P, Elhor Gbito KY, Joseph R, Li F, Scheet P, Chang S, Petrosino JF, Daniel CR. Baseline Oral Microbiome and All-cancer Incidence in a Cohort of Nonsmoking Mexican American Women. Cancer Prev Res (Phila) 2020; 14:383-392. [PMID: 33277317 DOI: 10.1158/1940-6207.capr-20-0405] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 10/12/2020] [Accepted: 11/18/2020] [Indexed: 12/15/2022]
Abstract
Given the increasing evidence that the oral microbiome is involved in obesity, diabetes, and cancer risk, we investigated baseline oral microbiota profiles in relation to all-cancer incidence among nonsmoking women enrolled in a Texas cohort of first- and second-generation immigrants of Mexican origin. We characterized the 16Sv4 rDNA microbiome in oral mouthwash samples collected at baseline from a representative subset of 305 nonsmoking women, ages 20-75 years. We evaluated within- (alpha) and between-sample (beta) diversity by incident cancer status and applied linear discriminant analysis (LDA) effect size analysis to assess differentially abundant taxa. Diversity and candidate taxa in relation to all-cancer incidence were evaluated in multivariable-adjusted Cox regression models. Over 8.8 median years of follow-up, 31 incident cancer cases were identified and verified. Advanced age, greater acculturation, and cardiometabolic risk factors were associated with all-cancer incidence. Higher alpha diversity (age-adjusted P difference < 0.01) and distinct biological communities (P difference = 0.002) were observed by incident cancer status. Each unit increase in the Shannon diversity index yielded >8-fold increase in all-cancer and obesity-related cancer risk [multivariable-adjusted HR (95% confidence interval), 8.11 (3.14-20.94) and 10.72 (3.30-34.84), respectively] with similar findings for the inverse Simpson index. Streptococcus was enriched among women who did not develop cancer, while Fusobacterium, Prevotella, Mogibacterium, Campylobacter, Lachnoanaerobaculum, Dialister, and Atopobium were higher among women who developed cancer (LDA score ≥ 3; q-value < 0.01). This initial study of oral microbiota and overall cancer risk in nonsmoking Mexican American women suggests the readily accessible oral microbiota as a promising biomarker. PREVENTION RELEVANCE: Mexican American women suffer a disproportionate burden of chronic health conditions that increase cancer risk. Few investigations of the microbiome, a key determinant of host health, have been conducted among this group. Oral microbiota profiles may provide early and accessible cancer biomarker data on invasive bacteria or community disruptions.
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Affiliation(s)
- Xiaotao Zhang
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.,Dan L Duncan Comprehensive Cancer Center, Epidemiology & Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Kristi L Hoffman
- Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas
| | - Peng Wei
- Division of Cancer Prevention and Population Sciences, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kplola Y Elhor Gbito
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Reji Joseph
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Fangyu Li
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Paul Scheet
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Shine Chang
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Joseph F Petrosino
- Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas
| | - Carrie R Daniel
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Jiang Y, Liao H, Zhang X, Cao S, Hu X, Yang Z, Fang Y, Wang H. IL-33 synergistically promotes the proliferation of lung cancer cells in vitro by inducing antibacterial peptide LL-37 and proinflammatory cytokines in macrophages. Immunobiology 2020; 225:152025. [PMID: 33190003 DOI: 10.1016/j.imbio.2020.152025] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 08/30/2020] [Accepted: 10/18/2020] [Indexed: 02/07/2023]
Abstract
Lung cancer is the primary cause of cancer-related deaths, and the persistent inflammation is inextricably linked with the lung cancer tumorigenesis. Pro-inflammatory cytokine interleukin-33 (IL-33) is able to serve as a potent modulator of cancer. Mounting evidence indicates IL-33 has significant effect on lung cancer progression by regulating host immune response, but the current opinions about the function and mechanism of IL-33 in lung cancer are still controversial. Meanwhile, antibacterial peptide LL-37 also exerts a momentous effect on immune responses to lung cancer. LL-37 is regarded as versatile, including antimicrobial activities, chemotaxis and immunoregulation. However, the immunomodulatory mechanism of IL-33 and LL-37 in lung cancer remains thoroughly not defined. Here, we determined the secretion of LL-37 was up-regulated in lung cancer serum samples. Similarly, the expression of CRAMP was enhancive in macrophages after co-cultured with lung cancer cells. Moreover, we expounded that IL-33 could up-regulate LL-37 secretion in macrophages, resulting in the massive releases of IL-6 and IL-1β. Additionally, LL-37 cooperated with IL-33 to increase the phosphorylation of p38 MAPK and NF-κB p65 pathways, and augmented IL-6 and IL-1β secretion, which resulting in the proliferation of lung cancer cells in vitro. In conclusion, our study identified that IL-33 aggravated the inflammation of lung cancer by increasing LL-37 expression in macrophages, thereby promoting lung cancer cell proliferation in vitro. It is contributed to our present understanding of the immunomodulatory relationship between pro-inflammatory cytokines and antibacterial peptides in the tumor immune response, and offer a novel perspective for controlling the progress of lung cancer.
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Affiliation(s)
- Yinting Jiang
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Hongyi Liao
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; Department of Clinical Laboratory Medicine, Yongchuan Hospital, Chongqing Medical University, Chongqing, China
| | - Xuemei Zhang
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Sijia Cao
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Xuexue Hu
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Zihan Yang
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Yuting Fang
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Hong Wang
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
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