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Dey S, Ghosh M, Dev A. Signalling and molecular pathways, overexpressed receptors of colorectal cancer and effective therapeutic targeting using biogenic silver nanoparticles. Gene 2025; 936:149099. [PMID: 39557372 DOI: 10.1016/j.gene.2024.149099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 10/18/2024] [Accepted: 11/13/2024] [Indexed: 11/20/2024]
Abstract
Increasing morbidity and mortality in CRC is a potential threat to human health. The major challenges for better treatment outcomes are the heterogeneity of CRC cases, complicated molecular pathway cross-talks, the influence of gut dysbiosis in CRC, and the lack of multimodal target-specific drug delivery. The overexpression of many receptors in CRC cells may pave the path for targeting them with multiple ligands. The design of a more target-specific drug-delivery device with multiple ligand-functionalized, green-synthesized silver nanoparticles is highly promising and may also deliver other approved chemotherapeutic agents. This review presents the various aspects of colorectal cancer and over-expressed receptors that can be targeted with appropriate ligands to enhance the specific drug delivery potency of green synthesised silver nanoparticles. This review aims to broaden further research into this multi-ligand functionalised, safer and effective silver nano drug delivery system.
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Affiliation(s)
- Sandip Dey
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Jharkhand, India
| | - Manik Ghosh
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Jharkhand, India
| | - Abhimanyu Dev
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Jharkhand, India.
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2
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Feizi H, Kafil HS, Plotnikov A, Kataev V, Balkin A, Filonchikova E, Rezaee MA, Ghotaslou R, Sadrkabir M, Kadkhoda H, Kamounah FS, Nikitin S. Polyp and tumor microenvironment reprogramming in colorectal cancer: insights from mucosal bacteriome and metabolite crosstalk. Ann Clin Microbiol Antimicrob 2025; 24:9. [PMID: 39881353 PMCID: PMC11780822 DOI: 10.1186/s12941-025-00777-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 01/20/2025] [Indexed: 01/31/2025] Open
Abstract
BACKGROUND Highly frequent colorectal cancer (CRC) is predicted to have 3.2 million novel cases by 2040. Tumor microenvironment (TME) bacteriome and metabolites are proposed to be involved in CRC development. In this regard, we aimed to investigate the bacteriome and metabolites of healthy, adenomatous polyp, and CRC tissues. METHODS Sixty samples including healthy (H), adenomatous polyps (AP), adenomatous polyps-adjacent (APA), cancer tumor (CT), and cancer tumor-adjacent (CA) tissues were collected and analyzed by 16 S rRNA sequencing and 1H NMR spectroscopy. RESULTS Our results revealed that the bacteriome and metabolites of the H, AP, and CT groups were significantly different. We observed that the Lachnospiraceae family depleted concomitant with acetoacetate and beta-hydroxybutyric acid (BHB) accumulations in the AP tissues. In addition, some bacterial species including Gemella morbillorum, and Morganella morganii were enriched in the AP compared to the H group. Furthermore, fumarate was accumulated concomitant to Aeromonas enteropelogenes, Aeromonas veronii, and Fusobacterium nucleatum subsp. animalis increased abundance in the CT compared to the H group. CONCLUSION These results proposed that beneficial bacteria including the Lachnospiraceae family depletion cross-talk with acetoacetate and BHB accumulations followed by an increased abundance of driver bacteria including G. morbillorum, and M. morganii may reprogram polyp microenvironment leading to tumor initiation. Consequently, passenger bacteria accumulation like A. enteropelogenes, A.veronii, and F. nucleatum subsp. animalis cross-talking fumarate in the TME may aggravate cancer development. So, knowledge of TME bacteriome and metabolites might help in cancer prevention, early diagnosis, and a good prognosis.
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Affiliation(s)
- Hadi Feizi
- Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Microbiology, Aalinasab Hospital, Social Security Organization, Tabriz, Iran
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Andrey Plotnikov
- Institute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Vladimir Kataev
- Institute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Alexander Balkin
- Institute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Ekaterina Filonchikova
- Institute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Mohammad Ahangarzadeh Rezaee
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Ghotaslou
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Sadrkabir
- Department of Internal Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Hiva Kadkhoda
- Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Mahabad Faculty of Medical Sciences, , Urmia University of Medical Sciences, Urmia, Iran
| | - Fadhil S Kamounah
- Department of Chemistry, University of Copenhagen, Copenhagen, Denmark
| | - Sergei Nikitin
- Department of Science and Environment, Roskilde University, Roskilde, Denmark
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Cheng M, Liu J, Liang Y, Xu J, Ma L, Liang J. Tissue-Resident Memory T Cells in Tumor Immunity and Immunotherapy of Digestive System Tumors. Immunol Invest 2025:1-22. [PMID: 39840686 DOI: 10.1080/08820139.2024.2447780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
Background: Tissue-resident memory T (TRM) cells possess unique abilities to migrate, establish themselves in tissues, and monitor peripheral tissues without circulating. They are crucial in providing long-lasting and local immune protection against surface infections. TRMs demonstrate distinct phenotypic and functional characteristics compared to central memory T (Tcm) cells and effector memory T (Tem) cells.Methods: We reviewed a large number of literature to explore the physiological and functional roles of tissue-resident memory T cells, as well as the link between TRM cells and the development and prognosis of digestive tract tumors. We also investigated the association between TRM cells, intestinal flora, and metabolites.Results: Recent studies have implicated TRMs in the immune response against tumors, making them a potential target for cancer therapy. However, research specifically focused on gastrointestinal tumors is limited.Conclusion: This review aims to compile and assess the most recent data on the role of TRM cells in gastrointestinal tumor immunity. Additionally, it explores recent advancements in immunotherapy and investigates how TRMs may influence intestinal flora and metabolites.
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Affiliation(s)
- Min Cheng
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, China
| | - Jie Liu
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Yue Liang
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of General Surgery (Breast Surgery), The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, China
| | - Jiamei Xu
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, China
| | - Lin Ma
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, China
| | - Jing Liang
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, China
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Aspesi A, La Vecchia M, Sala G, Ghelardi E, Dianzani I. Study of Microbiota Associated to Early Tumors Can Shed Light on Colon Carcinogenesis. Int J Mol Sci 2024; 25:13308. [PMID: 39769073 PMCID: PMC11677268 DOI: 10.3390/ijms252413308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 12/04/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
An increasingly important role for gut microbiota in the initiation and progression of colorectal cancer (CRC) has been described. Even in the early stages of transformation, i.e., colorectal adenomas, changes in gut microbiota composition have been observed, and several bacterial species, such as pks+Escherichia coli and enterotoxigenic Bacteroides fragilis, have been proposed to drive colon tumorigenesis. In recent years, several strategies have been developed to study mucosa-associated microbiota (MAM), which is more closely associated with CRC development than lumen-associated microbiota (LAM) derived from fecal samples. This review summarizes the state of the art about the oncogenic actions of gut bacteria and compares the different sampling strategies to collect intestinal microbiota (feces, biopsies, swabs, brushes, and washing aspirates). In particular, this article recapitulates the current knowledge on MAM in colorectal adenomas and serrated polyps, since studying the intestinal microbiota associated with early-stage tumors can elucidate the molecular mechanisms underpinning CRC carcinogenesis.
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Affiliation(s)
- Anna Aspesi
- Department of Health Sciences, Università Del Piemonte Orientale, 28100 Novara, Italy; (A.A.); (M.L.V.); (G.S.)
| | - Marta La Vecchia
- Department of Health Sciences, Università Del Piemonte Orientale, 28100 Novara, Italy; (A.A.); (M.L.V.); (G.S.)
| | - Gloria Sala
- Department of Health Sciences, Università Del Piemonte Orientale, 28100 Novara, Italy; (A.A.); (M.L.V.); (G.S.)
| | - Emilia Ghelardi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56123 Pisa, Italy;
| | - Irma Dianzani
- Department of Health Sciences, Università Del Piemonte Orientale, 28100 Novara, Italy; (A.A.); (M.L.V.); (G.S.)
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Sahin S, Gundogdu A, Nalbantoglu U, Karaca Z, Hacioglu A, Urhan ME, Unluhizarci K, Hora M, Tanrıverdi ES, Durcan E, Elbüken G, Dokmetas HS, Zuhur SS, Tanriover N, Türe U, Kelestimur F, Kadioglu P. The comprehensive evaluation of oral and fecal microbiota in patients with acromegaly. Pituitary 2024; 27:555-566. [PMID: 39158810 DOI: 10.1007/s11102-024-01444-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/05/2024] [Indexed: 08/20/2024]
Abstract
PURPOSE The alteration of the microbiota in the mouth and gut could potentially play a role in the pathogenesis of various diseases, and conversely, these diseases may have an influence on the composition of the gut microbiota. Acromegaly disease can potentially affect physiological processes in the mouth and gut. The present study was designed to investigate the relationship between acromegaly and the oral and gut microbiota, as data on this topic are scarce. METHODS This was a multicenter, cross-sectional study. Our study included individuals diagnosed with acromegaly (who were treated and followed up, and also as an another group of patients with newly diagnosed acromegaly) and healthy participants. All three groups were assessed and compared based on age, sex, serum IGF-1, body mass index BMI as well as their stool and oral microbiota We collected demographic information from the patients, collected fecal and oral samples, performed DNA isolation followed by 16 S rRNA sequencing, and then performed bioinformatic analysis. We also analyzed the oral and fecal samples with respect to medical and surgical treatment and disease control status, specific treatments received for acromegaly, presence of comorbidities, hypopituitarism status, presence of intestinal polyps. RESULTS One hundred and three patients with acromegaly, 15 newly diagnosed patients with acromegaly without comorbidities and 34 healthy controls were included in the study. The Firmicutes/Bacteroidetes ratio was significantly lower in patients with acromegaly who received treatment (medical and/or surgical) than in healthy controls. In addition, a significant difference was found in the fecal and oral microbiota of patients with acromegaly with disease control compared to healthy controls. Furthermore, a significant difference was found in the fecal and oral microbiota of patients with acromegaly without disease control. Nevertheless, it was not possible to establish a clear relationship between disease control status, the presence of intestinal polyps, the presence of type 2 diabetes and the composition of the oral and gut microbiota in acromegalic patients who had received different forms of treatment. CONCLUSION Patients with acromegaly show distinct gut microbiota profiles, and it is evident that factors beyond the GH/IGF-1 axis play a role in shaping the gut microbiota of individuals with acromegaly.
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Affiliation(s)
- Serdar Sahin
- Department of Endocrinology and Metabolic Diseases, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Aycan Gundogdu
- Department of Microbiology and Clinical Microbiology, School of Medicine, Erciyes University, Kayseri, Turkey
- Genome and Stem Cell Center (GenKok), Erciyes University, Kayseri, Turkey
| | - Ufuk Nalbantoglu
- Genome and Stem Cell Center (GenKok), Erciyes University, Kayseri, Turkey
- Department of Computer Engineering, Erciyes University, Kayseri, Turkey
| | - Zuleyha Karaca
- Department of Endocrinology and Metabolic Diseases, School of Medicine, Erciyes University, Kayseri, Turkey
| | - Aysa Hacioglu
- Department of Endocrinology and Metabolic Diseases, School of Medicine, Erciyes University, Kayseri, Turkey
| | - Muhammed Emre Urhan
- Department of Endocrinology and Metabolic Diseases, School of Medicine, Erciyes University, Kayseri, Turkey
| | - Kursad Unluhizarci
- Department of Endocrinology and Metabolic Diseases, School of Medicine, Erciyes University, Kayseri, Turkey
| | - Mehmet Hora
- Genome and Stem Cell Center (GenKok), Erciyes University, Kayseri, Turkey
| | - Elif Seren Tanrıverdi
- Medical Microbiology Laboratory, Malatya Training and Research Hospital, Malatya, Turkey
| | - Emre Durcan
- Department of Endocrinology and Metabolic Diseases, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Gülsah Elbüken
- Department of Endocrinology and Metabolic Diseases, School of Medicine, Namik Kemal University, Tekirdag, Turkey
| | - Hatice Sebile Dokmetas
- Department of Endocrinology and Metabolic Diseases, University of Health Sciences, Cemil Tascıoğlu City Hospital, Istanbul, Turkey
| | - Sayid Shafi Zuhur
- Department of Endocrinology and Metabolic Diseases, School of Medicine, Namik Kemal University, Tekirdag, Turkey
| | - Necmettin Tanriover
- Department of Neurosurgery, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ugur Türe
- Department of Neurosurgery, School of Medicine, Yeditepe University, Istanbul, Turkey
| | - Fahrettin Kelestimur
- Department of Endocrinology and Metabolic Diseases, School of Medicine, Yeditepe University, Istanbul, Turkey
| | - Pinar Kadioglu
- Department of Endocrinology and Metabolic Diseases, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
- Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Endocrinology-Metabolism and Diabetes, Istanbul University - Cerrahpasa, Kocamustafapasa Street No:53, Fatih, Istanbul, 34098, Turkey.
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Kuru-Yaşar R, Üstün-Aytekin Ö. The Crucial Roles of Diet, Microbiota, and Postbiotics in Colorectal Cancer. Curr Nutr Rep 2024; 13:126-151. [PMID: 38483752 PMCID: PMC11133122 DOI: 10.1007/s13668-024-00525-z] [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] [Accepted: 02/25/2024] [Indexed: 05/30/2024]
Abstract
PURPOSE OF REVIEW Colorectal cancer is the second deadliest cancer in the world, and its prevalence has been increasing alarmingly in recent years. After researchers discovered the existence of dysbiosis in colorectal cancer, they considered the use of probiotics in the treatment of colorectal cancer. However, for various reasons, including the low safety profile of probiotics in susceptible and immunocompromised patient5s, and the risk of developing antibiotic resistance, researchers have shifted their focus to non-living cells, their components, and metabolites. This review aims to comprehensively evaluate the literature on the effects of diet, microbiota, and postbiotics on colorectal cancer and the future of postbiotics. RECENT FINDINGS The link between diet, gut microbiota, and colorectal cancer has been established primarily as a relationship rather than a cause-effect relationship. The gut microbiota can convert gastrointestinal tract and dietary factors into either onco-metabolites or tumor suppressor metabolites. There is serious dysbiosis in the microbiota in colorectal cancer. Postbiotics appear to be promising agents in the prevention and treatment of colorectal cancer. It has been shown that various postbiotics can selectively induce apoptosis in CRC, inhibit cell proliferation, growth, invasion, and migration, modulate the immune system, suppress carcinogenic signaling pathways, maintain intestinal epithelial integrity, and have a synergistic effect with chemotherapy drugs. However, it is also reported that some postbiotics are ineffective and may be risky in terms of safety profile in some patients. Many issues need to be researched about postbiotics. Large-scale, randomized, double-blind clinical studies are needed.
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Affiliation(s)
- Rüya Kuru-Yaşar
- Department of Nutrition and Dietetics, Hamidiye Faculty of Health Sciences, University of Health Sciences, 34668, Istanbul, Türkiye
| | - Özlem Üstün-Aytekin
- Department of Nutrition and Dietetics, Hamidiye Faculty of Health Sciences, University of Health Sciences, 34668, Istanbul, Türkiye.
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Jones AN, Scheurlen KM, Macleod A, Simon HL, Galandiuk S. Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer. Cancers (Basel) 2024; 16:1403. [PMID: 38611081 PMCID: PMC11010915 DOI: 10.3390/cancers16071403] [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: 02/23/2024] [Revised: 03/27/2024] [Accepted: 04/01/2024] [Indexed: 04/14/2024] Open
Abstract
Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including 'EOCRC', 'obesity', 'obesity-related hormones', 'itaconate', 'adiponectin', 'leptin', 'M2a macrophage', and 'microbiome'. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC.
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Affiliation(s)
- Alexandra N. Jones
- Price Institute of Surgical Research, University of Louisville, Louisville, KY 40202, USA; (A.N.J.); (A.M.); (H.L.S.)
| | - Katharina M. Scheurlen
- Price Institute of Surgical Research, University of Louisville, Louisville, KY 40202, USA; (A.N.J.); (A.M.); (H.L.S.)
| | - Anne Macleod
- Price Institute of Surgical Research, University of Louisville, Louisville, KY 40202, USA; (A.N.J.); (A.M.); (H.L.S.)
| | - Hillary L. Simon
- Price Institute of Surgical Research, University of Louisville, Louisville, KY 40202, USA; (A.N.J.); (A.M.); (H.L.S.)
- Division of Colon and Rectal Surgery, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, KY 40202, USA
| | - Susan Galandiuk
- Price Institute of Surgical Research, University of Louisville, Louisville, KY 40202, USA; (A.N.J.); (A.M.); (H.L.S.)
- Division of Colon and Rectal Surgery, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, KY 40202, USA
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Faghfuri E, Gholizadeh P. The role of Akkermansia muciniphila in colorectal cancer: A double-edged sword of treatment or disease progression? Biomed Pharmacother 2024; 173:116416. [PMID: 38471272 DOI: 10.1016/j.biopha.2024.116416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 03/04/2024] [Accepted: 03/06/2024] [Indexed: 03/14/2024] Open
Abstract
Colorectal cancer (CRC) is the second most cancer-related death worldwide. In recent years, probiotics have been used to reduce the potential risks of CRC and tumors with various mechanisms. Different bacteria have been suggested to play different roles in the progression, prevention, or treatment of CRC. Akkermansia muciniphila is considered a next-generation probiotic for preventing and treating some diseases. Therefore, in this review article, we aimed to describe and discuss different mechanisms of A. muciniphila as an intestinal microbiota or probiotic in CRC. Some studies suggested that the abundance of A. muciniphila was higher or increased in CRC patients compared to healthy individuals. However, the decreased abundance of A. muciniphila was associated with severe symptoms of CRC, indicating that A. muciniphila did not play a role in the development of CRC. In addition, A. muciniphila administration elevates gene expression of proliferation-associated molecules such as S100A9, Dbf4, and Snrpd1, or markers for cell proliferation. Some other studies suggested that inflammation and tumorigenesis in the intestine might promoted by A. muciniphila. Overall, the role of A. muciniphila in CRC development or inhibition is still unclear and controversial. Various methods of bacterial supplementation, such as viability, bacterial number, and abundance, could all influence the colonization effect of A. muciniphila administration and CRC progression. Overall, A. mucinipila has been revealed to modulate the therapeutic potential of immune checkpoint inhibitors. Preliminary human data propose that oral consumption of A. muciniphila is safe, but its efficacy needs to be confirmed in more human clinical studies.
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Affiliation(s)
- Elnaz Faghfuri
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Pourya Gholizadeh
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
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Yadav D, Sainatham C, Filippov E, Kanagala SG, Ishaq SM, Jayakrishnan T. Gut Microbiome-Colorectal Cancer Relationship. Microorganisms 2024; 12:484. [PMID: 38543535 PMCID: PMC10974515 DOI: 10.3390/microorganisms12030484] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 02/10/2024] [Accepted: 02/13/2024] [Indexed: 11/12/2024] Open
Abstract
Traditionally, the role of gut dysbiosis was thought to be limited to pathologies like Clostridioides difficile infection, but studies have shown its role in other intestinal and extraintestinal pathologies. Similarly, recent studies have surfaced showing the strong potential role of the gut microbiome in colorectal cancer, which was traditionally attributed mainly to sporadic or germline mutations. Given that it is the third most common cancer and the second most common cause of cancer-related mortality, 78 grants totaling more than USD 28 million have been granted to improve colon cancer management since 2019. Concerted efforts by several of these studies have identified specific bacterial consortia inducing a proinflammatory environment and promoting genotoxin production, causing the induction or progression of colorectal cancer. In addition, changes in the gut microbiome have also been shown to alter the response to cancer chemotherapy and immunotherapy, thus changing cancer prognosis. Certain bacteria have been identified as biomarkers to predict the efficacy of antineoplastic medications. Given these discoveries, efforts have been made to alter the gut microbiome to promote a favorable diversity to improve cancer progression and the response to therapy. In this review, we expand on the gut microbiome, its association with colorectal cancer, and antineoplastic medications. We also discuss the evolving paradigm of fecal microbiota transplantation in the context of colorectal cancer management.
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Affiliation(s)
- Devvrat Yadav
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Chiranjeevi Sainatham
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Evgenii Filippov
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Sai Gautham Kanagala
- Department of Internal Medicine, NYC Health + Hospital/Metropolitan, New York, NY 10029, USA
| | - Syed Murtaza Ishaq
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Thejus Jayakrishnan
- Division of Hematology and Oncology, Cleveland Clinic, Cleveland, OH 44195, USA
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Grosicki GJ, Langan SP, Bagley JR, Galpin AJ, Garner D, Hampton‐Marcell JT, Allen JM, Robinson AT. Gut check: Unveiling the influence of acute exercise on the gut microbiota. Exp Physiol 2023; 108:1466-1480. [PMID: 37702557 PMCID: PMC10988526 DOI: 10.1113/ep091446] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 09/04/2023] [Indexed: 09/14/2023]
Abstract
The human gastrointestinal microbiota and its unique metabolites regulate a diverse array of physiological processes with substantial implications for human health and performance. Chronic exercise training positively modulates the gut microbiota and its metabolic output. The benefits of chronic exercise for the gut microbiota may be influenced by acute changes in microbial community structure and function that follow a single exercise bout (i.e., acute exercise). Thus, an improved understanding of changes in the gut microbiota that occur with acute exercise could aid in the development of evidence-based exercise training strategies to target the gut microbiota more effectively. In this review, we provide a comprehensive summary of the existing literature on the acute and very short-term (<3 weeks) exercise responses of the gut microbiota and faecal metabolites in humans. We conclude by highlighting gaps in the literature and providing recommendations for future research in this area. NEW FINDINGS: What is the topic of this review? The chronic benefits of exercise for the gut microbiota are likely influenced by acute changes in microbial community structure and function that follow a single exercise bout. This review provides a summary of the existing literature on acute exercise responses of the gut microbiota and its metabolic output in humans. What advances does it highlight? Acute aerobic exercise appears to have limited effects on diversity of the gut microbiota, variable effects on specific microbial taxa, and numerous effects on the metabolic activity of gut microbes with possible implications for host health and performance.
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Affiliation(s)
| | - Sean P. Langan
- Korey Stringer Institute, Department of KinesiologyUniversity of ConnecticutStorrsCTUSA
| | - James R. Bagley
- Muscle Physiology LaboratorySan Francisco State UniversitySan FranciscoCAUSA
| | - Andrew J. Galpin
- Center for Sport PerformanceCalifornia State University, FullertonFullertonCAUSA
| | - Dan Garner
- BioMolecular Athlete, LLCWilmingtonDEUSA
| | | | - Jacob M. Allen
- Department of Kinesiology and Community HealthUniversity of Illinois at Urbana‐ChampaignUrbanaIL
| | - Austin T. Robinson
- Neurovascular Physiology Laboratory, School of KinesiologyAuburn UniversityAuburnALUSA
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Cantu-Jungles TM, Hamaker BR. Tuning Expectations to Reality: Don't Expect Increased Gut Microbiota Diversity with Dietary Fiber. J Nutr 2023; 153:3156-3163. [PMID: 37690780 DOI: 10.1016/j.tjnut.2023.09.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 09/01/2023] [Indexed: 09/12/2023] Open
Abstract
Dietary approaches, particularly those including fiber supplementation, can be used to promote health benefits by shaping gut microbial communities. Whereas community diversity measures, such as richness and evenness, are often used in microbial ecology to make sense of these complex and vast microbial ecosystems, it is less clear how these concepts apply when dietary fiber supplementation is given. In this perspective, we summarize and demonstrate how factors including experimental approach, number of bacteria sharing a dietary fiber, and initial relative abundances of bacteria that use a fiber can significantly affect diversity outcomes in fiber fermentation studies. We also show that a reduction in alpha diversity is possible, and perhaps expected, for most approaches that use fermentable fibers to beneficially shape the gut microbial community while still achieving health-related improvements.
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Affiliation(s)
- Thaisa M Cantu-Jungles
- Department of Food Science, Whistler Center for Carbohydrate Research, Purdue University, West Lafayette, IN, United States.
| | - Bruce R Hamaker
- Department of Food Science, Whistler Center for Carbohydrate Research, Purdue University, West Lafayette, IN, United States
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12
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Welham Z, Li J, Engel AF, Molloy MP. Mucosal Microbiome in Patients with Early Bowel Polyps: Inferences from Short-Read and Long-Read 16S rRNA Sequencing. Cancers (Basel) 2023; 15:5045. [PMID: 37894412 PMCID: PMC10605900 DOI: 10.3390/cancers15205045] [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: 09/08/2023] [Revised: 10/13/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with Ruminococcus gnavus and Escherichia coli were elevated in mucosa from polyp patients, while ASVs associated with Parabacteroides merdae, Veillonella nakazawae, and Sutterella wadsworthensis were relatively decreased. Only R. gnavus was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche.
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Affiliation(s)
- Zoe Welham
- Bowel Cancer and Biomarker Laboratory, School of Medical Sciences, The University of Sydney, Sydney 2065, Australia; (Z.W.); (J.L.)
| | - Jun Li
- Bowel Cancer and Biomarker Laboratory, School of Medical Sciences, The University of Sydney, Sydney 2065, Australia; (Z.W.); (J.L.)
| | - Alexander F. Engel
- Colorectal Surgical Unit, Royal North Shore Hospital, Sydney 2065, Australia;
- Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney 2050, Australia
| | - Mark P. Molloy
- Bowel Cancer and Biomarker Laboratory, School of Medical Sciences, The University of Sydney, Sydney 2065, Australia; (Z.W.); (J.L.)
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13
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Jahankhani K, Ahangari F, Adcock IM, Mortaz E. Possible cancer-causing capacity of COVID-19: Is SARS-CoV-2 an oncogenic agent? Biochimie 2023; 213:130-138. [PMID: 37230238 PMCID: PMC10202899 DOI: 10.1016/j.biochi.2023.05.014] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 04/24/2023] [Accepted: 05/22/2023] [Indexed: 05/27/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown diverse life-threatening effects, most of which are considered short-term. In addition to its short-term effects, which has claimed many millions of lives since 2019, the long-term complications of this virus are still under investigation. Similar to many oncogenic viruses, it has been hypothesized that SARS-CoV-2 employs various strategies to cause cancer in different organs. These include leveraging the renin angiotensin system, altering tumor suppressing pathways by means of its nonstructural proteins, and triggering inflammatory cascades by enhancing cytokine production in the form of a "cytokine storm" paving the way for the emergence of cancer stem cells in target organs. Since infection with SARS-CoV-2 occurs in several organs either directly or indirectly, it is expected that cancer stem cells may develop in multiple organs. Thus, we have reviewed the impact of coronavirus disease 2019 (COVID-19) on the vulnerability and susceptibility of specific organs to cancer development. It is important to note that the cancer-related effects of SARS-CoV-2 proposed in this article are based on the ability of the virus and its proteins to cause cancer but that the long-term consequences of this infection will only be illustrated in the long run.
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Affiliation(s)
- Kasra Jahankhani
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ahangari
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ian M Adcock
- Airways Disease, National Heart and Lung Institute, Imperial College London, London, United Kingdom; Immune Health Program at Hunter Medical Research Institute and the College of Health and Medicine at the University of Newcastle, Australia
| | - Esmaeil Mortaz
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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14
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Zhang L, Ji Q, Chen Q, Wei Z, Liu S, Zhang L, Zhang Y, Li Z, Liu H, Sui H. Akkermansia muciniphila inhibits tryptophan metabolism via the AhR/β-catenin signaling pathway to counter the progression of colorectal cancer. Int J Biol Sci 2023; 19:4393-4410. [PMID: 37781044 PMCID: PMC10535706 DOI: 10.7150/ijbs.85712] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 08/03/2023] [Indexed: 10/03/2023] Open
Abstract
Akkermansia muciniphila (A. muciniphila), a gram-negative anaerobic bacterium, is selectively decreased in the fecal microbiota of patients with colorectal cancer (CRC), but its molecular mechanism in CRC development remains inconclusive. In this study, we first confirmed the inhibitory effect of A. muciniphila on CRC formation and analyzed the metabolic role of intestinal flora in human Polyps, A-CRA (advanced colorectal adenoma) and CRC samples. To better clarify the role of A. muciniphila in CRC development, a pseudo-germ-free (GF) azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model was established, followed by infection with or without A. muciniphila. Metabolomic analysis and RNA-seq analysis showed tryptophan-mediated aryl hydrocarbon receptor (AhR) was significantly down-regulated in A. muciniphila-infected CRC mice. Then, mice with intestinal specific AhR deficiency (AhRfl/fl Cre) were generated and were used in 2 murine models: AOM/DSS treatment as a model of carcinogen-induced colon cancer and a genetically induced model using ApcMin/+ mice. Notably, AhR deficiency inhibited CRC growth in the AOM/DSS and ApcMin/+ mouse model. Moreover, AhR deficiency inhibited, rather than enhanced, tumor formation and tumor-derived organoids in Apc-deficient cells both in vivo and in vitro by activating Wnt/β-catenin signaling and TCF4/LEF1-dependent transcription. Furthermore, the antitumor effectiveness of A. muciniphila was abolished either in a human colon cancer tumor model induced by subcutaneous transplantation of AhR-silenced CRC cells, or AhR-deficienty spontaneous colorectal cancer model. In conclusion, supplementation with A. muciniphila. protected mice from CRC development by specifically inhibiting tryptophan-mediated AhR/β-catenin signaling.
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Affiliation(s)
- Lu Zhang
- Department of Combine Traditional Chinese & Western, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Qing Ji
- Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Qian Chen
- Department of critical care medicine, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, 450002, China
| | - Zhenzhen Wei
- Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
- Shanghai General Hospital Jiading Branch-Pharmacy school of Shanghai University of Traditional Chinese Medicine Joint Laboratory, Translational medicine Research Center for Cancer Prevention and Treatment, Shanghai 201803, China
| | - Shuochuan Liu
- Department of Breast disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Long Zhang
- University of Shanghai for Science and Technology and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Institute of Biomedical Sciences and Clinical Technology Transformation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Yuli Zhang
- Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
- Shanghai General Hospital Jiading Branch-Pharmacy school of Shanghai University of Traditional Chinese Medicine Joint Laboratory, Translational medicine Research Center for Cancer Prevention and Treatment, Shanghai 201803, China
| | - Zan Li
- Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
- Shanghai General Hospital Jiading Branch-Pharmacy school of Shanghai University of Traditional Chinese Medicine Joint Laboratory, Translational medicine Research Center for Cancer Prevention and Treatment, Shanghai 201803, China
| | - Huaimin Liu
- Department of Combine Traditional Chinese & Western, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Hua Sui
- Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
- Shanghai General Hospital Jiading Branch-Pharmacy school of Shanghai University of Traditional Chinese Medicine Joint Laboratory, Translational medicine Research Center for Cancer Prevention and Treatment, Shanghai 201803, China
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15
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Li X, Feng J, Wang Z, Liu G, Wang F. Features of combined gut bacteria and fungi from a Chinese cohort of colorectal cancer, colorectal adenoma, and post-operative patients. Front Microbiol 2023; 14:1236583. [PMID: 37614602 PMCID: PMC10443710 DOI: 10.3389/fmicb.2023.1236583] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 07/20/2023] [Indexed: 08/25/2023] Open
Abstract
Colorectal cancer (CRC) accounts for the third highest morbidity burden among malignant tumors worldwide. Previous studies investigated gut microbiome changes that occur during colorectal adenomas (CRA) progression to overt CRC, thus highlighting the importance of the gut microbiome in carcinogenesis. However, few studies have examined gut microbiome characteristics across the entire spectrum, from CRC development to treatment. The study used 16S ribosomal ribonucleic acid and internal transcribed spacer amplicon sequencing to compare the composition of gut bacteria and fungi in a Chinese cohort of healthy controls (HC), CRC patients, CRA patients, and CRC postoperative patients (PP). Our analysis showed that beta diversity was significantly different among the four groups based on the gut bacterial and fungal data. A total of 51 species of bacteria and 8 species of fungi were identified in the HC, CRA, CRC, and PP groups. Correlation networks for both the gut bacteria and fungi in HC vs. CRA, HC vs. CRC, and HC vs. PP indicated some hub bacterial and fungal genera in each model, and the correlation between bacterial and fungal data indicated that a highly significant negative correlation exists among groups. Quantitative polymerase chain reaction (qPCR) analysis in a large cohort of HC, CRC, CRA, and PP patients demonstrated a significantly increasing trend of Fusobacterium nucleatum, Bifidobacterium bifidum, Candida albicans, and Saccharomyces cerevisiae in the feces of CRC patients than that of HC patients (p < 0.01). However, the abundance levels of CRA and PP were significantly lower in HC patients than those in CRC patients. Further studies are required to identify the functional consequences of the altered bacterial/fungal composition on metabolism and CRC tumorigenesis in the host.
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Affiliation(s)
- Xiaopeng Li
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Radiation Oncology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Jiahui Feng
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Zhanggui Wang
- Department of Radiation Oncology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Gang Liu
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Fan Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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16
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Wang J, Chen G, Chen H, Chen J, Su Q, Zhuang W. Exploring the characteristics of gut microbiome in patients of Southern Fujian with hypocitraturia urolithiasis and constructing clinical diagnostic models. Int Urol Nephrol 2023:10.1007/s11255-023-03662-6. [PMID: 37294502 DOI: 10.1007/s11255-023-03662-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/04/2023] [Indexed: 06/10/2023]
Abstract
PURPOSE Hypocitraturia is an important cause of urolithiasis. Exploring the characteristics of the gut microbiome (GMB) of hypocitriuria urolithiasis (HCU) patients can provide new ideas for the treatment and prevention of urolithiasis. METHODS The 24 h urinary citric acid excretion of 19 urolithiasis patients was measured, and patients were divided into the HCU group and the normal citrate urolithiasis (NCU) group. The 16 s ribosomal RNA (rRNA) was used to detect GMB composition differences and construct operational taxonomic units (OTUs) coexistence networks. The key bacterial community was determined by Lefse analysis, Metastats analysis and RandomForest analysis. Redundancy analysis (RDA) and Pearson correlation analysis visualized the correlation between key OTUs and clinical features and then established the disease diagnosis model of microbial-clinical indicators. Finally, PICRUSt2 was used to explore the metabolic pathway of related GMB in HCU patients. RESULTS The alpha diversity of GMB in HCU group was increased and Beta diversity analysis suggested significant differences between HCU and NCU groups, which was related to renal function damage and urinary tract infection. Ruminococcaceae_ge and Turicibacter are the characteristic bacterial groups of HCU. Correlation analysis showed that the characteristic bacterial groups were significantly associated with various clinical features. Based on this, the diagnostic models of microbiome-clinical indicators in HCU patients were constructed with the areas under the curve (AUC) of 0.923 and 0.897, respectively. Genetic and metabolic processes of HCU are affected by changes in GMB abundance. CONCLUSION GMB disorder may be involved in the occurrence and clinical characteristics of HCU by influencing genetic and metabolic pathways. The new microbiome-clinical indicator diagnostic model is effective.
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Affiliation(s)
- Jialiang Wang
- Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Licheng District Zhongshan North Road, Quanzhou, 362000, Fujian, China
| | - Guofeng Chen
- Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Licheng District Zhongshan North Road, Quanzhou, 362000, Fujian, China
| | - Heyi Chen
- Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Licheng District Zhongshan North Road, Quanzhou, 362000, Fujian, China
| | - Jiabi Chen
- Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Licheng District Zhongshan North Road, Quanzhou, 362000, Fujian, China
| | - Qingfu Su
- Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Licheng District Zhongshan North Road, Quanzhou, 362000, Fujian, China.
| | - Wei Zhuang
- Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Licheng District Zhongshan North Road, Quanzhou, 362000, Fujian, China.
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17
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Watson KM, Gardner IH, Anand S, Siemens KN, Sharpton TJ, Kasschau KD, Dewey EN, Martindale R, Gaulke CA, Liana Tsikitis V. Colonic Microbial Abundances Predict Adenoma Formers. Ann Surg 2023; 277:e817-e824. [PMID: 35129506 PMCID: PMC9023594 DOI: 10.1097/sla.0000000000005261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation. SUMMARY BACKGROUND DATA Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions. METHODS Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, nonadenoma and adenoma-adjacent mucosa were collected along with clinical and dietary information. 16S rRNA gene libraries were generated using V4 primers. DADA2 processed sequence reads and custom R-scripts quantified microbial diversity. Linear regression identified differential taxonomy and diversity in microbial communities and machine learning identified adenoma former microbial signatures. RESULTS One hundred four subjects were included, 46% with adenomas. Mucosal and fecal samples were dominated by Firmicutes and Bacteroidetes whereas Firmicutes and Proteobacteria were most abundant in oral communities. Mucosal communities harbored significant microbial diversity that was not observed in fecal or oral communities. Random forest classifiers predicted adenoma formation using fecal, oral, and mucosal amplicon sequence variant (ASV) abundances. The mucosal classifier reliably diagnosed adenoma formation with an area under the curve (AUC) = 0.993 and an out-of-bag (OOB) error of 3.2%. Mucosal classifier accuracy was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. In contrast, classifiers built using fecal and oral samples manifested high OOB error rates (47.3% and 51.1%, respectively) and poor diagnostic abilities (fecal and oral AUC = 0.53). CONCLUSION Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation.
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Affiliation(s)
| | - Ivy H. Gardner
- Department of Surgery, Oregon Health & Science University, Portland, OR
| | - Sudarshan Anand
- Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR
| | - Kyla N. Siemens
- Department of Surgery, Oregon Health & Science University, Portland, OR
| | - Thomas J. Sharpton
- Department of Microbiology, Oregon State University, Corvallis, OR
- Department of Statistics, Oregon State University, Corvallis, OR
| | | | | | - Robert Martindale
- Department of Surgery, Oregon Health & Science University, Portland, OR
| | - Christopher A. Gaulke
- Department of Microbiology, Oregon State University, Corvallis, OR
- Department of Pathobiology, University of Illinois Urbana-Champaign, Urbana, IL
- Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL
| | - V. Liana Tsikitis
- Department of Surgery, Oregon Health & Science University, Portland, OR
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18
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Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease. Nutrients 2023; 15:nu15061338. [PMID: 36986068 PMCID: PMC10052649 DOI: 10.3390/nu15061338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/06/2023] [Accepted: 03/07/2023] [Indexed: 03/12/2023] Open
Abstract
Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter fecal microbiome composition when compared to mice fed a healthy diet, i.e., AIN93G (AIN). However, it is unclear whether the gut microbiome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from donor mice fed either the AIN basal diet or the TWD would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either the AIN diet or the TWD, using a 2 × 2 factorial experiment design. Time-matched FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet. Conversely, FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD. Likewise, the composition of fecal microbiomes of the recipient mice was also affected to a much greater extent by the diet they consumed than by the source of FMT. In summary, FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed. These observations suggest that the gut microbiome may not contribute directly to the development of disease in this animal model.
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Byrd DA, Vogtmann E, Ortega-Villa AM, Wan Y, Gomez M, Hogue S, Warner A, Zhu B, Dagnall C, Jones K, Hicks B, Albert PS, Murphy G, Sinha R. Prospective and Cross-sectional Associations of the Rectal Tissue Microbiome with Colorectal Adenoma Recurrence. Cancer Epidemiol Biomarkers Prev 2023; 32:435-443. [PMID: 36525653 PMCID: PMC9992132 DOI: 10.1158/1055-9965.epi-22-0608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 08/19/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The gut microbiome is plausibly associated with colorectal cancer risk; however, previous studies mostly investigated this association cross-sectionally. We investigated cross-sectional and prospective associations of the rectal tissue microbiome with adenoma recurrence in the Polyp Prevention Trial (PPT). METHODS PPT is a 4-year randomized clinical trial of the effect of a dietary intervention on adenoma recurrence among community members. We extracted DNA from rectal biopsies at baseline, end of year 1, and end of year 4 among 455 individuals and sequenced the V4 region of the 16S rRNA gene. At each timepoint, we investigated associations of alpha diversity, beta diversity, and presence and relative abundance of select taxa with adenoma recurrence using multivariable logistic regression. RESULTS Variation in beta diversity was primarily explained by subject and minimally by year of collection or time between biopsy and colonoscopy. Cross-sectionally, year 4 alpha diversity was strongly, inversely associated with adenoma prevalence [ORQ3 vs. Q1 Shannon index = 0.40 (95% confidence interval, CI: 0.21-0.76)]. Prospective alpha diversity associations (i.e., baseline/year 1 alpha diversity with adenoma recurrence 3-4 years later) were weak or null, as were cross-sectional and prospective beta diversity-adenoma associations. Bacteroides abundance was more strongly, positively associated with adenoma prevalence cross-sectionally than prospectively. CONCLUSIONS Rectal tissue microbiome profiles may be associated with prevalent adenomas, with little evidence supporting prospective associations. IMPACT Additional prospective studies, with serial fecal and tissue samples, to explore microbiome-colorectal cancer associations are needed. Eventually, it may be possible to use microbiome characteristics as intervenable risk factors or screening tools.
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Affiliation(s)
- Doratha A. Byrd
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
| | - Emily Vogtmann
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Ana M. Ortega-Villa
- Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA
| | - Yunhu Wan
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
| | - Maria Gomez
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
| | - Stephanie Hogue
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
| | - Andrew Warner
- Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
| | - Bin Zhu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
| | - Casey Dagnall
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
| | - Kristine Jones
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
| | - Belynda Hicks
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
| | - Paul S. Albert
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Gwen Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Rashmi Sinha
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
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20
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Valciukiene J, Strupas K, Poskus T. Tissue vs. Fecal-Derived Bacterial Dysbiosis in Precancerous Colorectal Lesions: A Systematic Review. Cancers (Basel) 2023; 15:1602. [PMID: 36900392 PMCID: PMC10000868 DOI: 10.3390/cancers15051602] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/19/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and fecal sampling in the setting of human gut microbiota examination. This study aimed to review the literature and to consolidate the current evidence on the use of mucosa and a stool-based matrix investigating human gut microbiota changes in precancerous colorectal lesions. A systematic review of papers from 2012 until November 2022 published on the PubMed and Web of Science databases was conducted. The majority of the included studies have significantly associated gut microbial dysbiosis with premalignant polyps in the colorectum. Although methodological differences hampered the precise fecal and tissue-derived dysbiosis comparison, the analysis revealed several common characteristics in stool-based and fecal-derived gut microbiota structures in patients with colorectal polyps: simple or advanced adenomas, serrated lesions, and carcinomas in situ. The mucosal samples considered were more relevant for the evaluation of microbiota's pathophysiological involvement in CR carcinogenesis, while non-invasive stool sampling could be beneficial for early CRC detection strategies in the future. Further studies are required to identify and validate mucosa-associated and luminal colorectal microbial patterns and their role in CRC carcinogenesis, as well as in the clinical setting of human microbiota studies.
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Affiliation(s)
- Jurate Valciukiene
- Clinic of Gastroenterology, Nephro-Urology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
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21
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El-Sayed A, Aleya L, Kamel M. Epigenetics and the role of nutraceuticals in health and disease. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:28480-28505. [PMID: 36694069 DOI: 10.1007/s11356-023-25236-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 01/05/2023] [Indexed: 06/17/2023]
Abstract
In the post-genomic era, the data provided by complete genome sequencing could not answer several fundamental questions about the causes of many noninfectious diseases, diagnostic biomarkers, and novel therapeutic approaches. The rapidly expanding understanding of epigenetic mechanisms, as well as widespread acceptance of their hypothesized role in disease induction, facilitated the development of a number of novel diagnostic markers and therapeutic concepts. Epigenetic aberrations are reversible in nature, which enables the treatment of serious incurable diseases. Therefore, the interest in epigenetic modulatory effects has increased over the last decade, so about 60,000 publications discussing the expression of epigenetics could be detected in the PubMed database. Out of these, 58,442 were published alone in the last 10 years, including 17,672 reviews (69 historical articles), 314 clinical trials, 202 case reports, 197 meta-analyses, 156 letters to the editor, 108 randomized controlled trials, 87 observation studies, 40 book chapters, 22 published lectures, and 2 clinical trial protocols. The remaining publications are either miscellaneous or a mixture of the previously mentioned items. According to the species and gender, the publications included 44,589 human studies (17,106 females, 14,509 males, and the gender is not mentioned in the remaining papers) and 30,253 animal studies. In the present work, the role of epigenetic modulations in health and disease and the influencing factors in epigenetics are discussed.
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Affiliation(s)
- Amr El-Sayed
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Lotfi Aleya
- Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, 25030, Besançon Cedex, France
| | - Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
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22
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Domingues C, Cabral C, Jarak I, Veiga F, Dourado M, Figueiras A. The Debate between the Human Microbiota and Immune System in Treating Aerodigestive and Digestive Tract Cancers: A Review. Vaccines (Basel) 2023; 11:vaccines11030492. [PMID: 36992076 DOI: 10.3390/vaccines11030492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/10/2023] [Accepted: 02/13/2023] [Indexed: 02/23/2023] Open
Abstract
The human microbiota comprises a group of microorganisms co-existing in the human body. Unbalanced microbiota homeostasis may impact metabolic and immune system regulation, shrinking the edge between health and disease. Recently, the microbiota has been considered a prominent extrinsic/intrinsic element of cancer development and a promising milestone in the modulation of conventional cancer treatments. Particularly, the oral cavity represents a yin-and-yang target site for microorganisms that can promote human health or contribute to oral cancer development, such as Fusobacterium nucleatum. Moreover, Helicobacter pylori has also been implicated in esophageal and stomach cancers, and decreased butyrate-producing bacteria, such as Lachnospiraceae spp. and Ruminococcaceae, have demonstrated a protective role in the development of colorectal cancer. Interestingly, prebiotics, e.g., polyphenols, probiotics (Faecalibacterium, Bifidobacterium, Lactobacillus, and Burkholderia), postbiotics (inosine, butyrate, and propionate), and innovative nanomedicines can modulate antitumor immunity, circumventing resistance to conventional treatments and could complement existing therapies. Therefore, this manuscript delivers a holistic perspective on the interaction between human microbiota and cancer development and treatment, particularly in aerodigestive and digestive cancers, focusing on applying prebiotics, probiotics, and nanomedicines to overcome some challenges in treating cancer.
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Affiliation(s)
- Cátia Domingues
- Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
- LAQV-REQUIMTE, Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
- Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Cristiana Cabral
- Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ivana Jarak
- Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Francisco Veiga
- Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
- LAQV-REQUIMTE, Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Marília Dourado
- Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Center for Health Studies and Research of the University of Coimbra (CEISUC), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- Center for Studies and Development of Continuous and Palliative Care (CEDCCP), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ana Figueiras
- Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
- LAQV-REQUIMTE, Laboratory of Drug Development and Technologies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
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23
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Long Y, Tang L, Zhou Y, Zhao S, Zhu H. Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study. BMC Med 2023; 21:66. [PMID: 36810112 PMCID: PMC9945666 DOI: 10.1186/s12916-023-02761-6] [Citation(s) in RCA: 178] [Impact Index Per Article: 89.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 01/30/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with cancer. However, the causal association between gut microbiota and cancer remains to be determined. METHODS We first identified two sets of gut microbiota based on phylum, class, order, family, and genus level information, and cancer data were obtained from the IEU Open GWAS project. We then performed two-sample Mendelian randomisation (MR) to determine whether the gut microbiota is causally associated with eight cancer types. Furthermore, we performed a bi-directional MR analysis to examine the direction of the causal relations. RESULTS We identified 11 causal relationships between genetic liability in the gut microbiome and cancer, including those involving the genus Bifidobacterium. We found 17 strong associations between genetic liability in the gut microbiome and cancer. Moreover, we found 24 associations between genetic liability in the gut microbiome and cancer using multiple datasets. CONCLUSIONS Our MR analysis revealed that the gut microbiota was causally associated with cancers and may be useful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cancer.
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Affiliation(s)
- Yiwen Long
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China
| | - Lanhua Tang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China
| | - Yangying Zhou
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China
| | - Shushan Zhao
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China. .,Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
| | - Hong Zhu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
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24
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Pandey H, Tang DWT, Wong SH, Lal D. Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities. Cancers (Basel) 2023; 15:cancers15030866. [PMID: 36765824 PMCID: PMC9913759 DOI: 10.3390/cancers15030866] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer to the ~40 trillion microorganisms that inhabit the human gut. Advances in next-generation sequencing technologies and metagenomics have provided new insights into the gut microbial ecology and have helped in linking gut microbiota to CRC. Many studies carried out in humans and animal models have emphasized the role of certain gut bacteria, such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, in the onset and progression of CRC. Metagenomic studies have opened up new avenues for the application of gut microbiota in the diagnosis, prevention, and treatment of CRC. This review article summarizes the role of gut microbiota in CRC development and its use as a biomarker to predict the disease and its potential therapeutic applications.
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Affiliation(s)
- Himani Pandey
- Redcliffe Labs, Electronic City, Noida 201301, India
| | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Correspondence: (S.H.W.); (D.L.)
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India
- Correspondence: (S.H.W.); (D.L.)
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25
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Zhang Z, Bahaji Azami NL, Liu N, Sun M. Research Progress of Intestinal Microecology in the Pathogenesis of Colorectal Adenoma and Carcinogenesis. Technol Cancer Res Treat 2023; 22:15330338221135938. [PMID: 36740990 PMCID: PMC9903042 DOI: 10.1177/15330338221135938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 09/22/2022] [Accepted: 10/13/2022] [Indexed: 02/07/2023] Open
Abstract
Colorectal adenoma is a precancerous lesion that may progress to colorectal cancer. Patients with colorectal adenoma had a 4-fold higher risk of developing colorectal malignancy than the rest of the population, with approximately 80% of colorectal cancer originating from colorectal adenoma. Therefore, preventing the occurrence and progression of colorectal adenoma is crucial in reducing the risk for colorectal cancer. The human intestinal microecology is a complex system consisting of numerous microbial communities with a sophisticated structure. Interactions among intestinal microorganisms play crucial roles in maintaining normal intestinal structure, digestion, absorption, metabolism, and other functions. The colorectal system is the largest microbial bank or fermentation system in the human body. Studies suggest that intestinal microecological imbalance, one of the most important environmental factors, may play an essential role in the occurrence and development of colorectal adenoma and colorectal cancer. Based on the complexity of studying the gut microbiota ecosystem, its specific role in the occurrence and development of colorectal adenoma is yet to be elucidated. In addition, further studies are expected to provide new insights regarding the prevention and treatment of colorectal adenoma. This article reviews the relationship and mechanism of the diversity of the gut microbiota, the relevant inflammatory response, immune regulation, and metabolic changes in the presence of colorectal adenomas.
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Affiliation(s)
- Zhipeng Zhang
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Nisma Lena Bahaji Azami
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ningning Liu
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mingyu Sun
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
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26
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Islam MZ, Tran M, Xu T, Tierney BT, Patel C, Kostic AD. Reproducible and opposing gut microbiome signatures distinguish autoimmune diseases and cancers: a systematic review and meta-analysis. MICROBIOME 2022; 10:218. [PMID: 36482486 PMCID: PMC9733034 DOI: 10.1186/s40168-022-01373-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 09/16/2022] [Indexed: 05/28/2023]
Abstract
BACKGROUND The gut microbiome promotes specific immune responses, and in turn, the immune system has a hand in shaping the microbiome. Cancer and autoimmune diseases are two major disease families that result from the contrasting manifestations of immune dysfunction. We hypothesized that the opposing immunological profiles between cancer and autoimmunity yield analogously inverted gut microbiome signatures. To test this, we conducted a systematic review and meta-analysis on gut microbiome signatures and their directionality in cancers and autoimmune conditions. METHODOLOGY We searched PubMed, Web of Science, and Embase to identify relevant articles to be included in this study. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements and PRISMA 2009 checklist. Study estimates were pooled by a generic inverse variance random-effects meta-analysis model. The relative abundance of microbiome features was converted to log fold change, and the standard error was calculated from the p-values, sample size, and fold change. RESULTS We screened 3874 potentially relevant publications. A total of 82 eligible studies comprising 37 autoimmune and 45 cancer studies with 4208 healthy human controls and 5957 disease cases from 27 countries were included in this study. We identified a set of microbiome features that show consistent, opposite directionality between cancers and autoimmune diseases in multiple studies. Fusobacterium and Peptostreptococcus were the most consistently increased genera among the cancer cases which were found to be associated in a remarkable 13 (+0.5 log fold change in 5 studies) and 11 studies (+3.6 log fold change in 5 studies), respectively. Conversely, Bacteroides was the most prominent genus, which was found to be increased in 12 autoimmune studies (+0.2 log fold change in 6 studies) and decreased in six cancer studies (-0.3 log fold change in 4 studies). Sulfur-metabolism pathways were found to be the most frequent pathways among the member of cancer-increased genus and species. CONCLUSIONS The surprising reproducibility of these associations across studies and geographies suggests a shared underlying mechanism shaping the microbiome across cancers and autoimmune diseases. Video Abstract.
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Affiliation(s)
- Md Zohorul Islam
- Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston, MA, USA.
- Department of Microbiology, Harvard Medical School, Boston, MA, USA.
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Melissa Tran
- Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston, MA, USA
- Department of Microbiology, Harvard Medical School, Boston, MA, USA
| | - Tao Xu
- Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston, MA, USA
- Department of Microbiology, Harvard Medical School, Boston, MA, USA
| | - Braden T Tierney
- Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston, MA, USA
- Department of Microbiology, Harvard Medical School, Boston, MA, USA
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
- Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA, USA
| | - Chirag Patel
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
| | - Aleksandar David Kostic
- Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston, MA, USA.
- Department of Microbiology, Harvard Medical School, Boston, MA, USA.
- Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA, USA.
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27
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Attard TM, Septer S, Lawson CE, Attard MI, Lee STM, Umar S. Microbiome insights into pediatric familial adenomatous polyposis. Orphanet J Rare Dis 2022; 17:416. [PMID: 36376984 PMCID: PMC9664625 DOI: 10.1186/s13023-022-02569-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 10/30/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Individuals with familial adenomatous polyposis (FAP) harbor numerous polyps with inevitable early progression to colon cancer. Complex microbiotic-tumor microenvironment perturbations suggest a dysbiotic relationship between polyp and microbiome. In this study, we performed comprehensive analyses of stool and tissue microbiome of pediatric FAP subjects and compared with unaffected cohabiting relatives through 16S V4 region amplicon sequencing and machine learning platforms. RESULTS Within our FAP and control patient population, Firmicutes and Bacteroidetes were the predominant phyla in the tissue and stool samples, while Proteobacteria dominated the polyp/non-polyp mucosa. A decline in Faecalibacterium in polyps contrasted with a decline in Bacteroides in the FAP stool. The alpha- and beta-diversity indices differed significantly within the polyp/non-polyp groups, with a concurrent shift towards lower diversity in polyps. In a limited 3-year longitudinal study, the relative abundance of Proteobacteria and Fusobacteria was higher in polyps compared to non-polyp and stool specimens over time. Through machine learning, we discovered that Archaeon_enrichment_culture_clone_A13, Micrococcus_luteus, and Eubacterium_hallii in stool and PL-11B10, S1-80, and Blastocatellaceae in tissues were significantly different between patients with and without polyps. CONCLUSIONS Detection of certain bacterial concentrations within stool or biopsied polyps could serve as adjuncts to current screening modalities to help identify higher-risk patients.
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Affiliation(s)
- Thomas M. Attard
- Department of Gastroenterology, Children’s Mercy Hospital, 1MO2.37, 2401 Gilham Road, Kansas City, MO 64108 USA
| | - Seth Septer
- Department of Pediatric Gastroenterology, Children’s Hospital Colorado, Aurora, CO USA
| | - Caitlin E. Lawson
- Division of Genetics, Children’s Mercy Hospital, Kansas City, MO USA
| | - Mark I. Attard
- Neonatal Unit, Aberdeen Maternity Hospital, Aberdeen, AB25 2ZL UK
| | - Sonny T. M. Lee
- Division of Biology, Kansas State University, Manhattan, KS USA
| | - Shahid Umar
- Department of Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, 4028 Wahl Hall East, Kansas City, KS 66160 USA
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28
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Li Z, Ke H, Wang Y, Chen S, Liu X, Lin Q, Wang P, Chen Y. Global trends in Akkermansia muciniphila research: A bibliometric visualization. Front Microbiol 2022; 13:1037708. [PMID: 36439840 PMCID: PMC9685322 DOI: 10.3389/fmicb.2022.1037708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 10/28/2022] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND Akkermansia muciniphila is a member of the gut microbiome, using mucin as sources of carbon, nitrogen, and energy. Since the first discovery of this unique bacterium in 2004, A. muciniphila has been extensively studied. It is considered a promising "next-generation beneficial microbe." The purpose of this paper is to sort out the research status and summarize the hotspots through bibliometric analysis of the publications of A. muciniphila. METHODS The publications about A. muciniphila from January 2004 to February 2022 were obtained from the Web of Science Core Collection. Visualization analyses were performed using three bibliometric tools and GraphPad Prism. RESULTS A total of 1,478 published documents were analyzed. Annual publication number grew from 1 in 2004 to 336 in 2021, with China being the leading producer (33.36%). De Vos, Willem M was the most productive author with the highest H-index (documents = 56, H-index = 37), followed by Cani, Patrice D (documents = 35, H-index = 25). And Scientific Reports published the most papers. PNAS was the keystone taxa in this field, with high betweenness centrality (0.11) and high frequency. The keywords with high frequency in recent years include: oxidative stress, diet, metformin, fecal microbiota transplantation, short-chain fatty acids, polyphenols, microbiota metabolites and so on. The keyword "oxidative stress" was observed to be increasing in frequency recently. CONCLUSION Over time, the scope of the research on the clinical uses of A. muciniphila has gradually increased, and was gradually deepened and developed toward a more precise level. A. muciniphila is likely to remain a research hotspot in the foreseeable future and may contribute to human health.
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Affiliation(s)
- Zitong Li
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Haoran Ke
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ying Wang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuze Chen
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiuying Liu
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qianyun Lin
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Pu Wang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ye Chen
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Integrative Microecology Center, Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
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29
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Wang T, Brown NM, McCoy AN, Sandler RS, Keku TO. Omega-3 Polyunsaturated Fatty Acids, Gut Microbiota, Microbial Metabolites, and Risk of Colorectal Adenomas. Cancers (Basel) 2022; 14:4443. [PMID: 36139601 PMCID: PMC9496906 DOI: 10.3390/cancers14184443] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/02/2022] [Accepted: 09/08/2022] [Indexed: 11/17/2022] Open
Abstract
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are thought to protect against colorectal adenoma (CRA) development. We aimed to further understand the underlying mechanisms by examining the relationships between ω-3 PUFAs and the gut microbiota on CRAs. We assessed the mucosal microbiota via bacterial 16S rRNA sequencing among 217 CRA cases and 218 controls who completed PUFA intake questionnaires. The overall microbial composition was assessed by α-diversity measurements (diversity, richness, and evenness). Global metabolomics was conducted using a random subset of case−control pairs (n = 50). We compared microbiota and metabolite signatures between cases and controls according to fold change (FC). Odds ratios (OR) and confidence intervals (CI) were estimated from logistic regression for associations of ω-3 PUFAs and the microbiota with CRAs. We observed an inverse association between overall ω-3 PUFA intake and CRAs, especially for short-chain ω -3 PUFAs (OR = 0.45, 95% CI: 0.21, 0.97). Such inverse associations were modified by bacterial evenness (p-interaction = 0.03). Participants with higher levels (FC > 2) of bile acid-relevant metabolites were more likely to have CRAs than the controls, and the correlation between bile acids and bacterial diversity differed by case−control status. Our findings suggest that ω-3 PUFAs are inversely associated with CRA development, and the association may be modified by gut microbiota profiles.
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Affiliation(s)
- Tengteng Wang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Nicole M. Brown
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Amber N. McCoy
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Robert S. Sandler
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Temitope O. Keku
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
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30
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Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases. Clin Nutr 2022; 41:2333-2344. [DOI: 10.1016/j.clnu.2022.08.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/22/2022] [Accepted: 08/27/2022] [Indexed: 11/22/2022]
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31
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Yinhang W, Wei W, Jing Z, Qing Z, Yani Z, Yangyanqiu W, Shuwen H. Biological roles of toll-like receptors and gut microbiota in colorectal cancer. Future Microbiol 2022; 17:1071-1089. [PMID: 35916158 DOI: 10.2217/fmb-2021-0072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most considerably common malignancies of the alimentary system, with high mortality and incidence rates. The present study suggested that the occurrence of CRC is closely related to bacteria, as the large intestine is a gathering place for human micro-organisms. However, the nosogenesis of bacteria leading to tumorigenesis is still obscure. Recently, many studies have reported that toll-like receptors and their related molecular pathways are involved in the process of gut micro-organisms generating CRC. Gut micro-organisms can promote or inhibit the development of CRC via binding to special toll-like receptors. In this paper, the authors review the relationship among toll-like receptors, gut micro-organisms and CRC in order to provide a reference for future tumor immunotherapy and targeted therapy.
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Affiliation(s)
- Wu Yinhang
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,The Second School of Clinical Medicine, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, 310053, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Wu Wei
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhuang Jing
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhou Qing
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
| | - Zhou Yani
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Graduate School of Medicine Faculty, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang Province, 310058, China
| | - Wang Yangyanqiu
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Graduate School of Medicine Faculty, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang Province, 310058, China
| | - Han Shuwen
- Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University, 1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.,Key Laboratory of Multiomics Research & Clinical Transformation of Digestive Cancer of Huzhou,1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China
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32
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Elucidation of Anti-Hypertensive Mechanism by a Novel Lactobacillus rhamnosus AC1 Fermented Soymilk in the Deoxycorticosterone Acetate-Salt Hypertensive Rats. Nutrients 2022; 14:nu14153174. [PMID: 35956350 PMCID: PMC9370603 DOI: 10.3390/nu14153174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 12/13/2022] Open
Abstract
Dietary intake of fermented soymilk is associated with hypotensive effects, but the mechanisms involved have not been fully elucidated. We investigated the anti-hypertensive effects of soymilk fermented by L. rhamnosus AC1 on DOCA-salt hypertension from the point of view of oxidative stress, inflammatory response and alteration of the gut microbiome. The antioxidant assays in vitro indicated the ethanol extract (EE) of L. rhamnosus AC1 fermented soymilk showed better antioxidative effects than the water extract (WE). Those extracts displayed a hypotensive effect using a tail-cuff approach to measuring blood pressure and improved nitric oxide (NO), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α) and interleukin factor-6 (IL-6) on DOCA-salt hypertensive rats. Furthermore, cardiac and renal fibrosis were attenuated by those extracts. The gut microbiota analysis revealed that they significantly reduced the abundance of phylum Proteobacteria, its family Enterobacteriaceae and genus Escherichia-Shigella. Moreover, metabolomic profiling revealed several potential gut microbiota-related metabolites which appeared to involve in the development and recovery of hypertension. In conclusion, fermented soymilk is a promising nutritional intervention strategy to improve hypertension via reducing inflammation and reverting dysbiotic microbiota.
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Grenda A, Iwan E, Chmielewska I, Krawczyk P, Giza A, Bomba A, Frąk M, Rolska A, Szczyrek M, Kieszko R, Kucharczyk T, Jarosz B, Wasyl D, Milanowski J. Presence of Akkermansiaceae in gut microbiome and immunotherapy effectiveness in patients with advanced non-small cell lung cancer. AMB Express 2022; 12:86. [PMID: 35792976 PMCID: PMC9259768 DOI: 10.1186/s13568-022-01428-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
The significance of Akkermansia bacteria presence in gut micobiome, mainly Akkermansia mucinifila, is currently being investigated in the context of supporting therapy and marker for response to immunotherapy in cancer patients. It is indicated that patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) respond better to treatment if this bacterium is present in the intestine. We performed next-generation sequencing of the gut microbiome from patients treated in the first or second line therapy with anti-PD-1 (anti-programmed death 1) or anti-PD-L1 (anti-programmed death ligand 1) monoclonal antibodies. In our study group of 47 NSCLC patients, the percentage of Akkermansiaceae was higher in patients with disease stabilization and with partial response to immunotherapy compared to patients with disease progression. Moreover, we found that a higher percentage of Akkermansiaceae was present in patients with squamous cell carcinoma compared to adenocarcinoma. Our study showed that Akkermansiaceae could be supporting marker for response to immunotherapies in NSCLC patients, nonetheless further in-depth studies should be conducted in the role of Akkermansiaceae in cancer immunotherapy.
Composition of the microbiome can influence patients response to immunotherapy Response to immunotherapy of NSCLC patients is associated with the presence of Akkermansiaceae in the gut Akkermansia could be used as a predictor for patient treated with immunological checkpoint inhibitors
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Gupta I, Pedersen S, Vranic S, Al Moustafa AE. Implications of Gut Microbiota in Epithelial-Mesenchymal Transition and Cancer Progression: A Concise Review. Cancers (Basel) 2022; 14:2964. [PMID: 35740629 PMCID: PMC9221329 DOI: 10.3390/cancers14122964] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 12/04/2022] Open
Abstract
Advancement in the development of molecular sequencing platforms has identified infectious bacteria or viruses that trigger the dysregulation of a set of genes inducing the epithelial-mesenchymal transition (EMT) event. EMT is essential for embryogenesis, wound repair, and organ development; meanwhile, during carcinogenesis, initiation of the EMT can promote cancer progression and metastasis. Recent studies have reported that interactions between the host and dysbiotic microbiota in different tissues and organs, such as the oral and nasal cavities, esophagus, stomach, gut, skin, and the reproductive tract, may provoke EMT. On the other hand, it is revealed that certain microorganisms display a protective role against cancer growth, indicative of possible therapeutic function. In this review, we summarize recent findings elucidating the underlying mechanisms of pathogenic microorganisms, especially the microbiota, in eliciting crucial regulator genes that induce EMT. Such an approach may help explain cancer progression and pave the way for developing novel preventive and therapeutic strategies.
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Affiliation(s)
- Ishita Gupta
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
| | - Shona Pedersen
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
| | - Semir Vranic
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
| | - Ala-Eddin Al Moustafa
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
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Guo Q, Qin H, Liu X, Zhang X, Chen Z, Qin T, Chang L, Zhang W. The Emerging Roles of Human Gut Microbiota in Gastrointestinal Cancer. Front Immunol 2022; 13:915047. [PMID: 35784372 PMCID: PMC9240199 DOI: 10.3389/fimmu.2022.915047] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 05/16/2022] [Indexed: 12/14/2022] Open
Abstract
The gut microbiota is composed of a large number of microorganisms with a complex structure. It participates in the decomposition, digestion, and absorption of nutrients; promotes the development of the immune system; inhibits the colonization of pathogens; and thus modulates human health. In particular, the relationship between gut microbiota and gastrointestinal tumor progression has attracted widespread concern. It was found that the gut microbiota can influence gastrointestinal tumor progression in independent ways. Here, we focused on the distribution of gut microbiota in gastrointestinal tumors and further elaborated on the impact of gut microbiota metabolites, especially short-chain fatty acids, on colorectal cancer progression. Additionally, the effects of gut microbiota on gastrointestinal tumor therapy are outlined. Finally, we put forward the possible problems in gut microbiota and the gastrointestinal oncology field and the efforts we need to make.
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Affiliation(s)
- Qianqian Guo
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
- *Correspondence: Qianqian Guo, ; Wenzhou Zhang,
| | - Hai Qin
- Department of Clinical Laboratory, Guizhou Provincial Orthopedic Hospital, Guiyang City, China
| | - Xueling Liu
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xinxin Zhang
- The Second Clinical Medical School of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Zelong Chen
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Province Engineering Research Center of Artificial Intelligence and Internet of Things Wise Medical, Zhengzhou, China
| | - Tingting Qin
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Linlin Chang
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Wenzhou Zhang
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
- *Correspondence: Qianqian Guo, ; Wenzhou Zhang,
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Phycocyanin Ameliorates Colitis-Associated Colorectal Cancer by Regulating the Gut Microbiota and the IL-17 Signaling Pathway. Mar Drugs 2022; 20:md20040260. [PMID: 35447933 PMCID: PMC9030732 DOI: 10.3390/md20040260] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/05/2022] [Accepted: 04/07/2022] [Indexed: 02/06/2023] Open
Abstract
Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota and transcriptomic analyses to investigate the effects of PC on colitis-associated cancer (CAC). Our results indicated that PC ameliorated AOM/DSS induced inflammation. PC treatment significantly reduced the number of colorectal tumors and inhibited proliferation of epithelial cell in CAC mice. Moreover, PC reduced the relative abundance of Firmicutes, Deferribacteres, Proteobacteria and Epsilonbacteraeota at phylum level. Transcriptomic analysis showed that the expression of genes involved in the intestinal barrier were altered upon PC administration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the IL-17 signaling pathway was affected by PC treatment. The study demonstrated the protective therapeutic action of PC on CAC.
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Yang F, Yang Y, Chen L, Zhang Z, Liu L, Zhang C, Mai Q, Chen Y, Chen Z, Lin T, Chen L, Guo H, Zhou L, Shen H, Chen X, Liu L, Zhang G, Liao H, Zeng L, Zeng G. The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA. Gut Microbes 2022; 14:2029997. [PMID: 35343370 PMCID: PMC8966992 DOI: 10.1080/19490976.2022.2029997] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut microbiota may impact TB outcomes are not fully understood. Here, we found that broad-spectrum antibiotics treatment increased susceptibility to Mycobacterium tuberculosis (M. tuberculosis) infection and modulated pulmonary inflammatory responses in mouse M. tuberculosis infection model. We then identified a commensal gut bacteria-regulated lncRNA, termed lncRNA-CGB, which was down-regulated by dysbiosis of gut microbiota during TB infection. Furthermore, we found that Bacteroides fragilis (B. fragilis) was a direct regulator of lncRNA-CGB, and oral administration of B. fragilis enhanced expression of lncRNA-CGB and promoted anti-TB immunity. Genomic knock-out of lncRNA-CGB led to reduced IFN-γ expression and impaired anti-TB immunity, therefore leading to detrimental effects on M. tuberculosis infection. Mechanistically, lncRNA-CGB interacted with EZH2 and negatively regulated H3K27 tri-methylation (H3K27Me3) epigenetic programming, leading to enhanced IFN-γ expression. Thus, this work not only uncovered previously unrecognized importance of gut bacteria-lncRNA-EZH2-H3K27Me3 axis in conferring immune protection against TB but also identified a potential new paradigm to develop a microbiota-based treatment against TB and potentially other diseases.
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Affiliation(s)
- Fang Yang
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Yi Yang
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Lingming Chen
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Zhiyi Zhang
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Linna Liu
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina,Linna Liu Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China
| | - Chunmin Zhang
- Drepartment of Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Picu, GuangzhouChina
| | - Qiongdan Mai
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Yiwei Chen
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Zixu Chen
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Tao Lin
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Liang Chen
- Guangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, GuangzhouChina
| | - Huixin Guo
- Guangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, GuangzhouChina
| | - Lin Zhou
- Guangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, GuangzhouChina
| | - Hongbo Shen
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Institute for Advanced Study, Tongji University School of Medicine, Shanghai, China
| | - Xinchun Chen
- Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, GuangdongChina
| | - Lei Liu
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, National Clinical Research Center for Tuberculosis, Southern University of Science and Technology, National Clinical Research Center for Tuberculosis, Shenzhen, China
| | - Guoliang Zhang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, National Clinical Research Center for Tuberculosis, Southern University of Science and Technology, National Clinical Research Center for Tuberculosis, Shenzhen, China
| | - Hongying Liao
- De
partment of Thoracic Surgery, Thoracic Cancer Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China,Hongying Liao Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lingchan Zeng
- Clinical Research Center, Department of Medical Records Management, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China,Lingchan Zeng Clinical Research Center, Department of Medical Records Management, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Gucheng Zeng
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina,CONTACT Gucheng Zeng Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education
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Zhou Y, Feng Y, Cen R, Hou X, Yu H, Sun J, Zhou L, Ji Q, Zhao L, Wang Y, Li Q. San-Wu-Huang-Qin decoction attenuates tumorigenesis and mucosal barrier impairment in the AOM/DSS model by targeting gut microbiome. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 98:153966. [PMID: 35158238 DOI: 10.1016/j.phymed.2022.153966] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 01/07/2022] [Accepted: 01/25/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND A classic herbal formula San-Wu-Huang-Qin (SWHQ) decoction has been widely used in clinical practices to prevent and treat colorectal cancer (CRC) for years, but its anti-tumorigenic properties and the underlying mechanisms remain undetermined. PURPOSE The present study used a CRC mouse model to clarify whether and how SWHQ suppresses tumorigenesis. METHODS Different doses of SWHQ were gavaged to the AOM/DSS model mice to examine its anti-tumor efficacy in comparison with the positive control drug Aspirin. The underlying microbiota-driven anti-tumor action of SWHQ was proven with bacterial manipulations by fecal microbial transplantation (FMT) in vivo and anaerobic culturing in vitro. RESULTS SWHQ decoction dose-dependently reduced colonic tumor numbers/loads of AOM/DSS models and suppressed their disease activity index scores. SWHQ also recovered epithelial MUC2 secretion and colonic tight junction protein (ZO-1 and claudin1) expression in the mouse model. Such inhibitory impact on tumorigenesis and mucosal barrier impairment was found to be associated with modulation of gut dysbiosis, particularly for suppressing lipopolysaccharide (LPS) producers. The FMT experiment confirmed the substantial contribution of SWHQ-reshaped microbiota to anti-tumor function and mucosal barrier protection. Moreover, LPS-activated TLR4/NF-κB signaling and its downstream pro-inflammatory factors were significantly suppressed in the colon of SWHQ-treated models and SWHQ-reshaped microbiota recipients. CONCLUSIONS We demonstrated that the SWHQ effectively inhibited tumorigenesis and protect mucosal barrier in CRC at least partially by targeting gut microbiota. This study provides scientific basis for the clinical usage of SWHQ in CRC intervention and prevention.
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Affiliation(s)
- Yelu Zhou
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yuanyuan Feng
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Rong Cen
- Endoscopy center of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xinxin Hou
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Hao Yu
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jian Sun
- Laboratory Department of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lihong Zhou
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Qing Ji
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ling Zhao
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Yan Wang
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Qi Li
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Chang ZY, Liu HM, Leu YL, Hsu CH, Lee TY. Modulation of Gut Microbiota Combined with Upregulation of Intestinal Tight Junction Explains Anti-Inflammatory Effect of Corylin on Colitis-Associated Cancer in Mice. Int J Mol Sci 2022; 23:ijms23052667. [PMID: 35269806 PMCID: PMC8910903 DOI: 10.3390/ijms23052667] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/26/2022] [Accepted: 02/26/2022] [Indexed: 12/21/2022] Open
Abstract
Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The results showed corylin could improved the survival rate and colon length, maintained body weight, and ameliorated the inflammatory response in the colon. Then, we further identified the possible antitumor effects after 30-day treatment of corylin on an azoxymethane (AOM)/DSS-induced CAC mouse model. Biomarkers associated with inflammation, the colon tissue barrier, macrophage polarization (CD11c, CCR7, CD163, and CD206), and microbiota dysbiosis were monitored in the AOM/DSS group versus corylin groups. Corylin downregulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) mRNA expression and inflammatory signaling-associated markers (TLR4, MyD88, AP-1, CD11b, and F4/80). In addition, a colon barrier experiment revealed that epithelial cell proliferation of the mucus layer (Lgr5, Cyclin D1, and Olfm4) was downregulated and tight junction proteins (claudin-1 and ZO-1) were upregulated. Furthermore, the Firmicutes/Bacteroidetes ratio changed with corylin intervention, and the microbial diversity and community richness of the AOM/DSS mice were improved by corylin. The comparative analysis of gut microbiota revealed that Bacteroidetes, Patescibacteria, Candidatus Saccharimonas, Erysipelatoclostridium, and Enterorhabdus were significantly increased but Firmicutes, Turicibacter, Romboutsia, and Blautia decreased after corylin treatment. Altogether, corylin administration showed cancer-ameliorating effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Therefore, corylin could be a novel, potential health-protective, natural agent against CAC.
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Affiliation(s)
- Zi-Yu Chang
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan;
| | - Hsuan-Miao Liu
- Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;
| | - Yann-Lii Leu
- Graduate Institute of Nature Products, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan;
- Tissue Bank, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Chung-Hua Hsu
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan;
- Correspondence: (C.-H.H.); (T.-Y.L.); Tel.: +886-02-2388-7088 (ext. 3100) (C.-H.H.); +886-03-211-8800 (ext. 3537) (T.-Y.L.)
| | - Tzung-Yan Lee
- Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung 20401, Taiwan
- Correspondence: (C.-H.H.); (T.-Y.L.); Tel.: +886-02-2388-7088 (ext. 3100) (C.-H.H.); +886-03-211-8800 (ext. 3537) (T.-Y.L.)
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Ionica E, Gaina G, Tica M, Chifiriuc MC, Gradisteanu-Pircalabioru G. Contribution of Epithelial and Gut Microbiome Inflammatory Biomarkers to the Improvement of Colorectal Cancer Patients' Stratification. Front Oncol 2022; 11:811486. [PMID: 35198435 PMCID: PMC8859258 DOI: 10.3389/fonc.2021.811486] [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: 11/12/2021] [Accepted: 12/20/2021] [Indexed: 12/24/2022] Open
Abstract
In order to ensure that primary endpoints of clinical studies are attained, the patients' stratification is an important aspect. Selection criteria include age, gender, and also specific biomarkers, such as inflammation scores. These criteria are not sufficient to achieve a straightforward selection, however, in case of multifactorial diseases, with unknown or partially identified mechanisms, occasionally including host factors, and the microbiome. In these cases, the efficacy of interventions is difficult to predict, and as a result, the selection of subjects is often random. Colorectal cancer (CRC) is a highly heterogeneous disease, with variable clinical features, outcomes, and response to therapy; the CRC onset and progress involves multiple sequential steps with accumulation of genetic alterations, namely, mutations, gene amplification, and epigenetic changes. The gut microbes, either eubiotic or dysbiotic, could influence the CRC evolution through a complex and versatile crosstalk with the intestinal and immune cells, permanently changing the tumor microenvironment. There have been significant advances in the development of personalized approaches for CRC screening, treatment, and potential prevention. Advances in molecular techniques bring new criteria for patients' stratification-mutational analysis at the time of diagnosis to guide treatment, for example. Gut microbiome has emerged as the main trigger of gut mucosal homeostasis. This may impact cancer susceptibility through maintenance of the epithelial/mucus barrier and production of protective metabolites, such as short-chain fatty acids (SCFAs) via interactions with the hosts' diet and metabolism. Microbiome dysbiosis leads to the enrichment of cancer-promoting bacterial populations, loss of protective populations or maintaining an inflammatory chronic state, all of which contribute to the development and progression of CRC. Meanwhile, variations in patient responses to anti-cancer immuno- and chemotherapies were also linked to inter-individual differences in intestine microbiomes. The authors aim to highlight the contribution of epithelial and gut microbiome inflammatory biomarkers in the improvement of CRC patients' stratification towards a personalized approach of early diagnosis and treatment.
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Affiliation(s)
- Elena Ionica
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Gisela Gaina
- Laboratory of Cell Biology, Neuroscience and Experimental Miology, Victor Babes National Institute of Pathology, Bucharest, Romania
| | - Mihaela Tica
- Bucharest Emergency University Hospital, Bucharest, Romania
| | - Mariana-Carmen Chifiriuc
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Bucharest, Romania
- Biological Science Division, Romanian Academy of Sciences, Bucharest, Romania
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Wu H, Lam TYC, Shum TF, Tsai TY, Chiou J. Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration. Hypertens Res 2022; 45:270-282. [PMID: 34857899 PMCID: PMC8766282 DOI: 10.1038/s41440-021-00796-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 09/30/2021] [Accepted: 10/07/2021] [Indexed: 12/11/2022]
Abstract
The role of the gut microbiota in various metabolic diseases has been widely studied. This study aims to test the hypothesis that gut microbiota dysbiosis is associated with DOCA-salt-induced hypertension, while captopril, an antihypertensive drug, is able to rebalance the gut microbiota alterations caused by hypertension. Treatment with captopril resulted in an approximate 32 mmHg reduction in systolic blood pressure (162.57 vs. 194.61 mmHg) in DOCA-salt-induced hypertensive rats, although it was significantly higher than that in SHAM rats (136.10 mmHg). Moreover, the nitric oxide (NO) level was significantly increased (20.60 vs. 6.42 µM) while the angiotensin II (Ang II) content (42.40 vs. 59.47 pg/ml) was attenuated nonsignificantly by captopril treatment in comparison to those of DOCA-salt-induced hypertensive rats. The introduction of captopril significantly decreased the levels of tumor necrosis factor-α (TNF-ɑ) and interleukin-6 (IL-6). Hypertrophy and fibrosis in kidneys and hearts were also significantly attenuated by captopril. Furthermore, gut microbiota dysbiosis was observed in DOCA-salt-induced hypertensive rats. The abundances of several phyla and genera, including Proteobacteria, Cyanobacteria, Escherichia-Shigella, Eubacterium nodatum and Ruminococcus, were higher in DOCA-salt-induced hypertensive rats than in SHAM rats, while these changes were reversed by captopril treatment. Of particular interest, the genera Bifidobacterium and Akkermansia, reported as beneficial bacteria in the gut, were abundant in only hypertensive rats treated with captopril. These results provide evidence that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt-induced hypertensive rats, suggesting that the alteration of the gut flora by captopril may contribute to the hypotensive effect of this drug.
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Affiliation(s)
- Haicui Wu
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Theo Y C Lam
- Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Tim-Fat Shum
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
| | - Tsung-Yu Tsai
- Department of Food Science, Fu Jen Catholic University, New Taipei City, 24205, Taiwan
| | - Jiachi Chiou
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
- Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
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42
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Wang F, Cai K, Xiao Q, He L, Xie L, Liu Z. Akkermansia muciniphila administration exacerbated the development of colitis-associated colorectal cancer in mice. J Cancer 2022; 13:124-133. [PMID: 34976176 PMCID: PMC8692691 DOI: 10.7150/jca.63578] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 11/12/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common digestive tract malignancies and inflammation and gut microbiota are well-known key factors to influence CRC development. Akkermansia mucinipila is an important gram-negative anaerobic bacterium that can degrade mucin in gut. Previous studies suggested that A. muciniphila may affect inflammation and cell proliferation, but the relationship between A. muciniphila and CRC is not clarified. Here C57BL/6 mice were administrated with A. muciniphila or PBS and then treated with azoxymethane (AOM)/dextran sodium sulphate (DSS) to induce CRC. The mice receiving A. muciniphila administration had more serious weight loss, shorter colon length and more intestinal tumors than those receiving PBS administration after AOM/DSS treatment. More colon damage and less goblet cells were also observed in A. muciniphila treated mice. Furthermore, A. muciniphila administration induced more Ki67+ proliferating cells, higher PCNA expression and elevated gene expression of proliferation-associated molecules including Snrpd1, Dbf4 or S100A9. At early stage of CRC development, in comparison with controls, the mice receiving A. muciniphila administration also had more body weight loss and shorter colon length, as well as higher gene expression of inflammatory cytokines. Furthermore, the in vitro experimental results showed that the co-culture of colon epithelial cells with A. muciniphila enhanced the cell proliferation and gene expression of proliferation-associated molecules. Therefore, A. mucinipila may promote the formation of CRC in mice through increasing the early level of inflammation and the proliferation of intestinal epithelial cells.
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Affiliation(s)
- Fei Wang
- Gannan Medical University, Ganzhou, Jiangxi, 341000, China.,The Fifth People's Hospital of Jinan, Jinan, Shandong, 250000, China
| | - Kuntai Cai
- Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Qiuxiang Xiao
- School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China
| | - Lihua He
- Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Lu Xie
- School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China.,Center for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, China
| | - Zhiping Liu
- School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China.,Center for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, China
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43
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Cao P, Ye J, Su KL, Xu YH, Yang Y, Zhou Q, Gao W, Cai XT, Wei QY, Cao M. Effect of salivary antimicrobial factors on microbial composition of tongue coating in patients with coronary heart disease with phlegm-stasis syndrome. WORLD JOURNAL OF TRADITIONAL CHINESE MEDICINE 2022. [DOI: 10.4103/wjtcm.wjtcm_34_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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44
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Cao P, Ye J, Su KL, Xu YH, Yang Y, Zhou Q, Gao W, Cai XT, Wei QY, Cao M. Effect of salivary antimicrobial factors on microbial composition of tongue coating in patients with coronary heart disease with phlegm-stasis syndrome. WORLD JOURNAL OF TRADITIONAL CHINESE MEDICINE 2022. [DOI: 10.4103/2311-8571.321974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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45
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Sędzikowska A, Szablewski L. Human Gut Microbiota in Health and Selected Cancers. Int J Mol Sci 2021; 22:13440. [PMID: 34948234 PMCID: PMC8708499 DOI: 10.3390/ijms222413440] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/08/2021] [Accepted: 12/10/2021] [Indexed: 12/24/2022] Open
Abstract
The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These microbiota, particularly those of the intestines, play an important, beneficial role in digestion, metabolism, and the synthesis of vitamins. Their metabolites stimulate cytokine production by the human host, which are used against potential pathogens. The composition of the microbiota is influenced by several internal and external factors, including diet, age, disease, and lifestyle. Such changes, called dysbiosis, may be involved in the development of various conditions, such as metabolic diseases, including metabolic syndrome, type 2 diabetes mellitus, Hashimoto's thyroidis and Graves' disease; they can also play a role in nervous system disturbances, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and depression. An association has also been found between gut microbiota dysbiosis and cancer. Our health is closely associated with the state of our microbiota, and their homeostasis. The aim of this review is to describe the associations between human gut microbiota and cancer, and examine the potential role of gut microbiota in anticancer therapy.
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Affiliation(s)
| | - Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, ul. Chalubinskiego 5, 02-004 Warsaw, Poland;
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46
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Dalal P, Sharma D. Microbe defines the efficacy of chemotherapeutic drug: a complete paradigm. FEMS Microbiol Lett 2021; 368:6358522. [PMID: 34448860 DOI: 10.1093/femsle/fnab116] [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: 01/28/2021] [Accepted: 08/24/2021] [Indexed: 12/18/2022] Open
Abstract
The human body harbors a diverse microbiome that regulates host physiology and disease development. Several studies have also been reported where the human microbiome interferes with the efficacy of chemotherapeutics. Reports have also suggested the use of microbes in specific targeting and drug delivery. This review mainly focuses on the alteration in the efficacy of the drug by human microbiota. We have also discussed how the diversity in microbes can determine the therapeutic outcomes of a particular drug. The pathways involved in the alteration are also focused, with some highlights on microbes being used in cancer therapy.
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Affiliation(s)
- P Dalal
- Institute of Nanoscience and Technology, Knowledge City, Sector - 81, Mohali 140306, Punjab, India
| | - D Sharma
- Institute of Nanoscience and Technology, Knowledge City, Sector - 81, Mohali 140306, Punjab, India
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47
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Yu LCH, Wei SC, Li YH, Lin PY, Chang XY, Weng JP, Shue YW, Lai LC, Wang JT, Jeng YM, Ni YH. Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses. Cell Mol Gastroenterol Hepatol 2021; 13:57-79. [PMID: 34418587 PMCID: PMC8600093 DOI: 10.1016/j.jcmgh.2021.08.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/11/2021] [Accepted: 08/11/2021] [Indexed: 01/11/2023]
Abstract
BACKGROUND & AIMS Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesize that an interaction between virulent pathobionts and epithelial defense promotes tumorigenesis. METHODS Chemical-induced CRC mouse model was treated with antibiotics at various phases. Colonic tissues and fecal samples were collected in a time-serial mode and analyzed by gene microarray and 16S rRNA sequencing. Intraepithelial bacteria were isolated using a gentamicin resistance assay, and challenged in epithelial cultures. RESULTS Our study showed that antibiotic treatment at midphase but not early or late phase reduced mouse tumor burden, suggesting a time-specific host-microbe interplay. A unique antimicrobial transcriptome profile showing an inverse relationship between autophagy and oxidative stress genes was correlated with a transient surge in microbial diversity and virulence emergence in mouse stool during cancer initiation. Gavage with fimA/fimH/htrA-expressing invasive Escherichia coli isolated from colonocytes increased tumor burden in recipient mice, whereas inoculation of bacteria deleted of htrA or triple genes did not. The invasive E.coli suppressed epithelial autophagy activity through reduction of microtubule-associated protein 1 light-chain 3 transcripts and caused dual oxidase 2-dependent free radical overproduction and tumor cell hyperproliferation. A novel alternating spheroid culture model was developed for sequential bacterial challenge to address the long-term changes in host-microbe interaction for chronic tumor growth. Epithelial cells with single bacterial encounter showed a reduction in transcript levels of autophagy genes while those sequentially challenged with invasive E.coli showed heightened autophagy gene expression to eliminate intracellular microbes, implicating that bacteria-dependent cell hyperproliferation could be terminated at late phases. Finally, the presence of bacterial htrA and altered antimicrobial gene expression were observed in human colorectal cancer specimens. CONCLUSIONS Invasive pathobionts contribute to cancer initiation during a key time frame by counterbalancing autophagy and oxidative stress in the colonic epithelium. Monitoring gut microbiota and antimicrobial patterns may help identify the window of opportunity for intervention with bacterium-targeted precision medicine.
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Affiliation(s)
| | - Shu-Chen Wei
- Department of Internal Medicine, Taipei, Taiwan, Republic of China
| | - Yi-Hsuan Li
- Graduate Institute of Physiology, Taipei, Taiwan, Republic of China
| | - Po-Yu Lin
- Graduate Institute of Physiology, Taipei, Taiwan, Republic of China
| | - Xin-Yu Chang
- Graduate Institute of Physiology, Taipei, Taiwan, Republic of China
| | - Jui-Ping Weng
- Graduate Institute of Physiology, Taipei, Taiwan, Republic of China
| | - Yin-Wen Shue
- Graduate Institute of Physiology, Taipei, Taiwan, Republic of China,Department of Internal Medicine, Taipei, Taiwan, Republic of China
| | - Liang-Chuan Lai
- Graduate Institute of Physiology, Taipei, Taiwan, Republic of China,Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Jin-Town Wang
- Department of Internal Medicine, Taipei, Taiwan, Republic of China,Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China
| | - Yung-Ming Jeng
- Department of Pathology, Taipei, Taiwan, Republic of China
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, Republic of China,Correspondence Address correspondence to: Yen-Hsuan Ni, MD, PhD, Department of Pediatrics, National Taiwan University College of Medicine and Hospital, 7 Chung-Shan South Road, Taipei, Taiwan, Republic of China. fax: (886) 2-23938871.
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Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps. Cancers (Basel) 2021; 13:cancers13143382. [PMID: 34298598 PMCID: PMC8303543 DOI: 10.3390/cancers13143382] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/01/2021] [Accepted: 07/01/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Colorectal cancers (CRC) initiate from small cell clusters known as polyps. Colonoscopic surveillance and removal of polyps is an important strategy to prevent CRC progression. Recent advances in sequencing technologies have highlighted genetic mutations in polyps that potentially contribute to CRC development. However, CRC might be considered more than a genetic disease, as emerging evidence describes early changes to immune surveillance and gut microbiota in people with polyps. Here, we review the molecular landscape of colorectal polyps, considering their genomic, microbial and immunological features, and discuss the potential clinical utility of these data. Abstract Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium, known as polyps. Polyps themselves arise through the accumulation of mutations that disrupt the function of key tumour suppressor genes, activate proto-oncogenes and allow proliferation in an environment where immune control has been compromised. Consequently, colonoscopic surveillance and polypectomy are central pillars of cancer control strategies. Recent advances in genomic sequencing technologies have enhanced our knowledge of key driver mutations in polyp lesions that likely contribute to CRC. In accordance with the prognostic significance of Immunoscores for CRC survival, there is also a likely role for early immunological changes in polyps, including an increase in regulatory T cells and a decrease in mature dendritic cell numbers. Gut microbiotas are under increasing research interest for their potential contribution to CRC evolution, and changes in the gut microbiome have been reported from analyses of adenomas. Given that early changes to molecular components of bowel polyps may have a direct impact on cancer development and/or act as indicators of early disease, we review the molecular landscape of colorectal polyps, with an emphasis on immunological and microbial alterations occurring in the gut and propose the potential clinical utility of these data.
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Illescas O, Rodríguez-Sosa M, Gariboldi M. Mediterranean Diet to Prevent the Development of Colon Diseases: A Meta-Analysis of Gut Microbiota Studies. Nutrients 2021; 13:nu13072234. [PMID: 34209683 PMCID: PMC8308215 DOI: 10.3390/nu13072234] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/23/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota dysbiosis is a common feature in colorectal cancer (CRC) and inflammatory bowel diseases (IBD). Adoption of the Mediterranean diet (MD) has been proposed as a therapeutic approach for the prevention of multiple diseases, and one of its mechanisms of action is the modulation of the microbiota. We aimed to determine whether MD can be used as a preventive measure against cancer and inflammation-related diseases of the gut, based on its capacity to modulate the local microbiota. A joint meta-analysis of publicly available 16S data derived from subjects following MD or other diets and from patients with CRC, IBD, or other gut-related diseases was conducted. We observed that the microbiota associated with MD was enriched in bacteria that promote an anti-inflammatory environment but low in taxa with pro-inflammatory properties capable of altering intestinal barrier functions. We found an opposite trend in patients with intestinal diseases, including cancer. Some of these differences were maintained even when MD was compared to healthy controls without a defined diet. Our findings highlight the unique effects of MD on the gut microbiota and suggest that integrating MD principles into a person’s lifestyle may serve as a preventive method against cancer and other gut-related diseases.
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Affiliation(s)
- Oscar Illescas
- Genetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy;
| | - Miriam Rodríguez-Sosa
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla C.P. 54090, MEX, Mexico;
| | - Manuela Gariboldi
- Genetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy;
- Correspondence: ; Tel.: +39-2-23902042
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50
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Jiang R, Li WV, Li JJ. mbImpute: an accurate and robust imputation method for microbiome data. Genome Biol 2021; 22:192. [PMID: 34183041 PMCID: PMC8240317 DOI: 10.1186/s13059-021-02400-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 06/04/2021] [Indexed: 12/22/2022] Open
Abstract
A critical challenge in microbiome data analysis is the existence of many non-biological zeros, which distort taxon abundance distributions, complicate data analysis, and jeopardize the reliability of scientific discoveries. To address this issue, we propose the first imputation method for microbiome data-mbImpute-to identify and recover likely non-biological zeros by borrowing information jointly from similar samples, similar taxa, and optional metadata including sample covariates and taxon phylogeny. We demonstrate that mbImpute improves the power of identifying disease-related taxa from microbiome data of type 2 diabetes and colorectal cancer, and mbImpute preserves non-zero distributions of taxa abundances.
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Affiliation(s)
- Ruochen Jiang
- Department of Statistics, University of California, Los Angeles, 90095-1554, CA, USA
| | - Wei Vivian Li
- Department of Statistics, University of California, Los Angeles, 90095-1554, CA, USA
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, 08854, NJ, USA
| | - Jingyi Jessica Li
- Department of Statistics, University of California, Los Angeles, 90095-1554, CA, USA.
- Department of Human Genetics, University of California, Los Angeles, 90095-7088, CA, USA.
- Department of Computational Medicine, University of California, Los Angeles, 90095-1766, CA, USA.
- Department of Biostatistics, University of California, Los Angeles, 90095-1772, CA, USA.
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