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Li DL, Ma LL, Guan ZA, Zhao YX, Jiang C. Establishment and validation of a clinical prediction model for colorectal adenoma risk factors. Oncol Lett 2025; 30:322. [PMID: 40370646 PMCID: PMC12076052 DOI: 10.3892/ol.2025.15068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 04/01/2025] [Indexed: 05/16/2025] Open
Abstract
Colorectal adenomas are benign tumors of the colorectal mucosal epithelium that have malignant potential and are regarded as precancerous lesions of colorectal cancer, for which the specific risk factors are unclear. The present study aimed to identify independent risk factors for colorectal adenoma to develop a prediction model and test its predictive value. A retrospective analysis was performed using data from patients who underwent electronic colonoscopy at the Department of Proctology (Affiliated Hospital of Shandong University of Traditional Chinese Medicine; Jinan, China) from January 2013 to December 2023 and had polyps removed during colonoscopy. Patients with colorectal adenoma were included in the case group, whilst those with no visible abnormalities on endoscopy or with non-adenomatous polyps were included as a control group. The patients were randomly divided into a training and validation group in a 7:3 ratio. Variables were screened using single-component analysis and the filtered variables were employed in multivariate logistic regression to create a clinical prediction model. Finally, the model was internally and externally validated. A total of 730 patients were included in the present study, with 286 assigned to the case group and 444 to the control group. After the initial screening of 39 variables, 12 continued to the next round, resulting in four potential predictors including age, daily number of bowel movements, thrombin time and the number of polyps. A prediction model was created based on these variables. Regarding internal validation, the C-index was 0.7054 [95% confidence interval (CI), 0.6596-0.7512] and the prediction probability in the calibration curve was close to the diagonal line of the calibration graph, indicating that the prediction probability of the model was reasonable. Regarding external validation, the C-index in the validation cohort was 0.6306 (95% CI, 0.5560-0.7053) and the calibration curve also demonstrated good identification capabilities. The Hosmer-Lemeshow test revealed that the model had a reasonable calibration degree, with χ2=9.7893, degree of freedom=8 and P=0.28. The receiver operating characteristic curve and decision curve analysis for the training and validation cohorts demonstrated good efficacy and an ideal application value. In conclusion, the model constructed in the present study demonstrated moderate predictive accuracy for colorectal adenoma risk, laying the groundwork for early detection of colorectal adenoma and secondary prevention of colorectal cancer.
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Affiliation(s)
- Dong-Lin Li
- The First College of Clinical Medicine, Shandong Traditional Chinese Medicine University, Jinan, Shandong 250000, P.R. China
| | - Ling-Ling Ma
- Department of Gastroenterology, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong 257091, P.R. China
| | - Zhong-An Guan
- Department of Proctology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, P.R. China
| | - Yu-Xin Zhao
- The First College of Clinical Medicine, Shandong Traditional Chinese Medicine University, Jinan, Shandong 250000, P.R. China
| | - Chuan Jiang
- Department of Proctology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, P.R. China
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Mechlińska A, Frąckiewicz K, Gładyś-Cieszyńska K, Buczek D, Dziadziuszko R. Small intestinal bacterial overgrowth and intestinal methanogen overgrowth in gastrointestinal malignancies. Contemp Oncol (Pozn) 2025; 29:11-21. [PMID: 40330452 PMCID: PMC12051882 DOI: 10.5114/wo.2025.148643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 02/06/2025] [Indexed: 05/08/2025] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is defined by an abnormal proliferation of colon-specific bacteria in the small intestine, whereas intestinal methanogen overgrowth (IMO) manifests with an increase of methane-producing archaea, specifically Methanobrevibacter smithii. Both conditions can disrupt gastrointestinal motility and manifest with various clinical symptoms. Small intestinal bacterial overgrowth appears to increase the risk of malnutrition and negatively affect malabsorption of essential nutrients such as vitamin B12 and fat-soluble vitamins. This concern is particularly relevant for cancer patients as malnutrition can adversely affect treatment outcomes and mortality rates. Small intestinal bacterial overgrowth prevalence is 2.5-22% in the general population, with significantly higher rates observed in cancer patients, depending on a study, 65% of gastric and colorectal cancer patients, 63.3% of pancreatic cancer patients compared to 13.3% in healthy controls. Gastrointestinal complications, particularly in cases of gastrointestinal cancers, can arise from both the disease itself and its treatment. Managing symptoms becomes more challenging when SIBO occurs as its symptoms are often ambiguous and overlap with those of other conditions. This review summarizes the current state of knowledge on SIBO and IMO in gastrointestinal cancers. Current knowledge on SIBO and IMO, particularly in gastrointestinal cancer, is limited by the lack of validated diagnostic standards, evidence-based nutritional guidelines, and a focus on symptom control rather than underlying mechanisms. There is a need for research on recurrence despite treatment, as well as studies specifically targeting SIBO and IMO in cancer rather than as comorbidities. Future efforts should prioritize developing reliable diagnostics, understanding recurrence mechanisms, and exploring personalized therapies and nutritional interventions.
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Affiliation(s)
- Aleksandra Mechlińska
- Department of Oncology and Radiotherapy, Medical University of Gdańsk and University Clinical Center, Gdańsk, Poland
| | | | | | - Dagmara Buczek
- Department of Oncology and Radiotherapy, Medical University of Gdańsk and University Clinical Center, Gdańsk, Poland
| | - Rafał Dziadziuszko
- Department of Oncology and Radiotherapy, Medical University of Gdańsk and University Clinical Center, Gdańsk, Poland
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Peng Z, Song J, Zhu W, Bao H, Hu Y, Shi Y, Cheng X, Jiang M, Fang F, Chen J, Shu X. Impact of sleep deprivation on colon cancer: Unraveling the KynA-P4HA2-HIF-1α axis in tumor lipid metabolism and metastasis. Mol Metab 2025; 93:102109. [PMID: 39920992 PMCID: PMC11869867 DOI: 10.1016/j.molmet.2025.102109] [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: 10/14/2024] [Revised: 02/04/2025] [Accepted: 02/04/2025] [Indexed: 02/10/2025] Open
Abstract
OBJECTIVE There is growing evidence that sleep deprivation promotes cancer progression. In addition, colon cancer patients often experience sleep deprivation due to factors such as cancer pain and side effects of treatment. The occurrence of liver metastases is an important factor in the mortality of colon cancer patients. However, the relationship between sleep deprivation and liver metastases from colon cancer has not been elucidated. METHODS A sleep deprivation liver metastasis model was constructed to evaluate the effect of sleep deprivation on liver metastasis of colon cancer. Subsequently, mice feces were collected for untargeted metabolomics to screen and identify the key mediator, Kynurenic acid (KynA). Furthermore, HILPDA was screened by transcriptomics, and its potential mechanism was explored through ChIP, co-IP, ubiquitination experiments, phenotyping experiments, etc. RESULTS: Sleep deprivation promotes liver metastases in colon cancer. Functionally, sleep deprivation aggravates lipid accumulation and decreases the production of the microbiota metabolite KynA. In contrast, KynA inhibited colon cancer progression in vitro. In vivo, KynA supplementation reversed the promoting effects of sleep deprivation on liver metastases from colon cancer. Mechanistically, KynA downregulates the expression of P4HA2 to promote the ubiquitination and degradation of HIF-1α, which leads to a decrease in the transcription of HILPDA, and ultimately leads to an increase in lipolysis of colon cancer cells. CONCLUSIONS Our findings reveal that sleep deprivation impairs intracellular lipolysis by KynA, leading to lipid droplets accumulation in colon cancer cells. This process ultimately promotes colon cancer liver metastasis. This suggests a promising strategy for colon cancer treatment.
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Affiliation(s)
- Zuojie Peng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Jia Song
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Wenzhong Zhu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Haijun Bao
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Yuan Hu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Yongping Shi
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Xukai Cheng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Mi Jiang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Feifei Fang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China
| | - Jinhuang Chen
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China.
| | - Xiaogang Shu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No.1277, Wuhan 430022, Hubei, China.
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Zhou M, Wu J, Shao Y, Zhang J, Zheng R, Shi Q, Wang J, Liu B. Short-chain fatty acids reverses gut microbiota dysbiosis-promoted progression of glioblastoma by up-regulating M1 polarization in the tumor microenvironment. Int Immunopharmacol 2024; 141:112881. [PMID: 39159556 DOI: 10.1016/j.intimp.2024.112881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 07/28/2024] [Accepted: 08/03/2024] [Indexed: 08/21/2024]
Abstract
Glioblastoma (GBM), known as the most malignant and common primary brain tumor of the central nervous system, has finite therapeutic options and a poor prognosis. Studies have shown that host intestinal microorganisms play a role in the immune regulation of parenteral tumors in a number of different ways, either directly or indirectly. However, the potential impact of gut microbiota on tumor microenvironment, particularly glioma immunological milieu, has not been clarified exactly. In this study, by using an orthotopic GBM model, we found gut microbiota dysbiosis caused by antibiotic cocktail treatment boosted the tumor process in vivo. An obvious change that followed gut microbiota dysbiosis was the enhanced percentage of M2-like macrophages in the TME, in parallel with a decrease in the levels of gut microbial metabolite, short-chain fatty acids (SCFAs) in the blood and tumor tissues. Oral supplementation with SCFAs can increase the proportion of M1-like macrophages in the TME, which improves the outcomes of glioma. In terms of mechanism, SCFAs-activated glycolysis in the tumor-associated macrophages may be responsible for the elevated M1 polarization in the TME. This study will enable us to better comprehend the "gut-brain" axis and be meaningful for the development of TAM-targeting immunotherapeutic strategies for GBM patients.
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Affiliation(s)
- Mengnan Zhou
- Department of Pathogenic Microbiology, School of Basic Medical Science, China Medical University, Shenyang 110122, China; Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
| | - Jianqi Wu
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yang Shao
- Department of Pathogenic Microbiology, School of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Jiameng Zhang
- Department of Pathogenic Microbiology, School of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Rui Zheng
- Department of Pathogenic Microbiology, School of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Qi Shi
- Department of Pathogenic Microbiology, School of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Jia Wang
- Department of Pathogenic Microbiology, School of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Beixing Liu
- Department of Pathogenic Microbiology, School of Basic Medical Science, China Medical University, Shenyang 110122, China.
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Qu Y, Nie D, Song Y, Cai X, Gong Y, Chen S, Ye J, Li J. Bibliometric analysis of research on digestive system tumors and depression. Front Psychol 2024; 15:1414528. [PMID: 39156806 PMCID: PMC11327056 DOI: 10.3389/fpsyg.2024.1414528] [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: 04/11/2024] [Accepted: 07/15/2024] [Indexed: 08/20/2024] Open
Abstract
Background Malignant tumors of the digestive system pose a serious threat to human health due to their highly malignant nature. Depression, as the most common psychiatric symptom of digestive system tumors, has attracted much attention regarding its potential relationship with these tumors. A thorough investigation into the connection between digestive system tumors and depression is extremely important for strengthening patients' quality of life and treatment outcomes. Methods From 2014 to 2023, we conducted a literature search using specific keywords in the Web of Science Core Collection (WoSCC) and performed visual analysis of the selected literature using Microsoft Excel, CiteSpace, and VOSviewer software. In this study, we analyzed countries, institutions, authors, journals, and keywords. Results A total of 384 research articles on the relationship between digestive system tumors and depression were identified. The number of publications showed a gradual increase over time. In terms of disciplinary distribution, Oncology, Health Care Sciences Services, and Medicine General Internal ranked top in terms of publication volume. In terms of geographical distribution, China and the United States were the countries contributing the most publications. Additionally, Maastricht University contributed the most publications. Regarding authors, Beekman, Aartjan T.F. and Dekker, Joost had the highest number of publications, while Zigmond, A.S. had the most citations. It is worth mentioning that Supportive Care in Cancer was the journal with the most publications in this field. In terms of keyword analysis, research mainly focused on mechanisms and treatment strategies related to the relationship between digestive system tumors and depression. Conclusion The relationship between digestive system tumors and depression has become a new research hotspot in recent years, offering new directions for future research. This research reveals novel perspectives on comprehending the connection between the two, which can guide future research and practice.
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Affiliation(s)
- Ying Qu
- Department of Oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Duorui Nie
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Yuwei Song
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Xiaojun Cai
- Department of Oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yilin Gong
- Department of Oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Sheng Chen
- Department of Oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Jia Ye
- Department of Gynecology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Jing Li
- Department of Oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
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Rondepierre F, Meynier M, Gagniere J, Deneuvy V, Deneuvy A, Roche G, Baudu E, Pereira B, Bonnet R, Barnich N, Carvalho FA, Pezet D, Bonnet M, Jalenques I. Preclinical and clinical evidence of the association of colibactin-producing Escherichia coli with anxiety and depression in colon cancer. World J Gastroenterol 2024; 30:2817-2826. [PMID: 38899326 PMCID: PMC11185296 DOI: 10.3748/wjg.v30.i21.2817] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/17/2024] [Accepted: 04/23/2024] [Indexed: 06/03/2024] Open
Abstract
BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal carcinogenesis (CRC), as demonstrated with colibactin-producing Escherichia coli (CoPEC). AIM To evaluate the association between CoPEC prevalence and anxiety- and depressive-like behaviors with both preclinical and clinical approaches. METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview. Results were compared according to the CoPEC colonization. In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain. Their behavior was assessed using the Elevated Plus Maze test, the Forced Swimming Test and the Behavior recognition system PhenoTyper®. RESULTS In a limited cohort, all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis, whereas only one patient (17%) without CoPEC did. This result was confirmed in C57BL6/J wild-type mice and in a CRC susceptibility mouse model (adenomatous polyposis colimultiple intestinal neoplasia/+). Mice exhibited a significant increase in anxiety- and depressive-like behaviors after chronic infection with a CoPEC strain. CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.
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Affiliation(s)
- Fabien Rondepierre
- Service de Psychiatrie de l’Adulte A et Psychologie Médicale, CHU Clermont-Ferrand, Clermont-Ferrand 63000, France
| | - Maëva Meynier
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
- NeuroDol, UMR 1107, INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France
| | - Johan Gagniere
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
- Department of Digestive Surgery, CHU de Clermont-Ferrand, Clermont-Ferrand 63001, France
| | - Vincent Deneuvy
- Service de Psychiatrie de l’Adulte A et Psychologie Médicale, CHU Clermont-Ferrand, Clermont-Ferrand 63000, France
| | - Anissa Deneuvy
- Department of Digestive Surgery, CHU de Clermont-Ferrand, Clermont-Ferrand 63001, France
| | - Gwenaelle Roche
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
| | - Elodie Baudu
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
- NeuroDol, UMR 1107, INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France
| | - Bruno Pereira
- Biostatistics Unit, Department of Clinical Research and Innovation, CHU Clermont-Ferrand, Clermont-Ferrand 63000, France
| | - Richard Bonnet
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
- Department of Bacteriology, CHU de Clermont-Ferrand, Clermont-Ferrand 63001, France
| | - Nicolas Barnich
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
| | | | - Denis Pezet
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
- Department of Digestive Surgery, CHU de Clermont-Ferrand, Clermont-Ferrand 63001, France
| | - Mathilde Bonnet
- M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
| | - Isabelle Jalenques
- Service de Psychiatrie de l’Adulte A et Psychologie Médicale, CHU Clermont-Ferrand, Clermont-Ferrand 63000, France
- Université Clermont Auvergne, INP, CNRS, Clermont Auvergne Institut Pascal, Clermont-Ferrand 63000, France
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Zuo Y, Lu Y, Pang J, Jin S, Zhang X, Zhao E, Li Y. Detection and comparison of tumor cell-associated microbiota from different compartments of colorectal cancer. Front Oncol 2024; 14:1374769. [PMID: 38835371 PMCID: PMC11148212 DOI: 10.3389/fonc.2024.1374769] [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: 01/22/2024] [Accepted: 04/30/2024] [Indexed: 06/06/2024] Open
Abstract
Introduction Intratumoral microbes play an important role in the development of colorectal cancer (CRC). However, studying intratumoral microbes in CRC faces technical challenges, as tumor microbe communities are often contaminated by fecal microbes due to the structure of the gut folds and villi. The present study aimed to develop a new method for isolating tumor cell-associated microbiota and comparing microbial populations from different compartments. Materials and methods The distribution of intestinal bacteria was detected using immunohistochemistry combined with 5R-16s rRNA gene sequencing to explore the effects of the sampling site and number of washes on the detection of microbiota. The 5R-16s rRNA gene sequencing was performed using 44 samples from 11 patients with CRC, including CRC tumor tissues (TT), normal tissues adjacent to CRC (NT), tumor cells (TC), and normal cells (NC). TC and NC were obtained from the TT and NT using an enzymatic digestion method. The microbiota and their potential functions in the four groups were analyzed and compared to determine the differential microbiota related to CRC. Results Bacteria were mainly distributed in the feces covering intestinal tissues and in the epithelial cells and macrophages within the tissues. Different sampling sites and number of washes led to detection of different microbiota distributions. Although the cleaning method could be controlled, sampling sites varied and led to different microbiota distributions. The phyla of Firmicutes and Bacteroidetes were highly abundant in the conventionally used tissue samples, whereas Proteobacteria was the most abundant phyla in the cell samples isolated with the new method (i.e., after cell enzymatic hydrolysis). Detection of CRC cell-associated microbiota using a cell enzymatic digestion method showed that some bacteria, such as Fusobacterium, Eikenella, Shewanella, and Listeria, were more abundant in TT than NT, whereas the abundance of Akkermansia was lower in TT than NT. The tumor/normal ratios of some bacteria, such as Gemella, Escherichia, Shigella, and Blautia, were different between the cell and tissue samples. Conclusion The cell enzymatic digestion method reduced fecal bacterial contamination, enabling low biomass intratumoral microbiota to be detected and allowing prediction of bacterial distributions.
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Affiliation(s)
- Yanzhen Zuo
- Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei, China
| | - Yanjie Lu
- Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei, China
| | - Jiayu Pang
- Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei, China
| | - Shunkang Jin
- Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei, China
| | - Xinyu Zhang
- Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei, China
| | - Enhong Zhao
- Department of Gastrointestinal Surgery, Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China
| | - Yuhong Li
- Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei, China
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Flórez JES, Zapata JL, Duarte MCP, Acevedo VV, Calle JAZ, Montoya AR, Cardona LSG. Factors Associated With Quality of Life Among Colorectal Cancer Patients: Cross-Sectional Study. Cancer Control 2024; 31:10732748241302915. [PMID: 39557561 PMCID: PMC11574891 DOI: 10.1177/10732748241302915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2024] Open
Abstract
INTRODUCTION Colorectal cancer is a chronic condition that affects a substantial proportion of the global population. Ensuring a satisfactory quality of life (QoL) for these patients is, therefore, of critical importance. OBJECTIVE To examine the relationship between sociodemographic, economic, lifestyle, and health-related variables and quality of life in patients with colorectal cancer receiving treatment at a leading health institution in Medellín, Colombia. METHODS This cross-sectional study included all patients aged 18 years and older who were diagnosed with colorectal cancer and treated at the VIDA Clinic Foundation in 2022. Descriptive and bivariate analyses were conducted to characterize the population and explore factors associated with QoL, as assessed using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale. The Mann-Whitney U and Kruskal-Wallis tests were applied to compare median values across variables. A Generalized Linear Model (GLM) with a Gamma family distribution and identity link function was used to identify explanatory variables influencing QoL. Regression coefficients and 95% confidence intervals were calculated. RESULTS A total of 126 patients with colorectal cancer were evaluated, of whom 60.3% were women, with a median age of 61.5 years. The regression model identified poor sleep quality, lack of financial support, dissatisfaction with income, and unemployment as significant factors negatively associated with QoL, after adjusting for sociodemographic variables. CONCLUSION This study provides an initial exploration of health-related QoL in a Colombian population diagnosed with colorectal cancer. The findings highlight the critical influence of both health-related and socioeconomic factors on patients' QoL. A holistic approach to addressing these dimensions could enhance patient care and inform more effective support strategies.
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Affiliation(s)
- Jorge Emilio Salazar Flórez
- School of Health Sciences, Medicine Program, GEINCRO Research Group, San Martín University Foundation, Sabaneta, Colombia
| | - Juanita Lozano Zapata
- School of Health Sciences, Medicine Program, GEINCRO Research Group, San Martín University Foundation, Sabaneta, Colombia
| | - María Camila Pérez Duarte
- School of Health Sciences, Medicine Program, GEINCRO Research Group, San Martín University Foundation, Sabaneta, Colombia
| | - Valentina Valencia Acevedo
- School of Health Sciences, Medicine Program, GEINCRO Research Group, San Martín University Foundation, Sabaneta, Colombia
| | - José Alejandro Zapata Calle
- School of Health Sciences, Medicine Program, GEINCRO Research Group, San Martín University Foundation, Sabaneta, Colombia
| | - Alejandra Rendón Montoya
- School of Health Sciences, Medicine Program, GEINCRO Research Group, San Martín University Foundation, Sabaneta, Colombia
| | - Luz Stella Giraldo Cardona
- School of Health Sciences, Medicine Program, GEINCRO Research Group, San Martín University Foundation, Sabaneta, Colombia
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Enayati A, Soghi A, Butler AE, Rizzo M, Sahebkar A. The Effect of Curcumin on the Gut-Brain Axis: Therapeutic Implications. J Neurogastroenterol Motil 2023; 29:409-418. [PMID: 37814431 PMCID: PMC10577457 DOI: 10.5056/jnm23065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/23/2023] [Accepted: 08/11/2023] [Indexed: 10/11/2023] Open
Abstract
The gut-brain axis describes the bidirectional communication between the gut, the enteric nervous system, and the central nervous system. The gut-brain axis has attracted increasing attention owing to its regulatory effect on dysbiosis and a wide range of related diseases. Several types of nutrients, such as curcumin, have been proposed as regulators of the dysbiotic state, and preclinical experiments have suggested that curcumin is not only beneficial but also safe. This review focuses on the interplay between curcumin and the gut microbiota. Moreover, it provides a comprehensive review of the crosstalk between the gut-brain axis and disease, whilst also discussing curcumin-mediated gut-brain axis-dependent and -independent signaling about modulation of gut microbiota dysbiosis. This will help to define the utility of curcumin as a novel therapeutic agent to regulate intestinal microflora dysbiosis.
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Affiliation(s)
- Ayesheh Enayati
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Aida Soghi
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Alexandra E Butler
- Research Department, Royal College of Surgeons in Ireland, Adliya, Bahrain
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, Palermo, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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10
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Hou X, Du H, Deng Y, Wang H, Liu J, Qiao J, Liu W, Shu X, Sun B, Liu Y. Gut microbiota mediated the individualized efficacy of Temozolomide via immunomodulation in glioma. J Transl Med 2023; 21:198. [PMID: 36927689 PMCID: PMC10018922 DOI: 10.1186/s12967-023-04042-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 03/08/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Temozolomide (TMZ) is the preferred chemotherapy strategy for glioma therapy. As a second-generation alkylating agent, TMZ provides superior oral bio-availability. However, limited response rate (less than 50%) and high incidence of drug resistance seriously restricts TMZ's application, there still lack of strategies to increase the chemotherapy sensitivity. METHODS Luci-GL261 glioma orthotopic xenograft model combined bioluminescence imaging was utilized to evaluate the anti-tumor effect of TMZ and differentiate TMZ sensitive (S)/non-sensitive (NS) individuals. Integrated microbiomics and metabolomics analysis was applied to disentangle the involvement of gut bacteria in TMZ sensitivity. Spearman's correlation analysis was applied to test the association between fecal bacteria levels and pharmacodynamics indices. Antibiotics treatment combined TMZ treatment was used to confirm the involvement of gut microbiota in TMZ response. Flow cytometry analysis, ELISA and histopathology were used to explore the potential role of immunoregulation in gut microbiota mediated TMZ response. RESULTS Firstly, gut bacteria composition was significantly altered during glioma development and TMZ treatment. Meanwhile, in vivo anti-cancer evaluation suggested a remarkable difference in chemotherapy efficacy after TMZ administration. Moreover, 16s rRNA gene sequencing and non-targeted metabolomics analysis revealed distinct different gut microbiota and immune infiltrating state between TMZ sensitive and non-sensitive mice, while abundance of differential gut bacteria and related metabolites was significantly correlated with TMZ pharmacodynamics indices. Further verification suggested that gut microbiota deletion by antibiotics treatment could accelerate glioma development, attenuate TMZ efficacy and inhibit immune cells (macrophage and CD8α+ T cell) recruitment. CONCLUSIONS The current study confirmed the involvement of gut microbiota in glioma development and individualized TMZ efficacy via immunomodulation, hence gut bacteria may serve as a predictive biomarker as well as a therapeutic target for clinical TMZ application.
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Affiliation(s)
- Xiaoying Hou
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.,Cancer Institute, School of Medicine, Jianghan University, Wuhan, China
| | - Hongzhi Du
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Yufei Deng
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.,Cancer Institute, School of Medicine, Jianghan University, Wuhan, China
| | - Haiping Wang
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.,Cancer Institute, School of Medicine, Jianghan University, Wuhan, China
| | - Jinmi Liu
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.,Cancer Institute, School of Medicine, Jianghan University, Wuhan, China
| | - Jialu Qiao
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China
| | - Wei Liu
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China
| | - Xiji Shu
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China
| | - Binlian Sun
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China. .,Cancer Institute, School of Medicine, Jianghan University, Wuhan, China.
| | - Yuchen Liu
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China. .,Cancer Institute, School of Medicine, Jianghan University, Wuhan, China.
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11
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Han CJ, Reding KW, Kalady MF, Yung R, Greenlee H, Paskett ED. Factors associated with long-term gastrointestinal symptoms in colorectal cancer survivors in the women's health initiatives (WHI study). PLoS One 2023; 18:e0286058. [PMID: 37205667 DOI: 10.1371/journal.pone.0286058] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/08/2023] [Indexed: 05/21/2023] Open
Abstract
PURPOSE Colorectal cancer (CRC) survivors often experience long-term symptoms after cancer treatments. But gastrointestinal (GI) symptom experiences are under-investigated in CRC survivors. We described persistent GI symptoms after cancer treatments in female CRC survivors and assessed GI symptoms' risk and life-impact factors. METHODS A cross-sectional study utilized data from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. Correlation analyses and multivariable linear regression models were used. RESULTS CRC survivors after cancer treatments were included (N = 413, mean age 71.2 years old, mean time since diagnosis = 8.1 years). 81% of CRC survivors experienced persistent GI symptoms. Bloating/gas was the most prevalent (54.2%± 0.88) and severe GI symptom, followed by constipation (44.1%±1.06), diarrhea (33.4%±0.76), and abdominal/pelvic pain (28.6%±0.62). Significant risk factors for GI symptoms include time since cancer diagnosis (<5 years), advanced cancer stage, high psychological distress, poor dietary habits, and low physical activity. Fatigue and sleep disturbance were the most significant risk factors for long-term GI symptoms (β = 0.21, t = 3.557; β = 0.20, t = 3.336, respectively, Ps < .001). High severity of GI symptoms was positively associated with poor quality of life (QOL), increased daily life interferences (social and physical functions), and low body image satisfaction (Ps < .001). CONCLUSIONS Women CRC survivors experience a high GI symptom burden, highlighting the need to inform policy and improve the QOL of cancer survivors. Our findings will aid in identifying those more vulnerable to symptoms, and inform future survivorship care interventions (i.e., community-based cancer symptom management) by considering multiple risk factors (e.g., psychological distress).
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Affiliation(s)
- Claire J Han
- Center for Healthy Aging, Self-Management and Complex Care, Ohio State University, College of Nursing, Columbus, OH, United States of America
- Department of Cancer Control Survivorship, Ohio State University Comprehensive Cancer Center, Columbus, OH, United States of America
| | - Kerryn W Reding
- Department of Biobehavioral Nursing and Health Informatics, University of Washington, School of Nursing, Seattle, WA, United States of America
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America
| | - Matthew F Kalady
- Division of Colon and Rectal Surgery, Clinical Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH, United States of America
| | - Rachel Yung
- Fred Hutchinson Cancer Research Center, Clinical Research Division, University of Washington School of Medicine, Medical Oncology, Seattle, WA, United States of America
| | - Heather Greenlee
- Cancer Prevention Program, Public Health Sciences and Clinical Research Divisions, Fred Hutchinson Cancer Center, Seattle, WA, United States of America
- Department of Medical Oncology, University of Washington School of Medicine, Seattle, WA, United States of America
| | - Electra D Paskett
- Department of Internal Medicine in the College of Medicine, Ohio State University, Columbus, OH, United States of America
- Division of Epidemiology in the College of Public Health, Ohio State University, Columbus, OH, United States of America
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12
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The Oncobiome in Gastroenteric and Genitourinary Cancers. Int J Mol Sci 2022; 23:ijms23179664. [PMID: 36077063 PMCID: PMC9456244 DOI: 10.3390/ijms23179664] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/21/2022] [Accepted: 08/23/2022] [Indexed: 12/24/2022] Open
Abstract
Early evidence suggests a strong association of microorganisms with several human cancers, and great efforts have been made to understand the pathophysiology underlying microbial carcinogenesis. Bacterial dysbiosis causes epithelial barrier failure, immune dysregulation and/or genotoxicity and, consequently, creates a tumor-permissive microenvironment. The majority of the bacteria in our body reside in the gastrointestinal tract, known as gut microbiota, which represents a complex and delicate ecosystem. Gut microbes can reach the pancreas, stomach and colon via the bloodstream. Oral bacterial translocations can also occur. In the stomach, pancreas and colon, low microbial diversity is associated with cancer, in particular with a bad prognosis. The urogenital tract also harbors unique microbiota, distinct from the gut microbiota, which might have a role in the urinary and female/male reproductive cancers’ pathogenesis. In healthy women, the majority of bacteria reside in the vagina and cervix and unlike other mucosal sites, the vaginal microbiota exhibits low microbial diversity. Genital dysbiosis might have an active role in the development and/or progression of gynecological malignancies through mechanisms including modulation of oestrogen metabolism. Urinary dysbiosis may influence the pathogenesis of bladder cancer and prostate cancer in males. Modulation of the microbiome via pre, pro and postbiotics, fecal or vaginal microbiota transplantation and engineering bacteria might prove useful in improving cancer treatment response and quality of life. Elucidating the complex host-microbiome interactions will result in prevention and therapeutic efficacy interventions.
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13
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Chen M, Lin W, Li N, Wang Q, Zhu S, Zeng A, Song L. Therapeutic approaches to colorectal cancer via strategies based on modulation of gut microbiota. Front Microbiol 2022; 13:945533. [PMID: 35992678 PMCID: PMC9389535 DOI: 10.3389/fmicb.2022.945533] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/14/2022] [Indexed: 11/27/2022] Open
Abstract
Colorectal cancer (CRC) ranks third in terms of global incidence and second in terms of death toll among malignant tumors. Gut microbiota are involved in the formation, development, and responses to different treatments of CRC. Under normal physiological conditions, intestinal microorganisms protect the intestinal mucosa, resist pathogen invasion, and regulate the proliferation of intestinal mucosal cells via a barrier effect and inhibition of DNA damage. The composition of gut microbiota and the influences of diet, drugs, and gender on the composition of the intestinal flora are important factors in the early detection of CRC and prediction of the results of CRC treatment. Regulation of gut microbiota is one of the most promising new strategies for CRC treatment, and it is essential to clarify the effect of gut microbiota on CRC and its possible mechanisms to facilitate the prevention and treatment of CRC. This review discusses the role of gut microbiota in the pathogenesis of CRC, the potential of gut microbiota as biomarkers for CRC, and therapeutic approaches to CRC based on the regulation of gut microbiota. It might provide new ideas for the use of gut microbiota in the prevention and treatment of CRC in the near future and thus reduce the incidence of CRC.
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Affiliation(s)
- Maohua Chen
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wei Lin
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
| | - Nan Li
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qian Wang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shaomi Zhu
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Anqi Zeng
- Institute of Translational Pharmacology and Clinical Application, Sichuan Academy of Chinese Medical Sciences, Chengdu, China
- Anqi Zeng,
| | - Linjiang Song
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Linjiang Song,
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