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Shastry RP, Hameed A, Banerjee S, Prabhu A, Bajire SK, Pavan SR, Dhanyashree HR, Kotimoole CN, Stothard P, Surya S, Keshava Prasad TS, Shetty R, Shen FT, Bhandary YP. Tryptic oncopeptide secreted from the gut bacterium Cronobacter malonaticus PO3 promotes colorectal cancer. Sci Rep 2025; 15:9958. [PMID: 40121280 PMCID: PMC11929907 DOI: 10.1038/s41598-025-94666-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/17/2025] [Indexed: 03/25/2025] Open
Abstract
The involvement of Cronobacter, which is frequently associated with meningitis and necrotizing enterocolitis, in human colorectal cancer remains unexplored. In this study, we isolate and characterize a novel strain of C. malonaticus designated PO3 from a fecal sample of a colon cancer patient and demonstrate its proliferative effects on colorectal cancer both in vitro and in vivo. The secretome of PO3 significantly promoted cell proliferation, as evidenced by increased cell viability, fluorescence intensity, and Ki-67 expression, without inducing cell death. Furthermore, using high-resolution mass spectrometry (HRMS), we identified a novel tryptic oncopeptide designated P506, in the PO3 secretome that promotes colorectal cancer. Synthetic P506 further stimulated human colorectal adenocarcinoma cell line HT-29 cell proliferation in a dose-dependent manner. Experiments with the BALB/c mouse model in vivo revealed that both the PO3 secretome and P506 contributed to the development of colorectal polyps and associated histological changes, including dysplasia and altered colonic architecture. These findings suggest that P506, a potent peptide from the PO3 secretome, may have oncogenic potential, promoting colorectal cancer progression.
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Affiliation(s)
- Rajesh Padumane Shastry
- Division of Microbiology and Biotechnology, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India.
| | - Asif Hameed
- Division of Microbiology and Biotechnology, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India.
| | - Shukla Banerjee
- Division of Microbiology and Biotechnology, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Ashwini Prabhu
- Division of Cancer Research and Therapeutics, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Sukesh Kumar Bajire
- Division of Microbiology and Biotechnology, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Sonnenahalli Rudramurthy Pavan
- Division of Cancer Research and Therapeutics, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Honagodu Ravichandra Dhanyashree
- Division of Microbiology and Biotechnology, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Chinmaya Narayana Kotimoole
- Division of Microbiology and Biotechnology, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Paul Stothard
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada
| | - Suprith Surya
- Advanced Surgical Skill ENhancement Division (ASSEND), Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | | | - Rohan Shetty
- Department of Surgical Oncology, Yenepoya Medical College Hospital, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Fo-Ting Shen
- Department of Soil and Environmental Sciences, National Chung Hsing University, Taichung, 40227, Taiwan.
- Innovation and Development Center of Sustainable Agriculture (IDCSA), National Chung Hsing University, Taichung, 40227, Taiwan.
| | - Yashodhar Prabhakar Bhandary
- Division of Cell Biology and Molecular Genetics, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
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Shanti I, Samardali M, Gebremedhen AI. Prosthetic Joint Infection by Streptococcus lutetiensis (Bovis) With Noncancerous Polyps and Negative Blood Cultures: A Case Report. Cureus 2024; 16:e74264. [PMID: 39712796 PMCID: PMC11663499 DOI: 10.7759/cureus.74264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/22/2024] [Indexed: 12/24/2024] Open
Abstract
Prosthetic joint infection (PJI), caused by Streptococcus bovis group (SBG), is uncommon and related to colorectal cancer. We present here a case of an 84-year-old male who had a past medical history of chronic obstructive pulmonary disease (COPD), congestive heart failure, pulmonary arterial hypertension, iron deficiency anemia, chronic kidney disease, diabetes mellitus, gout, hypertension, bilateral knee replacement with left knee pain and swelling. We initially suspected gout and treated him with prednisolone, but it did not relieve him. Joint aspiration revealed high WBC, predominantly neutrophils, and polymerase chain reaction (PCR)-identified Streptococcus lutetiensis. The patient underwent knee incision, drainage, poly exchange, and wound vacuum-assisted closure (VAC) placement. Sensitivity testing led us to treat him with ceftriaxone. Echocardiography revealed no endocarditis. A colonoscopy revealed multiple non-bleeding polyps and adenomas. After discharge, our patient completed six weeks of ceftriaxone via a peripherally inserted central catheter (PICC) line. At follow-up, our patient reported no complaints of fever and knee swelling.
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Affiliation(s)
- Ibrahim Shanti
- Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Malik Samardali
- Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Adamsegd I Gebremedhen
- Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
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Chen G, Ren Q, Zhong Z, Li Q, Huang Z, Zhang C, Yuan H, Feng Z, Chen B, Wang N, Feng Y. Exploring the gut microbiome's role in colorectal cancer: diagnostic and prognostic implications. Front Immunol 2024; 15:1431747. [PMID: 39483461 PMCID: PMC11524876 DOI: 10.3389/fimmu.2024.1431747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 09/30/2024] [Indexed: 11/03/2024] Open
Abstract
The intricate interplay between the gut microbiome and colorectal cancer (CRC) presents novel avenues for early diagnosis and prognosis, crucial for improving patient outcomes. This comprehensive review synthesizes current findings on the gut microbiome's contribution to CRC pathogenesis, highlighting its potential as a biomarker for non-invasive CRC screening strategies. We explore the mechanisms through which the microbiome influences CRC, including its roles in inflammation, metabolism, and immune response modulation. Furthermore, we assess the viability of microbial signatures as predictive tools for CRC prognosis, offering insights into personalized treatment approaches. Our analysis underscores the necessity for advanced metagenomic studies to elucidate the complex microbiome-CRC nexus, aiming to refine diagnostic accuracy and prognostic assessment in clinical settings. This review propels forward the understanding of the microbiome's diagnostic and prognostic capabilities, paving the way for microbiome-based interventions in CRC management.
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Affiliation(s)
- Guoming Chen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Qing Ren
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Zilan Zhong
- The First Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qianfan Li
- The First Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhiqiang Huang
- The First Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Cheng Zhang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Hongchao Yuan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Zixin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Bonan Chen
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
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AlZaabi A, Younus HA, Al-Reasi HA, Al-Hajri R. Could environmental exposure and climate change Be a key factor in the rising incidence of early onset colorectal cancer? Heliyon 2024; 10:e35935. [PMID: 39258208 PMCID: PMC11386049 DOI: 10.1016/j.heliyon.2024.e35935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 08/02/2024] [Accepted: 08/06/2024] [Indexed: 09/12/2024] Open
Abstract
The emergence of early onset colorectal cancer (EOCRC) is believed to result from the complex interplay between external environmental factors and internal molecular processes. This review investigates the potential association between environmental exposure to chemicals and climate change and the increased incidence of EOCRC, focusing on their effects on gut microbiota (GM) dynamics. The manuscript explores the birth cohort effect, suggesting that individuals born after 1950 may be at higher risk of developing EOCRC due to cumulative environmental exposures. Furthermore, we also reviewed the impact of environmental pollution, including particulate matter and endocrine disrupting chemicals (EDCs), as well as global warming, on GM disturbance. Environmental exposures have the potential to disrupt GM composition and diversity, leading to dysbiosis, chronic inflammation, and oxidative stress, which are known risk factors associated with EOCRC. Particulate matter can enter the gastrointestinal tract, modifying GM composition and promoting the proliferation of pathogenic bacteria while diminishing beneficial bacteria. Similarly, EDCs, can induce GM alterations and inflammation, further increasing the risk of EOCRC. Additionally, global warming can influence GM through shifts in gut environmental conditions, affecting the host's immune response and potentially increasing EOCRC risk. To summarize, environmental exposure to chemicals and climate change since 1950 has been implicated as contributing factors to the rising incidence of EOCRC. Disruptions in gut microbiota homeostasis play a crucial role in mediating these associations. Consequently, there is a pressing need for enhanced environmental policies aimed at minimizing exposure to pollutants, safeguarding public health, and mitigating the burden of EOCRC.
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Affiliation(s)
- Adhari AlZaabi
- College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman
| | - Hussein A Younus
- Nanotechnology Research Center, Sultan Qaboos University, PO Box 17, Al-Khoud, PC 123 Oman
| | - Hassan A Al-Reasi
- Department of Biology, College of Science, Sultan Qaboos University, PO Box 36, PC 123, Al-Khoud, Muscat, Oman
- Faculty of Education and Arts, Sohar University, PO Box 44, PC 311, Sohar, Oman
| | - Rashid Al-Hajri
- Department of Petrolleum and Chemical Engineering, College of Engineering, Sultan Qaboos University, P. O. Box 33, Al Khoud, Muscat, PC 123, Oman
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Cagri MA, Sahin M, Ersoy Y, Aydin C, Buyuk F. Geese as reservoirs of human colon cancer-associated Streptococcus gallolyticus. Res Vet Sci 2024; 176:105341. [PMID: 38963992 DOI: 10.1016/j.rvsc.2024.105341] [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: 02/25/2024] [Revised: 06/21/2024] [Accepted: 06/23/2024] [Indexed: 07/06/2024]
Abstract
Recently, an increased number of reports have described pathogens of animal origin that cause a variety of infections and a rise in their transmission to humans. Streptococcus gallolyticus, a member of the Streptococcus bovis/Streptococcus equinus complex (SBSEC), is one of these pathogens and infects a wide range of hosts from mammals to poultry and has a broad functionality ranging from pathogenicity to food fermentation. As S. gallolyticus causes complications including bacteremia, infective endocarditis, and colorectal malignancy in humans, it is important to investigate its occurrence in various hosts, including geese, to prevent potential zoonotic transmissions. This study aimed to investigate the presence of S. gallolyticus in the droppings of clinically healthy and diarrheic geese, which were raised intensively and semi-intensively, by the in vitro culture method, characterize the isolates recovered by PCR and sequence-based molecular methods and determine their antibiotic susceptibility by the disk diffusion and gradient test methods. For this purpose, 150 samples of fresh goose droppings were used. Culture positivity for S. gallolyticus was determined as 8% (12/150). PCR analysis identified 54.55% (n = 6) of the isolates as S. gallolyticus subsp. gallolyticus and 45.45% (n = 5) as S. gallolyticus subsp. pasteurianus. Following the 16S rRNA sequence and ERIC-PCR analyses, S. gallolyticus subspecies exhibited identical cluster and band profiles that could be easily distinguished from each other and were clonally identified. High rates of susceptibility to florfenicol, penicillin, rifampicin, and vancomycin were detected among the isolates, regardless of the subspecies diversity. Both subspecies showed high levels of resistance to bacitracin, clindamycin, doxycycline, tetracycline, trimethoprim-sulfamethoxazole, and erythromycin and multiple MDR profiles, indicating their potential to become superbugs. This first report from Türkiye demonstrates the occurrence of the S. gallolyticus subspecies in geese. In view of the recent increase of geese production and the consumption of goose meat in Türkiye, the occurrence of S. gallolyticus in geese should not be ignored to prevent zoonotic transmission.
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Affiliation(s)
| | - Mitat Sahin
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye; Faculty of Veterinary Medicine, Kyrgyz-Turkish Manas University, Bishkek, Kyrgyz Republic
| | - Yaren Ersoy
- Institute of Health Sciences, Department of Microbiology, Kafkas University, Kars, Türkiye
| | - Cansu Aydin
- Institute of Health Sciences, Department of Microbiology, Erciyes University, Kayseri, Türkiye
| | - Fatih Buyuk
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye.
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Ma L, Zhu Y, Zhu La ALT, Lourenco JM, Callaway TR, Bu D. Schizochytrium sp. and lactoferrin supplementation alleviates Escherichia coli K99-induced diarrhea in preweaning dairy calves. J Dairy Sci 2024; 107:1603-1619. [PMID: 37769949 DOI: 10.3168/jds.2023-23466] [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: 03/07/2023] [Accepted: 09/04/2023] [Indexed: 10/03/2023]
Abstract
Calf diarrhea, a common disease mainly induced by Escherichia coli infection, is one of the main reasons for nonpredator losses. Hence, an effective nonantibacterial approach to prevent calf diarrhea has become an emerging requirement. This study evaluated the microalgae Schizochytrium sp. (SZ) and lactoferrin (LF) as a nutrient intervention approach against E. coli O101:K99-induced preweaning calve diarrhea. Fifty 1-d-old male Holstein calves were randomly divided into 5 groups (n = 10): (1) control, (2) blank (no supplement or challenge), (3) 1 g/d LF, (4) 20 g/d SZ, or (5) 1 g/d LF plus 20 g/d SZ (LFSZ). The experimental period lasted 14 d. On the morning of d 7, calves were challenged with 1 × 1011 cfu of E. coli O101:K99, and rectum feces were collected on 3, 12, 24, and 168 h postchallenge for the control, LF, SZ, and LFSZ groups. The rectal feces of the blank group were collected on d 14. Data were analyzed using the mixed procedure of SAS (version 9.4; SAS Institute Inc.). The E. coli K99 challenge decreased the average daily gain (ADG) and increased feed-to-gain ratio (F:G) and diarrhea frequency (control vs. blank). Compared with the control group, the LFSZ group had a higher ADG and lower F:G, and the LFSZ and SZ groups had lower diarrhea frequency compared with the control group. In addition, the LFSZ and SZ groups have no differences in diarrhea frequency compared with the blank group. Compared with the control group, the blank group had lower serum nitric oxide (NO), endothelin-1, d-lactic acid (D-LA), and lipopolysaccharide (LPS) concentrations, as well as serum IgG, IL-1β, IL-6, IL-10, and TNF-α levels on d 7 and 14. On d 7, compared with the control group, all treatment groups had lower serum NO level, the SZ group had a lower serum D-LA concentration, and the LF and LFSZ groups had lower serum LPS concentration. On d 14, compared with the control group, the fecal microbiota of the blank group had lower Shannon, Simpson, Chao1, and ACE indexes, the LFSZ group had lower Shannon and Simpson indexes, the SZ and LFSZ groups had a higher Chao1 index, and all treatment groups had a higher ACE index. In fecal microbiota, Bifidobacterium and Actinobacteria were negatively associated with IL-10 and d-lactate, while Akkermansia was negatively associated with endothelin-1 and positively correlated with LPS, fecal scores, and d-lactate levels. Our results indicated that LF and SZ supplements could alleviate E. coli O101:K99-induced calf diarrhea individually or in combination. Supplementing 1 g/d LF and 20 g/d SZ could be a potential nutrient intervention approach to prevent bacterial diarrhea in calves.
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Affiliation(s)
- Lu Ma
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yingkun Zhu
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; School of Agriculture & Food Science, University College Dublin, Belfield, Dublin 4, Ireland
| | - A La Teng Zhu La
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - J M Lourenco
- Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602
| | - T R Callaway
- Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602
| | - Dengpan Bu
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; CAAS-ICRAF Joint Lab on Agroforestry and Sustainable Animal Husbandry, World Agroforestry Centre, East and Central Asia, Beijing 100193, China.
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Dai R, Kelly BN, Ike A, Berger D, Chan A, Drew DA, Ljungman D, Mutiibwa D, Ricciardi R, Tumusiime G, Cusack JC. The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development. Cancers (Basel) 2024; 16:676. [PMID: 38339427 PMCID: PMC10854951 DOI: 10.3390/cancers16030676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 01/26/2024] [Accepted: 02/02/2024] [Indexed: 02/12/2024] Open
Abstract
Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma.
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Affiliation(s)
- Rui Dai
- Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
- Harvard Medical School, Harvard University, Boston, MA 02115, USA; (D.B.); (A.C.); (D.A.D.); (R.R.)
| | - Bridget N. Kelly
- Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA (A.I.)
| | - Amarachi Ike
- Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA (A.I.)
| | - David Berger
- Harvard Medical School, Harvard University, Boston, MA 02115, USA; (D.B.); (A.C.); (D.A.D.); (R.R.)
- Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA (A.I.)
| | - Andrew Chan
- Harvard Medical School, Harvard University, Boston, MA 02115, USA; (D.B.); (A.C.); (D.A.D.); (R.R.)
- Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - David A. Drew
- Harvard Medical School, Harvard University, Boston, MA 02115, USA; (D.B.); (A.C.); (D.A.D.); (R.R.)
- Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - David Ljungman
- Sahlgrenska University Hospital, University of Gothenburg, 413 45 Gothenburg, Sweden;
| | - David Mutiibwa
- Department of Surgery, Mbarara University of Science and Technology, Mbarara P.O. Box 1410, Uganda;
| | - Rocco Ricciardi
- Harvard Medical School, Harvard University, Boston, MA 02115, USA; (D.B.); (A.C.); (D.A.D.); (R.R.)
- Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA (A.I.)
| | - Gerald Tumusiime
- School of Medicine, Uganda Christian University, Mukono P.O. Box 4, Uganda;
| | - James C. Cusack
- Harvard Medical School, Harvard University, Boston, MA 02115, USA; (D.B.); (A.C.); (D.A.D.); (R.R.)
- Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA (A.I.)
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Jiang S, Ma W, Ma C, Zhang Z, Zhang W, Zhang J. An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome. Gut Microbes 2024; 16:2341717. [PMID: 38717360 PMCID: PMC11085971 DOI: 10.1080/19490976.2024.2341717] [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: 01/29/2024] [Revised: 03/31/2024] [Accepted: 04/08/2024] [Indexed: 05/12/2024] Open
Abstract
The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.
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Affiliation(s)
- Shuaiming Jiang
- School of Food Science and Engineering, Hainan University, Haikou, PR China
| | - Wenyao Ma
- School of Food Science and Engineering, Hainan University, Haikou, PR China
| | - Chenchen Ma
- Department of Human Cell Biology and Genetics, Southern University of Science and Technology, Shenzhen, PR China
| | - Zeng Zhang
- School of Food Science and Engineering, Hainan University, Haikou, PR China
| | - Wanli Zhang
- School of Food Science and Engineering, Hainan University, Haikou, PR China
| | - Jiachao Zhang
- School of Food Science and Engineering, Hainan University, Haikou, PR China
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Corredoira Sánchez J, Ayuso García B, Romay Lema EM, García-Pais MJ, Rodríguez-Macias AI, Capón González P, Otero López R, Rabuñal Rey R, Alonso García P. Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2024; 42:4-12. [PMID: 37076331 DOI: 10.1016/j.eimce.2022.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/22/2022] [Indexed: 04/21/2023]
Abstract
OBJECTIVES To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. METHODS Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. RESULTS 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). CONCLUSIONS CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.
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Affiliation(s)
| | | | | | | | | | | | - Rocio Otero López
- Neurosurgery Department, Universitary Hospital Lucus Augusti, Lugo, Spain
| | - Ramón Rabuñal Rey
- Infectious Disease Unit, Universitary Hospital Lucus Augusti, Lugo, Spain
| | - Pilar Alonso García
- Clinical Microbiology Department, Universitary Hospital Lucus Augusti, Lugo, Spain
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Mima K, Hamada T, Inamura K, Baba H, Ugai T, Ogino S. The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities. Gut Microbes 2023; 15:2269623. [PMID: 37902043 PMCID: PMC10730181 DOI: 10.1080/19490976.2023.2269623] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 10/06/2023] [Indexed: 10/31/2023] Open
Abstract
Accumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers. While a minority of early-onset cancers in the digestive system are associated with cancer-predisposing high penetrance germline genetic variants, the majority of those cancers are sporadic and multifactorial. Although potential etiological roles of diets, lifestyle, environment, and the microbiome from early life to adulthood (i.e. in one's life course) have been hypothesized, exact contribution of each of these factors remains uncertain. Diets, lifestyle patterns, and environmental exposures have been shown to alter the oral and intestinal microbiome. To address the rising trend of early-onset cancers, transdisciplinary research approaches including lifecourse epidemiology and molecular pathological epidemiology frameworks, nutritional and environmental sciences, multi-omics technologies, etc. are needed. We review current evidence and discuss emerging research opportunities, which can improve our understanding of their etiologies and help us design better strategies for prevention and treatment to reduce the cancer burden in populations.
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Affiliation(s)
- Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic Medicine, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kentaro Inamura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Cancer Epidemiology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Cancer Epidemiology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
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11
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Ouranos K, Gardikioti A, Bakaloudi DR, Mylona EK, Shehadeh F, Mylonakis E. Association of the Streptococcus bovis/Streptococcus equinus Complex With Colorectal Neoplasia: A Systematic Review and Meta-analysis. Open Forum Infect Dis 2023; 10:ofad547. [PMID: 38023558 PMCID: PMC10655943 DOI: 10.1093/ofid/ofad547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023] Open
Abstract
Background Invasive infection with Streptococcus bovis/Streptococcus equinus complex (SBSEC) bacteria is associated with underlying colorectal neoplasia. However, the link between intestinal or fecal colonization with SBSEC isolates or antibody responses to SBSEC members and colorectal cancer is not thoroughly investigated in the literature. Methods We searched the PubMed, EMBASE, and Web of Science databases for case-control studies as well as retrospective or prospective cohort studies reporting an association between SBSEC bacteria and colorectal neoplasia. Results We identified 22 studies (15 case-control and 7 cohort) that met our inclusion criteria. Among the cohort studies, patients with SBSEC bacteremia were 3.73 times more likely to have underlying colorectal cancer compared with individuals with no bacteremia (relative risk [RR], 3.73; 95% CI, 2.79-5.01), whereas the risk of underlying colorectal adenoma in patients with SBSEC bacteremia was not significantly increased (RR, 5.00; 95% CI, 0.83-30.03). In case-control studies, patients with colorectal cancer were 2.27 times more likely to have evidence of intestinal or fecal colonization with SBSEC isolates (odds ratio [OR], 2.27; 95% CI, 1.11-4.62) and immunoglobulin G (IgG) antibody responses to SBSEC antigens (OR, 2.27; 95% CI, 1.06-4.86) compared with controls. Patients with colorectal adenoma were not more likely to be colonized with SBSEC isolates compared with controls (OR, 1.12; 95% CI, 0.55-2.25). Conclusions Apart from the well-established association of SBSEC bacteremia and underlying colorectal cancer, intestinal or fecal colonization with SBSEC isolates and IgG antibody responses to SBSEC antigens were higher in patients with colorectal cancer compared with controls. Neither bacteremia from SBSEC isolates nor colonization with SBSEC bacteria was associated with underlying colorectal adenoma.
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Affiliation(s)
- Konstantinos Ouranos
- Department of Medicine, Houston Methodist Research Institute, Houston, Texas, USA
| | - Angeliki Gardikioti
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York, USA
| | | | - Evangelia K Mylona
- Department of Medicine, Houston Methodist Research Institute, Houston, Texas, USA
| | - Fadi Shehadeh
- Department of Medicine, Houston Methodist Research Institute, Houston, Texas, USA
- School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece
| | - Eleftherios Mylonakis
- Department of Medicine, Houston Methodist Research Institute, Houston, Texas, USA
- Weill Cornell Medicine, New York, New York, USA
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12
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Wu J, Dong W, Pan Y, Wang J, Wu M, Yu Y. Crosstalk between gut microbiota and metastasis in colorectal cancer: implication of neutrophil extracellular traps. Front Immunol 2023; 14:1296783. [PMID: 37936694 PMCID: PMC10626548 DOI: 10.3389/fimmu.2023.1296783] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 10/10/2023] [Indexed: 11/09/2023] Open
Abstract
Primary colorectal cancer (CRC) often leads to liver metastasis, possibly due to the formation of pre-metastatic niche (PMN) in liver. Thus, unravelling the key modulator in metastasis is important for the development of clinical therapies. Gut microbiota dysregulation is a key event during CRC progression and metastasis. Numerous studies have elucidated the correlation between specific gut bacteria strains (e.g., pks + E. coli and Bacteroides fragilis) and CRC initiation, and gut bacteria translocation is commonly witnessed during CRC progression. Gut microbiota shapes tumor microenvironment (TME) through direct contact with immune cells or through its functional metabolites. However, how gut microbiota facilitates CRC metastasis remains controversial. Meanwhile, recent studies identify the dissemination of bacteria from gut lumen to liver, suggesting the role of gut microbiota in shaping tumor PMN. A pro-tumoral PMN is characterized by the infiltration of immunosuppressive cells and increased pro-inflammatory immune responses. Notably, neutrophils form web-like structures known as neutrophil extracellular traps (NETs) both in primary TME and metastatic sites, NETs are involved in cancer progression and metastasis. In this review, we focus on the role of gut microbiota in CRC progression and metastasis, highlight the multiple functions of different immune cell types in TME, especially neutrophils and NETs, discuss the possible mechanisms of gut microbiota in shaping PMN formation, and provide therapeutical indications in clinic.
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Affiliation(s)
- Jiawei Wu
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Clinical Research and Lab Center, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China
| | - Wenyan Dong
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Yayun Pan
- Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Jingjing Wang
- Department of Burn and Plastic Surgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China
| | - Minliang Wu
- Department of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Yue Yu
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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13
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Gu M, Yin W, Zhang J, Yin J, Tang X, Ling J, Tang Z, Yin W, Wang X, Ni Q, Zhu Y, Chen T. Role of gut microbiota and bacterial metabolites in mucins of colorectal cancer. Front Cell Infect Microbiol 2023; 13:1119992. [PMID: 37265504 PMCID: PMC10229905 DOI: 10.3389/fcimb.2023.1119992] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 05/03/2023] [Indexed: 06/03/2023] Open
Abstract
Colorectal cancer (CRC) is a major health burden, accounting for approximately 10% of all new cancer cases worldwide. Accumulating evidence suggests that the crosstalk between the host mucins and gut microbiota is associated with the occurrence and development of CRC. Mucins secreted by goblet cells not only protect the intestinal epithelium from microorganisms and invading pathogens but also provide a habitat for commensal bacteria. Conversely, gut dysbiosis results in the dysfunction of mucins, allowing other commensals and their metabolites to pass through the intestinal epithelium, potentially triggering host responses and the subsequent progression of CRC. In this review, we summarize how gut microbiota and bacterial metabolites regulate the function and expression of mucin in CRC and novel treatment strategies for CRC.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiangjun Wang
- *Correspondence: Xiangjun Wang, ; Qing Ni, ; Yunxiang Zhu, ; Tuo Chen,
| | - Qing Ni
- *Correspondence: Xiangjun Wang, ; Qing Ni, ; Yunxiang Zhu, ; Tuo Chen,
| | - Yunxiang Zhu
- *Correspondence: Xiangjun Wang, ; Qing Ni, ; Yunxiang Zhu, ; Tuo Chen,
| | - Tuo Chen
- *Correspondence: Xiangjun Wang, ; Qing Ni, ; Yunxiang Zhu, ; Tuo Chen,
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14
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Wong CC, Yu J. Gut microbiota in colorectal cancer development and therapy. Nat Rev Clin Oncol 2023:10.1038/s41571-023-00766-x. [PMID: 37169888 DOI: 10.1038/s41571-023-00766-x] [Citation(s) in RCA: 190] [Impact Index Per Article: 95.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2023] [Indexed: 05/13/2023]
Abstract
Colorectal cancer (CRC) is one of the commonest cancers globally. A unique aspect of CRC is its intimate association with the gut microbiota, which forms an essential part of the tumour microenvironment. Research over the past decade has established that dysbiosis of gut bacteria, fungi, viruses and Archaea accompanies colorectal tumorigenesis, and these changes might be causative. Data from mechanistic studies demonstrate the ability of the gut microbiota to interact with the colonic epithelia and immune cells of the host via the release of a diverse range of metabolites, proteins and macromolecules that regulate CRC development. Preclinical and some clinical evidence also underscores the role of the gut microbiota in modifying the therapeutic responses of patients with CRC to chemotherapy and immunotherapy. Herein, we summarize our current understanding of the role of gut microbiota in CRC and outline the potential translational and clinical implications for CRC diagnosis, prevention and treatment. Emphasis is placed on how the gut microbiota could now be better harnessed by developing targeted microbial therapeutics as chemopreventive agents against colorectal tumorigenesis, as adjuvants for chemotherapy and immunotherapy to boost drug efficacy and safety, and as non-invasive biomarkers for CRC screening and patient stratification. Finally, we highlight the hurdles and potential solutions to translating our knowledge of the gut microbiota into clinical practice.
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Affiliation(s)
- Chi Chun Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
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15
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Corredoira J, Miguez E, Mateo LM, Fernández-Rodríguez R, García-Rodríguez JF, Pérez-González A, Sanjurjo A, Pulian MV, Ayuso-García B. The interaction between liver cirrhosis, infection by Streptococcus bovis, and colon cancer. Eur J Clin Microbiol Infect Dis 2023:10.1007/s10096-023-04618-5. [PMID: 37145237 DOI: 10.1007/s10096-023-04618-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 04/28/2023] [Indexed: 05/06/2023]
Abstract
Whether cirrhotic patients with Streptococcus bovis bacteremia have an increased risk of colorectal neoplasm is uncertain. A multicentric retrospective cohort study was conducted investigating associations between S. bovis biotype and species, cirrhosis, and colorectal neoplasm. Out of 779 patients with S. bovis bacteremia, 69 (8.7%) had cirrhosis. No differences were found in the prevalence of colorectal neoplasm between cirrhotic and non-cirrhotic patients undergoing colonoscopy. Among cirrhotic patients, prevalence of colorectal neoplasms was higher in S. bovis biotype I (S. gallolyticus) bacteremia (80%) than in S. bovis biotype II (33.3%; p < 0.007). In conclusion, risk of colorectal neoplasm is high among cirrhotic patients with S. gallolyticus bacteremia.
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Affiliation(s)
- Juan Corredoira
- Infectious Diseases Unit, University Hospital Lucus Augusti, Lugo, Spain
| | - Enrique Miguez
- Infectious Diseases Unit, A Coruña University Hospital Complex, A Coruña, Spain
| | - Lara María Mateo
- Internal Medicine Department, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
| | | | | | | | - Ana Sanjurjo
- Internal Medicine Department, POVISA Hospital, Vigo, Spain
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16
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Senchukova MA. Genetic heterogeneity of colorectal cancer and the microbiome. World J Gastrointest Oncol 2023; 15:443-463. [PMID: 37009315 PMCID: PMC10052667 DOI: 10.4251/wjgo.v15.i3.443] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/06/2023] [Accepted: 02/22/2023] [Indexed: 03/14/2023] Open
Abstract
In 2020, the International Agency for Research on Cancer and the World Health Organization's GLOBOCAN database ranked colorectal cancer (CRC) as the third most common cancer in the world. Most cases of CRC (> 95%) are sporadic and develop from colorectal polyps that can progress to intramucosal carcinoma and CRC. Increasing evidence is accumulating that the gut microbiota can play a key role in the initiation and progression of CRC, as well as in the treatment of CRC, acting as an important metabolic and immunological regulator. Factors that may determine the microbiota role in CRC carcinogenesis include inflammation, changes in intestinal stem cell function, impact of bacterial metabolites on gut mucosa, accumulation of genetic mutations and other factors. In this review, I discuss the major mechanisms of the development of sporadic CRC, provide detailed characteristics of the bacteria that are most often associated with CRC, and analyze the role of the microbiome and microbial metabolites in inflammation initiation, activation of proliferative activity in intestinal epithelial and stem cells, and the development of genetic and epigenetic changes in CRC. I consider long-term studies in this direction to be very important, as they open up new opportunities for the treatment and prevention of CRC.
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Affiliation(s)
- Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
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17
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Yang S, Hao S, Ye H, Zhang X. Global research on the crosstalk between intestinal microbiome and colorectal cancer: A visualization analysis. Front Cell Infect Microbiol 2023; 13:1083987. [PMID: 37009513 PMCID: PMC10050574 DOI: 10.3389/fcimb.2023.1083987] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 03/03/2023] [Indexed: 03/17/2023] Open
Abstract
BackgroundIncreasing evidence has shown that the intestinal microbiome (IM) is highly linked to colorectal cancer (CRC). To investigate scientific output, identify highly cited papers, and explore research hotspots and trends in the field of IM/CRC, we conducted a bibliometric and visualized analysis.MethodsA bibliographic search regarding IM/CRC research (2012-2021) was implemented on October 17, 2022. The terms attached to IM and CRC were searched for in the titles (TI), abstracts (AB), and author keywords (AK). The main information was extracted from the Web of Science Core Collection (WoSCC). Biblioshiny from R packages and VOSviewer were used for data visualization.ResultsA total of 1725 papers related to IM/CRC were retrieved. Publications on IM/CRC have grown rapidly from 2012 to 2021. China and the United States were in the leading position for publications in this field and made the most significant contributions to IM/CRC research. Shanghai Jiao Tong University and Harvard University were the most productive institutions. The high-yield authors were Yu Jun and Fang Jing Yuan. The International Journal of Molecular Sciences published the most papers, whereas Gut had the most citations. Historical citation analysis showed the evolution of IM/CRC research. Current status and hotspots were highlighted using keyword cluster analysis. The hot topics include the effect of IM on tumorigenesis, the effect of IM on CRC treatment, the role of IM in CRC screening, the mechanisms of IM involvement in CRC, and IM modulation for CRC management. Some topics, such as chemotherapy, immunotherapy, Fusobacterium nucleatum and short-chain fatty acids could be the focus of IM/CRC research in the coming years.ConclusionThis research evaluated the global scientific output of IM/CRC research and its quantitative features, identified some significant papers, and gathered information on the status and trends of IM/CRC research, which may shape future paths for academics and practitioners.
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Affiliation(s)
- Shanshan Yang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Shaodong Hao
- Spleen-Stomach Department, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Ye
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
- *Correspondence: Xuezhi Zhang, ; Hui Ye,
| | - Xuezhi Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
- *Correspondence: Xuezhi Zhang, ; Hui Ye,
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18
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El-Sayed A, Aleya L, Kamel M. Epigenetics and the role of nutraceuticals in health and disease. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:28480-28505. [PMID: 36694069 DOI: 10.1007/s11356-023-25236-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 01/05/2023] [Indexed: 06/17/2023]
Abstract
In the post-genomic era, the data provided by complete genome sequencing could not answer several fundamental questions about the causes of many noninfectious diseases, diagnostic biomarkers, and novel therapeutic approaches. The rapidly expanding understanding of epigenetic mechanisms, as well as widespread acceptance of their hypothesized role in disease induction, facilitated the development of a number of novel diagnostic markers and therapeutic concepts. Epigenetic aberrations are reversible in nature, which enables the treatment of serious incurable diseases. Therefore, the interest in epigenetic modulatory effects has increased over the last decade, so about 60,000 publications discussing the expression of epigenetics could be detected in the PubMed database. Out of these, 58,442 were published alone in the last 10 years, including 17,672 reviews (69 historical articles), 314 clinical trials, 202 case reports, 197 meta-analyses, 156 letters to the editor, 108 randomized controlled trials, 87 observation studies, 40 book chapters, 22 published lectures, and 2 clinical trial protocols. The remaining publications are either miscellaneous or a mixture of the previously mentioned items. According to the species and gender, the publications included 44,589 human studies (17,106 females, 14,509 males, and the gender is not mentioned in the remaining papers) and 30,253 animal studies. In the present work, the role of epigenetic modulations in health and disease and the influencing factors in epigenetics are discussed.
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Affiliation(s)
- Amr El-Sayed
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Lotfi Aleya
- Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, 25030, Besançon Cedex, France
| | - Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
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19
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Masood M, Nasser MI. Gut microbial metabolites and colorectal cancer. MICROBIAL BIOMOLECULES 2023:353-373. [DOI: 10.1016/b978-0-323-99476-7.00011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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20
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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] [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.
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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.
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21
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First Report on the Streptococcus gallolyticus (S. bovis Biotype I) DSM 13808 Exopolysaccharide Structure. Int J Mol Sci 2022; 23:ijms231911797. [PMID: 36233098 PMCID: PMC9570385 DOI: 10.3390/ijms231911797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 09/30/2022] [Accepted: 10/03/2022] [Indexed: 11/17/2022] Open
Abstract
Streptococcus gallolyticus subspecies gallolyticus, known as Streptococcus bovis biotype I, is a facultative pathogen causing bacteraemia, infective endocarditis and sepsis that has been linked with colorectal cancer (CRC), but this correlation is still unclear. Bacterial surface structures, such as the major sugar antigens exposed to the outside of the microorganism, are potential virulence factors. One of the primary sugar antigens loosely attached to the cell surface is the biofilm component, exopolysaccharide (EPS). EPSs of S. bovis are poorly characterized molecules. Until now, only one S. macedonicus Sc136 EPS structure was known to the entire S. bovis group. The S. gallolyticus DSM 13808 EPS was investigated by chemical analysis, mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. The hexasaccharide repeating unit of the EPS, containing four Glc, two Rha residues and one phosphate group, has been described “ →6)-α-d-Glcp-(1→3)-β-l-Rhap-(1→4)-β-d-Glcp-(1→3)-[β-d-Glcp-(1→2)]-α-l-Rhap-(1→2)-α-d-Glcp-(1→P→”.
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22
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Kumar R, Taylor JC, Jain A, Jung SY, Garza V, Xu Y. Modulation of the extracellular matrix by Streptococcus gallolyticus subsp. gallolyticus and importance in cell proliferation. PLoS Pathog 2022; 18:e1010894. [PMID: 36191045 PMCID: PMC9560553 DOI: 10.1371/journal.ppat.1010894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 10/13/2022] [Accepted: 09/22/2022] [Indexed: 11/15/2022] Open
Abstract
Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. Previous work showed that this organism stimulates CRC cells proliferation and tumor growth. However, the molecular mechanisms underlying these activities are not well understood. Here, we found that Sgg upregulates the expression of several type of collagens in HT29 and HCT116 cells, with type VI collagen (ColVI) being the highest upregulated type. Knockdown of ColVI abolished the ability of Sgg to induce cell proliferation and reduced the adherence of Sgg to CRC cells. The extracellular matrix (ECM) is an important regulator of cell proliferation. Therefore, we further examined the role of decellularized matrix (dc-matrix), which is free of live bacteria or cells, in Sgg-induced cell proliferation. Dc-matrix prepared from Sgg-treated cells showed a significantly higher pro-proliferative activity than that from untreated cells or cells treated with control bacteria. On the other hand, dc-matrix from Sgg-treated ColVI knockdown cells showed no difference in the capacity to support cell proliferation compared to that from untreated ColVI knockdown cells, suggesting that the ECM by itself is a mediator of Sgg-induced cell proliferation. Furthermore, Sgg treatment of CRC cells but not ColVI knockdown CRC cells resulted in significantly larger tumors in vivo, suggesting that ColVI is important for Sgg to promote tumor growth in vivo. These results highlight a dynamic bidirectional interplay between Sgg and the ECM, where Sgg upregulates collagen expression. The Sgg-modified ECM in turn affects the ability of Sgg to adhere to host cells and more importantly, acts as a mediator for Sgg-induced CRC cell proliferation. Taken together, our results reveal a novel mechanism in which Sgg stimulates CRC proliferation through modulation of the ECM.
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Affiliation(s)
- Ritesh Kumar
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America
| | - John Culver Taylor
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America
| | - Antrix Jain
- MS Proteomics Core, Baylor College of Medicine, Houston, Texas, United States of America
| | - Sung Yun Jung
- Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America
| | - Victor Garza
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America
| | - Yi Xu
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America
- Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, College Station, Texas, United States of America
- Department of Microbiology and Molecular Genetics, McGovern Medical School, UT Health, Houston, Texas, United States of America
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23
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The crosstalk of the human microbiome in breast and colon cancer: A metabolomics analysis. Crit Rev Oncol Hematol 2022; 176:103757. [PMID: 35809795 DOI: 10.1016/j.critrevonc.2022.103757] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/28/2022] [Accepted: 07/04/2022] [Indexed: 11/20/2022] Open
Abstract
The human microbiome's role in colon and breast cancer is described in this review. Understanding how the human microbiome and metabolomics interact with breast and colon cancer is the chief area of this study. First, the role of the gut and distal microbiome in breast and colon cancer is investigated, and the direct relationship between microbial dysbiosis and breast and colon cancer is highlighted. This work also focuses on the many metabolomic techniques used to locate prospective biomarkers, make an accurate diagnosis, and research new therapeutic targets for cancer treatment. This review clarifies the influence of anti-tumor medications on the microbiota and the proactive measures that can be taken to treat cancer using a variety of therapies, including radiotherapy, chemotherapy, next-generation biotherapeutics, gene-based therapy, integrated omics technology, and machine learning.
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24
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Corredoira Sánchez J, Ayuso García B, Romay Lema EM, García-Pais MJ, Rodríguez-Macias AI, Capón González P, Otero López R, Rabuñal Rey R, Alonso García P. Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review. Enferm Infecc Microbiol Clin 2022. [DOI: 10.1016/j.eimc.2022.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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25
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Allen J, Rosendahl Huber A, Pleguezuelos-Manzano C, Puschhof J, Wu S, Wu X, Boot C, Saftien A, O’Hagan HM, Wang H, van Boxtel R, Clevers H, Sears CL. Colon Tumors in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized Mice Do Not Display a Unique Mutational Signature but Instead Possess Host-Dependent Alterations in the APC Gene. Microbiol Spectr 2022; 10:e0105522. [PMID: 35587635 PMCID: PMC9241831 DOI: 10.1128/spectrum.01055-22] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 03/31/2022] [Indexed: 12/13/2022] Open
Abstract
Enterotoxigenic Bacteroides fragilis (ETBF) is consistently found at higher frequency in individuals with sporadic and hereditary colorectal cancer (CRC) and induces tumorigenesis in several mouse models of CRC. However, whether specific mutations induced by ETBF lead to colon tumor formation has not been investigated. To determine if ETBF-induced mutations impact the Apc gene, and other tumor suppressors or proto-oncogenes, we performed whole-exome sequencing and whole-genome sequencing on tumors isolated after ETBF and sham colonization of Apcmin/+ and Apcmin/+Msh2fl/flVC mice, as well as whole-genome sequencing of organoids cocultured with ETBF. Our results indicate that ETBF-induced tumor formation results from loss of heterozygosity (LOH) of Apc, unless the mismatch repair system is disrupted, in which case, tumor formation results from new acquisition of protein-truncating mutations in Apc. In contrast to polyketide synthase-positive Escherichia coli (pks+ E. coli), ETBF does not produce a unique mutational signature; instead, ETBF-induced tumors arise from errors in DNA mismatch repair and homologous recombination DNA damage repair, established pathways of tumor formation in the colon, and the same genetic mechanism accounting for sham tumors in these mouse models. Our analysis informs how this procarcinogenic bacterium may promote tumor formation in individuals with inherited predispositions to CRC, such as Lynch syndrome or familial adenomatous polyposis (FAP). IMPORTANCE Many studies have shown that microbiome composition in both the mucosa and the stool differs in individuals with sporadic and hereditary colorectal cancer (CRC). Both human and mouse models have established a strong association between particular microbes and colon tumor induction. However, the genetic mechanisms underlying putative microbe-induced colon tumor formation are not well established. In this paper, we applied whole-exome sequencing and whole-genome sequencing to investigate the impact of ETBF-induced genetic changes on tumor formation. Additionally, we performed whole-genome sequencing of human colon organoids exposed to ETBF to validate the mutational patterns seen in our mouse models and begin to understand their relevance in human colon epithelial cells. The results of this study highlight the importance of ETBF colonization in the development of sporadic CRC and in individuals with hereditary tumor conditions, such as Lynch syndrome and familial adenomatous polyposis (FAP).
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Affiliation(s)
- Jawara Allen
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Axel Rosendahl Huber
- Oncode Institute, Utrecht, The Netherlands
- The Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Cayetano Pleguezuelos-Manzano
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
| | - Jens Puschhof
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
| | - Shaoguang Wu
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Xinqun Wu
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Charelle Boot
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, The Netherlands
| | - Aurelia Saftien
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, The Netherlands
| | - Heather M. O’Hagan
- Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana, USA
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA
- Cell, Molecular and Cancer Biology Program, Indiana University School of Medicine, Bloomington, Indiana, USA
| | - Hao Wang
- Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine Institutions, Baltimore, Maryland, USA
| | - Ruben van Boxtel
- Oncode Institute, Utrecht, The Netherlands
- The Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Hans Clevers
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
- The Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Cynthia L. Sears
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Oncology, Johns Hopkins Medicine Institutions, Baltimore, Maryland, USA
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine Institutions, Baltimore, Maryland, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine Institutions, Baltimore, Maryland, USA
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The role of microbiota in colorectal cancer. Folia Microbiol (Praha) 2022; 67:683-691. [PMID: 35534716 DOI: 10.1007/s12223-022-00978-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 05/02/2022] [Indexed: 11/04/2022]
Abstract
Cancer is one of the most important causes of death throughout the world, and the mortality rate is increasing significantly due to the aging of the population. One of the most common types of cancer is colorectal cancer (CRC). Human microbial ecosystems use metabolism to make important impacts on the body physiology. An intensive literature review was made to investigate the correlations between human gut microbiota and the incidence of CRC. The results of these studies show that there are differences in the composition of microbiota between CRC patients and normal people and the microorganisms in CRC patients are very different from healthy individuals. Therefore, changes in the microbiome can be used as a biomarker for the early detection of CRC. On the other hand, the intestinal flora is may be act as a powerful weapon against CRC in the future.
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Corredoira J, Ayuso B. Bacteremia and colon cancer: Causality or coincidence? Enferm Infecc Microbiol Clin 2022. [DOI: 10.1016/j.eimc.2022.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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28
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Corredoira J, Ayuso B. Bacteremia and colon cancer: Causality or coincidence? ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2022; 40:221-223. [PMID: 35577440 DOI: 10.1016/j.eimce.2022.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 06/15/2023]
Affiliation(s)
- Juan Corredoira
- Unidad de Enfermedades Infecciosas, Hospital Lucus Augusti, Lugo, Spain.
| | - Blanca Ayuso
- Unidad de Enfermedades Infecciosas, Hospital Lucus Augusti, Lugo, Spain
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Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series. J Clin Med 2022; 11:jcm11082181. [PMID: 35456274 PMCID: PMC9030725 DOI: 10.3390/jcm11082181] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/07/2022] [Accepted: 04/11/2022] [Indexed: 11/22/2022] Open
Abstract
Objectives: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. Methods: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979–2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. Results: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34–156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. Conclusions: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms.
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Pugalenthi LS, Ahmad M, Reddy S, Barkhane Z, Elmadi J, Satish Kumar L. Malignancy and Endocarditis: Divulging Into the Intertwined Association. Cureus 2022; 14:e24089. [PMID: 35573527 PMCID: PMC9098766 DOI: 10.7759/cureus.24089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2022] [Indexed: 12/02/2022] Open
Abstract
Cancer is an immunosuppressive disorder with characteristic features of unchecked cell growth, invasion, and sometimes thromboembolism leading to multiple systemic sequelae, including infective endocarditis. This article has compiled some of the crucial mechanisms by which infective endocarditis occurs in cancer patients, its risk factors, and the existing treatment interventions. It has focused on the necessity of being aware that these multiple pathogeneses are involved in the development of infective endocarditis (IE) in cancer patients, which would help delineate the risk factors associated with the condition and help physicians screen better for specific red flags. Identifying these risk factors and patient-oriented therapy, targeting the necessary elements such as causative organism, patient immune status, type of cancer, choosing evidence-based treatment modalities, and to improve the outcome of the disease in an already exasperating condition called cancer.
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31
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D'Amico F, Barone M, Tavella T, Rampelli S, Brigidi P, Turroni S. Host microbiomes in tumor precision medicine: how far are we? Curr Med Chem 2022; 29:3202-3230. [PMID: 34986765 DOI: 10.2174/0929867329666220105121754] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/13/2021] [Accepted: 11/22/2021] [Indexed: 11/22/2022]
Abstract
The human gut microbiome has received a crescendo of attention in recent years, due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.
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Affiliation(s)
- Federica D'Amico
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Monica Barone
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Teresa Tavella
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Simone Rampelli
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Patrizia Brigidi
- Microbiome Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
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Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls. Cancers (Basel) 2021; 13:cancers13246363. [PMID: 34944982 PMCID: PMC8699505 DOI: 10.3390/cancers13246363] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 11/24/2022] Open
Abstract
Simple Summary In colorectal cancer patients, epithelial barrier dysfunction can lead to increased intestinal permeability, and gut microbiome was found to vary compared to healthy subjects. We conducted a study to investigate whether bacterial translocation from gastrointestinal tract to bloodstream is associated to intestinal adenoma and/or colorectal cancer. In particular, an epidemiological and metagenomic approach was used to evaluate the relation of the bacterial DNA load and the bacterial taxonomic groups—assessed by 16S rRNA profiling—in blood with the risks of intestinal adenoma and colorectal cancer. These findings can confirm the presence of bacterial DNA in blood in healthy adults and serve as a basis to evaluate new non-invasive techniques for an early CRC diagnosis through the analyses of bacterial DNA circulating in peripheral blood. Abstract Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.
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33
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Özkan ER, Öztürk Hİ, Demirci T, Akın N. Detection of biofilm formation, virulence factor genes, antibiotic-resistance, adherence properties, and some beneficial properties of cheese origin S. infantarius, S. gallolyticus, and S. lutetiensis strains belonging to the S. bovis/S. equinus complex. Lebensm Wiss Technol 2021. [DOI: 10.1016/j.lwt.2021.112077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Wang F, Song M, Lu X, Zhu X, Deng J. Gut microbes in gastrointestinal cancers. Semin Cancer Biol 2021; 86:967-975. [PMID: 33812983 DOI: 10.1016/j.semcancer.2021.03.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/26/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023]
Abstract
Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.
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Affiliation(s)
- Fei Wang
- Division of Gastroenterology, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Meiyi Song
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiya Lu
- Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xuefeng Zhu
- University of Shanghai for Science and Technology, Shanghai, China.
| | - Jiali Deng
- Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai, 200444, China.
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35
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Ladaycia A, Loretz B, Passirani C, Lehr CM, Lepeltier E. Microbiota and cancer: In vitro and in vivo models to evaluate nanomedicines. Adv Drug Deliv Rev 2021; 170:44-70. [PMID: 33388279 DOI: 10.1016/j.addr.2020.12.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 12/23/2020] [Accepted: 12/27/2020] [Indexed: 02/08/2023]
Abstract
Nanomedicine implication in cancer treatment and diagnosis studies witness huge attention, especially with the promising results obtained in preclinical studies. Despite this, only few nanomedicines succeeded to pass clinical phase. The human microbiota plays obvious roles in cancer development. Nanoparticles have been successfully used to modulate human microbiota and notably tumor associated microbiota. Taking the microbiota involvement under consideration when testing nanomedicines for cancer treatment might be a way to improve the poor translation from preclinical to clinical trials. Co-culture models of bacteria and cancer cells, as well as animal cancer-microbiota models offer a better representation for the tumor microenvironment and so potentially better platforms to test nanomedicine efficacy in cancer treatment. These models would allow closer representation of human cancer and might smoothen the passage from preclinical to clinical cancer studies for nanomedicine efficacy.
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36
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Taylor JC, Gao X, Xu J, Holder M, Petrosino J, Kumar R, Liu W, Höök M, Mackenzie C, Hillhouse A, Brashear W, Nunez MP, Xu Y. A type VII secretion system of Streptococcus gallolyticus subsp. gallolyticus contributes to gut colonization and the development of colon tumors. PLoS Pathog 2021; 17:e1009182. [PMID: 33406160 PMCID: PMC7815207 DOI: 10.1371/journal.ppat.1009182] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/19/2021] [Accepted: 11/23/2020] [Indexed: 02/06/2023] Open
Abstract
Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. However, the molecular determinants involved in Sgg pathogenicity in the gut are unknown. Bacterial type VII secretion systems (T7SS) mediate pathogen interactions with their host and are important for virulence in pathogenic mycobacteria and Staphylococcus aureus. Through genome analysis, we identified a locus in Sgg strain TX20005 that encodes a putative type VII secretion system (designated as SggT7SST05). We showed that core genes within the SggT7SST05 locus are expressed in vitro and in the colon of mice. Western blot analysis showed that SggEsxA, a protein predicted to be a T7SS secretion substrate, is detected in the bacterial culture supernatant, indicating that this SggT7SST05 is functional. Deletion of SggT7SST05 (TX20005Δesx) resulted in impaired bacterial adherence to HT29 cells and abolished the ability of Sgg to stimulate HT29 cell proliferation. Analysis of bacterial culture supernatants suggest that SggT7SST05-secreted factors are responsible for the pro-proliferative activity of Sgg, whereas Sgg adherence to host cells requires both SggT7SST05-secreted and bacterial surface-associated factors. In a murine gut colonization model, TX20005Δesx showed significantly reduced colonization compared to the parent strain. Furthermore, in a mouse model of CRC, mice exposed to TX20005 had a significantly higher tumor burden compared to saline-treated mice, whereas those exposed to TX20005Δesx did not. Examination of the Sgg load in the colon in the CRC model suggests that SggT7SST05-mediated activities are directly involved in the promotion of colon tumors. Taken together, these results reveal SggT7SST05 as a previously unrecognized pathogenicity determinant for Sgg colonization of the colon and promotion of colon tumors.
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Affiliation(s)
- John Culver Taylor
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
| | - Xinsheng Gao
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
| | - Juan Xu
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
| | - Michael Holder
- Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, United States of America
| | - Joseph Petrosino
- Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, United States of America
| | - Ritesh Kumar
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
| | - Wen Liu
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
| | - Magnus Höök
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
| | - Chris Mackenzie
- Department of Microbiology and Molecular Genetics, McGovern Medical School, UT Health, Houston, Texas, United States of America
| | - Andrew Hillhouse
- Texas A&M Institute for Genome Sciences and Society, Texas A&M, Texas, United States of America
| | - Wesley Brashear
- Texas A&M Institute for Genome Sciences and Society, Texas A&M, Texas, United States of America
| | - Maria Patricia Nunez
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
| | - Yi Xu
- Center for Infectious and Inflammatory Diseases, Texas A&M Health Science Center Institute of Biosciences of Technology, Houston, Texas, United States of America
- Department of Microbiology and Molecular Genetics, McGovern Medical School, UT Health, Houston, Texas, United States of America
- Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, Texas, United States of America
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Zhong M, Xiong Y, Ye Z, Zhao J, Zhong L, Liu Y, Zhu Y, Tian L, Qiu X, Hong X. Microbial Community Profiling Distinguishes Left-Sided and Right-Sided Colon Cancer. Front Cell Infect Microbiol 2020; 10:498502. [PMID: 33324571 PMCID: PMC7726112 DOI: 10.3389/fcimb.2020.498502] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 10/21/2020] [Indexed: 12/17/2022] Open
Abstract
The difference between left- and right-sided colon cancer has become the focus of global attention, and researchers have found differences in the morbidity, molecular biological characteristics, and response to targeted drug therapy between left- and right-sided colon cancer. Therefore, the identification of more effective predictive indicators is critical for providing guidance to future clinical work. We collected samples from different colon sites and regions and analyzed the identities and distributions of differentially expressed species in the microbiota in the left and right sides of the colon to better explore the pathogenesis of colon cancer and provided a basis for individualized drug therapy. We collected samples from different regions in the body of 40 patients with colon cancer, including stool and tissues. The Subjects were classified into four groups, and this classification was mainly based on the colon cancer distribution. The microbiota composition of the left-sided and right-sided colon samples was assessed by specifically amplifying the V3-V4 region of the 16S rDNA gene from DNA extracts from the samples. These amplicons were examined by Illumina HiSeq 2500 sequencing. The microbial taxa in the left-sided colon samples are more abundant than those in the right-sided colon samples. The flora in the left-sided colon samples, such as Clostridium perfringens and Fusobacterium nucleatum, might be associated with VEGF expression and are more likely to promote colon cancer. The microbiota distribution in the right-sided colon samples is less invasive and harmful and particularly rich in Bifidobacterium dentium. In addition, Streptococcus, which is the target of EGFR, was found to be expressed in both the left- and right-sided colon samples but was found at a higher level in the left-sided colon samples. Additionally, the differential pathways involved in the left-sided colon samples mainly mediate DNA damage, methylation, and histone modifications, whereas those in the right-sided colon samples are dominated by DNA synthesis. The comparison of only the geographical differences revealed a significant difference in the distribution of the microbial population. The adherent microbiota composition and structural changes between the left- and right-sided colon samples might contribute to the development of colon cancer, lead to different morbidities, and further affect the prognosis of patients and their sensitivity to targeted drugs. Therefore, the identification of the differential flora in the colon could be used as an indicator for predicting the occurrence and development of colon cancer, which is also beneficial for future individualized drug therapy.
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Affiliation(s)
- Mengya Zhong
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Yubo Xiong
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Zhijian Ye
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Jiabao Zhao
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Lifeng Zhong
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Yu Liu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Yuekun Zhu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lantian Tian
- Department of Hepatopancreatobiliary Surgery of the Affiliated Hospital, Qingdao University, Qingdao, China
| | - Xingfeng Qiu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Xuehui Hong
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
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The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to analyze the tumor-immune-microbiome interaction. Hum Genet 2020; 140:725-746. [PMID: 33180176 DOI: 10.1007/s00439-020-02235-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023]
Abstract
Metagenomic studies using next-generation sequencing technologies have revealed rich human intestinal microbiome, which likely influence host immunity and health conditions including cancer. Evidence indicates a biological link between altered microbiome and cancers in the digestive system. Escherichia coli and Bacteroides fragilis have been found to be enriched in colorectal mucosal tissues from patients with familial adenomatous polyposis that is caused by germline APC mutations. In addition, recent studies have found enrichment of certain oral bacteria, viruses, and fungi in tumor tissue and fecal specimens from patients with gastrointestinal cancer. An integrative approach is required to elucidate the role of microorganisms in the pathogenic process of gastrointestinal cancers, which develop through the accumulation of somatic genetic and epigenetic alterations in neoplastic cells, influenced by host genetic variations, immunity, microbiome, and environmental exposures. The transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to link germline genetics and environmental factors (including diet, lifestyle, and pharmacological factors) to pathologic phenotypes. The integration of microbiology into the MPE model (microbiology-MPE) can contribute to better understanding of the interactive role of environment, tumor cells, immune cells, and microbiome in various diseases. We review major clinical and experimental studies on the microbiome, and describe emerging evidence from the microbiology-MPE research in gastrointestinal cancers. Together with basic experimental research, this new research paradigm can help us to develop new prevention and treatment strategies for gastrointestinal cancers through targeting of the microbiome.
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Taddese R, Garza DR, Ruiter LN, de Jonge MI, Belzer C, Aalvink S, Nagtegaal ID, Dutilh BE, Boleij A. Growth rate alterations of human colorectal cancer cells by 157 gut bacteria. Gut Microbes 2020; 12:1-20. [PMID: 32915102 PMCID: PMC7524400 DOI: 10.1080/19490976.2020.1799733] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Several bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effects on cell growth. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play. Secretomes of Bacteroidaceae, Enterobacteriaceae, and Erysipelotrichaceae bacteria enhanced cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. In some bacteria, the presence of specific functional genes was associated with cell growth rates, including the virulence genes TcdA, TcdB in Clostridiales and FadA in Fusobacteriaceae, which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes of the ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cell growth, contribute a better understanding of the effects of the gut microbiome on host cells, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies.
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Affiliation(s)
- Rahwa Taddese
- Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands
| | - Daniel R. Garza
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Lilian N. Ruiter
- Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands
| | - Marien I. de Jonge
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Center for Infectious Diseases (RCI), Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, The Netherlands
| | - Steven Aalvink
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, The Netherlands
| | - Iris D. Nagtegaal
- Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands
| | - Bas E. Dutilh
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands,Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands,CONTACT Bas E.Dutilh Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Annemarie Boleij
- Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands,Annemarie Boleij Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands
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Salmonella enterica Serovar Typhimurium Temporally Modulates the Enteric Microbiota and Host Responses To Overcome Colonization Resistance in Swine. Appl Environ Microbiol 2020; 86:AEM.01569-20. [PMID: 32859592 DOI: 10.1128/aem.01569-20] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/19/2020] [Indexed: 02/07/2023] Open
Abstract
Salmonella enterica serovar Typhimurium is a prevalent incitant of enteritis in human beings and nonhuman animals. It has been proposed that host defense responses incited by Salmonella allow the bacterium to overcome colonization resistance. Piglets (n = 24) were orally inoculated with S. enterica serovar Typhimurium DT104 or buffer alone, and the host and microbial responses were temporally examined at the acute (2 days postinoculation [dpi]), subacute (6 dpi), and recovery (10 dpi) stages of salmonellosis. At the acute stage of disease, body temperatures were elevated, and feed consumption and weight gain were reduced. The densities of Salmonella associated with the gut mucosa decreased over time, with higher densities of the bacterium in the ileum and the large intestine. Moreover, substantive histopathological changes were observed as a function of time, with prominent epithelial injury and neutrophil infiltration observed at 2 dpi. Correspondingly, a variety of host metrics were temporally affected in piglets with salmonellosis (e.g., TNFα, IFNγ, PR39, βD2, iNOS, IL8, REGIIIγ). The enteric microbiota was characterized using culture-independent and -dependent methods in concert, and taxon- and location-specific changes to the microbiota were observed in infected piglets. Bacteroides spp. (e.g., Bacteroides uniformis, Bacteroides fragilis), Streptococcus spp. (e.g., Streptococcus gallolyticus), and various Gammaproteobacteria were highly associated with inflamed tissues, while bacteria within the Ruminococcaceae and Veillonellaceae families were mainly associated with healthy mucosae. In conclusion, the study findings showed that S Typhimurium incited temporal and spatial modifications to the swine autochthonous microbiota, and to host defense responses, that were consistent with overcoming colonization resistance to incite salmonellosis in swine.IMPORTANCE Limited information is available on host and enteric microbiota responses incited by Salmonella enterica serovar Typhimurium in swine and on possible mechanisms by which the bacterium overcomes colonization resistance to incite salmonellosis. Temporal characterization of a variety of host metrics in piglets (e.g., physiological, histopathological, and immunological) showed the importance of studying the progression of salmonellosis. A number of host responses integrally associated with disease development were identified. Utilization of next-generation sequence analysis to characterize the enteric microbiota was found to lack sufficient resolution; however, culture-dependent and -independent methods in combination identified taxon- and location-specific changes to bacterial communities in infected piglets. The study identified bacterial and host responses associated with salmonellosis, which will be beneficial in understanding colonization resistance and in the development of effective alternatives to antibiotics to mitigate salmonellosis.
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Søgaard KK, Veres K, Vandenbroucke-Grauls CMJE, Vandenbroucke JP, Sørensen HT, Schønheyder HC. Community-Acquired Escherichia coli Bacteremia after Age 50 and Subsequent Incidence of a Cancer Diagnosis: A Danish Population-Based Cohort Study. Cancer Epidemiol Biomarkers Prev 2020; 29:2626-2632. [PMID: 32998944 DOI: 10.1158/1055-9965.epi-20-0705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 07/03/2020] [Accepted: 09/25/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Community-acquired bacteremia (CAB) with Escherichia coli may signal occult cancer. This might differ between phylogenetic groups. METHODS We conducted a population-based cohort study in northern Denmark (1994-2013) to examine whether E. coli CAB after age 50 is associated with incident cancer. We followed patients from their bacteremia diagnosis date to identify subsequent gastrointestinal, hepatobiliary, and urinary tract cancer diagnoses. We calculated 1- and 5-year cumulative cancer incidence. We compared the observed incidence with that expected based on national cancer incidence rates, and computed standardized incidence ratios (SIR) at 0-<1 year and ≥1 year. In a subcohort, we assessed the prevalence of phylogenetic groups. RESULTS Among 2,735 patients with E. coli CAB, 173 later were diagnosed with cancer. The 1-year cumulative incidence of a gastrointestinal or hepatobiliary tract cancer was 1.9%, and the 0-<1-year SIR was 5.44 [95% confidence interval (CI), 4.06-7.14]. For urinary tract cancer, the corresponding estimates were 1.0% and 3.41 (95% CI, 2.27-4.93). All individual cancers occurred more often than expected during the first year following E. coli CAB, but thereafter the relative risks declined toward unity. Still, the ≥1-year SIR for colorectal cancer remained 1.4-fold elevated, and the SIR for liver, pancreas, gallbladder, and biliary tract cancer was 2-fold elevated. The prevalence of phylogenetic groups was similar among patients with and without cancer. CONCLUSIONS Gastrointestinal, hepatobiliary, and urinary tract cancer may debut with E. coli CAB. IMPACT Owing to the high incidence of E. coli bacteremia, cancers missed at the time of bacteremia diagnosis represent a clinically significant problem.
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Affiliation(s)
- Kirstine K Søgaard
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark. .,Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Katalin Veres
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Jan P Vandenbroucke
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Henrik T Sørensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik C Schønheyder
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Firuzi P, Asl Hashemi A, Samadi Kafil H, Gholizadeh P, Aslani H. Comparative study on the microbial quality in the swimming pools disinfected by the ozone-chlorine and chlorine processes in Tabriz, Iran. ENVIRONMENTAL MONITORING AND ASSESSMENT 2020; 192:516. [PMID: 32666262 DOI: 10.1007/s10661-020-08470-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 07/01/2020] [Indexed: 06/11/2023]
Abstract
Applying a desirable disinfestation process is necessary to control the pathogenic microorganisms in the swimming pools and prevent both dermal and intestinal effects. Therefore, the present study was conducted to compare the bacterial community and diversity in the two swimming pools disinfected by the chlorine and ozone (O3)-chlorine processes. A total of 24 samples were taken from the two swimming pools in three distinct seasons to analyze the bacterial and physico-chemical indicators. Culture and molecular methods were used to evaluate the microbial quality. Two sets of sample taken from the pools with the maximum swimmer load in the summer were investigated by the next-generation sequencing (NGS) technique. In total, 410 and 406 bacterial species were identified in the chlorine- and ozone-chlorine-disinfected pools, respectively. Among the eight dominant bacterial species in each swimming pool, Pseudomonas alcaliphila, Pseudomonas stutzeri, and Pseudomonas acnes were common species between the two studied pools. Oleomonas sagaranensis (350 reads/18593), Staphylococcus caprae (302 reads /18593), and Anaerococcus octavius (110 reads/18593) were among the dominant bacteria in the chlorine-disinfected pool. Bacterial diversity was lower in the ozone-chlorine-disinfected pool than the other one, and the highest bacterial sequencing belonged to the genus Pseudomonas (85.79%). Results showed that water quality of in O3-chlorine-disinfected pool was more desirable than the chlorine-disinfected pool. Molecular methods along with conventional culture methods would be advantageous for microbial assessment in the swimming pools.
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Affiliation(s)
- Parisa Firuzi
- Department of Environmental Health Engineering, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmad Asl Hashemi
- Department of Environmental Health Engineering, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Pourya Gholizadeh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Aslani
- Health and Environment Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Liu CZ, Chen W, Wang MX, Wang Y, Chen LQ, Zhao F, Shi Y, Liu HJ, Dou XB, Liu C, Chen H. Dendrobium officinale Kimura et Migo and American ginseng mixture: A Chinese herbal formulation for gut microbiota modulation. Chin J Nat Med 2020; 18:446-459. [PMID: 32503736 DOI: 10.1016/s1875-5364(20)30052-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Indexed: 02/07/2023]
Abstract
Dendrobium officinale Kimura et Migo (D. officinale) is a famous traditional Chinese medicine (TCM). A mixture of D. officinale and American ginseng has been shown to enhance cell-mediated immunity, humoral immunity, and monocyte/macrophage functions in mice. Here, the effects of a D. officinale and American ginseng mixture on the structure of gut microbial community in dogs were examined using high-throughput 16S rRNA gene amplicon sequencing. The data revealed that while the mixture did not change the diversity of gut microbial community significantly, differences among individuals were significantly reduced. Furthermore, the mixture-responsive operational taxonomic units (OTUs) exhibited a phase-dependent expression pattern. Fifty-five OTUs were found to exhibit a mixture-induced expression pattern, among which one third were short-chain fatty acid (SCFA)-producing genera and the others were probiotic genera included Lactobacillus spp., Sutterella, Alistipes, Anaerovorax, Bilophila, Coprococcus, Gordonibacter, Oscillibacter, among others. By contrast, 36% of the OTUs exhibiting a mixture-repressed expression pattern were disease-associated microorganisms, and six genera, namely Actinomyces, Escherichia/Shigella, Fusobacterium, Slackia, Streptococcus and Solobacterium, were associated with cancer. In addition, five genera were closely associated with diabetes, namely Collinsella, Rothia, Howardella, Slackia and Intestinibacter. Our results indicate that this D. officinale and American ginseng mixture may be used as a prebiotic agent to enhance SCFA-producing genera and prevent gut dysbiosis.
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Affiliation(s)
- Cheng-Zhi Liu
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Wei Chen
- Hangzhou Huqing yu tang Traditional Chinese Medicine Mordernize Institute, Hangzhou 311100, China
| | - Mei-Xia Wang
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Ying Wang
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Li-Qing Chen
- Hangzhou Huqing yu tang Traditional Chinese Medicine Mordernize Institute, Hangzhou 311100, China
| | - Feng Zhao
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Ya Shi
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Hui-Jun Liu
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Xiao-Bing Dou
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Chao Liu
- Department of Orthopaedics, Sir Sun Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
| | - Huan Chen
- Key laboratory of Microbial technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310012, China; NMPA Key laboratory for Testing and Risk Warning of Pharmaceutical Microbiology, Zhejiang Institute of Microbiology, Hangzhou 310012, China.
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Hu P, Zhao F, Wang J, Zhu W. Early-life lactoferrin intervention modulates the colonic microbiota, colonic microbial metabolites and intestinal function in suckling piglets. Appl Microbiol Biotechnol 2020; 104:6185-6197. [DOI: 10.1007/s00253-020-10675-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 04/22/2020] [Accepted: 05/10/2020] [Indexed: 12/13/2022]
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García López E, Martín-Galiano AJ. The Versatility of Opportunistic Infections Caused by Gemella Isolates Is Supported by the Carriage of Virulence Factors From Multiple Origins. Front Microbiol 2020; 11:524. [PMID: 32296407 PMCID: PMC7136413 DOI: 10.3389/fmicb.2020.00524] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 03/11/2020] [Indexed: 12/29/2022] Open
Abstract
The molecular basis of the pathogenesis of the opportunistic invasive infections caused by isolates of the Gemella genus remains largely unknown. Moreover, inconsistencies in the current species assignation were detected after genome-level comparison of 16 public Gemella isolates. A literature search detected that, between the two most pathogenic species, Gemella morbillorum causes about twice the number of cases compared to Gemella haemolysans. These two species shared their mean diseases - sepsis and endocarditis - but differed in causing other syndromes. A number of well-known virulence factors were harbored by all species, such as a manganese transport/adhesin sharing 83% identity from oral endocarditis-causing streptococci. Likewise, all Gemellae carried the genes required for incorporating phosphorylcholine into their cell walls and encoded some choline-binding proteins. In contrast, other proteins were species-specific, which may justify the known epidemiological differences. G. haemolysans, but not G. morbillorum, harbor a gene cluster potentially encoding a polysaccharidic capsule. Species-specific surface determinants also included Rib and MucBP repeats, hemoglobin-binding NEAT domains, peptidases of C5a complement factor and domains that recognize extracellular matrix molecules exposed in damaged heart valves, such as collagen and fibronectin. Surface virulence determinants were associated with several taxonomically dispersed opportunistic genera of the oral microbiota, such as Granulicatella, Parvimonas, and Streptococcus, suggesting the existence of a horizontally transferrable gene reservoir in the oral environment, likely facilitated by close proximity in biofilms and ultimately linked to endocarditis. The identification of the Gemella virulence pool should be implemented in whole genome-based protocols to rationally predict the pathogenic potential in ongoing clinical infections caused by these poorly known bacterial pathogens.
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Affiliation(s)
- Ernesto García López
- Departamento de Biotecnología Microbiana y de Plantas, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain
- CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Antonio J. Martín-Galiano
- Intrahospital Infections Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, Spain
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Garza DR, Taddese R, Wirbel J, Zeller G, Boleij A, Huynen MA, Dutilh BE. Metabolic models predict bacterial passengers in colorectal cancer. Cancer Metab 2020; 8:3. [PMID: 32055399 PMCID: PMC7008539 DOI: 10.1186/s40170-020-0208-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 01/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a complex multifactorial disease. Increasing evidence suggests that the microbiome is involved in different stages of CRC initiation and progression. Beyond specific pro-oncogenic mechanisms found in pathogens, metagenomic studies indicate the existence of a microbiome signature, where particular bacterial taxa are enriched in the metagenomes of CRC patients. Here, we investigate to what extent the abundance of bacterial taxa in CRC metagenomes can be explained by the growth advantage resulting from the presence of specific CRC metabolites in the tumor microenvironment. METHODS We composed lists of metabolites and bacteria that are enriched on CRC samples by reviewing metabolomics experimental literature and integrating data from metagenomic case-control studies. We computationally evaluated the growth effect of CRC enriched metabolites on over 1500 genome-based metabolic models of human microbiome bacteria. We integrated the metabolomics data and the mechanistic models by using scores that quantify the response of bacterial biomass production to CRC-enriched metabolites and used these scores to rank bacteria as potential CRC passengers. RESULTS We found that metabolic networks of bacteria that are significantly enriched in CRC metagenomic samples either depend on metabolites that are more abundant in CRC samples or specifically benefit from these metabolites for biomass production. This suggests that metabolic alterations in the cancer environment are a major component shaping the CRC microbiome. CONCLUSION Here, we show with in sillico models that supplementing the intestinal environment with CRC metabolites specifically predicts the outgrowth of CRC-associated bacteria. We thus mechanistically explain why a range of CRC passenger bacteria are associated with CRC, enhancing our understanding of this disease. Our methods are applicable to other microbial communities, since it allows the systematic investigation of how shifts in the microbiome can be explained from changes in the metabolome.
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Affiliation(s)
- Daniel R. Garza
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
| | - Rahwa Taddese
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 Nijmegen, HB Netherlands
| | - Jakob Wirbel
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
| | - Georg Zeller
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
| | - Annemarie Boleij
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 Nijmegen, HB Netherlands
| | - Martijn A. Huynen
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
| | - Bas E. Dutilh
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
- Theoretical Biology and Bioinformatics, Sience4Life, Utrecht University, Hugo R. Kruytgebouw, Room Z-509, Padualaan 8, Utrecht, The Netherlands
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Martins M, du Merle L, Trieu-Cuot P, Dramsi S. Heterogeneous expression of Pil3 pilus is critical for Streptococcus gallolyticus translocation across polarized colonic epithelial monolayers. Microbes Infect 2020; 22:55-59. [DOI: 10.1016/j.micinf.2019.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 11/30/2019] [Accepted: 12/02/2019] [Indexed: 01/10/2023]
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Song M, Chan AT, Sun J. Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer. Gastroenterology 2020; 158:322-340. [PMID: 31586566 PMCID: PMC6957737 DOI: 10.1053/j.gastro.2019.06.048] [Citation(s) in RCA: 465] [Impact Index Per Article: 93.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 06/11/2019] [Accepted: 06/16/2019] [Indexed: 02/07/2023]
Abstract
Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.
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Affiliation(s)
- Mingyang Song
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
| | - Jun Sun
- Division of Gastroenterology and Hepatology, Medicine, Microbiology/Immunology, UIC Cancer Center, University of Illinois at Chicago, Illinois.
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Tarashi S, Siadat SD, Ahmadi Badi S, Zali M, Biassoni R, Ponzoni M, Moshiri A. Gut Bacteria and their Metabolites: Which One Is the Defendant for Colorectal Cancer? Microorganisms 2019; 7:E561. [PMID: 31766208 PMCID: PMC6920974 DOI: 10.3390/microorganisms7110561] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 08/22/2019] [Accepted: 09/04/2019] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.
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Affiliation(s)
- Samira Tarashi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Sara Ahmadi Badi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Mohammadreza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
| | - Roberto Biassoni
- Laboratory of Molecular Medicine, IRCCS Instituto Giannina Gaslini, 16147 Genova, Italy;
| | - Mirco Ponzoni
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
| | - Arfa Moshiri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol 2019; 16:690-704. [PMID: 31554963 DOI: 10.1038/s41575-019-0209-8] [Citation(s) in RCA: 753] [Impact Index Per Article: 125.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/27/2019] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) accounts for about 10% of all new cancer cases globally. Located at close proximity to the colorectal epithelium, the gut microbiota comprises a large population of microorganisms that interact with host cells to regulate many physiological processes, such as energy harvest, metabolism and immune response. Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. These findings give new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as gut microbiota analysis as screening, prognostic or predictive biomarkers, or modulating microorganisms to prevent cancer, augment therapies and reduce adverse effects of treatment. This Review aims to provide an overview and discussion of the gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, and the prospect for modulating the microbiota for CRC prevention or treatment. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.
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