|
1
|
Li F, Peng X, Li W. The interaction between various food components and intestinal microbiota improves human health through the gut-X axis: independently or synergistically. Food Funct 2025; 16:2172-2193. [PMID: 39996355 DOI: 10.1039/d4fo04430d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
Food contains various components that improve health by affecting the gut microbiota, primarily by modulating its abundance or altering its diversity. Active substances in food have different effects on the gut microbiota when they act alone or in synergy, resulting in varying impacts on health. The bioactive compounds in food exert different effects on various gut microbiota through multiple pathways, thereby delaying or preventing different kinds of disease. The combination of two or more active compounds may have a synergistic effect, which can more effectively alter the gut microbiota and alleviate diseases through the microbiota-gut-organ axis. According to reports, multiple different food components have similar effects, some of which have been shown to have a synergistic effect on the gut microbiota to promote health. However, there is currently no systematic review of its synergistic effects and mechanisms. There may be more compounds with synergistic effects that have not yet been discovered, while their mechanisms of synergy and ways of impacting host health through the gut microbiota deserve further investigation. The purpose of this review is to systematically summarize the effects of different food components on intestinal flora and health, and further analyze the potential synergies between different food components. PubMed and Google Scholar databases were searched in this review.
Collapse
Affiliation(s)
- Fenfa Li
- Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Xichun Peng
- Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Wenzhi Li
- Infinitus (China) Company Ltd, Guangzhou 510405, China.
| |
Collapse
|
|
2
|
He Z, Yu J, Gong J, Wu J, Zong X, Luo Z, He X, Cheng WM, Liu Y, Liu C, Zhang Q, Dai L, Ding T, Gao B, Gharaibeh RZ, Huang J, Jobin C, Lan P. Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis. Cell Host Microbe 2024; 32:2080-2091.e6. [PMID: 39626677 DOI: 10.1016/j.chom.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 09/13/2024] [Accepted: 11/07/2024] [Indexed: 12/14/2024]
Abstract
Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (ΔcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.
Collapse
Affiliation(s)
- Zhen He
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510655, China
| | - Jing Yu
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510655, China
| | - Junli Gong
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510655, China
| | - Jinjie Wu
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510655, China
| | - Xuan Zong
- Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, China
| | - Zhanhao Luo
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
| | - Xiaowen He
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
| | - Wai Ming Cheng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
| | - Yugeng Liu
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China
| | - Chen Liu
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
| | - Qiang Zhang
- School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
| | - Lei Dai
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China
| | - Tao Ding
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
| | - Beile Gao
- CAS Key Laboratory of Tropical Marine Bio Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong 510301, China
| | - Raad Z Gharaibeh
- Department of Medicine, Division of Gastroenterology, University of Florida, Gainesville, FL 32610, USA; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA
| | - Jinlin Huang
- Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, China.
| | - Christian Jobin
- Department of Medicine, Division of Gastroenterology, University of Florida, Gainesville, FL 32610, USA; Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
| | - Ping Lan
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
| |
Collapse
|
|
3
|
Chen Y, Ye X, Li X, Wang F, Yang J, Sun X, Yan S. Dynamic change of gut microbiota in head and neck concurrent chemoradiotherapy patients and its potential value in the prediction of acute oral mucositis grade as well as quality of life. Clin Transl Oncol 2024; 26:3191-3201. [PMID: 38844739 DOI: 10.1007/s12094-024-03542-0] [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: 01/30/2024] [Accepted: 05/28/2024] [Indexed: 11/15/2024]
Abstract
PURPOSE Radiotherapy is the major therapy for head and neck squamous cell carcinoma (HNSCC). However, whether gut microbiota changes in HNSCC patients who received concurrent chemoradiotherapy remains unclear. This study aimed to investigate the dynamic change of gut microbiota composition, construct the first radiotherapy-related gut microbiota database in these patients and identify the potential value of the gut microbiota changing in the prediction of acute oral mucositis grade as well as patients' life quality. METHODS We enrolled 47 HNSCC patients who scheduled with concurrent chemoradiotherapy. The field was irradiated with a total dose of 66-70 Gy in 33-35 fractions. All the patients received 2-3 cycles of platinum-based chemotherapy. After feces specimens collected, bacterial genomic DNA was isolated using magnetic beads and then analyzed by the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. RESULTS 194 genera which belonged to 27 phyla were found in 141 samples. Increased abundance of microbiota in diversity and richness was observed in mid-radiotherapy group. Bacteroides, Blautia, Phascolarctobacterium were three main genera in all three groups and the mid-radiotherapy group had the highest relative abundance of Phascolarctobacterium. What is more, most significantly altered bacteria shared the same variation pattern which was increased in mid-radiotherapy while decreased to the almost same level of as pre-radiotherapy in post-radiotherapy group. Further analysis indicated that Bacteroidetes showing an upward trend while Proteobacteria declining in higher grade of acute mucositis. Moreover, relatively low abundant Proteobacteria was significantly correlated with high-grade acute oral mucositis. As for the quality of life, Lactobacillales and Actinomycetales were specifically found in better life quality group. However, Clostridia_UCG_014, Eubacteriaceae, UCG_010 and Moraxellaceae were unique abundantly present in worse life quality group. CONCLUSION Chemoradiotherapy can affect the composition of the gut microbiota in HNSCC patients during the mid-term of treatment. Yet self-stabilized ability maintained the gut microbiota homeostasis. Dynamic change of specific species could help predict acute oral mucositis grade and characterize different quality of life group in these patients.
Collapse
Affiliation(s)
- Ying Chen
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China
| | - Xianghua Ye
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China
| | - Xinke Li
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China
| | - Fang Wang
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China
| | - Jinsong Yang
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China
| | - Xiaoli Sun
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China
| | - Senxiang Yan
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
| |
Collapse
|
|
4
|
González A, Fullaondo A, Navarro D, Rodríguez J, Tirnauca C, Odriozola A. New Insights into Mucosa-Associated Microbiota in Paired Tumor and Non-Tumor Adjacent Mucosal Tissues in Colorectal Cancer Patients. Cancers (Basel) 2024; 16:4008. [PMID: 39682194 DOI: 10.3390/cancers16234008] [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: 10/21/2024] [Revised: 11/24/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVE Colorectal cancer (CRC) is one of the most common cancers worldwide. Increasing scientific evidence supports the idea that gut microbiota dysbiosis accompanies colorectal tumorigenesis, and these changes could be causative. Implementing gut microbiota analysis in clinical practice is limited by sample type, sequencing platform and taxonomic classification. This article aims to address these limitations, providing new insights into the microbiota associated with CRC pathogenesis and implementing its analyses in personalized medicine. METHODS To that aim, we evaluate differences in the bacterial composition of 130 paired tumor and non-tumor adjacent tissues from a cohort of CRC patients from the Biobank of the University of Navarra, Spain. The V3-V4 region of the 16S rRNA gene was amplified, sequenced using the MinION platform, and taxonomically classified using the NCBI database. RESULTS To our knowledge, this is the first study to report an increased relative abundance of Streptococcus periodonticum and a decreased relative abundance of Corynebacterium associated with CRC. Genera such as Fusobacterium, Leptotrichia and Streptococcus showed higher relative abundances in tumor than in non-tumor tissues, as previously described in the literature. Specifically, we identified higher levels of Fusobacterium animalis, Fusobacterium nucleatum, Fusobacterium polymorphum and S. periodonticum in tumor tissues. In contrast, genera such as Bacteroides and Corynebacterium showed lower relative abundances in tumor tissues. There were also differences at the taxonomic level between tumor locations. CONCLUSIONS These results, consistent with previous studies, further support the hypothesis that Leptotrichia and Fusobacterium contribute to CRC progression, with F. nucleatum and F. animalis proposed as key CRC pathogenic taxa. Overall, these results contribute to a better understanding of the CRC-associated microbiota, addressing critical barriers to its implementation in personalized medicine.
Collapse
Affiliation(s)
- Adriana González
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, 48940 Bilbao, Spain
| | - Asier Fullaondo
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, 48940 Bilbao, Spain
| | | | - Javier Rodríguez
- Department of Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Cristina Tirnauca
- Department of Mathematics, Statistics and Computer Science, University of Cantabria, 39005 Santander, Spain
| | - Adrian Odriozola
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, 48940 Bilbao, Spain
| |
Collapse
|
|
5
|
García Menéndez G, Sichel L, López MDC, Hernández Y, Arteaga E, Rodríguez M, Fleites V, Fernández LT, Cano RDJ. From colon wall to tumor niche: Unraveling the microbiome's role in colorectal cancer progression. PLoS One 2024; 19:e0311233. [PMID: 39436937 PMCID: PMC11495602 DOI: 10.1371/journal.pone.0311233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 09/16/2024] [Indexed: 10/25/2024] Open
Abstract
Colorectal cancer (CRC) is influenced by perturbations in the colonic microbiota, characterized by an imbalance favoring pathogenic bacteria over beneficial ones. This dysbiosis contributes to CRC initiation and progression through mechanisms such as carcinogenic metabolite production, inflammation induction, DNA damage, and oncogenic signaling activation. Understanding the role of external factors in shaping the colonic microbiota is crucial for mitigating CRC progression. This study aims to elucidate the gut microbiome's role in CRC progression by analyzing paired tumor and mucosal tissue samples obtained from the colon walls of 17 patients. Through sequencing of the V3-V4 region of the 16S rRNA gene, we characterized the tumor microbiome and assessed its association with clinical variables. Our findings revealed a significant reduction in alpha diversity within tumor samples compared to paired colon biopsy samples, indicating a less diverse microbial environment within the tumor microenvironment. While both tissues exhibited dominance of similar bacterial phyla, their relative abundances varied, suggesting potential colon-specific effects. Fusobacteriota enrichment, notably in the right colon, may be linked to MLH1 deficiency. Taxonomy analysis identified diverse bacterial genera, with some primarily associated with the colon wall and others unique to this region. Conversely, several genera were exclusively expressed in tumor tissue. Functional biomarker analysis identified three key genes with differential abundance between tumor microenvironment and colon tissue, indicating distinct metabolic activities. Functional biomarker analysis revealed three key genes with differential abundance: K11076 (putrescine transport system) and K10535 (nitrification) were enriched in the tumor microenvironment, while K11329 (SasA-RpaAB circadian timing mediator) dominated colon tissue. Metabolic pathway analysis linked seven metabolic pathways to the microbiome. Collectively, these findings highlight significant gut microbiome alterations in CRC and strongly suggest that long-term dysbiosis profoundly impacts CRC progression.
Collapse
Affiliation(s)
- Gissel García Menéndez
- Pathology Department, Clinical Hospital Hermanos Ameijeiras, Centro Habana, La Habana, Cuba
| | - Liubov Sichel
- Stellar Biotics, LLC, Rockleigh, New Jersey, United States of America
| | | | - Yasel Hernández
- Pathology Department, Clinical Hospital Hermanos Ameijeiras, Centro Habana, La Habana, Cuba
| | - Ernesto Arteaga
- Pathology Department, Clinical Hospital Hermanos Ameijeiras, Centro Habana, La Habana, Cuba
| | - Marisol Rodríguez
- Pathology Department, Clinical Hospital Hermanos Ameijeiras, Centro Habana, La Habana, Cuba
| | - Vilma Fleites
- Oncology Department Clinical Hospital Hermanos Ameijeiras, Centro Habana, La Habana, Cuba
| | - Lipsy Teresa Fernández
- Surgery Department Clinical Hospital Hermanos Ameijeiras, Centro Habana, La Habana, Cuba
| | - Raúl De Jesus Cano
- Biological Sciences Department, California Polytechnic State University, San Luis Obispo, CA, United States of America
| |
Collapse
|
|
6
|
González A, Fullaondo A, Odriozola A. Host genetics and microbiota data analysis in colorectal cancer research. ADVANCES IN GENETICS 2024; 112:31-81. [PMID: 39396840 DOI: 10.1016/bs.adgen.2024.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) is a heterogeneous disease with a complex aetiology influenced by a myriad of genetic and environmental factors. Despite advances in CRC research, it is a major burden of disease, with the second highest incidence and third leading cause of cancer deaths worldwide. To individualise diagnosis, prognosis, and treatment of CRC, developing new strategies combining precision medicine and bioinformatic procedures is promising. Precision medicine is based on omics technologies and aims to individualise the management of CRC based on patient host genetic characteristics and microbiota. Bioinformatics is central to the application of personalised medicine because it enables the analysis of large datasets generated by these technologies. At the level of host genetics, bioinformatics allows the identification of mutations, genes, molecular pathways, biomarkers and drugs relevant to colorectal carcinogenesis. At the microbiota level, bioinformatics is fundamental to analysing microbial communities' composition and functionality and developing biomarkers and personalised microbiota-based therapies. This paper explores the host and microbiota genetic data analysis in CRC research.
Collapse
Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
| |
Collapse
|
|
7
|
Shieh C, Thompson HJ, McLaughlin E, Chiang CW, Hussan H. Advancements in Understanding and Preventing Obesity-Related Colon Cancer. Cancer J 2024; 30:357-369. [PMID: 39312456 DOI: 10.1097/ppo.0000000000000744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
ABSTRACT Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes. We also consider whether those linkages can be disrupted via weight loss therapies, including lifestyle modifications, pharmacotherapy, bariatric surgery, and endobariatrics.
Collapse
Affiliation(s)
- Christine Shieh
- From the Department of Gastroenterology, University of California, Davis, Sacramento, CA
| | - Henry J Thompson
- Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO
| | | | - Chien-Wei Chiang
- Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH
| | | |
Collapse
|
|
8
|
Furuta S. Microbiome-Stealth Regulator of Breast Homeostasis and Cancer Metastasis. Cancers (Basel) 2024; 16:3040. [PMID: 39272898 PMCID: PMC11394247 DOI: 10.3390/cancers16173040] [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: 08/21/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/15/2024] Open
Abstract
Cumulative evidence attests to the essential roles of commensal microbes in the physiology of hosts. Although the microbiome has been a major research subject since the time of Luis Pasteur and William Russell over 140 years ago, recent findings that certain intracellular bacteria contribute to the pathophysiology of healthy vs. diseased tissues have brought the field of the microbiome to a new era of investigation. Particularly, in the field of breast cancer research, breast-tumor-resident bacteria are now deemed to be essential players in tumor initiation and progression. This is a resurrection of Russel's bacterial cause of cancer theory, which was in fact abandoned over 100 years ago. This review will introduce some of the recent findings that exemplify the roles of breast-tumor-resident microbes in breast carcinogenesis and metastasis and provide mechanistic explanations for these phenomena. Such information would be able to justify the utility of breast-tumor-resident microbes as biomarkers for disease progression and therapeutic targets.
Collapse
Affiliation(s)
- Saori Furuta
- MetroHealth Medical Center, Case Western Reserve University School of Medicine, 2500 MetroHealth Drive, Cleveland, OH 44109, USA;
- Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| |
Collapse
|
|
9
|
Yin LL, Qi PQ, Hu YF, Fu XJ, He RS, Wang MM, Deng YJ, Xiong SY, Yu QW, Hu JP, Zhou L, Zhou ZB, Xiong Y, Deng H. Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum. World J Gastrointest Oncol 2024; 16:3600-3623. [PMID: 39171160 PMCID: PMC11334022 DOI: 10.4251/wjgo.v16.i8.3600] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/19/2024] [Accepted: 06/14/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.
Collapse
Affiliation(s)
- Li-Li Yin
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Ping-Qian Qi
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yun-Fei Hu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Xiao-Jun Fu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Rui-Shan He
- The Second College of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Meng-Meng Wang
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yan-Juan Deng
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Su-Yi Xiong
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Qi-Wen Yu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Jin-Ping Hu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Lv Zhou
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zhi-Bin Zhou
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Ying Xiong
- Department of General Medicine, The Second College of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi Province, China
| | - Huan Deng
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Ministry of Education Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi Province, China
| |
Collapse
|
|
10
|
Schwarz C, Mathieu J, Laverde Gomez J, Miller MR, Tikhonova M, Hamor C, Alvarez PJJ. Isolation and Characterization of Six Novel Fusobacterium necrophorum Phages. PHAGE (NEW ROCHELLE, N.Y.) 2024; 5:63-75. [PMID: 39119211 PMCID: PMC11304844 DOI: 10.1089/phage.2023.0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
Introduction Fusobacterium necrophorum, a human and animal pathogen, is the primary etiologic agent of bovine liver abscesses and a driving factor for prophylactic antibiotic use in the fed cattle industry. Considering calls to reduce agricultural antibiotic use, we isolated phages capable of killing F. necrophorum as an alternative or complementary biocontrol strategy. Methods Six novel phages (φFN37, φRTG5, φKSUM, φHugo, φPaco, and φBB) were isolated from rumen fluid or ruminal F. necrophorum isolates and subjected to host range testing on both F. necrophorum subspecies. Four F. necrophorum subspecies, necrophorum phages, were tested for cross-resistance and host growth inhibition individually and in pairs. Additionally, genomic sequencing, annotation, and analysis were performed.s. Results Four of six isolated phages were able to form lysogens, although all six contained lysogeny-related genes. φKSUM and φBB, did not form lysogens and were able to infect both subspecies. Four phages could infect F. necrophorum 8L1 (a liver abscess model challenge strain) in vitro. Genomic analysis showed that these phages belong to class Caudoviricetes with genome sizes ranging from 35 kbp to 111 kbp and GC values ranging from 26% to 36% and have extremely limited similarity to other deposited phage genomes infecting Fusobacterium or other genera. Conclusions Although all phages isolated contained sequences bearing similarities to genes implicated in lysogeny, the four selected for use in cocktails showed potential in inhibiting host growth, with several demonstrating promising attributes for biocontrol and therapeutic applications. Phage cocktails that may offer enhanced antibacterial activity were also identified, indicating the potential of some lysogenic phages to be adapted for biocontrol or therapeutic purposes when lytic phages are difficult to obtain.
Collapse
Affiliation(s)
- Cory Schwarz
- Department of Civil and Environmental Engineering, Rice University, Houston, Texas, USA
- Sentinel Environmental, Houston, Texas, USA
| | - Jacques Mathieu
- Department of Civil and Environmental Engineering, Rice University, Houston, Texas, USA
- Sentinel Environmental, Houston, Texas, USA
| | | | - Megan R. Miller
- Department of Civil and Environmental Engineering, Rice University, Houston, Texas, USA
| | | | - Clark Hamor
- Department of Biosciences, Rice University, Houston, Texas, USA
| | - Pedro J. J. Alvarez
- Department of Civil and Environmental Engineering, Rice University, Houston, Texas, USA
- Sentinel Environmental, Houston, Texas, USA
| |
Collapse
|
|
11
|
de Deus A, Gonçalves G, da Silva J, de Jesus LC, Azevedo-Santos APS, Dall Agnol H, Pereira SR. Microbiome reveals inflammatory-related bacteria and putative functional pathways involved in human papillomavirus-associated penile squamous cell carcinoma. Andrology 2024; 12:809-820. [PMID: 37840240 DOI: 10.1111/andr.13545] [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: 04/24/2023] [Revised: 09/07/2023] [Accepted: 10/03/2023] [Indexed: 10/17/2023]
Abstract
BACKGROUND Penile squamous cell carcinoma (PSCC) is a rare disease that is more prevalent in developing countries, such as Brazil, and is linked to poor genital hygiene, which promotes the proliferation of microorganisms. Dysbiosis has an effect on the local immune response, increases the risk of viral infection, and can generate inflammatory processes. Current knowledge of the microbiota found in penile tissues is limited, and the bacterial diversity of the PSCC remains unknown. In this investigation, the microbiota associated with penile cancer and its potential role in tumor development and progression were identified. METHODS The 16S rRNA gene was analyzed by next-generation sequencing in 19 tumors and their respective non-tumor adjacent tissues to perform taxonomic classification, analysis of core microbiome, abundance, and diversity of amplicon sequence variants (ASVs) (QIIME2 v.2020.2), and in silico functional prediction (PICRUST2, p < 0.05). RESULTS In both tissues, the phyla Proteobacteria and Firmicutes, and genera Alcaligenes and Fusobaterium, were the most prevalent. Tumors presented a greater relative abundance of Fusobacteriota, Campilobacteria, and Fusobacterium (p = 0.04, p = 0.04, and p = 0.039, respectively). In addition, the beta diversity analysis revealed a tendency for the formation of two distinct groups when only advanced tumors (pT2 and pT3) were considered. Further, the functional analysis identified the top 35 pathways, and 79.5% of PSCC samples contained pro-inflammatory microorganisms. CONCLUSION We describe the first microbiome of penile carcinoma, which revealed an abundant and diverse microbiota as well as inflammatory-related taxa (the phyla Proteobacteria and Firmicutes, the genera Fusobacterium and Prevotella, and the species Finegoldia magma and Pseudomonas geniculata) and molecular pathways (chitin derivates degradation, the protocatechuic acid pathway, inositol metabolism, and the sucrose pathway), which have also been linked to inflammation and carcinogenesis. Moreover, we found specific and abundant ASVs in both tumor and non-tumor tissues. Our data encourage further study to better understand the role of these microorganisms in penile carcinogenesis, offering an opportunity for advances in diagnosis, prognosis, and early therapy.
Collapse
Affiliation(s)
- Amanda de Deus
- Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil
- Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, Brazil
| | - Gabriele Gonçalves
- Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, Brazil
| | - Jenilson da Silva
- Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil
- Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, Brazil
| | - Luís Cláudio de Jesus
- Department of Genetics, Ecology, and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Hivana Dall Agnol
- Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, Brazil
- Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| | - Silma Regina Pereira
- Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, Brazil
| |
Collapse
|
|
12
|
Guo J, Shi W, Li X, Yang B, Qin C, Su L. Comparative Analysis of Gut Microbiomes in Laboratory Chinchillas, Ferrets, and Marmots: Implications for Pathogen Infection Research. Microorganisms 2024; 12:646. [PMID: 38674591 PMCID: PMC11051751 DOI: 10.3390/microorganisms12040646] [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: 02/20/2024] [Revised: 03/17/2024] [Accepted: 03/21/2024] [Indexed: 04/28/2024] Open
Abstract
Gut microbes play a vital role in the health and disease of animals, especially in relation to pathogen infections. Chinchillas, ferrets, and marmots are commonly used as important laboratory animals for infectious disease research. Here, we studied the bacterial and fungal microbiota and discovered that chinchillas had higher alpha diversity and a higher abundance of bacteria compared to marmots and ferrets by using the metabarcoding of 16S rRNA genes and ITS2, coupled with co-occurrence network analysis. The dominant microbes varied significantly among the three animal species, particularly in the gut mycobiota. In the ferrets, the feces were dominated by yeast such as Rhodotorula and Kurtzmaniella, while in the chinchillas, we found Teunomyces and Penicillium dominating, and Acaulium, Piromyces, and Kernia in the marmots. Nevertheless, the dominant bacterial genera shared some similarities, such as Clostridium and Pseudomonas across the three animal species. However, there were significant differences observed, such as Vagococcus and Ignatzschineria in the ferrets, Acinetobacter and Bacteroides in the chinchillas, and Bacteroides and Cellvibrio in the marmots. Additionally, our differential analysis revealed significant differences in classification levels among the three different animal species, as well as variations in feeding habitats that resulted in distinct contributions from the host microbiome. Therefore, our data are valuable for monitoring and evaluating the impacts of the microbiome, as well as considering potential applications.
Collapse
Affiliation(s)
| | | | | | | | | | - Lei Su
- NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, International Center for Technology and Innovation of Animal Model, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing 100021, China; (J.G.); (W.S.); (X.L.); (B.Y.); (C.Q.)
| |
Collapse
|
|
13
|
Rezasoltani S, Azizmohammad Looha M, Asadzadeh Aghdaei H, Jasemi S, Sechi LA, Gazouli M, Sadeghi A, Torkashvand S, Baniali R, Schlüter H, Zali MR, Feizabadi MM. 16S rRNA sequencing analysis of the oral and fecal microbiota in colorectal cancer positives versus colorectal cancer negatives in Iranian population. Gut Pathog 2024; 16:9. [PMID: 38378690 PMCID: PMC10880352 DOI: 10.1186/s13099-024-00604-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 02/06/2024] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers. MATERIAL AND METHODS A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform. RESULTS Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs. CONCLUSION Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.
Collapse
Grants
- RIGLD1065 Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- RIGLD1065 Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Regione Autonoma della Sardegna, legge regionale 12 dicembre 2022, n. 22 UNISS FAR fondi ricercar 2021, 2022 and Fondazione di Sardegna 2017
- Regione Autonoma della Sardegna, legge regionale 12 dicembre 2022, n. 22 UNISS FAR fondi ricercar 2021, 2022 and Fondazione di Sardegna 2017
Collapse
Affiliation(s)
- Sama Rezasoltani
- Section Mass Spectrometric Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf (UKE), 20246, Hamburg, Germany
- Division of Oral Microbiology and Immunology, Department of Operative Dentistry, Periodontology and Preventive Dentistry, RWTH University Hospital, 52057 Aachen, Germany
| | - Mehdi Azizmohammad Looha
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 19835-178, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 19835-178, Iran
| | - Seyedesomayeh Jasemi
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43b, 07100, Sassari, Italy
| | - Leonardo Antonio Sechi
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43b, 07100, Sassari, Italy.
- Struttura Complessa Microbiologia e Virologia, Azienda Ospedaliera Universitaria, 07100 Sassari, Italy.
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 19835-178, Iran
| | - Shirin Torkashvand
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 19835-178, Iran
| | - Reyhaneh Baniali
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 19835-178, Iran
| | - Hartmut Schlüter
- Section Mass Spectrometric Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf (UKE), 20246, Hamburg, Germany
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 19835-178, Iran
| | - Mohammad Mehdi Feizabadi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, 19835-178, Iran.
- Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
14
|
Martin-Gallausiaux C, Salesse L, Garcia-Weber D, Marinelli L, Beguet-Crespel F, Brochard V, Le Gléau C, Jamet A, Doré J, Blottière HM, Arrieumerlou C, Lapaque N. Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation. Gut Microbes 2024; 16:2295384. [PMID: 38126163 PMCID: PMC10761154 DOI: 10.1080/19490976.2023.2295384] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 12/12/2023] [Indexed: 12/23/2023] Open
Abstract
The anaerobic bacterium Fusobacterium nucleatum is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms underlying the promotion of intestinal tumor formation by F. nucleatum have only been partially uncovered. Here, we showed that F. nucleatum releases a metabolite into the microenvironment that strongly activates NF-κB in intestinal epithelial cells via the ALPK1/TIFA/TRAF6 pathway. Furthermore, we showed that the released molecule had the biological characteristics of ADP-heptose. We observed that F. nucleatum induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, BIRC3 and TNFAIP3. Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity in vitro. Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in Fusobacterium induced-CRC pathogenesis, and identify the role of ADP-H in this process.
Collapse
Affiliation(s)
| | - Laurène Salesse
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| | | | - Ludovica Marinelli
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| | | | - Vincent Brochard
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| | - Camille Le Gléau
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| | - Alexandre Jamet
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| | - Joël Doré
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
- Université Paris-Saclay, INRAE, Metagenopolis, Jouy-en-Josas, France
| | - Hervé M. Blottière
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
- Université Paris-Saclay, INRAE, Metagenopolis, Jouy-en-Josas, France
| | | | - Nicolas Lapaque
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| |
Collapse
|
|
15
|
Austin GI, Park H, Meydan Y, Seeram D, Sezin T, Lou YC, Firek BA, Morowitz MJ, Banfield JF, Christiano AM, Pe'er I, Uhlemann AC, Shenhav L, Korem T. Contamination source modeling with SCRuB improves cancer phenotype prediction from microbiome data. Nat Biotechnol 2023; 41:1820-1828. [PMID: 36928429 PMCID: PMC10504420 DOI: 10.1038/s41587-023-01696-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 01/23/2023] [Indexed: 03/18/2023]
Abstract
Sequencing-based approaches for the analysis of microbial communities are susceptible to contamination, which could mask biological signals or generate artifactual ones. Methods for in silico decontamination using controls are routinely used, but do not make optimal use of information shared across samples and cannot handle taxa that only partially originate in contamination or leakage of biological material into controls. Here we present Source tracking for Contamination Removal in microBiomes (SCRuB), a probabilistic in silico decontamination method that incorporates shared information across multiple samples and controls to precisely identify and remove contamination. We validate the accuracy of SCRuB in multiple data-driven simulations and experiments, including induced contamination, and demonstrate that it outperforms state-of-the-art methods by an average of 15-20 times. We showcase the robustness of SCRuB across multiple ecosystems, data types and sequencing depths. Demonstrating its applicability to microbiome research, SCRuB facilitates improved predictions of host phenotypes, most notably the prediction of treatment response in melanoma patients using decontaminated tumor microbiome data.
Collapse
Affiliation(s)
- George I Austin
- Department of Computer Science, Columbia University, New York, NY, USA
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Heekuk Park
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, NY, USA
| | - Yoli Meydan
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Dwayne Seeram
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, NY, USA
| | - Tanya Sezin
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, USA
| | - Yue Clare Lou
- Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA
| | - Brian A Firek
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Michael J Morowitz
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Jillian F Banfield
- Department of Earth and Planetary Science, University of California, Berkeley, CA, USA
- Department of Environmental Science, Policy, and Management, University of California, Berkeley, CA, USA
- Innovative Genomics Institute, University of California, Berkeley, CA, USA
- Chan Zuckerberg Biohub, San Francisco, CA, USA
| | - Angela M Christiano
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, USA
- Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA
| | - Itsik Pe'er
- Department of Computer Science, Columbia University, New York, NY, USA
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
- Data Science Institute, Columbia University, New York, NY, USA
| | - Anne-Catrin Uhlemann
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, NY, USA
| | - Liat Shenhav
- Center for Studies in Physics and Biology, Rockefeller University, New York, NY, USA.
| | - Tal Korem
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
- Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA.
- CIFAR Azrieli Global Scholars program, CIFAR, Toronto, Canada.
| |
Collapse
|
|
16
|
White MG, Damania A, Alshenaifi J, Sahasrabhojane P, Peacock O, Losh J, Wong MC, Lutter-Berkova Z, Chang GJ, Futreal A, Wargo JA, Ajami NJ, Kopetz S, You YN. Young-onset Rectal Cancer: Unique Tumoral Microbiome and Correlation With Response to Neoadjuvant Therapy. Ann Surg 2023; 278:538-548. [PMID: 37465976 PMCID: PMC10528779 DOI: 10.1097/sla.0000000000006015] [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: 07/20/2023]
Abstract
OBJECTIVE External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology. BACKGROUND YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown. METHODS YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR. RESULTS Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P <0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum , Bacteroides dorei, and Ruminococcus bromii (all P <0.001), but MPR in LORC was associated with R. bromii ( P <0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors. CONCLUSIONS Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.
Collapse
Affiliation(s)
- Michael G. White
- Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ashish Damania
- Platform for Innovative Microbiome and Translational research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jumanah Alshenaifi
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Pranoti Sahasrabhojane
- Platform for Innovative Microbiome and Translational research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Oliver Peacock
- Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jillian Losh
- Platform for Innovative Microbiome and Translational research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Matthew C Wong
- Platform for Innovative Microbiome and Translational research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Zuzana Lutter-Berkova
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - George J. Chang
- Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Andrew Futreal
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jennifer A. Wargo
- Platform for Innovative Microbiome and Translational research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Nadim J. Ajami
- Platform for Innovative Microbiome and Translational research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Y. Nancy You
- Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| |
Collapse
|
|
17
|
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.
Collapse
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
| |
Collapse
|
|
18
|
Robinson AV, Allen-Vercoe E. Strain specificity in fusobacterial co-aggregation with colorectal cancer-relevant species. Anaerobe 2023; 82:102758. [PMID: 37423597 DOI: 10.1016/j.anaerobe.2023.102758] [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: 03/27/2023] [Revised: 06/22/2023] [Accepted: 06/26/2023] [Indexed: 07/11/2023]
Abstract
OBJECTIVES The purpose of the present study was to characterize co-aggregation interactions between isolates of Fusobacterium nucleatum subsp. animalis and other colorectal cancer (CRC)-relevant species. METHODS Co-aggregation interactions were assessed by comparing optical density values following 2-h stationary strain co-incubations to strain optical density values when incubated alone. Co-aggregation was characterized between strains from a previously isolated, CRC biopsy-derived community and F. nucleatum subsp. animalis, a species linked to CRC and known to be highly aggregative. Interactions were also investigated between the fusobacterial isolates and strains sourced from alternate human gastrointestinal samples whose closest species match aligned with species in the CRC biopsy-derived community. RESULTS Co-aggregation interactions were observed to be strain-specific, varying between both F. nucleatum subsp. animalis strains and different strains of the same co-aggregation partner species. F. nucleatum subsp. animalis strains were observed to co-aggregate strongly with several taxa linked to CRC: Campylobacter concisus, Gemella spp., Hungatella hathewayi, and Parvimonas micra. CONCLUSIONS Co-aggregation interactions suggest the ability to encourage the formation of biofilms, and colonic biofilms, in turn, have been linked to promotion and/or progression of CRC. Co-aggregation between F. nucleatum subsp. animalis and CRC-linked species such as C. concisus, Gemella spp., H. hathewayi, and P. micra may contribute to both biofilm formation along CRC lesions and to disease progression.
Collapse
Affiliation(s)
- Avery V Robinson
- University of Guelph, 50 Stone Rd E, Guelph, ON, N1G 2W1, Canada.
| | | |
Collapse
|
|
19
|
Li H, Sheng D, Jin C, Zhao G, Zhang L. Identifying and ranking causal microbial biomarkers for colorectal cancer at different cancer subsites and stages: a Mendelian randomization study. Front Oncol 2023; 13:1224705. [PMID: 37538123 PMCID: PMC10395834 DOI: 10.3389/fonc.2023.1224705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 06/26/2023] [Indexed: 08/05/2023] Open
Abstract
Introduction The gut microbiome is directly involved in colorectal carcinogenesis, but much of the epidemiological evidence for the effect of the gut microbiome on colorectal cancer (CRC) risk comes from observational studies, and it is unclear whether identified microbial alterations are the cause or consequence of CRC development. Methods Univariate Mendelian randomization (MR) analysis and multivariate MR analysis based on Bayesian model averaging were performed to comprehensively explore the microbial risk factors associated with CRC. The Network Module Structure Shift method was used to identify microbial biomarkers associated with CRC. Mediation analysis was used to explore the dietary habits-microbiota-CRC pathway. Results The results of the four methods showed that 9 bacteria had a robust causal relationship with the development of CRC. Among them, Streptococcus thermophilus reduced the risk of CRC; Eubacterium ventriosum and Streptococcus were beneficial bacteria of malignant tumors of colon (CC); Erysipelotrichaceae was a protective factor for malignant tumors of rectal (CR); Bacteroides ovatus was a risk factor for benign tumors. Finally, the mediation analysis revealed 10 pathways by which dietary regulation bacteria affected the risk of CRC, including alcohol consumption increased the risk of CC by reducing the abundance of Eubacterium ventriosum (mediated proportion: 43.044%), and the mediated proportion of other pathways was 7.026%-34.22%. Discussion These findings will contribute to the understanding of the different carcinogenic mechanisms of intestinal flora in the colon and rectum and the risk of tumor transformation, thereby aiding CRC prevention, early screening, and the development of future strategies to reduce CRC risk.
Collapse
Affiliation(s)
- Hongfeng Li
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Dashuang Sheng
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chuandi Jin
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Guoping Zhao
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan, China
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
- CAS Key Laboratory of Computational Biology, Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Lei Zhang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan, China
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
- Shandong Children’s Microbiome Center, Children’s Hospital Affiliated to Shandong University, Jinan, China
| |
Collapse
|
|
20
|
Mouradov D, Greenfield P, Li S, In EJ, Storey C, Sakthianandeswaren A, Georgeson P, Buchanan DD, Ward RL, Hawkins NJ, Skinner I, Jones IT, Gibbs P, Ma C, Liew YJ, Fung KYC, Sieber OM. Oncomicrobial Community Profiling Identifies Clinicomolecular and Prognostic Subtypes of Colorectal Cancer. Gastroenterology 2023; 165:104-120. [PMID: 36933623 DOI: 10.1053/j.gastro.2023.03.205] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 02/10/2023] [Accepted: 03/09/2023] [Indexed: 03/20/2023]
Abstract
BACKGROUND & AIMS Dysbiosis of gut microbiota is linked to the development of colorectal cancer (CRC). However, microbiota-based stratification of CRC tissue and how this relates to clinicomolecular characteristics and prognosis remains to be clarified. METHODS Tumor and normal mucosa from 423 patients with stage I to IV CRC were profiled by bacterial 16S rRNA gene sequencing. Tumors were characterized for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), APC, BRAF, KRAS, PIK3CA, FBXW7, SMAD4, and TP53 mutations, subsets for chromosome instability (CIN), mutation signatures, and consensus molecular subtypes (CMS). Microbial clusters were validated in an independent cohort of 293 stage II/III tumors. RESULTS Tumors reproducibly stratified into 3 oncomicrobial community subtypes (OCSs) with distinguishing features: OCS1 (Fusobacterium/oral pathogens, proteolytic, 21%), right-sided, high-grade, MSI-high, CIMP-positive, CMS1, BRAF V600E, and FBXW7 mutated; OCS2 (Firmicutes/Bacteroidetes, saccharolytic, 44%), and OCS3 (Escherichia/Pseudescherichia/Shigella, fatty acid β-oxidation, 35%) both left-sided and exhibiting CIN. OCS1 was associated with MSI-related mutation signatures (SBS15, SBS20, ID2, and ID7) and OCS2 and OCS3 with SBS18 related to damage by reactive oxygen species. Among stage II/III patients, OCS1 and OCS3 both had poorer overall survival compared with OCS2 for microsatellite stable tumors (multivariate hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.15-2.99; P = .012; and HR, 1.52; 95% CI 1.01-2.29; P = .044, respectively) and left-sided tumors (multivariate HR, 2.66; 95% CI, 1.45-4.86; P = .002; and HR, 1.76; 95% CI, 1.03-3.02; P = .039, respectively). CONCLUSIONS OCS classification stratified CRCs into 3 distinct subgroups with different clinicomolecular features and outcomes. Our findings provide a framework for a microbiota-based stratification of CRC to refine prognostication and to inform the development of microbiota-targeted interventions.
Collapse
Affiliation(s)
- Dmitri Mouradov
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Paul Greenfield
- Energy Business Unit, Commonwealth Scientific and Industrial Research Organization, Lindfield, New South Wales, Australia; School of Natural Sciences, Macquarie University, North Ryde, New South Wales, Australia
| | - Shan Li
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
| | - Eun-Jung In
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Claire Storey
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
| | - Anuratha Sakthianandeswaren
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Peter Georgeson
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia; University of Melbourne Center for Cancer Research, Victorian Comprehensive Cancer Center, Melbourne, Victoria, Australia
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia; University of Melbourne Center for Cancer Research, Victorian Comprehensive Cancer Center, Melbourne, Victoria, Australia; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Robyn L Ward
- Prince of Wales Clinical School and Lowy Cancer Research Center, UNSW Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Nicholas J Hawkins
- School of Medical Sciences, UNSW Sydney, Sydney, New South Wales, Australia
| | - Iain Skinner
- Department of Surgery, Western Health, Footscray, Victoria, Australia
| | - Ian T Jones
- Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia; Department of Medical Oncology, Western Health, St Albans, Victoria, Australia; Department of Medical Oncology, Western Health, Footscray, Victoria, Australia
| | - Chenkai Ma
- Molecular Diagnostics Solutions, Commonwealth Scientific and Industrial Research Organization Health and Biosecurity, Westmead, New South Wales, Australia
| | - Yi Jin Liew
- Molecular Diagnostics Solutions, Commonwealth Scientific and Industrial Research Organization Health and Biosecurity, Westmead, New South Wales, Australia
| | - Kim Y C Fung
- Molecular Diagnostics Solutions, Commonwealth Scientific and Industrial Research Organization Health and Biosecurity, Westmead, New South Wales, Australia
| | - Oliver M Sieber
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia; Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
| |
Collapse
|
|
21
|
Kato I, Minkevitch J, Sun J. Oncogenic potential of Campylobacter infection in the gastrointestinal tract: narrative review. Scand J Gastroenterol 2023; 58:1453-1465. [PMID: 37366241 DOI: 10.1080/00365521.2023.2228954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/26/2023] [Accepted: 06/16/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND Campylobacter jejuni is the leading cause of zoonotic gastroenteritis. The other emerging group of Campylobacters spp. are part of human oral commensal, represented by C. concisus (CC), which has been recently linked to non-oral conditions. Although long-term gastrointestinal (GI) complications from these two groups of Campylobacters have been previously reviewed individually, overall impact of Campylobacter infection on GI carcinogenesis and their inflammatory precursor lesions has not been assessed collectively. AIMS To evaluate the available evidence concerning the association between Campylobacter infection/colonization and inflammatory bowel disease (IBD), reflux esophagitis/metaplasia colorectal cancer (CRC) and esophageal cancer (EC). METHODS We performed a comprehensive literature search of PubMed for relevant original publications and systematic reviews/meta-analyses of epidemiological and clinical studies. In addition, we gathered additional information concerning microbiological data, animal models and mechanistic data from in vitro studies. RESULTS Both retrospective and prospective studies on IBD showed relatively consistent increased risk associated with Campylobacter infection. Despite lack of supporting prospective studies, retrospective studies based on tissue/fecal microbiome revealed consistent enrichment of Campylobacter in CRC samples. Studies on EC precursor lesions (esophagitis and metaplasia) were generally supportive for the association with Campylobacter, while inconsistent observations on EC. Studies on both IBD and EC precursors suggested the predominant role of CC, but studies on CRC were not informative of species. CONCLUSIONS There is sufficient evidence calling for concerted effort in unveiling direct and indirect connection of this organism to colorectal and esophageal cancer in humans.
Collapse
Affiliation(s)
- Ikuko Kato
- Department of Oncology and Pathology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Julia Minkevitch
- Rosalind Franklin University of Medicine and Science, Chicago, IL, USA
| | - Jun Sun
- Department of Microbiology/Immunology, University of Illinois at Chicago (UIC), Chicago, IL, USA
- UIC Cancer Center, Chicago, IL, USA
| |
Collapse
|
|
22
|
Duizer C, de Zoete MR. The Role of Microbiota-Derived Metabolites in Colorectal Cancer. Int J Mol Sci 2023; 24:8024. [PMID: 37175726 PMCID: PMC10178193 DOI: 10.3390/ijms24098024] [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: 03/19/2023] [Revised: 04/25/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
The impact of bacterial members of the microbiota on the development of colorectal cancer (CRC) has become clear in recent years. However, exactly how bacteria contribute to the development of cancer is often still up for debate. The impact of bacteria-derived metabolites, which can influence the development of CRC either in a promoting or inhibiting manner, is undeniable. Here, we discuss the effects of the most well-studied bacteria-derived metabolites associated with CRC, including secondary bile acids, short-chain fatty acids, trimethylamine-N-oxide and indoles. We show that the effects of individual metabolites on CRC development are often nuanced and dose- and location-dependent. In the coming years, the array of metabolites involved in CRC development will undoubtedly increase further, which will emphasize the need to focus on causation and mechanisms and the clearly defined roles of bacterial species within the microbiota.
Collapse
Affiliation(s)
| | - Marcel R. de Zoete
- Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| |
Collapse
|
|
23
|
Palmieri O, Castellana S, Latiano A, Latiano T, Gentile A, Panza A, Nardella M, Ciardiello D, Latiano TP, Corritore G, Mazza T, Perri F, Biscaglia G. Mucosal Microbiota from Colorectal Cancer, Adenoma and Normal Epithelium Reveals the Imprint of Fusobacterium nucleatum in Cancerogenesis. Microorganisms 2023; 11:1147. [PMID: 37317121 DOI: 10.3390/microorganisms11051147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/17/2023] [Accepted: 04/25/2023] [Indexed: 06/16/2023] Open
Abstract
An increasing amount of evidence suggests the emerging role of the gut microbiota in the development of colorectal cancer (CRC). This study aimed to elucidate the architecture of microbial communities within normal and neoplastic colonic mucosa. METHODS Microbiota were analyzed by NGS and by an ensemble of metagenomics analysis tools in a total of 69 tissues from 9 patients with synchronous colorectal neoplasia and adenomas (27 specimens: 9 from normal tissues, 9 adenomas, and 9 tumours), 16 patients with only colonic adenomas (32 specimens: 16 from normal tissues and 16 adenomas), and from healthy subjects (10 specimens of normal mucosa). RESULTS Weak differences were observed in alpha and beta metrics among the synchronous tissues from CRC and controls. Through pairwise differential abundance analyses of sample groups, an increasing trend of Rikenellaceae, Pseudomonas and Fusobacterium, and decreasing trends of Staphylococcus, Actinobacillus and Gemmiger were observed in CRC, while Staphylococcus and Bifidobacterium were decreased in patients with only adenomas. At RT-qPCR analysis, Fusobacterium nucleatum was significantly enriched in all the tissues of subjects with synchronous colorectal neoplasia. CONCLUSION Our findings provide a comprehensive view of the human mucosa-associated gut microbiota, emphasizing global microbial diversity mostly in synchronous lesions and proving the constant presence of Fusobacterium nucleatum, with its ability to drive carcinogenesis.
Collapse
Affiliation(s)
- Orazio Palmieri
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Stefano Castellana
- Unit of Bioinformatics, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Anna Latiano
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Tiziana Latiano
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Annamaria Gentile
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Anna Panza
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Marianna Nardella
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Davide Ciardiello
- Division of Oncology, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
- Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Tiziana Pia Latiano
- Division of Oncology, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Giuseppe Corritore
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Tommaso Mazza
- Unit of Bioinformatics, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Francesco Perri
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| | - Giuseppe Biscaglia
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo, Italy
| |
Collapse
|
|
24
|
Iadsee N, Chuaypen N, Techawiwattanaboon T, Jinato T, Patcharatrakul T, Malakorn S, Petchlorlian A, Praditpornsilpa K, Patarakul K. Identification of a novel gut microbiota signature associated with colorectal cancer in Thai population. Sci Rep 2023; 13:6702. [PMID: 37095272 PMCID: PMC10126090 DOI: 10.1038/s41598-023-33794-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 04/19/2023] [Indexed: 04/26/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. Dysbiosis of human gut microbiota has been linked to sporadic CRC. This study aimed to compare the gut microbiota profiles of 80 Thai volunteers over 50 years of age among 25 CRC patients, 33 patients with adenomatous polyp, and 22 healthy controls. The 16S rRNA sequencing was utilized to characterize the gut microbiome in both mucosal tissue and stool samples. The results revealed that the luminal microbiota incompletely represented the intestinal bacteria at the mucus layer. The mucosal microbiota in beta diversity differed significantly among the three groups. The stepwise increase of Bacteroides and Parabacteroides according to the adenomas-carcinomas sequence was found. Moreover, linear discriminant analysis effect size showed a higher level of Erysipelatoclostridium ramosum (ER), an opportunistic pathogen in the immunocompromised host, in both sample types of CRC patients. These findings indicated that the imbalance of intestinal microorganisms might involve in CRC tumorigenesis. Additionally, absolute quantitation of bacterial burden by quantitative real-time PCR (qPCR) confirmed the increasing ER levels in both sample types of cancer cases. Using ER as a stool-based biomarker for CRC detection by qPCR could predict CRC in stool samples with a specificity of 72.7% and a sensitivity of 64.7%. These results suggested ER might be a potential noninvasive marker for CRC screening development. However, a larger sample size is required to validate this candidate biomarker in diagnosing CRC.
Collapse
Affiliation(s)
- Nutta Iadsee
- Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand
| | - Natthaya Chuaypen
- Department of Biochemistry, Faculty of Medicine, Center of Excellence in Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand
| | - Teerasit Techawiwattanaboon
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Bangkok, Thailand
| | - Thananya Jinato
- Department of Biochemistry, Faculty of Medicine, Center of Excellence in Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand
- Doctor of Philosophy Program in Medical Sciences, Graduate Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Tanisa Patcharatrakul
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
- Faculty of Medicine, Center of Excellence in Neurogastroenterology and Motility, Chulalongkorn University, Bangkok, Thailand
| | - Songphol Malakorn
- Division of Colorectal Surgery, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Aisawan Petchlorlian
- Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Geriatric Excellence Center, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Kearkiat Praditpornsilpa
- Geriatric Excellence Center, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kanitha Patarakul
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
- Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Bangkok, Thailand.
| |
Collapse
|
|
25
|
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.
Collapse
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.)
| |
Collapse
|
|
26
|
Ağagündüz D, Cocozza E, Cemali Ö, Bayazıt AD, Nanì MF, Cerqua I, Morgillo F, Saygılı SK, Berni Canani R, Amero P, Capasso R. Understanding the role of the gut microbiome in gastrointestinal cancer: A review. Front Pharmacol 2023; 14:1130562. [PMID: 36762108 PMCID: PMC9903080 DOI: 10.3389/fphar.2023.1130562] [Citation(s) in RCA: 95] [Impact Index Per Article: 47.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 01/10/2023] [Indexed: 01/26/2023] Open
Abstract
Gastrointestinal cancer represents one of the most diagnosed types of cancer. Cancer is a genetic and multifactorial disease, influenced by the host and environmental factors. It has been stated that 20% of cancer is caused by microorganisms such as Helicobacter pylori, hepatitis B and C virus, and human papillomavirus. In addition to these well-known microorganisms associated with cancer, it has been shown differences in the composition of the microbiota between healthy individuals and cancer patients. Some studies have suggested the existence of the selected microorganisms and their metabolites that can promote or inhibit tumorigenesis via some mechanisms. Recent findings have shown that gut microbiome and their metabolites can act as cancer promotors or inhibitors. It has been shown that gastrointestinal cancer can be caused by a dysregulation of the expression of non-coding RNA (ncRNA) through the gut microbiome. This review will summarize the latest reports regarding the relationship among gut microbiome, ncRNAs, and gastrointestinal cancer. The potential applications of diagnosing and cancer treatments will be discussed.
Collapse
Affiliation(s)
- Duygu Ağagündüz
- Department of Nutrition and Dietetics, Gazi University, Emek, Ankara, Turkey
| | | | - Özge Cemali
- Department of Nutrition and Dietetics, Gazi University, Emek, Ankara, Turkey
| | - Ayşe Derya Bayazıt
- Department of Nutrition and Dietetics, Gazi University, Emek, Ankara, Turkey
| | | | - Ida Cerqua
- Department of Pharmacy, University of Naples “Federico II”, Naples, Italy
| | - Floriana Morgillo
- Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
| | - Suna Karadeniz Saygılı
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,Department of Histology and Embryology, Kütahya Health Sciences University, Kütahya, Turkey
| | - Roberto Berni Canani
- Department of Translational Medical Science and ImmunoNutritionLab at CEINGE Biotechnologies Research Center and Task Force for Microbiome Studies, University of Naples Federico II, Naples, Italy
| | - Paola Amero
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,*Correspondence: Raffaele Capasso, ; Paola Amero,
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy,*Correspondence: Raffaele Capasso, ; Paola Amero,
| |
Collapse
|
|
27
|
Dolislager CG, Callahan SM, Donohoe DR, Johnson JG. Campylobacter jejuni induces differentiation of human neutrophils to the CD16 hi /CD62L lo subtype. J Leukoc Biol 2022; 112:1457-1470. [PMID: 35866361 DOI: 10.1002/jlb.4a0322-155rr] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 06/29/2022] [Indexed: 01/04/2023] Open
Abstract
The discovery of neutrophil subtypes has expanded what is known about neutrophil functions, yet there is still much to learn about the role of these subtypes during bacterial infection. We investigated whether Campylobacter jejuni induced differentiation of human neutrophils into the hypersegmented, CD16hi /CD62Llo subtype. In addition, we investigated whether C. jejuni-dependent differentiation of this neutrophil subtype induced cancer-promoting activities of human T cells and colonocytes, which were observed in other studies of hypersegmented, CD16hi /CD62Llo neutrophils. We found that C. jejuni causes a significant shift in human neutrophil populations to the hypersegmented, CD16hi /CD62Llo subtype and that those populations exhibit delayed apoptosis, elevated arginase-1 expression, and increased reactive oxygen species production. Furthermore, incubation of C. jejuni-infected neutrophils with human T cells resulted in decreased expression of the ζ-chain of the TCR, which was restored upon supplementation with exogenous l-arginine. In addition, incubation of C. jejuni-infected neutrophils with human colonocytes resulted in increased HIF-1α stabilization and NF-κB activation in those colonocytes, which may result in the up-regulation of protumorigenic genes.
Collapse
Affiliation(s)
| | - Sean M Callahan
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| | - Dallas R Donohoe
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.,Department of Nutrition, University of Tennessee, Knoxville, Tennessee, USA
| | - Jeremiah G Johnson
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| |
Collapse
|
|
28
|
Karpiński TM, Ożarowski M, Stasiewicz M. Carcinogenic microbiota and its role in colorectal cancer development. Semin Cancer Biol 2022; 86:420-430. [PMID: 35090978 DOI: 10.1016/j.semcancer.2022.01.004] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 12/30/2021] [Accepted: 01/13/2022] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is one of the most common malignancies worldwide. The main risk factors for CRC are family history of colon or rectal cancer, familial polyposis syndrome or hereditary nonpolyposis, and chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease). Recent studies show that the gastrointestinal microbiota play a significant role in colorectal carcinogenesis. In this review we present the microorganisms, whose influence on the development of CRC has been proven: Bacteroides fragilis, Clostridioides and Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Helicobacter pylori, Peptostreptococcus anaerobius, Streptococcus bovis group, and sulfate-reducing bacteria. Moreover, the carcinogenic mechanisms of action mediated by the above bacteria are laid out.
Collapse
Affiliation(s)
- Tomasz M Karpiński
- Chair and Department of Medical Microbiology, Poznań University of Medical Sciences, Wieniawskiego 3, 61-712 Poznań, Poland.
| | - Marcin Ożarowski
- Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants - National Research Institute, Wojska Polskiego 71b, 60-630 Poznań, Poland.
| | - Mark Stasiewicz
- Research Group of Medical Microbiology, Chair and Department of Medical Microbiology, Poznań University of Medical Sciences, Wieniawskiego 3, 61-712 Poznań, Poland.
| |
Collapse
|
|
29
|
Chang Y, Li X, Ding L, Yang C, Pan Z, Han N, Cui Y, Zhi F, Yang R, Gao H, Bi Y. Genetic and Functional Differences of Escherichia coli Strains from Colorectal Cancer Mucosal Tissues. ENGINEERING 2022; 16:210-219. [DOI: 10.1016/j.eng.2021.03.028] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
|
|
30
|
Piazzesi A, Putignani L. Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention. Front Microbiol 2022; 13:958346. [PMID: 36071979 PMCID: PMC9441770 DOI: 10.3389/fmicb.2022.958346] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 07/25/2022] [Indexed: 11/15/2022] Open
Abstract
Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.
Collapse
Affiliation(s)
- Antonia Piazzesi
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
- *Correspondence: Lorenza Putignani,
| |
Collapse
|
|
31
|
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: 6] [Impact Index Per Article: 2.0] [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.
Collapse
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
| |
Collapse
|
|
32
|
The Tissue-Associated Microbiota in Colorectal Cancer: A Systematic Review. Cancers (Basel) 2022; 14:cancers14143385. [PMID: 35884445 PMCID: PMC9317273 DOI: 10.3390/cancers14143385] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 07/05/2022] [Accepted: 07/08/2022] [Indexed: 11/28/2022] Open
Abstract
Simple Summary Growing evidence shows a close relationship between the microbiome and colorectal cancer, but most studies analyze fecal samples. However, solid information on the microbial community that is present locally in the intestinal tumor tissues is lacking. Therefore, the aim of this systematic review was to compile evidence on the relationship between tissue-associated microbiota and colorectal cancer. Among 5080 screened publications, 39 were eligible and included in the analysis. Despite the heterogeneity in methodologies and reporting between studies, 12 groups of bacteria with strong positive and 18 groups of bacteria with strong negative associations with colorectal cancer were identified. Such knowledge may ultimately be used in novel strategies that aim to prevent, detect, and treat colorectal cancer in the upcoming years. Abstract The intestinal microbiome is associated with colorectal cancer. Although the mucosal microbiota better represents an individual’s local microbiome, studies on the colorectal cancer microbiota mainly reflect knowledge obtained from fecal samples. This systematic review aimed to summarize the current evidence on the relationship between the mucosal-associated bacterial microbiota and colorectal cancer. Searches were conducted in PubMed and Web of Science databases for publications comparing the mucosal microbiome of colorectal cancer patients with that of healthy controls, or with that of non-cancerous mucosal tissues. The primary outcomes were differences in microbial diversity and taxonomy. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Of the 5080 studies identified, 39 were eligible and included in the systematic review. No consistent results were identified for the α- and β-diversity, due to high heterogeneity in reporting and to differences in metrics and statistical approaches, limiting study comparability. Qualitative synthesis of microbial taxonomy identified 12 taxa with strong positive and 18 taxa with strong negative associations with colorectal cancer. Fusobacterium, Campylobacter, Parvimonas, Peptostreptococcus, Streptococcus, and Granulicatella were defined as enriched in colorectal cancer. Despite the methodological limitations of the studies, consistent evidence on bacterial taxa associated with colorectal cancer was identified. Prospective studies in large and well-characterized patient populations will be crucial to validate these findings.
Collapse
|
|
33
|
Wei J, Li R, Lu Y, Meng F, Xian B, Lai X, Lin X, Deng Y, Yang D, Zhang H, Li L, Ben X, Qiao G, Liu W, Li Z. Salivary microbiota may predict the presence of esophageal squamous cell carcinoma. Genes Dis 2022; 9:1143-1151. [PMID: 35685473 PMCID: PMC9170574 DOI: 10.1016/j.gendis.2021.02.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/25/2021] [Accepted: 02/09/2021] [Indexed: 01/11/2023] Open
Abstract
The aim is to explore the predictive value of salivary bacteria for the presence of esophageal squamous cell carcinoma (ESCC). Saliva samples were obtained from 178 patients with ESCC and 101 healthy controls, and allocated to screening and verification cohorts, respectively. In the screening phase, after saliva DNA was extracted, 16S rRNA V4 regions of salivary bacteria were amplified by polymerase chain reaction (PCR) with high-throughput sequencing. Highly expressed target bacteria were screened by Operational Taxonomic Units clustering, species annotation and microbial diversity assessment. In the verification phase, the expression levels of target bacteria identified in the screening phase were verified by absolute quantitative PCR (Q-PCR). Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of target salivary bacteria. LEfSe analysis revealed higher proportions of Fusobacterium, Streptococcus and Porphyromonas, and Q-PCR assay showed significantly higher numbers of Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in patients with ESCC, when compared with healthy controls (all P < 0.05). The areas under the ROC curves for Streptococcus salivarius, Fusobacterium nucleatum, Porphyromonas gingivalis and the combination of the three bacteria for predicting patients with ESCC were 69%, 56.5%, 61.8% and 76.4%, respectively. The sensitivities corresponding to cutoff value were 69.3%, 22.7%, 35.2% and 86.4%, respectively, and the matched specificity were 78.4%, 96.1%, 90.2% and 58.8%, respectively. These highly expressed Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in the saliva, alone or in combination, indicate their predictive value for ESCC.
Collapse
Affiliation(s)
- Junmin Wei
- Guangdong Provincial Institute of Geriatrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China
| | - Ruifeng Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China
- Wuhan No. 1 Hospital, Wuhan, Hubei 430022, PR China
| | - Yanxian Lu
- Guangdong Provincial Institute of Geriatrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China
| | - Fan Meng
- The First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi 341000, PR China
| | - Bohong Xian
- Guangdong Provincial Institute of Geriatrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China
| | - Xiaorong Lai
- Medicine-Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Xiayi Lin
- Concord Medical Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Yu Deng
- Concord Medical Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Dongyang Yang
- Medicine-Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Huabin Zhang
- Concord Medical Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Liangfang Li
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Xiaosong Ben
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Guibin Qiao
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Wanwei Liu
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
| | - Zijun Li
- Guangdong Provincial Institute of Geriatrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, PR China
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China
- Corresponding author. Department of Gastroenterology of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Institute of Geriatrics, Concorde Medical Center, 106 Zhongshan Er Rd., Guangdong 510080, PR China. Fax: +008620 83826085.
| |
Collapse
|
|
34
|
Dai W, Li C, Li T, Hu J, Zhang H. Super-taxon in human microbiome are identified to be associated with colorectal cancer. BMC Bioinformatics 2022; 23:243. [PMID: 35729515 PMCID: PMC9215102 DOI: 10.1186/s12859-022-04786-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 06/06/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that microbial communities play in healthy and disease hosts remain largely unknown. The microbial communities are typically recorded through the taxa counts of operational taxonomic units (OTUs). The sparsity and high correlations among OTUs pose major challenges for understanding the microbiota-disease relation. Furthermore, the taxa data are structured in the sense that OTUs are related evolutionarily by a hierarchical structure. RESULTS In this study, we borrow the idea of super-variant from statistical genetics, and propose a new concept called super-taxon to exploit hierarchical structure of taxa for microbiome studies, which is essentially a combination of taxonomic units. Specifically, we model a genus which consists of a set of OTUs at low hierarchy and is designed to reflect both marginal and joint effects of OTUs associated with the risk of CRC to address these issues. We first demonstrate the power of super-taxon in detecting highly correlated OTUs. Then, we identify CRC-associated OTUs in two publicly available datasets via a discovery-validation procedure. Specifically, four species of two genera are found to be associated with CRC: Parvimonas micra, Parvimonas sp., Peptostreptococcus stomatis, and Peptostreptococcus anaerobius. More importantly, for the first time, we report the joint effect of Parvimonas micra and Parvimonas sp. (p = 0.0084) as well as that of Peptostrepto-coccus stomatis and Peptostreptococcus anaerobius (p = 8.21e-06) on CRC. The proposed approach provides a novel and useful tool for identifying disease-related microbes by taking the hierarchical structure of taxa into account and further sheds new lights on their potential joint effects as a community in disease development. CONCLUSIONS Our work shows that proposed approaches are effective to study the microbiota-disease relation taking into account for the sparsity, hierarchical and correlated structure among microbes.
Collapse
Affiliation(s)
- Wei Dai
- Department of Biostatistics, Yale University School of Public Health, 300 George Street, Ste 523, New Haven, CT, 06511, USA
| | - Cai Li
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
| | - Ting Li
- Department of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong, China
| | - Jianchang Hu
- Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Heping Zhang
- Department of Biostatistics, Yale University School of Public Health, 300 George Street, Ste 523, New Haven, CT, 06511, USA.
| |
Collapse
|
|
35
|
Srivastava A, Mishra S, Garg PK, Dubey AK, Deo SVS, Verma D. Comparative and analytical characterization of the oral bacteriome of smokeless tobacco users with oral squamous cell carcinoma. Appl Microbiol Biotechnol 2022; 106:4115-4128. [PMID: 35596785 DOI: 10.1007/s00253-022-11980-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 05/09/2022] [Accepted: 05/10/2022] [Indexed: 12/24/2022]
Abstract
Oral cavity squamous cell carcinoma (OSCC) is the most common type of head and neck cancer worldwide. Smokeless tobacco (SLT) has been well proven for its role in oral carcinogenesis due to the abundance of several carcinogens. However, the role of inhabitant microorganisms in the oral cavity of smokeless tobacco users has not yet been well explored in the context of OSCC. Therefore, the present investigation was conceived to analyze the oral bacteriome of smokeless tobacco users having OSCC (CP group). With the assistance of illumina-based sequencing of bacterial-specific V3 hypervariable region of 16S rDNA gene, 71,969 OTUs (operational taxonomic units) were categorized into 18 phyla and 166 genera. The overall analysis revealed that the oral bacteriome of the patients with OSCC, who were smokeless tobacco users, was significantly different compared to the healthy smokeless tobacco users (HTC group) and non-users (HI users). The appearance of 14 significantly abundant genera [FDR (false discovery rate) adjusted probability value of significance (p value) < 0.05] among the CP group showed the prevalence of tobacco-specific nitrosamines forming bacteria (Staphylococcus, Fusobacterium, and Campylobacter). The functional attributes of the oral bacteriome of the CP group can also be correlated with the genes involved in oncogenesis. This study is the first report on the oral bacteriome of Indian patients with OSCC who were chronic tobacco chewers. The results of the present study will pave the way to understand the influence of smokeless tobacco on the oral bacteriome of OSCC patients. KEY POINTS: • Oral bacteriome of OSCC patients differ from healthy smokeless tobacco (SLT) users and SLT non-users. • Smokeless tobacco influences the oral bacteriome of OSCC group. • Oral bacteriome specific diagnostics may be developed for pre-diagnosis of oral cancer.
Collapse
Affiliation(s)
- Ankita Srivastava
- Department of Environmental Microbiology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
| | - SukhDev Mishra
- Department of Bio-Statistics and Data Management, ICMR-National Institute of Occupational Health, Ahmedabad, India
| | - Pankaj Kumar Garg
- Department of Surgical Oncology, Shri Guru Ram Rai Institute of Medical and Health Sciences and Shri Mahant Indiresh Hospital, Dehradun, Uttarakhand, India
| | - Ashok Kumar Dubey
- Division of Biological Sciences and Engineering, Netaji Subhas University of Technology, New Delhi, India
| | - S V S Deo
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Digvijay Verma
- Department of Environmental Microbiology, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
| |
Collapse
|
|
36
|
Microbiome Analysis in Patients with Colorectal Cancer by 16S Ribosomal RNA Sequencing in the Southeast of Iran. Jundishapur J Microbiol 2022. [DOI: 10.5812/jjm-121119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Emerging evidence suggests that dysbiosis of the colon microbiome may be involved in CRC development. Objectives: The present study aimed to compare the composition and diversity of the colon microbiome by high-throughput 16S ribosomal RNA (rRNA) sequencing between CRC patients and healthy controls. Microbiome composition and diversity were also examined based on gender. Methods: The colon microbiome richness and diversity of samples from 17 CRC patients and 13 healthy controls were analyzed by 16S rRNA sequencing. Alpha and beta diversity were calculated to determine the differences in colon microbiome diversity. Results: Alpha and beta diversity showed significant differences between the CRC and healthy control groups regarding the microbiome. Our results showed that CRC samples had the highest richness and diversity. The total number (P ≤ 0.01), phylogenetic diversity (P ≤ 0.01), Chao1 (P ≤ 0.01), Shannon (P ≤ 0.05), and Simpson (P ≤ 0.01) indices were significantly higher in the CRC group than in the healthy control group. In addition, the comparison between females and males showed that the microbiome diversity was higher in the CRC female (CRC-F) group than in other groups. Prevotella, Fusobacterium, Akkermansia, Leptotrichia, Streptococcus, and ParaBacteroides were more commonly observed in the CRC group, while Bacteroides, Enterobacteriaceae (unknown genus), Ruminococcus, and Campylobacter were more commonly observed in the healthy control group. Conclusions: This study showed differences between the CRC and healthy control groups regarding the diversity and composition of the colon microbiome, suggesting a contribution of the microbiome in the development and progression of CRC.
Collapse
|
|
37
|
Mo S, Ru H, Huang M, Cheng L, Mo X, Yan L. Oral-Intestinal Microbiota in Colorectal Cancer: Inflammation and Immunosuppression. J Inflamm Res 2022; 15:747-759. [PMID: 35153499 PMCID: PMC8824753 DOI: 10.2147/jir.s344321] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 01/07/2022] [Indexed: 12/11/2022] Open
Abstract
It is widely recognized that microbial disorders are involved in the pathogenesis of many malignant tumors. The oral and intestinal tract are two of the overriding microbial habitats in the human body. Although they are anatomically and physiologically continuous, belonging to the openings at both ends of the digestive tract, the oral and intestinal microbiome do not cross talk with each other due to a variety of reasons, including intestinal microbial colonization resistance and chemical barriers in the upper digestive tract. However, this balance can be upset in certain circumstances, such as disruption of colonization resistance of gut microbes, intestinal inflammation, and disruption of the digestive tract chemical barrier. Evidence is now accruing to suggest that the oral microbiome can colonize the gut, leading to dysregulation of the gut microbes. Furthermore, the oral-gut microbes create an intestinal inflammatory and immunosuppressive microenvironment conducive to tumorigenesis and progression of colorectal cancer (CRC). Here, we review the oral to intestinal microbial transmission and the inflammatory and immunosuppressive microenvironment, induced by oral-gut axis microbes in the gut. A superior comprehension of the contribution of the oral-intestinal microbes to CRC provides new insights into the prevention and treatment of CRC in the future.
Collapse
Affiliation(s)
- Sisi Mo
- Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Haiming Ru
- Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Maosen Huang
- Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Linyao Cheng
- Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xianwei Mo
- Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Linhai Yan
- Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| |
Collapse
|
|
38
|
Intestinal Organoids: New Tools to Comprehend the Virulence of Bacterial Foodborne Pathogens. Foods 2022; 11:foods11010108. [PMID: 35010234 PMCID: PMC8750402 DOI: 10.3390/foods11010108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/18/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022] Open
Abstract
Foodborne diseases cause high morbidity and mortality worldwide. Understanding the relationships between bacteria and epithelial cells throughout the infection process is essential to setting up preventive and therapeutic solutions. The extensive study of their pathophysiology has mostly been performed on transformed cell cultures that do not fully mirror the complex cell populations, the in vivo architectures, and the genetic profiles of native tissues. Following advances in primary cell culture techniques, organoids have been developed. Such technological breakthroughs have opened a new path in the study of microbial infectious diseases, and thus opened onto new strategies to control foodborne hazards. This review sheds new light on cellular messages from the host–foodborne pathogen crosstalk during in vitro organoid infection by the foodborne pathogenic bacteria with the highest health burden. Finally, future perspectives and current challenges are discussed to provide a better understanding of the potential applications of organoids in the investigation of foodborne infectious diseases.
Collapse
|
|
39
|
Duijster JW, Franz E, Neefjes J, Mughini-Gras L. Bacterial and Parasitic Pathogens as Risk Factors for Cancers in the Gastrointestinal Tract: A Review of Current Epidemiological Knowledge. Front Microbiol 2021; 12:790256. [PMID: 34956157 PMCID: PMC8692736 DOI: 10.3389/fmicb.2021.790256] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/11/2021] [Indexed: 12/12/2022] Open
Abstract
The oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and progression of cancers has only recently gained momentum, resulting in a rapid growth of publications on the topic. Indeed, various bacteria and parasites have been suggested to play a role in the development of gastrointestinal cancer in particular. Therefore, an overview of the current epidemiological knowledge on the association between infections with bacteria and parasites and cancers of the gastrointestinal tract is needed. In this review, we summarized the methodological characteristics and main results of epidemiological studies investigating the association of 10 different bacteria (Bacteroides fragilis, Campylobacter spp., Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Porphyromonas gingivalis, non-typhoidal Salmonella, Salmonella Typhi, and Streptococcus spp.) and three parasites (Cryptosporidium spp., Schistosoma spp., and Strongyloides stercoralis) with gastrointestinal cancer. While the large body of studies based on microbiome sequencing provides valuable insights into the relative abundance of different bacterial taxa in cancer patients as compared to individuals with pre-malignant conditions or healthy controls, more research is needed to fulfill Koch's postulates, possibly making use of follow-up data, to assess the complex role of bacterial and parasitic infections in cancer epidemiology. Studies incorporating follow-up time between detection of the bacterium or parasite and cancer diagnosis remain valuable as these allow for estimation of cause-effect relationships.
Collapse
Affiliation(s)
- Janneke W. Duijster
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Eelco Franz
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
| | - Jacques Neefjes
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Lapo Mughini-Gras
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
| |
Collapse
|
|
40
|
Abstract
Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.
Collapse
|
|
41
|
Abstract
Microbial communities associated with deep-sea animals are critical to the establishment of novel biological communities in unusual environments. Over the past few decades, rapid exploration of the deep sea has enabled the discovery of novel microbial communities, some of which form symbiotic relationships with animal hosts. Symbiosis in the deep sea changes host physiology, behavior, ecology, and evolution over time and space. Symbiont diversity within a host is often aligned with diverse metabolic pathways that broaden the environmental niche for the animal host. In this review, we focus on microbiomes and obligate symbionts found in different deep-sea habitats and how they facilitate survival of the organisms that live in these environments. In addition, we discuss factors that govern microbiome diversity, host specificity, and biogeography in the deep sea. Finally, we highlight the current limitations of microbiome research and draw a road map for future directions to advance our knowledge of microbiomes in the deep sea. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Collapse
Affiliation(s)
- Eslam O Osman
- Biology Department, Eberly College, Pennsylvania State University, State College, Pennsylvania, USA; .,Red Sea Research Center (RSRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.,Marine Biology Lab, Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Alexis M Weinnig
- Biology Department, Temple University, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
42
|
Huang X, Pan T, Yan L, Jin T, Zhang R, Chen B, Feng J, Duan T, Xiang Y, Zhang M, Chen X, Yang Z, Zhang W, Ding X, Xie T, Sui X. The inflammatory microenvironment and the urinary microbiome in the initiation and progression of bladder cancer. Genes Dis 2021; 8:781-797. [PMID: 34522708 PMCID: PMC8427242 DOI: 10.1016/j.gendis.2020.10.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 10/05/2020] [Accepted: 10/06/2020] [Indexed: 12/24/2022] Open
Abstract
Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies, including bladder cancer. This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment. Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of inflammatory molecules and signals. Recently, it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer, which can be mediated through the stimulation of chronic inflammation. In effect, the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer. In other words, chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer. Here, we provide a detailed and comprehensive account of the link between chronic inflammation, the microbiome and bladder cancer. Finally, we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.
Collapse
Affiliation(s)
- Xingxing Huang
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Ting Pan
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Lili Yan
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Ting Jin
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Ruonan Zhang
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Bi Chen
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Jiao Feng
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Ting Duan
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Yu Xiang
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Mingming Zhang
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Xiaying Chen
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Zuyi Yang
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Wenzheng Zhang
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Xia Ding
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, PR China
| | - Tian Xie
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
| | - Xinbing Sui
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310015, PR China
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang Province, 311121, PR China
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, PR China
| |
Collapse
|
|
43
|
Silva M, Brunner V, Tschurtschenthaler M. Microbiota and Colorectal Cancer: From Gut to Bedside. Front Pharmacol 2021; 12:760280. [PMID: 34658896 PMCID: PMC8514721 DOI: 10.3389/fphar.2021.760280] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 09/20/2021] [Indexed: 12/21/2022] Open
Abstract
Colorectal cancer (CRC) is a complex condition with heterogeneous aetiology, caused by a combination of various environmental, genetic, and epigenetic factors. The presence of a homeostatic gut microbiota is critical to maintaining host homeostasis and determines the delicate boundary between health and disease. The gut microbiota has been identified as a key environmental player in the pathogenesis of CRC. Perturbations of the gut microbiota structure (loss of equilibrium and homeostasis) are associated with several intestinal diseases including cancer. Such dysbiosis encompasses the loss of beneficial microorganisms, outgrowth of pathogens and pathobionts and a general loss of local microbiota diversity and richness. Notably, several mechanisms have recently been identified how bacteria induce cellular transformation and promote tumour progression. In particular, the formation of biofilms, the production of toxic metabolites or the secretion of genotoxins that lead to DNA damage in intestinal epithelial cells are newly discovered processes by which the microbiota can initiate tumour formation. The gut microbiota has also been implicated in the metabolism of therapeutic drugs (conventional chemotherapy) as well as in the modulation of radiotherapy responses and targeted immunotherapy. These new findings suggest that the efficacy of a given therapy depends on the composition of the host’s gut microbiota and may therefore vary from patient to patient. In this review we discuss the role of host-microbiota interactions in cancer with a focus on CRC pathogenesis. Additionally, we show how gut bacteria can be exploited in current therapies and how mechanisms directed by microbiota, such as immune cell boost, probiotics and oncolytic bacteria, can be applied in the development of novel therapies.
Collapse
Affiliation(s)
- Miguel Silva
- Institute of Molecular Oncology and Functional Genomics, Center for Translational Cancer Research (TranslaTUM), Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.,Graduate Program in Areas of Basic and Applied Biology (GABBA)/ICBAS - Institute for the Biomedical Sciences Abel Salazar, Porto University, Porto, Portugal
| | - Valentina Brunner
- Institute for Experimental Cancer Therapy, Center for Translational Cancer Research (TranslaTUM), Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.,Department of Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Markus Tschurtschenthaler
- Institute for Experimental Cancer Therapy, Center for Translational Cancer Research (TranslaTUM), Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.,Department of Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| |
Collapse
|
|
44
|
Nardelli C, Granata I, Nunziato M, Setaro M, Carbone F, Zulli C, Pilone V, Capoluongo ED, De Palma GD, Corcione F, Matarese G, Salvatore F, Sacchetti L. 16S rRNA of Mucosal Colon Microbiome and CCL2 Circulating Levels Are Potential Biomarkers in Colorectal Cancer. Int J Mol Sci 2021; 22:10747. [PMID: 34639088 PMCID: PMC8509685 DOI: 10.3390/ijms221910747] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/30/2021] [Accepted: 09/30/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies in the Western world and intestinal dysbiosis might contribute to its pathogenesis. The mucosal colon microbiome and C-C motif chemokine 2 (CCL2) were investigated in 20 healthy controls (HC) and 20 CRC patients using 16S rRNA sequencing and immunoluminescent assay, respectively. A total of 10 HC subjects were classified as overweight/obese (OW/OB_HC) and 10 subjects were normal weight (NW_HC); 15 CRC patients were classified as OW/OB_CRC and 5 patients were NW_CRC. Results: Fusobacterium nucleatum and Escherichia coli were more abundant in OW/OB_HC than in NW_HC microbiomes. Globally, Streptococcus intermedius, Gemella haemolysans, Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were significantly increased in CRC patient tumor/lesioned tissue (CRC_LT) and CRC patient unlesioned tissue (CRC_ULT) microbiomes compared to HC microbiomes. CCL2 circulating levels were associated with tumor presence and with the abundance of Fusobacterium nucleatum, Bacteroides fragilis and Gemella haemolysans. Our data suggest that mucosal colon dysbiosis might contribute to CRC pathogenesis by inducing inflammation. Notably, Fusobacterium nucleatum, which was more abundant in the OW/OB_HC than in the NW_HC microbiomes, might represent a putative link between obesity and increased CRC risk.
Collapse
Affiliation(s)
- Carmela Nardelli
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
- Task Force on Microbiome Studies, University of Naples Federico II, 80131 Naples, Italy
| | - Ilaria Granata
- Institute for High Performance Computing and Networking (ICAR), National Research Council (CNR), 80131 Naples, Italy;
| | - Marcella Nunziato
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Mario Setaro
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Fortunata Carbone
- Laboratory of Immunology, Institute of Endocrinology and Experimental Oncology, Consiglio Nazionale Delle Ricerche (IEOS-CNR), 80131 Naples, Italy;
- Neuroimmunology Unit, IRCCS Fondazione Santa Lucia, 00143 Roma, Italy
| | - Claudio Zulli
- Digestive Endoscopy Unit, Gaetano Fucito Hospital, Mercato San Severino, 84085 Salerno, Italy;
| | - Vincenzo Pilone
- Department of Medicine and Surgery, AOU San Giovanni di Dio e Ruggi D’Aragona, University of Salerno, 84084 Salerno, Italy;
| | - Ettore Domenico Capoluongo
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Giovanni Domenico De Palma
- Department Clinical Medicine and Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy;
| | - Francesco Corcione
- Department of Public Health, School of Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy;
| | - Giuseppe Matarese
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- Laboratory of Immunology, Institute of Endocrinology and Experimental Oncology, Consiglio Nazionale Delle Ricerche (IEOS-CNR), 80131 Naples, Italy;
| | - Francesco Salvatore
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Lucia Sacchetti
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
- Task Force on Microbiome Studies, University of Naples Federico II, 80131 Naples, Italy
| |
Collapse
|
|
45
|
Smet A, Kupcinskas J, Link A, Hold GL, Bornschein J. The Role of Microbiota in Gastrointestinal Cancer and Cancer Treatment: Chance or Curse? Cell Mol Gastroenterol Hepatol 2021; 13:857-874. [PMID: 34506954 PMCID: PMC8803618 DOI: 10.1016/j.jcmgh.2021.08.013] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 08/18/2021] [Accepted: 08/18/2021] [Indexed: 02/08/2023]
Abstract
The gastrointestinal (GI) tract is home to a complex and dynamic community of microorganisms, comprising bacteria, archaea, viruses, yeast, and fungi. It is widely accepted that human health is shaped by these microbes and their collective microbial genome. This so-called second genome plays an important role in normal functioning of the host, contributing to processes involved in metabolism and immune modulation. Furthermore, the gut microbiota also is capable of generating energy and nutrients (eg, short-chain fatty acids and vitamins) that are otherwise inaccessible to the host and are essential for mucosal barrier homeostasis. In recent years, numerous studies have pointed toward microbial dysbiosis as a key driver in many GI conditions, including cancers. However, comprehensive mechanistic insights on how collectively gut microbes influence carcinogenesis remain limited. In addition to their role in carcinogenesis, the gut microbiota now has been shown to play a key role in influencing clinical outcomes to cancer immunotherapy, making them valuable targets in the treatment of cancer. It also is becoming apparent that, besides the gut microbiota's impact on therapeutic outcomes, cancer treatment may in turn influence GI microbiota composition. This review provides a comprehensive overview of microbial dysbiosis in GI cancers, specifically esophageal, gastric, and colorectal cancers, potential mechanisms of microbiota in carcinogenesis, and their implications in diagnostics and cancer treatment.
Collapse
Affiliation(s)
- Annemieke Smet
- Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Juozas Kupcinskas
- Institute for Digestive Research, Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Georgina L Hold
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Jan Bornschein
- Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
| |
Collapse
|
|
46
|
Kabwe M, Dashper S, Bachrach G, Tucci J. Bacteriophage manipulation of the microbiome associated with tumour microenvironments-can this improve cancer therapeutic response? FEMS Microbiol Rev 2021; 45:6188389. [PMID: 33765142 DOI: 10.1093/femsre/fuab017] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 03/21/2021] [Indexed: 12/11/2022] Open
Abstract
Some cancer treatment failures have been attributed to the tumour microbiota, with implications that microbiota manipulation may improve treatment efficacy. While antibiotics have been used to control bacterial growth, their dysbiotic effects on the microbiome, failure to penetrate biofilms and decreased efficacy due to increasing antimicrobial resistance by bacteria, suggest alternatives are needed. Bacteriophages may provide a precise means for targeting oncobacteria whose relative abundance is increased in tumour tissue microbiomes. Fusobacterium, Streptococcus, Peptostreptococcus, Prevotella, Parvimonas, and Treponema species are prevalent in tumour tissue microbiomes of some cancers. They may promote cancer growth by dampening immunity, stimulating release of proinflammatory cytokines, and directly interacting with cancer cells to stimulate proliferation. Lytic bacteriophages against some of these oncobacteria have been isolated and characterised. The search continues for others. The possibility exists for their testing as adjuncts to complement existing therapies. In this review, we highlight the role of oncobacteria, specifically those whose relative abundance in the intra-tumour microbiome is increased, and discuss the potential for bacteriophages against these micro-organisms to augment existing cancer therapies. The capacity for bacteriophages to modulate immunity and kill specific bacteria makes them suitable candidates to manipulate the tumour microbiome and negate the effects of these oncobacteria.
Collapse
Affiliation(s)
- Mwila Kabwe
- Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Sharon St. Bendigo, Victoria 3550, Australia
| | - Stuart Dashper
- Melbourne Dental School, University of Melbourne, 720 Swanston St, Parkville, Victoria 3010, Australia
| | - Gilad Bachrach
- The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, PO Box 12272, Jerusalem 9112102, Israel
| | - Joseph Tucci
- Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Sharon St. Bendigo, Victoria 3550, Australia
| |
Collapse
|
|
47
|
Zong Y, Zhou Y, Liao B, Liao M, Shi Y, Wei Y, Huang Y, Zhou X, Cheng L, Ren B. The Interaction Between the Microbiome and Tumors. Front Cell Infect Microbiol 2021; 11:673724. [PMID: 34532297 PMCID: PMC8438519 DOI: 10.3389/fcimb.2021.673724] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 08/09/2021] [Indexed: 12/24/2022] Open
Abstract
Cancer is a significant global health problem and is characterized by a consistent increase in incidence and mortality rate. Deciphering the etiology and risk factors are essential parts of cancer research. Recently, the altered microbiome has been identified within the tumor microenvironment, tumor tissue, and even nonadjacent environments, which indicates a strong correlation between the microbiome and tumor development. However, the causation and mechanisms of this correlation remain unclear. Herein, we summarized and discussed the interaction between the microbiome and tumor progression. Firstly, the microbiome, which can be located in the tumor microenvironment, inside tumor tissues and in the nonadjacent environment, is different between cancer patients and healthy individuals. Secondly, the tumor can remodel microbial profiles by creating a more beneficial condition for the shifted microbiome. Third, the microbiome can promote tumorigenesis through a direct pathogenic process, including the establishment of an inflammatory environment and its effect on host immunity. The interactions between the microbiome and tumors can promote an understanding of the carcinogenesis and provide novel therapeutic strategies for cancers.
Collapse
Affiliation(s)
- Yawen Zong
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Yujie Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Binyou Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Min Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Yangyang Shi
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Yu Wei
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Yuyao Huang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Lei Cheng
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Biao Ren
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
| |
Collapse
|
|
48
|
Fan X, Jin Y, Chen G, Ma X, Zhang L. Gut Microbiota Dysbiosis Drives the Development of Colorectal Cancer. Digestion 2021; 102:508-515. [PMID: 32932258 DOI: 10.1159/000508328] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Accepted: 04/29/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND The gut microbiota is a diverse community of microbes that maintain the stability of the intestinal environment. Dysbiosis of the gut microbiota has been linked to gastrointestinal diseases, such as colorectal cancer (CRC) - a leading cause of death for cancer patients. SUMMARY Candidate pathogens have been identified using bacterial culture and high-throughput sequencing techniques. Currently, there is evidence to show that specific intestinal microbes drive CRC development and progression, yet their pathogenic mechanisms are still unclear. Key Messages: In this review, we describe the known healthy gut microbiota and its changes in CRC. We especially focus on exploring the pathogenic mechanisms of gut microbiota dysbiosis in CRC. This is crucial for explaining how gut microbiota dysbiosis drives the process of colorectal carcinogenesis and tumor progression. Evaluation of changes in the gut microbiota during CRC development and progression offers a new strategy for the diagnosis and treatment of this disease.
Collapse
Affiliation(s)
- Xiaoyan Fan
- Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, Taizhou, China.,Department of Neurology, Taizhou Second People's Hospital, Taizhou, China
| | - Yuelei Jin
- Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, Taizhou, China
| | - Guang Chen
- Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, Taizhou, China
| | - Xueqiang Ma
- Department of Gastrointestinal Surgery, Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, China
| | - Lixia Zhang
- Department of Neurology, Taizhou Second People's Hospital, Taizhou, China,
| |
Collapse
|
|
49
|
Lopez Chiloeches M, Bergonzini A, Frisan T. Bacterial Toxins Are a Never-Ending Source of Surprises: From Natural Born Killers to Negotiators. Toxins (Basel) 2021; 13:426. [PMID: 34204481 PMCID: PMC8235270 DOI: 10.3390/toxins13060426] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/07/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open
Abstract
The idea that bacterial toxins are not only killers but also execute more sophisticated roles during bacteria-host interactions by acting as negotiators has been highlighted in the past decades. Depending on the toxin, its cellular target and mode of action, the final regulatory outcome can be different. In this review, we have focused on two families of bacterial toxins: genotoxins and pore-forming toxins, which have different modes of action but share the ability to modulate the host's immune responses, independently of their capacity to directly kill immune cells. We have addressed their immuno-suppressive effects with the perspective that these may help bacteria to avoid clearance by the host's immune response and, concomitantly, limit detrimental immunopathology. These are optimal conditions for the establishment of a persistent infection, eventually promoting asymptomatic carriers. This immunomodulatory effect can be achieved with different strategies such as suppression of pro-inflammatory cytokines, re-polarization of the immune response from a pro-inflammatory to a tolerogenic state, and bacterial fitness modulation to favour tissue colonization while preventing bacteraemia. An imbalance in each of those effects can lead to disease due to either uncontrolled bacterial proliferation/invasion, immunopathology, or both.
Collapse
Affiliation(s)
| | | | - Teresa Frisan
- Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Umeå University, 901 87 Umeå, Sweden; (M.L.C.); (A.B.)
| |
Collapse
|
|
50
|
Bruggeling CE, Garza DR, Achouiti S, Mes W, Dutilh BE, Boleij A. Optimized bacterial DNA isolation method for microbiome analysis of human tissues. Microbiologyopen 2021; 10:e1191. [PMID: 34180607 PMCID: PMC8208965 DOI: 10.1002/mbo3.1191] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/13/2021] [Accepted: 04/13/2021] [Indexed: 12/14/2022] Open
Abstract
Recent advances in microbiome sequencing have rendered new insights into the role of the microbiome in human health with potential clinical implications. Unfortunately, the presence of host DNA in tissue isolates has hampered the analysis of host‐associated bacteria. Here, we present a DNA isolation protocol for tissue, optimized on biopsies from resected human colons (~2–5 mm in size), which includes reduction of human DNA without distortion of relative bacterial abundance at the phylum level. We evaluated which concentrations of Triton and saponin lyse human cells and leave bacterial cells intact, in combination with DNAse treatment to deplete released human DNA. Saponin at a concentration of 0.0125% in PBS lysed host cells, resulting in a 4.5‐fold enrichment of bacterial DNA while preserving the relative abundance of Firmicutes, Bacteroidetes, γ‐Proteobacteria, and Actinobacteria assessed by qPCR. Our optimized protocol was validated in the setting of two large clinical studies on 521 in vivo acquired colon biopsies of 226 patients using shotgun metagenomics. The resulting bacterial profiles exhibited alpha and beta diversities that are similar to the diversities found by 16S rRNA amplicon sequencing. A direct comparison between shotgun metagenomics and 16S rRNA amplicon sequencing of 15 forceps tissue biopsies showed similar bacterial profiles and a similar Shannon diversity index between the sequencing methods. Hereby, we present the first protocol for enriching bacterial DNA from tissue biopsies that allows efficient isolation of all bacteria. Our protocol facilitates analysis of a wide spectrum of bacteria of clinical tissue samples improving their applicability for microbiome research.
Collapse
Affiliation(s)
- Carlijn E Bruggeling
- Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands
| | - Daniel R Garza
- Radboud Institute for Molecular Life Sciences (RIMLS), Center for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.,KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Bacteriology, Rega Institute, Leuven, Belgium
| | - Soumia Achouiti
- Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands
| | - Wouter Mes
- Department of Animal Ecology & Physiology, Institute for Water and Wetland Research (IWWR), Radboud University, Nijmegen, The Netherlands.,Department of Microbiology, Institute for Water and Wetland Research (IWWR), Radboud University, Nijmegen, The Netherlands
| | - Bas E Dutilh
- Radboud Institute for Molecular Life Sciences (RIMLS), Center for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.,Theoretical Biology and Bioinformatics, Science for Life, Utrecht University, Utrecht, The Netherlands
| | - Annemarie Boleij
- Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands
| |
Collapse
|