|
1
|
Huang M, Zhang Y, Ni M, Shen M, Tao Y, Shen W, Sun D, Li L, Xu C, Tan J, Lai Y, Yu C, Tao L, Fan M, Cheng H. Shen-Bai-Jie-Du decoction suppresses the progression of colorectal adenoma to carcinoma through regulating gut microbiota and short-chain fatty acids. Chin Med 2024; 19:149. [PMID: 39465423 PMCID: PMC11514841 DOI: 10.1186/s13020-024-01019-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 10/07/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUND Shen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herb formula developed based on evidence-based medicine, is efficacy to reduce the recurrence and carcinogenesis of colorectal adenoma. However, the mechanism of SBJDD to treat colorectal adenoma remains unclear. The present study aims to investigate the efficacy and mechanism of SBJDD on colorectal adenoma carcinogenesis from the aspects of regulating gut microbiota and short-chain fatty acids (SCFAs). METHODS Twenty-one patients diagnosed with colorectal adenoma were recruited in the study and required to take SBJDD for four consecutive weeks. Analysis of gut microbiota was conducted using 16S rRNA gene amplicon sequencing, while levels of SCFAs in fecal and serum samples were determined through HPLC-MS/MS. Additionally, twenty-four Apcmin/+ mice were randomly assigned to normal diet (ND), high-fat diet (HFD), and SBJDD groups. The pharmacological effects and mechanism of SBJDD on colorectal adenoma carcinogenesis were assessed using RT-qPCR, HE staining, IHC staining, Western blot, IF staining, and Flow cytometry assays. RESULTS Our clinical study has shown that SBJDD can regulate the gut microbiota composition and enhance SCFAs production in patients with colorectal adenoma. SBJDD alleviated colorectal adenoma formation and carcinogenesis, as well as protected the integrity of the intestinal barrier in the Apcmin/+ mice model compared to the HFD group. Additionally, SBJDD was found to regulate gut microbiota capable of producing SCFAs. G protein-coupled receptors GPR43, GPR41, and GPR109a were effectively activated in the SBJDD group, while HDAC1 and HDAC3 were inhibited. Furthermore, decreased expression levels of interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), along with elevated expression level of interleukin 10 (IL-10), were observed in the colorectal tissue of the SBJDD group. Finally, SBJDD exhibited the ability to reduce the proportion of M1-type macrophages while increasing the proportion of M2-type macrophages. CONCLUSIONS Our study objectively demonstrated the pharmacological effects of SBJDD in inhibiting the progression of colorectal adenoma and investigated its mechanisms in terms of regulating gut microbiota, increasing SCFAs, and reducing colorectal inflammation.
Collapse
Affiliation(s)
- Min Huang
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ye Zhang
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
| | - Mingxin Ni
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Meng Shen
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- The First Affiliated Hospital of Soochow University, Soochow, 215123, China
| | - Yuquan Tao
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Weixing Shen
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Dongdong Sun
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Liu Li
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Changliang Xu
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jiani Tan
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yueyang Lai
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Chengtao Yu
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Lihuiping Tao
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Minmin Fan
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Haibo Cheng
- The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
| |
Collapse
|
|
2
|
Magnusson MK, Bas Forsberg A, Verveda A, Sapnara M, Lorent J, Savolainen O, Wettergren Y, Strid H, Simrén M, Öhman L. Exposure of Colon-Derived Epithelial Monolayers to Fecal Luminal Factors from Patients with Colon Cancer and Ulcerative Colitis Results in Distinct Gene Expression Patterns. Int J Mol Sci 2024; 25:9886. [PMID: 39337373 PMCID: PMC11431989 DOI: 10.3390/ijms25189886] [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: 08/22/2024] [Revised: 09/05/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) on the colonic epithelium using a standardized colon-derived two-dimensional epithelial monolayer. The complex primary human stem cell-derived intestinal epithelium model, termed RepliGut® Planar, was expanded and passaged in a two-dimensional culture which underwent stimulation for 48 h with fecal supernatants (FS) from CC patients (n = 6), UC patients with active disease (n = 6), and healthy subjects (HS) (n = 6). mRNA sequencing of monolayers was performed and cytokine secretion in the basolateral cell culture compartment was measured. The addition of fecal supernatants did not impair the integrity of the colon-derived epithelial monolayer. However, monolayers stimulated with fecal supernatants from CC patients and UC patients presented distinct gene expression patterns. Comparing UC vs. CC, 29 genes were downregulated and 33 genes were upregulated, for CC vs. HS, 17 genes were downregulated and five genes were upregulated, and for UC vs. HS, three genes were downregulated and one gene was upregulated. The addition of FS increased secretion of IL8 with no difference between the study groups. Fecal luminal factors from CC patients and UC patients induce distinct colonic epithelial gene expression patterns, potentially reflecting the disease pathophysiology. The culture of colonic epithelial monolayers with fecal supernatants derived from patients may facilitate the exploration of IBD- and CC-related intestinal microenvironmental and barrier interactions.
Collapse
Affiliation(s)
- Maria K Magnusson
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Anna Bas Forsberg
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Alexandra Verveda
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Maria Sapnara
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Julie Lorent
- National Bioinformatics Infrastructure Stockholm (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden
| | - Otto Savolainen
- Chalmers Mass Spectrometry Infrastructure, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
| | - Yvonne Wettergren
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
- Department of Surgery, Sahlgrenska University Hospital, Region Västra Götaland, 416 85 Gothenburg, Sweden
| | - Hans Strid
- Department of Internal Medicine, Södra Älvsborg Hospital, 501 82 Borås, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
- Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| |
Collapse
|
|
3
|
Dicks LMT. Gut Bacteria Provide Genetic and Molecular Reporter Systems to Identify Specific Diseases. Int J Mol Sci 2024; 25:4431. [PMID: 38674014 PMCID: PMC11050607 DOI: 10.3390/ijms25084431] [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: 03/22/2024] [Revised: 04/15/2024] [Accepted: 04/17/2024] [Indexed: 04/28/2024] Open
Abstract
With genetic information gained from next-generation sequencing (NGS) and genome-wide association studies (GWAS), it is now possible to select for genes that encode reporter molecules that may be used to detect abnormalities such as alcohol-related liver disease (ARLD), cancer, cognitive impairment, multiple sclerosis (MS), diabesity, and ischemic stroke (IS). This, however, requires a thorough understanding of the gut-brain axis (GBA), the effect diets have on the selection of gut microbiota, conditions that influence the expression of microbial genes, and human physiology. Bacterial metabolites such as short-chain fatty acids (SCFAs) play a major role in gut homeostasis, maintain intestinal epithelial cells (IECs), and regulate the immune system, neurological, and endocrine functions. Changes in butyrate levels may serve as an early warning of colon cancer. Other cancer-reporting molecules are colibactin, a genotoxin produced by polyketide synthetase-positive Escherichia coli strains, and spermine oxidase (SMO). Increased butyrate levels are also associated with inflammation and impaired cognition. Dysbiosis may lead to increased production of oxidized low-density lipoproteins (OX-LDLs), known to restrict blood vessels and cause hypertension. Sudden changes in SCFA levels may also serve as a warning of IS. Early signs of ARLD may be detected by an increase in regenerating islet-derived 3 gamma (REG3G), which is associated with changes in the secretion of mucin-2 (Muc2). Pro-inflammatory molecules such as cytokines, interferons, and TNF may serve as early reporters of MS. Other examples of microbial enzymes and metabolites that may be used as reporters in the early detection of life-threatening diseases are reviewed.
Collapse
Affiliation(s)
- Leon M T Dicks
- Department of Microbiology, Stellenbosch University, Stellenbosch 7600, South Africa
| |
Collapse
|
|
4
|
Pérez-Valero Á, Magadán-Corpas P, Ye S, Serna-Diestro J, Sordon S, Huszcza E, Popłoński J, Villar CJ, Lombó F. Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention. Nutrients 2024; 16:1161. [PMID: 38674851 PMCID: PMC11054239 DOI: 10.3390/nu16081161] [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: 03/13/2024] [Revised: 04/09/2024] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
Colorectal cancer stands as the third most prevalent form of cancer worldwide, with a notable increase in incidence in Western countries, mainly attributable to unhealthy dietary habits and other factors, such as smoking or reduced physical activity. Greater consumption of vegetables and fruits has been associated with a lower incidence of colorectal cancer, which is attributed to their high content of fiber and bioactive compounds, such as flavonoids. In this study, we have tested the flavonoids quercetin, luteolin, and xanthohumol as potential antitumor agents in an animal model of colorectal cancer induced by azoxymethane and dodecyl sodium sulphate. Forty rats were divided into four cohorts: Cohort 1 (control cohort), Cohort 2 (quercetin cohort), Cohort 3 (luteolin cohort), and Cohort 4 (xanthohumol cohort). These flavonoids were administered intraperitoneally to evaluate their antitumor potential as pharmaceutical agents. At the end of the experiment, after euthanasia, different physical parameters and the intestinal microbiota populations were analyzed. Luteolin was effective in significantly reducing the number of tumors compared to the control cohort. Furthermore, the main significant differences at the microbiota level were observed between the control cohort and the cohort treated with luteolin, which experienced a significant reduction in the abundance of genera associated with disease or inflammatory conditions, such as Clostridia UCG-014 or Turicibacter. On the other hand, genera associated with a healthy state, such as Muribaculum, showed a significant increase in the luteolin cohort. These results underline the anti-colorectal cancer potential of luteolin, manifested through a modulation of the intestinal microbiota and a reduction in the number of tumors.
Collapse
Affiliation(s)
- Álvaro Pérez-Valero
- Research Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, Spain (J.S.-D.); (C.J.V.)
- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006 Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Patricia Magadán-Corpas
- Research Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, Spain (J.S.-D.); (C.J.V.)
- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006 Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Suhui Ye
- Research Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, Spain (J.S.-D.); (C.J.V.)
- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006 Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Juan Serna-Diestro
- Research Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, Spain (J.S.-D.); (C.J.V.)
- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006 Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Sandra Sordon
- Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland; (S.S.); (E.H.); (J.P.)
| | - Ewa Huszcza
- Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland; (S.S.); (E.H.); (J.P.)
| | - Jarosław Popłoński
- Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland; (S.S.); (E.H.); (J.P.)
| | - Claudio J. Villar
- Research Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, Spain (J.S.-D.); (C.J.V.)
- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006 Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Felipe Lombó
- Research Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, Spain (J.S.-D.); (C.J.V.)
- Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006 Oviedo, Spain
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| |
Collapse
|
|
5
|
Wang X, Pan L, Wang F, Long F, Yang B, Tang D. Interventional effects of oral microecological agents on perioperative indicators of colorectal cancer: a meta-analysis. Front Oncol 2023; 13:1229177. [PMID: 37681033 PMCID: PMC10482437 DOI: 10.3389/fonc.2023.1229177] [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: 05/26/2023] [Accepted: 08/07/2023] [Indexed: 09/09/2023] Open
Abstract
Purpose To investigate the efficacy of the application of microecological agents in patients with perioperative colorectal cancer. Methods The seven electronic databases including PubMed, Cochrane Library, Excerpt Medica Database (Embase), Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang Database were systematically searched for eligible studies from 2000 to February 2023. Results A total of 38 randomized controlled clinical trials were included in this study, with a total of 1765 patients in the microecological preparation group and 1769 patients in the control group. All data were analyzed using Review Manager 5.4 and R 4.2.2 software. Meta-analysis showed that in the perioperative period of colorectal cancer, the microecological agents group reduced patients' adverse drug reactions, improved intestinal flora with Lactobacillus (SMD, 3.0858, [2.0197; 4.1520], p< 0. 0001), Bifidobacterium (SMD, 2.1551, [1.6145; 2.6956], p< 0.0001) and Escherichia coli (SMD, -1.1393, [-1.6247; -0.6538], p< 0.0001); protection of intestinal mucosal barrier function, endotoxin (SMD, -2.6850 [-4.1399; -1.2301], p=0.0003), DAO (SMD, -2.5916, [-3.4694; -1.7137], p<0.0001) and plasma D-lactate (SMD, -5.4726, [-9.8901; -1.0551], p= 0.0152), reduced inflammatory response, IL-6 (SMD, -3.1279 [-5.7706; -0.4852], p=0.0204) and CRP (SMD, -3.9698 [-7.6296; -0.3100], p=0.0335); improved the immune function of the organism, CD4+ (SMD, 1.5817 [1.0818; 2.0817], p< 0.0001), CD4+/CD8+ (SMD, 1.2938 [0.9693; 1.6183] p< 0.0001) and IgG (SMD, 1.1376 [0.2993; 1.9759] p=0.0078), improved short-term clinical efficacy, ORR (RR, 1.5105 [1.2306; 1.8541], p< 0.0001) and DCR (RR, 0.3896 [0.2620; 0.5795], p< 0.0001). Conclusion By increasing the number of beneficial flora such as Lactobacillus and Bifidobacterium and decreasing the number of harmful flora such as Escherichia coli, the micro-ecological preparation group is beneficial in improving the ecological dysregulation in colorectal cancer patients receiving different treatments in the perioperative period. The microecological preparation group was able to reduce many types of adverse drug reactions, such as infections and gastrointestinal discomfort, compared to the control group. The microecological agents also reduced inflammatory responses, decreased the increase in harmful metabolites, enhanced patients' immune function, protected intestinal mucosal barrier function, and improved short-term clinical outcomes. Systematic review registration https://inplasy.com/inplasy-2023-4-0051/, identifier INPLASY202340051.
Collapse
Affiliation(s)
- Xueyan Wang
- The First College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Lijun Pan
- Department of Medical Affairs, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Feiqing Wang
- Research Laboratory, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Fengxi Long
- Development Planning Division, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Bing Yang
- Student Management Office, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Dongxin Tang
- Dean’s Office, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| |
Collapse
|
|
6
|
Bester A, O'Brien M, Cotter PD, Dam S, Civai C. Shotgun Metagenomic Sequencing Revealed the Prebiotic Potential of a Fruit Juice Drink with Fermentable Fibres in Healthy Humans. Foods 2023; 12:2480. [PMID: 37444219 DOI: 10.3390/foods12132480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/13/2023] [Accepted: 06/08/2023] [Indexed: 07/15/2023] Open
Abstract
Fibre-based dietary interventions are at the forefront of gut microbiome modulation research, with a wealth of 16S rRNA information to demonstrate the prebiotic effects of isolated fibres. However, there is a distinct lack of data relating to the effect of a combination of soluble and insoluble fibres in a convenient-to-consume fruit juice food matrix on gut microbiota structure, diversity, and function. Here, we aimed to determine the impact of the MOJU Prebiotic Shot, an apple, lemon, ginger, and raspberry fruit juice drink blend containing chicory inulin, baobab, golden kiwi, and green banana powders, on gut microbiota structure and function. Healthy adults (n = 20) were included in a randomised, double-blind, placebo-controlled, cross-over study, receiving 60 mL MOJU Prebiotic Shot or placebo (without the fibre mix) for 3 weeks with a 3-week washout period between interventions. Shotgun metagenomics revealed significant between-group differences in alpha and beta diversity. In addition, the relative abundance of the phyla Actinobacteria and Desulfobacteria was significantly increased as a result of the prebiotic intervention. Nine species were observed to be differentially abundant (uncorrected p-value of <0.05) as a result of the prebiotic treatment. Of these, Bifidobacterium adolescentis and CAG-81 sp900066785 (Lachnospiraceae) were present at increased abundance relative to baseline. Additionally, KEGG analysis showed an increased abundance in pathways associated with arginine biosynthesis and phenylacetate degradation during the prebiotic treatment. Our results show the effects of the daily consumption of 60 mL MOJU Prebiotic Shot for 3 weeks and provide insight into the functional potential of B. adolescentis.
Collapse
Affiliation(s)
- Adri Bester
- London Agri Food Innovation Clinic (LAFIC), School of Applied Sciences, London South Bank University, London SE1 0AA, UK
| | | | | | | | - Claudia Civai
- London Agri Food Innovation Clinic (LAFIC), School of Applied Sciences, London South Bank University, London SE1 0AA, UK
| |
Collapse
|
|
7
|
Gozdzik P, Magkos F, Sledzinski T, Mika A. Monomethyl branched-chain fatty acids: Health effects and biological mechanisms. Prog Lipid Res 2023; 90:101226. [PMID: 37094753 DOI: 10.1016/j.plipres.2023.101226] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/19/2023] [Accepted: 04/20/2023] [Indexed: 04/26/2023]
Abstract
Branched-chain fatty acids (BCFA) are a group of lipids that are widely present in various organisms; they take part in numerous biochemical processes and affect multiple signaling pathways. However, BCFA are not well explored in terms of their effects on human health. Recently, they have been gaining interest, especially in relation to various human diseases. This review describes the occurrence of BCFA, their dietary sources, their potential health effects, and the current state of knowledge concerning their mechanism(s) of action. Many studies have been conducted so far in cellular and animal models, which reveal potent anti-cancer, lipid lowering, anti-inflammatory and neuroprotective actions. Research in humans is scarce. Therefore, further studies on animals and humans should be performed to confirm and expand these findings, and improve our understanding of the potential relevance of BCFA to human health and disease.
Collapse
Affiliation(s)
- Paulina Gozdzik
- Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland
| | - Faidon Magkos
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg C, Denmark
| | - Tomasz Sledzinski
- Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland.
| | - Adriana Mika
- Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland; Department of Environmental Analytics, Faculty of Chemistry, University of Gdansk, Gdansk, Poland
| |
Collapse
|
|
8
|
Keane JM, Walsh CJ, Cronin P, Baker K, Melgar S, Cotter PD, Joyce SA, Gahan CGM, Houston A, Hyland NP. Investigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepoints. Br J Cancer 2023; 128:528-536. [PMID: 36418894 PMCID: PMC9938136 DOI: 10.1038/s41416-022-02062-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 11/03/2022] [Accepted: 11/08/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Distinct sets of microbes contribute to colorectal cancer (CRC) initiation and progression. Some occur due to the evolving intestinal environment but may not contribute to disease. In contrast, others may play an important role at particular times during the tumorigenic process. Here, we describe changes in the microbiota and host over the course of azoxymethane (AOM)-induced tumorigenesis. METHODS Mice were administered AOM or PBS and were euthanised 8, 12, 24 and 48 weeks later. Samples were analysed using 16S rRNA gene sequencing, UPLC-MS and qRT-PCR. RESULTS The microbiota and bile acid profile showed distinct changes at each timepoint. The inflammatory response became apparent at weeks 12 and 24. Moreover, significant correlations between individual taxa, cytokines and bile acids were detected. One co-abundance group (CAG) differed significantly between PBS- and AOM-treated mice at week 24. Correlation analysis also revealed significant associations between CAGs, bile acids and the bile acid transporter, ASBT. Aberrant crypt foci and adenomas were first detectable at weeks 24 and 48, respectively. CONCLUSION The observed changes precede host hyperplastic transformation and may represent early therapeutic targets for the prevention or management of CRC at specific timepoints in the tumorigenic process.
Collapse
Affiliation(s)
- J M Keane
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
- Department of Medicine, University College Cork, Cork, Ireland
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
- Department of Physiology, University College Cork, Cork, Ireland
| | - C J Walsh
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - P Cronin
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
| | - K Baker
- Department of Medicine, University College Cork, Cork, Ireland
- Department of Pathology, University College Cork, Cork, Ireland
| | - S Melgar
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - P D Cotter
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - S A Joyce
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
| | - C G M Gahan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
- School of Pharmacy, University College Cork, Cork, Ireland
| | - A Houston
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Medicine, University College Cork, Cork, Ireland.
| | - N P Hyland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Physiology, University College Cork, Cork, Ireland
| |
Collapse
|
|
9
|
Vignoli A, Meoni G, Ghini V, Di Cesare F, Tenori L, Luchinat C, Turano P. NMR-Based Metabolomics to Evaluate Individual Response to Treatments. Handb Exp Pharmacol 2023; 277:209-245. [PMID: 36318327 DOI: 10.1007/164_2022_618] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
The aim of this chapter is to highlight the various aspects of metabolomics in relation to health and diseases, starting from the definition of metabolic space and of how individuals tend to maintain their own position in this space. Physio-pathological stimuli may cause individuals to lose their position and then regain it, or move irreversibly to other positions. By way of examples, mostly selected from our own work using 1H NMR on biological fluids, we describe the effects on the individual metabolomic fingerprint of mild external interventions, such as diet or probiotic administration. Then we move to pathologies (such as celiac disease, various types of cancer, viral infections, and other diseases), each characterized by a well-defined metabolomic fingerprint. We describe the effects of drugs on the disease fingerprint and on its reversal to a healthy metabolomic status. Drug toxicity can be also monitored by metabolomics. We also show how the individual metabolomic fingerprint at the onset of a disease may discriminate responders from non-responders to a given drug, or how it may be prognostic of e.g., cancer recurrence after many years. In parallel with fingerprinting, profiling (i.e., the identification and quantification of many metabolites and, in the case of selected biofluids, of the lipoprotein components that contribute to the 1H NMR spectral features) can provide hints on the metabolic pathways that are altered by a disease and assess their restoration after treatment.
Collapse
Affiliation(s)
- Alessia Vignoli
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Gaia Meoni
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Veronica Ghini
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Francesca Di Cesare
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy
| | - Leonardo Tenori
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy.,Consorzio Interuniversitario Risonanze Magnetiche MetalloProteine (CIRMMP), Sesto Fiorentino, Italy
| | - Claudio Luchinat
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.,Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy.,Consorzio Interuniversitario Risonanze Magnetiche MetalloProteine (CIRMMP), Sesto Fiorentino, Italy
| | - Paola Turano
- Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy. .,Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy. .,Consorzio Interuniversitario Risonanze Magnetiche MetalloProteine (CIRMMP), Sesto Fiorentino, Italy.
| |
Collapse
|
|
10
|
Holst LM, Iribarren C, Sapnara M, Savolainen O, Törnblom H, Wettergren Y, Strid H, Simrén M, Magnusson MK, Öhman L. Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids. Int J Mol Sci 2022; 23:ijms232415505. [PMID: 36555145 PMCID: PMC9779506 DOI: 10.3390/ijms232415505] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.
Collapse
Affiliation(s)
- Luiza Moraes Holst
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Cristina Iribarren
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Maria Sapnara
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Otto Savolainen
- Chalmers Mass Spectrometry Infrastructure, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Yvonne Wettergren
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska University Hospital, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Hans Strid
- Department of Internal Medicine, Södra Älvsborgs Hospital, 501 82 Borås, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Maria K. Magnusson
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
- Correspondence:
| |
Collapse
|
|
11
|
Preethy S, Ikewaki N, Levy GA, Raghavan K, Dedeepiya VD, Yamamoto N, Srinivasan S, Ranganathan N, Iwasaki M, Senthilkumar R, Abraham SJK. Two unique biological response-modifier glucans beneficially regulating gut microbiota and faecal metabolome in a non-alcoholic steatohepatitis animal model, with potential applications in human health and disease. BMJ Open Gastroenterol 2022; 9:e000985. [PMID: 36167455 PMCID: PMC9516208 DOI: 10.1136/bmjgast-2022-000985] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 09/04/2022] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE The gut microbiome and its metabolites are influenced by age and stress and reflect the metabolism and health of the immune system. We assessed the gut microbiota and faecal metabolome in a static animal model of non-alcoholic steatohepatitis (NASH). DESIGN This model was subjected to the following treatments: reverse osmosis water, AFO-202, N-163, AFO-202+N-163 and telmisartan treatment. Faecal samples were collected at 6 and 9 weeks of age. The gut microbiome was analysed using 16S ribosomal RNA sequences acquired by next-generation sequencing, and the faecal metabolome was analysed using gas chromatography-mass spectrometry. RESULTS Gut microbial diversity increased greatly in the AFO-202+N-163 group. Postintervention, the abundance of Firmicutes decreased, whereas that of Bacteroides increased and was the highest in the AFO-202+N-163 group. The decrease in the abundance of Enterobacteriaceae and other Firmicutes and the abundance of Turicibacter and Bilophila were the highest in the AFO-202 and N-163 groups, respectively. Lactobacillus abundance was highest in the AFO-202+N-163 group. The faecal metabolite spermidine, which is beneficial against inflammation and NASH, was significantly decreased (p=0.012) in the N-163 group. Succinic acid, which is beneficial in neurodevelopmental and neurodegenerative diseases, was increased in the AFO-202 group (p=0.06). The decrease in fructose was the highest in the N-163 group (p=0.0007). Isoleucine and Leucine decreased with statistical significance (p=0.004 and 0.012, respectively), and tryptophan also decreased (p=0.99), whereas ornithine, which is beneficial against chronic immune-metabolic-inflammatory pathologies, increased in the AFO-202+N-163 group. CONCLUSION AFO-202 treatment in mice is beneficial against neurodevelopmental and neurodegenerative diseases, and has prophylactic potential against metabolic conditions. N-163 treatment exerts anti-inflammatory effects against organ fibrosis and neuroinflammation. In combination, these compounds exhibit anticancer activity.
Collapse
Affiliation(s)
- Senthilkumar Preethy
- Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
| | - Nobunao Ikewaki
- Dept. of Medical Life Science, Kyushu University of Health and Welfare, Nobeoka, Japan
- Institute of Immunology, Junsei Educational Institute, Nobeoka, Japan
| | - Gary A Levy
- Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Kadalraja Raghavan
- Dept of Paediatric Neurology, Jesuit Antonyraj memorial Inter-disciplinary Centre for Advanced Recovery and Education (JAICARE), Madurai, India
| | | | - Naoki Yamamoto
- Genome Medical Sciences Project, National Center for Global Health and Medicine (NCGM), Kohnodai, Chiba, Japan
| | - Subramaniam Srinivasan
- Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
| | | | - Masaru Iwasaki
- Centre for Advancing Clinical Research (CACR), University of Yamanashi - School of Medicine, Chuo, Japan
| | - Rajappa Senthilkumar
- Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
| | - Samuel J K Abraham
- Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
- Centre for Advancing Clinical Research (CACR), University of Yamanashi - School of Medicine, Chuo, Japan
- Antony- Xavier Interdisciplinary Scholastics (AXIS), GN Corporation Co. Ltd, Kofu, Japan
| |
Collapse
|
|
12
|
Wang Z, Li H, Yun Y, Wang H, Meng B, Mu Y, Gao S, Tao X, Chen W. A dynamic multiple reaction monitoring strategy to develop and optimize targeted metabolomics methods: Analyzing bile acids in capecitabine-induced diarrhea. J Pharm Biomed Anal 2022; 219:114938. [PMID: 35850015 DOI: 10.1016/j.jpba.2022.114938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/17/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022]
Abstract
OBJECTIVE We sought to develop and optimize a targeted bile acids (BAs) metabolomics method based on a dynamic multiple reaction monitoring (dMRM) strategy and explored the dynamic alterations of BAs in diarrhea induced by capecitabine in a mouse model. METHOD The targeted metabolomics method was developed using an Agilent 6460A triple quadrupole mass spectrometer, and 41 types of BAs were monitored in negative ionization mode. The mass spectrometer detection was optimized using dMRM to enhance the responses, separation, and peak shape and to shorten the analysis time. A mouse model of diarrhea was established by multiple administration of capecitabine, and plasma samples were collected at baseline and the end of drug administration for subsequent BAs analysis. RESULTS The targeted BA metabolomics method achieved shorter chromatographic separation time (10 min) for 41 BAs, with good peak shapes and response increases of 3- to 10-fold after application of dMRM. The mouse model of capecitabine-induced diarrhea was established, and the three BAs 23-norcholic acid, isolithocholic acid, and isodeoxycholic acid in the baseline samples contributed the most to differentiating mice with diarrhea from those without diarrhea. For mice that ultimately developed diarrhea, apocholic acid, isodeoxycholic acid, and 7-ketodeoxycholic acid exhibited the largest change in concentrations compared with their baseline concentrations. CONCLUSION The dMRM strategy has obvious advantages compared with common MRM. The results in model mice showed that a differentiated profile of BAs in the baseline may indicate biomarkers of diarrhea induced by capecitabine, and disturbed homeostasis may explain the metabolomic mechanism of diarrhea occurrence.
Collapse
Affiliation(s)
- Zhipeng Wang
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Hanglin Li
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; Chemistry and Biological Engineering College, Yichun University, Yichun 336000, China
| | - Yunlei Yun
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Hongsen Wang
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; Chemistry and Biological Engineering College, Yichun University, Yichun 336000, China
| | - Bosu Meng
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China
| | - Yuhui Mu
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China
| | - Shouhong Gao
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
| | - Xia Tao
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
| | - Wansheng Chen
- Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
| |
Collapse
|
|
13
|
Kellingray L, Le Gall G, Doleman JF, Narbad A, Mithen RF. Effects of in vitro metabolism of a broccoli leachate, glucosinolates and S-methylcysteine sulphoxide on the human faecal microbiome. Eur J Nutr 2021; 60:2141-2154. [PMID: 33067661 PMCID: PMC8137612 DOI: 10.1007/s00394-020-02405-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 10/02/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Brassica are an important food source worldwide and are characterised by the presence of compounds called glucosinolates. Studies indicate that the glucosinolate derived bioactive metabolite sulphoraphane can elicit chemoprotective benefits on human cells. Glucosinolates can be metabolised in vivo by members of the human gut microbiome, although the prevalence of this activity is unclear. Brassica and Allium plants also contain S-methylcysteine sulphoxide (SMCSO), that may provide additional health benefits but its metabolism by gut bacteria is not fully understood. METHODS We examined the effects of a broccoli leachate (BL) on the composition and function of human faecal microbiomes of five different participants under in vitro conditions. Bacterial isolates from these communities were then tested for their ability to metabolise glucosinolates and SMCSO. RESULTS Microbial communities cultured in vitro in BL media were observed to have enhanced growth of lactic acid bacteria, such as lactobacilli, with a corresponding increase in the levels of lactate and short-chain fatty acids. Members of Escherichia isolated from these faecal communities were found to bioconvert glucosinolates and SMCSO to their reduced analogues. CONCLUSION This study uses a broccoli leachate to investigate the bacterial-mediated bioconversion of glucosinolates and SMCSO, which may lead to further products with additional health benefits to the host. We believe that this is the first study that shows the reduction of the dietary compound S-methylcysteine sulphoxide by bacteria isolated from human faeces.
Collapse
Affiliation(s)
- Lee Kellingray
- Food Innovation and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ UK
| | - Gwénaëlle Le Gall
- Analytical Sciences Unit, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ UK
| | - Joanne F. Doleman
- Food Innovation and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ UK
| | - Arjan Narbad
- Gut Microbes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ UK
| | - Richard F. Mithen
- Food Innovation and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ UK
| |
Collapse
|
|
14
|
Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13092215. [PMID: 34063108 PMCID: PMC8124679 DOI: 10.3390/cancers13092215] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/29/2021] [Accepted: 05/01/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Gut microbiota is emerging as new diagnostic and prognostic marker and/or therapeutic target to improve the management of cancer. This review aims to summarize microbial signatures that have been associated with digestive and other cancers. We report the clinical relevance of these microbial markers to predict the response to cancer therapy. Among these biomarkers, colibactin-producing E. coli are prevalent in the colonic mucosa of patients with colorectal cancer and they promote colorectal carcinogenesis in several pre-clinical models. Here we discuss the promising use of colibactin-producing E. coli as a new predictive factor and a therapeutic target in colon cancer management. Abstract The gut microbiota is crucial for physiological development and immunological homeostasis. Alterations of this microbial community called dysbiosis, have been associated with cancers such colorectal cancers (CRC). The pro-carcinogenic potential of this dysbiotic microbiota has been demonstrated in the colon. Recently the role of the microbiota in the efficacy of anti-tumor therapeutic strategies has been described in digestive cancers and in other cancers (e.g., melanoma and sarcoma). Different bacterial species seem to be implicated in these mechanisms: F. nucleatum, B. fragilis, and colibactin-associated E. coli (CoPEC). CoPEC bacteria are prevalent in the colonic mucosa of patients with CRC and they promote colorectal carcinogenesis in susceptible mouse models of CRC. In this review, we report preclinical and clinical data that suggest that CoPEC could be a new factor predictive of poor outcomes that could be used to improve cancer management. Moreover, we describe the possibility of using these bacteria as new therapeutic targets.
Collapse
|
|
15
|
Kumar P, Kumar V. Role of NMR Metabolomics and MR Imaging in Colon Cancer. COLON CANCER DIAGNOSIS AND THERAPY 2021:43-66. [DOI: 10.1007/978-3-030-63369-1_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
16
|
Mandal R, Cano R, Davis CD, Hayashi D, Jackson SA, Jones CM, Lampe JW, Latulippe ME, Lin NJ, Lippa KA, Piotrowski P, Da Silva SM, Swanson KS, Wishart DS. Workshop report: Toward the development of a human whole stool reference material for metabolomic and metagenomic gut microbiome measurements. Metabolomics 2020; 16:119. [PMID: 33164148 PMCID: PMC7649161 DOI: 10.1007/s11306-020-01744-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 10/29/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION To date, there has been little effort to develop standards for metabolome-based gut microbiome measurements despite the significant efforts toward standard development for DNA-based microbiome measurements. OBJECTIVES The National Institute of Standards and Technology (NIST), The BioCollective (TBC), and the North America Branch of the International Life Sciences Institute (ILSI North America) are collaborating to extend NIST's efforts to develop a Human Whole Stool Reference Material for the purpose of method harmonization and eventual quality control. METHODS The reference material will be rationally designed for adequate quality assurance and quality control (QA/QC) for underlying measurements in the study of the impact of diet and nutrition on functional aspects of the host gut microbiome and relationships of those functions to health. To identify which metabolites deserve priority in their value assignment, NIST, TBC, and ILSI North America jointly conducted a workshop on September 12, 2019 at the NIST campus in Gaithersburg, Maryland. The objective of the workshop was to identify metabolites for which evidence indicates relevance to health and disease and to decide on the appropriate course of action to develop a fit-for-purpose reference material. RESULTS This document represents the consensus opinions of workshop participants and co-authors of this manuscript, and provides additional supporting information. In addition to developing general criteria for metabolite selection and a preliminary list of proposed metabolites, this paper describes some of the strengths and limitations of this initiative given the current state of microbiome research. CONCLUSIONS Given the rapidly evolving nature of gut microbiome science and the current state of knowledge, an RM (as opposed to a CRM) measured for multiple metabolites is appropriate at this stage. As the science evolves, the RM can evolve to match the needs of the research community. Ultimately, the stool RM may exist in sequential versions. Beneficial to this evolution will be a clear line of communication between NIST and the stakeholder community to ensure alignment with current scientific understanding and community needs.
Collapse
Affiliation(s)
- Rupasri Mandal
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada
| | - Raul Cano
- The BioCollective, LLC, 5650 N Washington St, Denver, CO, 80216, USA
| | - Cindy D Davis
- Office of Dietary Supplements, National Institutes of Health, Bethesda, MD, 20852, USA
| | | | - Scott A Jackson
- Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - Christina M Jones
- Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - Johanna W Lampe
- Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B802, PO Box 19024, Seattle, WA, 98109, USA
| | - Marie E Latulippe
- North American Branch of the International Life Sciences Institute (ILSI North America), 740 15th Street NW, Suite 600, Washington, DC, 20005, USA.
| | - Nancy J Lin
- Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - Katrice A Lippa
- Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - Paulina Piotrowski
- Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - Sandra M Da Silva
- Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - Kelly S Swanson
- University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - David S Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada
| |
Collapse
|
|
17
|
Zeinali-Rafsanjani B, Jalli R, Saeedi-Moghadam M, Pishdad P. Magnetic resonance spectroscopy and its application in colorectal cancer diagnosis and screening: A narrative review. J Med Imaging Radiat Sci 2020; 51:654-661. [PMID: 32718849 DOI: 10.1016/j.jmir.2020.07.004] [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: 01/08/2020] [Revised: 06/28/2020] [Accepted: 07/10/2020] [Indexed: 12/01/2022]
Abstract
There are several slightly invasive methods to detect colorectal carcinoma (CRC) including colonoscopy and sigmoidoscopy; but there is no noninvasive, accurate screening test. It is recommended to initiate screening at the age of 50 for non-familial CRC. Laboratory tests are routinely suggested if internal observation and imaging are recommended for further evaluation. Spectroscopic-based imaging, such as magnetic resonance spectroscopy (MRS) is an interesting and promising tool with the potential to be an alternative to some minimally invasive procedures, such as biopsy. Accordingly, MRS might be a suitable substitution for invasive methods, such as colonoscopy. This article aimed to review the studies that have evaluated the MRS technique as a screening tool in CRC.
Collapse
Affiliation(s)
- Banafsheh Zeinali-Rafsanjani
- Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Nuclear Medicine and Molecular Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Jalli
- Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Radiology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahdi Saeedi-Moghadam
- Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Parisa Pishdad
- Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Radiology, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
18
|
Nannini G, Meoni G, Amedei A, Tenori L. Metabolomics profile in gastrointestinal cancers: Update and future perspectives. World J Gastroenterol 2020; 26:2514-2532. [PMID: 32523308 PMCID: PMC7265149 DOI: 10.3748/wjg.v26.i20.2514] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 05/11/2020] [Accepted: 05/15/2020] [Indexed: 02/06/2023] Open
Abstract
Despite recent progress in diagnosis and therapy, gastrointestinal (GI) cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis. Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers; however, these tests are not useful as diagnostic screening since they have low specificity and low sensitivity. Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems, is now clear that this -omics could open a new way to study cancer. In the last years, nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for diseases' diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers. For these reasons in this review, we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.
Collapse
Affiliation(s)
- Giulia Nannini
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gaia Meoni
- Giotto Biotech Srl, and CERM (University of Florence), Florence 50019, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
- SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Leonardo Tenori
- Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine, Florence 50019, Italy
| |
Collapse
|
|
19
|
Mi K, Jiang Y, Chen J, Lv D, Qian Z, Sun H, Shang D. Construction and Analysis of Human Diseases and Metabolites Network. Front Bioeng Biotechnol 2020; 8:398. [PMID: 32426349 PMCID: PMC7203444 DOI: 10.3389/fbioe.2020.00398] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 04/08/2020] [Indexed: 11/13/2022] Open
Abstract
The relationship between aberrant metabolism and the initiation and progression of diseases has gained considerable attention in recent years. To gain insights into the global relationship between diseases and metabolites, here we constructed a human diseases-metabolites network (HDMN). Through analyses based on network biology, the metabolites associated with the same disorder tend to participate in the same metabolic pathway or cascade. In addition, the shortest distance between disease-related metabolites was shorter than that of all metabolites in the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic network. Both disease and metabolite nodes in the HDMN displayed slight clustering phenomenon, resulting in functional modules. Furthermore, a significant positive correlation was observed between the degree of metabolites and the proportion of disease-related metabolites in the KEGG metabolic network. We also found that the average degree of disease metabolites is larger than that of all metabolites. Depicting a comprehensive characteristic of HDMN could provide great insights into understanding the global relationship between disease and metabolites.
Collapse
Affiliation(s)
- Kai Mi
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Yanan Jiang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.,Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.,Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
| | - Jiaxin Chen
- School of Medical Informatics, Harbin Medical University, Daqing, China
| | - Dongxu Lv
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Zhipeng Qian
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Hui Sun
- Pharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Desi Shang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| |
Collapse
|
|
20
|
Graça G, Lau CHE, Gonçalves LG. Exploring Cancer Metabolism: Applications of Metabolomics and Metabolic Phenotyping in Cancer Research and Diagnostics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1219:367-385. [PMID: 32130709 DOI: 10.1007/978-3-030-34025-4_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Altered metabolism is one of the key hallmarks of cancer. The development of sensitive, reproducible and robust bioanalytical tools such as Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry techniques offers numerous opportunities for cancer metabolism research, and provides additional and exciting avenues in cancer diagnosis, prognosis and for the development of more effective and personalized treatments. In this chapter, we introduce the current state of the art of metabolomics and metabolic phenotyping approaches in cancer research and clinical diagnostics.
Collapse
Affiliation(s)
- Gonçalo Graça
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.
| | - Chung-Ho E Lau
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Luís G Gonçalves
- Proteomics of Non-Model Organisms Lab, ITQB Nova-Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
| |
Collapse
|
|
21
|
Association of Flavonifractor plautii, a Flavonoid-Degrading Bacterium, with the Gut Microbiome of Colorectal Cancer Patients in India. mSystems 2019; 4:4/6/e00438-19. [PMID: 31719139 PMCID: PMC7407896 DOI: 10.1128/msystems.00438-19] [Citation(s) in RCA: 121] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC. The study gains additional significance, as India is among the countries with a very low incidence of CRC, and the diet and lifestyle in India have been associated with a distinct gut microbiome in healthy Indians compared to other global populations. Thus, in this study, we hypothesize a unique relationship between CRC and the gut microbiome in an Indian population. Recently, dysbiosis in the human gut microbiome and shifts in the relative abundances of several bacterial species have been recognized as important factors in colorectal cancer (CRC). However, these studies have been carried out mainly in developed countries where CRC has a high incidence, and it is unclear whether the host-microbiome relationships deduced from these studies can be generalized to the global population. To test if the documented associations between the microbiome and CRC are conserved in a distinct context, we performed metagenomic and metabolomic association studies on fecal samples from 30 CRC patients and 30 healthy controls from two different locations in India, followed by a comparison of CRC data available from other populations. We confirmed the association of Bacteroides and other bacterial taxa with CRC that have been previously reported in other studies. However, the association of CRC with Flavonifractor plautii in Indian patients emerged as a novel finding. The plausible role of F. plautii appears to be linked with the degradation of beneficial anticarcinogenic flavonoids, which was also found to be significantly correlated with the enzymes and modules involved in flavonoid degradation within Indian CRC samples. Thus, we hypothesize that the degradation of beneficial flavonoids might be playing a role in cancer progression within this Indian cohort. We also identified 20 potential microbial taxonomic markers and 33 potential microbial gene markers that discriminate the Indian CRC from healthy microbiomes with high accuracy based on machine learning approaches. IMPORTANCE This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC. The study gains additional significance, as India is among the countries with a very low incidence of CRC, and the diet and lifestyle in India have been associated with a distinct gut microbiome in healthy Indians compared to other global populations. Thus, in this study, we hypothesize a unique relationship between CRC and the gut microbiome in an Indian population.
Collapse
|
|
22
|
Waters JL, Ley RE. The human gut bacteria Christensenellaceae are widespread, heritable, and associated with health. BMC Biol 2019; 17:83. [PMID: 31660948 PMCID: PMC6819567 DOI: 10.1186/s12915-019-0699-4] [Citation(s) in RCA: 419] [Impact Index Per Article: 69.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 09/17/2019] [Indexed: 12/18/2022] Open
Abstract
The Christensenellaceae, a recently described family in the phylum Firmicutes, is emerging as an important player in human health. The relative abundance of Christensenellaceae in the human gut is inversely related to host body mass index (BMI) in different populations and multiple studies, making its relationship with BMI the most robust and reproducible link between the microbial ecology of the human gut and metabolic disease reported to date. The family is also related to a healthy status in a number of other different disease contexts, including obesity and inflammatory bowel disease. In addition, Christensenellaceae is highly heritable across multiple populations, although specific human genes underlying its heritability have so far been elusive. Further research into the microbial ecology and metabolism of these bacteria should reveal mechanistic underpinnings of their host-health associations and enable their development as therapeutics.
Collapse
Affiliation(s)
- Jillian L Waters
- Department of Microbiome Science, Max Planck Institute for Developmental Biology, Max-Planck-Ring 5, 72076, Tuebingen, Germany
| | - Ruth E Ley
- Department of Microbiome Science, Max Planck Institute for Developmental Biology, Max-Planck-Ring 5, 72076, Tuebingen, Germany.
| |
Collapse
|
|
23
|
Tran TTT, Corsini S, Kellingray L, Hegarty C, Le Gall G, Narbad A, Müller M, Tejera N, O'Toole PW, Minihane AM, Vauzour D. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology. FASEB J 2019; 33:8221-8231. [PMID: 30958695 PMCID: PMC6593891 DOI: 10.1096/fj.201900071r] [Citation(s) in RCA: 121] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer's disease (AD). Numerous studies have provided insights into the pathologic mechanisms. However, a comprehensive understanding of the impact of APOE genotype on microflora speciation and metabolism is completely lacking. In this study, we investigated the association between APOE genotype and the gut microbiome composition in human and APOE-targeted replacement (TR) transgenic mice. Fecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity in group-aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gut microbiota of APOE-TR mice. Furthermore, metabolomic analysis of murine fecal water detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, these findings indicate that APOE genotype is associated with specific gut microbiome profiles in both humans and APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention of AD.-Tran, T. T. T., Corsini, S., Kellingray, L., Hegarty, C., Le Gall, G., Narbad, A., Müller, M., Tejera, N., O'Toole, P. W., Minihane, A.-M., Vauzour, D. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology.
Collapse
Affiliation(s)
- Tam T T Tran
- Alimentary Pharmabiotic Centre (APC) Microbiome Ireland, University College Cork, Cork, Ireland.,School of Microbiology, University College Cork, Cork, Ireland
| | - Simone Corsini
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; and
| | - Lee Kellingray
- Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom
| | - Claire Hegarty
- Alimentary Pharmabiotic Centre (APC) Microbiome Ireland, University College Cork, Cork, Ireland.,School of Microbiology, University College Cork, Cork, Ireland
| | - Gwénaëlle Le Gall
- Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom
| | - Arjan Narbad
- Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom
| | - Michael Müller
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; and
| | - Noemi Tejera
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; and
| | - Paul W O'Toole
- Alimentary Pharmabiotic Centre (APC) Microbiome Ireland, University College Cork, Cork, Ireland.,School of Microbiology, University College Cork, Cork, Ireland
| | - Anne-Marie Minihane
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; and
| | - David Vauzour
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; and
| |
Collapse
|
|
24
|
Wang H, Zhang S, Shen Q, Zhu MJ. A metabolomic explanation on beneficial effects of dietary Goji on intestine inflammation. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.12.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
|