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Jankowski WM, Fichna J, Tarasiuk-Zawadzka A. Molecular mechanisms and pathophysiological implications of mucin-type O-glycosylation dysregulation in colorectal cancer progression. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04181-0. [PMID: 40257491 DOI: 10.1007/s00210-025-04181-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Accepted: 04/12/2025] [Indexed: 04/22/2025]
Abstract
Colorectal cancer (CRC) is among the most prevalent malignancies globally, with 1.9 million new cases annually. While CRC pathogenesis has been widely attributed to the adenoma-carcinoma and serrated sequences, our study highlights the critical and multifaceted role of O-glycosylation impairment in this malignancy. Mucin-type O-glycosylation, a key post-translational modification, exerts significant effects on tumor cells, impacting their proliferation, migration, and invasiveness. Additionally, its influence on the immune response to CRC presents novel perspectives for potential therapeutic interventions. The authors conducted a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using databases such as Google Scholar, PubMed, and Scopus. In this article, we provide a comprehensive analysis of the mechanisms underlying mucin-type O-glycosylation disruption in CRC and examine how these mechanisms could serve as biomarkers for early diagnosis and personalized treatment strategies. Our findings contribute to a more detailed understanding of CRC pathogenesis and offer promising directions for innovative diagnostic and therapeutic approaches, which in the future may lead to improved patient prognosis.
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Affiliation(s)
- Wojciech Michał Jankowski
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92 - 215, Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92 - 215, Lodz, Poland
| | - Aleksandra Tarasiuk-Zawadzka
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92 - 215, Lodz, Poland.
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2
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Pan Y, Lee YJ, Kim JH, Song MJ, Kwack K, Park SH, Sin SI, Chung JH, Park KY. Suppressor effects of carrots on azoxymethane/dextran sulfate sodium-induced colon cancer according to cultivation method. Front Immunol 2025; 16:1554801. [PMID: 40292300 PMCID: PMC12021845 DOI: 10.3389/fimmu.2025.1554801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Introduction This study investigated the suppressor effects of carrots depending on cultivation method on AOM/DSS-induced colon cancer in mice by examining cell apoptosis, inflammation response, and metabolites. Carrots grown using different fertilizers significantly suppressed tumor development by modulating cell apoptosis and inflammatory responses in our experimental settings. Methods and Results Naturaldream Fertilizer Carrot (NFC) cultivated with deep sea water minerals (DSWM) showed effectively increased the expression of apoptosis-related genes and proteins including p53, p21, Bim, Bad, Bax, Bak, Caspase 9, and Caspase 3 in colon tissue, while inhibiting the production of inflammatory factors and related genes and proteins such as TNF-a, IL-1b, IL-6, IFN-g, NF-kB, and iNOS in serum, spleen cells, and liver tissues. Intestinal microbiota analysis revealed a distinct composition in mice receiving carrots compared to the control group, with accumulation of intestinal microorganisms such as Lachnospiraceae, and Mucispirillum schaedleri closely associated with anti-tumor effects. Discussion and Conclusion Overall, our results indicate that carrots, especially carrots grown with DSWM fertilizers, play a crucial role in inhibiting AOM/DSS-induced colon cancer in mice by regulating cell apoptosis and inflammation responses. The present findings provide valuable insights for further exploration of carrots depending on the cultivation method, as a potential dietary source against colon cancer.
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Affiliation(s)
- Yanni Pan
- Collaborative Innovation Center for Child Nutrition and Health Development, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China
| | - Yeon-Jun Lee
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - Jin Hyeop Kim
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - Min Ji Song
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - KyuBum Kwack
- Department of Biomedical Science, CHA University, Seongnam, Republic of Korea
| | - Seung-Hwan Park
- Organic Anti-Cancer Agriculture Institute, iCOOP Natural Dream Company, Goesan-gun, Chungcheongbuk-do, Republic of Korea
| | - Sin-Il Sin
- Organic Anti-Cancer Agriculture Institute, iCOOP Natural Dream Company, Goesan-gun, Chungcheongbuk-do, Republic of Korea
| | - Ji Hyung Chung
- Department of Biotechnology, CHA University, Seongnam, Republic of Korea
| | - Kun-Young Park
- Graduate School of Integrative Medicine, CHA University, Seongnam, Republic of Korea
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3
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Wu XR, He XH, Xie YF. Characteristics of gut microbiota dysbiosis in patients with colorectal polyps. World J Gastrointest Oncol 2025; 17:98872. [PMID: 39817124 PMCID: PMC11664624 DOI: 10.4251/wjgo.v17.i1.98872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/05/2024] [Accepted: 09/19/2024] [Indexed: 12/12/2024] Open
Abstract
This editorial, inspired by a recent study published in the World Journal of Gastrointestinal Oncology, covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of Klebsiella, Parvimonas, and Clostridium increase, while those of Bifidobacterium and Lactobacillus decrease. This dysbiosis may promote the formation and recurrence of polyps. Similar microbial changes have also been observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome, indicating the role of increased pathogens and decreased probiotics in these conditions. Regulating the gut microbiota, particularly by increasing probiotic levels, may help prevent polyp recurrence and promote gut health. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.
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Affiliation(s)
- Xian-Rong Wu
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
| | - Xiao-Hong He
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
| | - Yong-Fang Xie
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
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Chin KW, Khoo SC, Paul RPM, Luang-In V, Lam SD, Ma NL. Potential of Synbiotics and Probiotics as Chemopreventive Agent. Probiotics Antimicrob Proteins 2024; 16:2085-2101. [PMID: 38896220 DOI: 10.1007/s12602-024-10299-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2024] [Indexed: 06/21/2024]
Abstract
Cancer remains a global problem, with millions of new cases diagnosed yearly and countless lives lost. The financial burden of cancer therapy, along with worries about the long-term safety of existing medicines, necessitates the investigation of alternative approaches to cancer prevention. Probiotics generate chemopreventive compounds such as bacteriocins, short-chain fatty acids (SCFA), and extracellular polymeric substances (EPS), which have demonstrated the ability to impede cancer cell proliferation, induce apoptosis, and bolster the expression of pro-apoptotic genes. On the other hand, prebiotics, classified as non-digestible food ingredients, promote the proliferation of probiotics within the colon, thereby ensuring sustained functionality of the gut microbiota. Consequently, the synergistic effect of combining prebiotics with probiotics, known as the synbiotic effect, in dietary interventions holds promise for potentially mitigating cancer risk and augmenting preventive measures. The utilization of gut microbiota in cancer treatment has shown promise in alleviating adverse health effects. This review explored the potential and the role of probiotics and synbiotics in enhancing health and contributing to cancer prevention efforts. In this review, the applications of functional probiotics and synbiotics, the mechanisms of action of probiotics in cancer, and the relationship of probiotics with various drugs were discussed, shedding light on the potential of probiotics and synbiotics to alleviate the burdens of cancer treatment.
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Affiliation(s)
- Kah Wei Chin
- Bioses Research Interest Group (BIOSES), Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus, 21030, Terengganu, Malaysia
| | - Shing Ching Khoo
- Bioses Research Interest Group (BIOSES), Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus, 21030, Terengganu, Malaysia
| | - Richard Paul Merisha Paul
- Bioses Research Interest Group (BIOSES), Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus, 21030, Terengganu, Malaysia
| | - Vijitra Luang-In
- Natural Antioxidant Innovation Research Unit, Department of Biotechnology, Faculty of Technology, Mahasarakham University, Khamriang, 44150, Kantarawichai, Maha Sarakham, Thailand
| | - Su Datt Lam
- School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, 43600, Selangor, Malaysia
| | - Nyuk Ling Ma
- Bioses Research Interest Group (BIOSES), Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus, 21030, Terengganu, Malaysia.
- Department of Sustainable Engineering, Institute of Biotechnology, Saveetha School of Engineering, SIMATS, Chennai, 602105, India.
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5
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Li T, Chiang JYL. Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development. Pharmacol Rev 2024; 76:1221-1253. [PMID: 38977324 PMCID: PMC11549937 DOI: 10.1124/pharmrev.124.000978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/10/2024] Open
Abstract
Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders. SIGNIFICANCE STATEMENT: Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling holds promise for treating metabolic and inflammatory diseases.
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Affiliation(s)
- Tiangang Li
- Department of Biochemistry and Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (T.L.); and Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (J.Y.L.C.)
| | - John Y L Chiang
- Department of Biochemistry and Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (T.L.); and Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (J.Y.L.C.)
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Śliżewska K, Włodarczyk M, Barczyńska R, Kapuśniak J, Socha P, Wierzbicka-Rucińska A, Kotowska A. Impact of a Fruit-Vegetable Preparation Fortified with Potato Starch Resistant Dextrin on Selected Health Indicators in Overweight Children. Nutrients 2024; 16:2321. [PMID: 39064763 PMCID: PMC11279421 DOI: 10.3390/nu16142321] [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: 05/27/2024] [Revised: 06/25/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Developing modified dietary fibers that maintain prebiotic benefits without significantly affecting meal taste is of high importance in the midst of the obesity pandemic. These benefits include regulating the composition of gut microbiota, increasing feelings of fullness, and improving human metabolic parameters. This study investigated the use of a resistant dextrin (RD) derived from potato starch, which possesses prebiotic properties, as a potential additive in vegetable-fruit preparations that aid weight loss and improve health markers in overweight children. HPLC was employed to examine metabolites like lactic acid, short-chain fatty acids (SCFAs; formic, acetic, propionic, butyric, and valeric acids), and branched-chain fatty acids (BCFAs; isobutyric and isovaleric acids). The activities of α-glucosidase, β-glucosidase, α-galactosidase, β-galactosidase, and β-glucuronidase enzymes in fecal samples were measured using spectrophotometric analysis at a wavelength of 400 nm. Incorporating the RD into vegetable-fruit preparations yielded favorable outcomes in terms of increased concentrations of the tested metabolites (SCFAs and BCFAs) and enhanced fecal enzyme activities after 6 months of consuming the preparations. Furthermore, these effects were found to last for an extended period of 3 months even after discontinuing the treatment. The study has shown that including RD into vegetable-fruit preparations enhances the metabolic parameters of obese and overweight children, hence providing a strong rationale for the widespread usage of these preparations in the industry.
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Affiliation(s)
- Katarzyna Śliżewska
- Institute of Fermentation Technology and Microbiology, Department of Biotechnology and Food Sciences, Technical University of Lodz, Wolczanska 171/173, 90-924 Lodz, Poland;
| | - Michał Włodarczyk
- Institute of Fermentation Technology and Microbiology, Department of Biotechnology and Food Sciences, Technical University of Lodz, Wolczanska 171/173, 90-924 Lodz, Poland;
| | - Renata Barczyńska
- Department of Dietetics and Food Studies, Faculty of Science and Technology, Jan Dlugosz University, Armi Krajowej 13/15, 42-200 Czestochowa, Poland; (R.B.); (J.K.)
| | - Janusz Kapuśniak
- Department of Dietetics and Food Studies, Faculty of Science and Technology, Jan Dlugosz University, Armi Krajowej 13/15, 42-200 Czestochowa, Poland; (R.B.); (J.K.)
| | - Piotr Socha
- The Children’s Memorial Health Institute, Aleja Dzieci Polskich 20, 04-736 Warsaw, Poland; (P.S.); (A.W.-R.); (A.K.)
| | - Aldona Wierzbicka-Rucińska
- The Children’s Memorial Health Institute, Aleja Dzieci Polskich 20, 04-736 Warsaw, Poland; (P.S.); (A.W.-R.); (A.K.)
| | - Aneta Kotowska
- The Children’s Memorial Health Institute, Aleja Dzieci Polskich 20, 04-736 Warsaw, Poland; (P.S.); (A.W.-R.); (A.K.)
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7
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Shi J, Shen H, Huang H, Zhan L, Chen W, Zhou Z, Lv Y, Xiong K, Jiang Z, Chen Q, Liu L. Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions. Front Microbiol 2024; 15:1395514. [PMID: 38962132 PMCID: PMC11220721 DOI: 10.3389/fmicb.2024.1395514] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/27/2024] [Indexed: 07/05/2024] Open
Abstract
The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.
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Affiliation(s)
- Jianguo Shi
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hexiao Shen
- School of Life Sciences and Health Engineering, Hubei University, Wuhan, China
| | - Hui Huang
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lifang Zhan
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Chen
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhuohui Zhou
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yongling Lv
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Kai Xiong
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhiwei Jiang
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qiyi Chen
- Department of Colorectal Disease, Intestinal Microenvironment Treatment Center, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Lei Liu
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Naderi N, Mosahebi A, Williams NR. Microorganisms and Breast Cancer: An In-Depth Analysis of Clinical Studies. Pathogens 2023; 13:6. [PMID: 38276152 PMCID: PMC10819802 DOI: 10.3390/pathogens13010006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/24/2023] [Accepted: 12/15/2023] [Indexed: 01/27/2024] Open
Abstract
Breast cancer is a multifactorial disease that affects millions of women worldwide. Recent work has shown intriguing connections between microorganisms and breast cancer, which might have implications for prevention and treatment. This article analyzed 117 relevant breast cancer clinical studies listed on ClinicalTrials.gov selected using a bespoke set of 38 search terms focused on bacteria, viruses, and fungi. This was supplemented with 20 studies found from a search of PubMed. The resulting 137 studies were described by their characteristics such as geographic distribution, interventions used, start date and status, etc. The studies were then collated into thematic groups for a descriptive analysis to identify knowledge gaps and emerging trends.
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Affiliation(s)
- Naghmeh Naderi
- Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK; (N.N.); (A.M.)
- Division of Surgery & Interventional Science, University College London, London W1W 7TY, UK
| | - Afshin Mosahebi
- Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK; (N.N.); (A.M.)
- Division of Surgery & Interventional Science, University College London, London W1W 7TY, UK
| | - Norman R. Williams
- Division of Surgery & Interventional Science, University College London, London W1W 7TY, UK
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9
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Ruiz-Saavedra S, González Del Rey C, Suárez A, Díaz Y, Zapico A, Arboleya S, Salazar N, Gueimonde M, de Los Reyes-Gavilán CG, González S. Associations of dietary factors and xenobiotic intake with faecal microbiota composition according to the presence of intestinal mucosa damage. Food Funct 2023; 14:9591-9605. [PMID: 37740374 DOI: 10.1039/d3fo01356a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/24/2023]
Abstract
Diet is a major modulator of gut microbiota, which plays a key role in the health status, including colorectal cancer (CRC) development. Several studies and meta-analyses have evidenced an association of certain dietary factors and xenobiotic intake with the incidence of CRC. Nevertheless, how these dietary factors impact the first stages of intestinal mucosa damage is still uncertain. This study aimed at exploring the associations of relevant dietary factors with the gut microbiota of control individuals and subjects diagnosed with intestinal polyps. A total of 60 volunteers were recruited, clinically classified according to colonoscopy criteria and interviewed using food frequency questionnaires (FFQs). The nutritional status of each volunteer was determined and the intake of dietary xenobiotics was quantified. The relative abundance of faecal microbiota taxonomic groups was obtained through 16S rRNA gene sequencing. The association of dietary factors and xenobiotics with faecal microbiota composition showed differences according to the clinical diagnosis group. Our results showed that the intake of red meat (≥50 g day-1) and total polycyclic aromatic hydrocarbons (PAHs) (≥0.75 μg day-1) was associated with a decreased abundance of the family Bacteroidaceae and an increased abundance of Coriobacteriaceae in control subjects. The intake of the heterocyclic amines 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (≥40 ng day-1) and 2-amino-3,8 dimethylimidazo(4,5,f) quinoxaline (MeIQx) (≥50 ng day-1) was associated with a decreased abundance of Akkermansiaceae in the control diagnosis group. Moreover, N-nitroso compounds (NOCs), nitrites (≥1.69 mg day-1) and N-nitrosodimethylamine (NDMA) (≥0.126 μg day-1) were associated with a decreased abundance of Bifidobacteriaceae. The intake of ethanol (≥12 g day-1) in the polyps group was associated with an increased abundance of Peptostreptococcaceae and a decreased abundance of Veillonellaceae. Moreover, linear regression analyses allowed us to identify ethanol, calcium, bioactive compounds such as flavonoids, stilbenes, cellulose, phenolic acids or total polyphenols, and dietary xenobiotics such as PhIP and MeIQx, the NOC N-nitrosopyrrolidine (NPYR) or the total PAHs as potential predictors of faecal microbiota group abundances. These results indicated that the consumption of milk, red meat, processed meat and ethanol and the intake of polyphenols, dietary PAHs, HAs and NOCs are associated with specific groups of the intestinal microbiota, depending on the clinical diagnosis group.
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Affiliation(s)
- Sergio Ruiz-Saavedra
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain.
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Carmen González Del Rey
- Anatomical Pathology Service, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain
| | - Adolfo Suárez
- Digestive Service, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain
| | - Ylenia Díaz
- Digestive Service, Carmen and Severo Ochoa Hospital, 33819 Cangas del Narcea, Spain
| | - Aida Zapico
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
- Department of Functional Biology, University of Oviedo, 33006 Oviedo, Spain
| | - Silvia Arboleya
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain.
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Nuria Salazar
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain.
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain.
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Clara G de Los Reyes-Gavilán
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain.
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Sonia González
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
- Department of Functional Biology, University of Oviedo, 33006 Oviedo, Spain
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10
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Deng X, Yang J, Zhang Y, Chen X, Wang C, Suo H, Song J. An Update on the Pivotal Roles of Probiotics, Their Components, and Metabolites in Preventing Colon Cancer. Foods 2023; 12:3706. [PMID: 37835359 PMCID: PMC10572180 DOI: 10.3390/foods12193706] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/01/2023] [Accepted: 10/08/2023] [Indexed: 10/15/2023] Open
Abstract
Diet, lifestyle, and gut microbiota composition are key risk factors for the progression of colon cancer. Probiotics are living microorganisms that can offer health benefits to the parasitifer when ingested in competent quantities. Several in vivo, in vitro, and clinical studies have demonstrated that probiotics can prevent and mitigate the development of colon cancer. The anti-colon cancer mechanisms of probiotics include the suppression of cell proliferation and the promotion of cancer cell apoptosis, immunomodulation, the modulation of intestinal microorganisms and their metabolism, strengthening the intestinal barrier, and antioxidant effects. This article describes the pathogenesis of colon cancer and the available therapeutic options. In addition, this paper reviews the mechanisms by which probiotics mitigate colon cancer as well as the mitigating effects of probiotic components and metabolites on colon cancer.
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Affiliation(s)
- Xue Deng
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Jing Yang
- Chongqing Engineering Research Center for Processing & Storage of Distinct Agricultural Products, Chongqing Technology and Business University, Chongqing 400067, China;
| | - Yu Zhang
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Xiaoyong Chen
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Chen Wang
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Huayi Suo
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
- National Citrus Engineering Research Center, Southwest University, Chongqing 400712, China
| | - Jiajia Song
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
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11
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Elmowafy M, Shalaby K, Elkomy MH, Alsaidan OA, Gomaa HAM, Hendawy OM, Abdelgawad MA, Ali HM, Ahmed YM, El-Say KM. Exploring the potential of quercetin/aspirin-loaded chitosan nanoparticles coated with Eudragit L100 in the treatment of induced-colorectal cancer in rats. Drug Deliv Transl Res 2023; 13:2568-2588. [PMID: 37000409 DOI: 10.1007/s13346-023-01338-3] [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] [Accepted: 03/20/2023] [Indexed: 04/01/2023]
Abstract
Growing evidence suggests quercetin and aspirin may have anticancer properties, notably in the case of colorectal cancer. The goal of this study was to create Pluronic F127 and polyethylene glycol4000 solid dispersion-loaded chitosan nanoparticles for colonic quercetin and aspirin delivery. In 1:1 polymeric stoichiometric ratio, solubility and complex formation were verified. Solid dispersion-loaded chitosan nanoparticles with a diameter of 244.45 ± 8.5 nm, a surface charge of 34.1 ± 3.3 mV, and encapsulation effectiveness of 76.3 ± 4.3% were generated under ideal conditions. In some cases, coating with Eudragit L100 resulted in a decrease in zeta potential and an increase in particle size. The coated formulation released the actives in a pH-dependent manner, considering their physicochemical features. Surprisingly, when compared to the actives' suspension and uncoated formulation, the coated formulation had greater anti-inflammatory efficacy, with a substantial reduction of PGE2 and IL-8 production in colonic tissues (16.9 ± 7.9 ng/g tissue and 134.9 ± 10.1 pg/g tissue, respectively). It also reversed most of the dimethyl hydrazine-induced histological alterations in the colon. It also demonstrated a greater reduction in TNF expression in colonic tissues. As a result, Eudragit L100-coated QT/AS-loaded chitosan nanoparticles are suggested to provide a potential platform for colonic delivery of quercetin and aspirin.
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Affiliation(s)
- Mohammed Elmowafy
- Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia.
| | - Khaled Shalaby
- Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia
| | - Mohammed H Elkomy
- Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia
| | - Omar Awad Alsaidan
- Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia
| | - Hesham A M Gomaa
- Department of Pharmacology, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia
| | - Omnia M Hendawy
- Department of Pharmacology, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia
| | - Mohamed A Abdelgawad
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
| | - Hazim M Ali
- Department of Chemistry, College of Science, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia
| | - Yasmin M Ahmed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt
| | - Khalid M El-Say
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
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12
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Bahuguna A, Dubey SK. Overview of the Mechanistic Potential of Probiotics and Prebiotics in Cancer Chemoprevention. Mol Nutr Food Res 2023; 67:e2300221. [PMID: 37552810 DOI: 10.1002/mnfr.202300221] [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] [Received: 04/11/2023] [Revised: 06/15/2023] [Indexed: 08/10/2023]
Abstract
Despite of strides in modern cancer therapeutic strategies, there has not been a successful cure for it until now and prognostic side effects and substantial toxicity to chemotherapy and subsequent homeostatic imbalance remains a major concern for professionals in this field. The significance of the human microbiome in the pathogenesis of cancer is being recognized, documented, and established worldwide. Probiotics and prebiotics are some of the most extensively researched approaches to modulate the microbiota for therapeutic purposes, and research on their potential to prevent and treat cancer has sparked an immense amount of interest. The characteristics of probiotics and prebiotics allow for an array of efficient applications in cancer preventive measures. Probiotics can also be administered coupled with chemotherapy and surgery to alleviate their side effects and help promote the effectiveness of chemotherapeutic drugs. Besides showing promising results they are accompanied by potential risks and controversies that may eventually result in clinical repercussions. This review emphasizes the mechanistic potential and oncosuppressive effects of probiotic and prebiotics through maintenance of intestinal barrier function, modifying innate immune system, immunomodulation, intestinal microbiota metabolism, inhibition of host cell proliferation, preventing pathogen colonization, and exerting selective cytotoxicity against tumor cells.
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Affiliation(s)
- Ananya Bahuguna
- Department of Biochemistry, C.B.S.H., G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India
| | - Shiv Kumar Dubey
- Department of Biochemistry, C.B.S.H., G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India
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13
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Zeighamy Alamdary S, Halimi S, Rezaei A, Afifirad R. Association between Probiotics and Modulation of Gut Microbial Community Composition in Colorectal Cancer Animal Models: A Systematic Review (2010-2021). THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2023; 2023:3571184. [PMID: 37719797 PMCID: PMC10505085 DOI: 10.1155/2023/3571184] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 07/09/2023] [Accepted: 07/21/2023] [Indexed: 09/19/2023]
Abstract
Background Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies and is considered the third major cause of mortality globally. Probiotics have been shown to protect against the CRC cascade in numerous studies. Aims The goal of this systematic review was to gather the preclinical studies that examined the impact of probiotics on the alteration of gut microbiota profiles (bacterial communities) and their link to colorectal carcinogenesis as well as the potential processes involved. Methods The search was performed using Scopus, Web of Science, and PubMed databases. Five parameters were used to develop search filters: "probiotics," "prebiotics," "synbiotics," "colorectal cancer," and "animal model." Results Of the 399 full texts that were screened, 33 original articles met the inclusion criteria. According to the current findings, probiotics/synbiotics could significantly attenuate aberrant crypt foci (ACF) formation, restore beneficial bacteria in the microbiota population, increase short-chain fatty acids (SCFAs), and change inflammatory marker expression. Conclusions The present systematic review results indicate that probiotics could modulate the gut microbial composition and immune regulation to combat/inhibit CRC in preclinical models. However, where the evidence is more limited, it is critical to transfer preclinical research into clinical data.
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Affiliation(s)
| | - Shahnaz Halimi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Rezaei
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Roghayeh Afifirad
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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14
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Saeed H, Leibowitz BJ, Zhang L, Yu J. Targeting Myc-driven stress addiction in colorectal cancer. Drug Resist Updat 2023; 69:100963. [PMID: 37119690 DOI: 10.1016/j.drup.2023.100963] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 04/06/2023] [Accepted: 04/17/2023] [Indexed: 05/01/2023]
Abstract
MYC is a proto-oncogene that encodes a powerful regulator of transcription and cellular programs essential for normal development, as well as the growth and survival of various types of cancer cells. MYC rearrangement and amplification is a common cause of hematologic malignancies. In epithelial cancers such as colorectal cancer, genetic alterations in MYC are rare. Activation of Wnt, ERK/MAPK, and PI3K/mTOR pathways dramatically increases Myc levels through enhanced transcription, translation, and protein stability. Elevated Myc promotes stress adaptation, metabolic reprogramming, and immune evasion to drive cancer development and therapeutic resistance through broad changes in transcriptional and translational landscapes. Despite intense interest and effort, Myc remains a difficult drug target. Deregulation of Myc and its targets has profound effects that vary depending on the type of cancer and the context. Here, we summarize recent advances in the mechanistic understanding of Myc-driven oncogenesis centered around mRNA translation and proteostress. Promising strategies and agents under development to target Myc are also discussed with a focus on colorectal cancer.
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Affiliation(s)
- Haris Saeed
- UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA; Dept. of Pathology, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA
| | - Brian J Leibowitz
- UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA; Dept. of Pathology, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA
| | - Lin Zhang
- UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA; Dept. of Chemical Biology and Pharmacology, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA
| | - Jian Yu
- UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA; Dept. of Pathology, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA; Dept. of Radiation Oncology, University of Pittsburgh School of Medicine, 5117 Centre Ave., Pittsburgh, PA 15213, USA.
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15
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Gates TJ, Yuan C, Shetty M, Kaiser T, Nelson AC, Chauhan A, Starr TK, Staley C, Subramanian S. Fecal Microbiota Restoration Modulates the Microbiome in Inflammation-Driven Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15082260. [PMID: 37190186 DOI: 10.3390/cancers15082260] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 03/29/2023] [Accepted: 04/07/2023] [Indexed: 05/17/2023] Open
Abstract
Chronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (id-CRCs), and intestinal microbiota has been implicated in the etiology of id-CRCs. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRCs. To understand the microbiome changes that occur over time in id-CRCs, we used a mouse model of id-CRCs with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases in Akkermansia in mice receiving horizontal microbiome transfer (HMT) via cage bedding swapping, while the control cohort had consistent longitudinal increases in Anaeroplasma and Alistipes. Additionally, fecal lipocalin-2 (Lcn-2), a marker of intestinal inflammation, was elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role for Akkermansia, Anaeroplasma, and Alistipes in regulating colonic inflammation in id-CRCs.
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Affiliation(s)
- Travis J Gates
- Department of Molecular Pharmacology and Therapeutics, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Ce Yuan
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Mihir Shetty
- Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Thomas Kaiser
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Andrew C Nelson
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Aastha Chauhan
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Timothy K Starr
- Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Medical School, Minneapolis, MN 55455, USA
- Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Christopher Staley
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
- Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Subbaya Subramanian
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
- Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA
- Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
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16
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Liang Y, Yang L, Wang Y, Tang T, Liu F, Zhang F. Peptidoglycan recognition protein SC (PGRP-SC) shapes gut microbiota richness, diversity and composition by modulating immunity in the house fly Musca domestica. INSECT MOLECULAR BIOLOGY 2023; 32:200-212. [PMID: 36522831 DOI: 10.1111/imb.12824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 12/09/2022] [Indexed: 06/17/2023]
Abstract
The gastrointestinal tract of all animals, including insects, is colonized by a remarkable array of microorganisms which are referred to collectively as the gut microbiota. The hosts establish mutually beneficial interactions with the gut microbiota. However, the mechanisms shaping these interactions remain to be better understood. Here, we investigated the roles of Musca domestica peptidoglycan recognition protein SC (MdPGRP-SC), a secreted pattern recognition receptor, in shaping the gut microbial community structure by using biochemical and high-throughput sequencing approaches. The recombinant MdPGRP-SC (rMdPGRP-SC) could strongly bind various pathogen-associated molecular patterns (PAMPs) including peptidoglycan, lipopolysaccharide and D-galactose, and exhibited mild affinity to β-1, 3-glucan and D-mannose. Meanwhile, rMdPGRP-SC could also bind different kinds of microorganisms, including gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and yeast (Pichia pastoris). rMdPGRP-SC also exhibited weak antibacterial activity against Bacillus subtilis. Knockdown of MdPGRP-SC by RNAi reduced the persistence of ingested E. coli and a load of indigenous microbiota in the larval gut significantly. In addition, depleted MdPGRP-SC also altered the gut microbiota composition and led to increased ratios of Gram-negative bacteria. We hypothesize that MdPGRP-SC is involved in maintaining gut homeostasis by modulating the immune intensity of the gut through multiple mechanisms, including degrading or neutralizing various PAMPs and selectively suppressing the growth of some bacteria. Considering the functional conservation of the peptidoglycan recognition protein (PGRP) family in insects, the catalytic PGRPs might be promising candidate targets not only for pest and vector control but also for the treatment of bacterial infection in insect farming.
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Affiliation(s)
- Yadi Liang
- The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, China
| | - Lan Yang
- The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, China
| | - Yongpeng Wang
- The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, China
| | - Ting Tang
- The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, China
| | - Fengsong Liu
- The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, China
| | - Feng Zhang
- The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, China
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17
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Śliżewska K, Włodarczyk M, Sobczak M, Barczyńska R, Kapuśniak J, Socha P, Wierzbicka-Rucińska A, Kotowska A. Comparison of the Activity of Fecal Enzymes and Concentration of SCFA in Healthy and Overweight Children. Nutrients 2023; 15:nu15040987. [PMID: 36839343 PMCID: PMC9966664 DOI: 10.3390/nu15040987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023] Open
Abstract
In modern societies obesity has become a serious issue which must be urgently addressed. The health implications of neglected obesity are substantial, as not only does it affect individuals' everyday lives, but it also leads to significantly increased mortality due to the development of several disorders such as type-2 diabetes, cardiovascular diseases, cancers, and depression. The objective of this research was to investigate the alterations in selected health markers caused by overweight and obesity in children. The measured parameters were the activity of the fecal enzymes, the concentration of short-chain fatty acids (SCFAs), and the concentration of branched-chain fatty acids (BCFAs). The activity of the fecal enzymes, specifically α-glucosidase, α-galactosidase, β-glucosidase, β-galactosidase, and β-glucuronidase, was determined using spectrophotometry at a wavelength of 400 nm. Furthermore, concentrations of lactic acid, SCFAs (formic, acetic, propionic, butyric, and valeric acids), and BCFAs (isobutyric and isovaleric acids) were determined using the HPLC method. The obtained results reveal that obese children have different fecal enzyme activity and a different profile of fatty acids from children of normal weight. The group of obese children, when compared to children of normal weight, had increased concentrations of BCFAs (p < 0.05) and higher activity of potentially harmful enzymes such as β-glucosidase and β-glucuronidase (p < 0.05). In comparison, children of normal weight exhibited significantly increased concentrations of lactic acid and SCFAs (especially formic and butyric acids) (p < 0.05). Furthermore, their α-glucosidase and α-galactosidase activity were higher when compared to the group of obese children (p < 0.05). These results suggest that the prevalence of obesity has a significant impact on metabolites produced in the gastrointestinal tract, which might result in a higher chance of developing serious diseases.
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Affiliation(s)
- Katarzyna Śliżewska
- Institute of Fermentation Technology and Microbiology, Department of Biotechnology and Food Sciences, Technical University of Lodz, Wolczanska 171/173, 90-924 Łódź, Poland
- Correspondence: (K.Ś.); (M.W.)
| | - Michał Włodarczyk
- Institute of Fermentation Technology and Microbiology, Department of Biotechnology and Food Sciences, Technical University of Lodz, Wolczanska 171/173, 90-924 Łódź, Poland
- Correspondence: (K.Ś.); (M.W.)
| | - Martyna Sobczak
- Institute of Fermentation Technology and Microbiology, Department of Biotechnology and Food Sciences, Technical University of Lodz, Wolczanska 171/173, 90-924 Łódź, Poland
| | - Renata Barczyńska
- Department of Dietetics and Food Studies, Faculty of Science and Technology, Jan Dlugosz University, Armii Krajowej 13/15, 42-200 Czestochowa, Poland
| | - Janusz Kapuśniak
- Department of Dietetics and Food Studies, Faculty of Science and Technology, Jan Dlugosz University, Armii Krajowej 13/15, 42-200 Czestochowa, Poland
| | - Piotr Socha
- The Children’s Memorial Health Institute, aleja Dzieci Polskich 20, 04-736 Warsaw, Poland
| | | | - Aneta Kotowska
- The Children’s Memorial Health Institute, aleja Dzieci Polskich 20, 04-736 Warsaw, Poland
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18
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Zhang H, Chong H, Yu Q, Zha Y, Cheng M, Ning K. Tracing human life trajectory using gut microbial communities by context-aware deep learning. Brief Bioinform 2023; 24:6984796. [PMID: 36631408 DOI: 10.1093/bib/bbac629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/15/2022] [Accepted: 12/25/2022] [Indexed: 01/13/2023] Open
Abstract
The gut microbial communities are highly plastic throughout life, and the human gut microbial communities show spatial-temporal dynamic patterns at different life stages. However, the underlying association between gut microbial communities and time-related factors remains unclear. The lack of context-awareness, insufficient data, and the existence of batch effect are the three major issues, making the life trajection of the host based on gut microbial communities problematic. Here, we used a novel computational approach (microDELTA, microbial-based deep life trajectory) to track longitudinal human gut microbial communities' alterations, which employs transfer learning for context-aware mining of gut microbial community dynamics at different life stages. Using an infant cohort, we demonstrated that microDELTA outperformed Neural Network for accurately predicting the age of infant with different delivery mode, especially for newborn infants of vaginal delivery with the area under the receiver operating characteristic curve of microDELTA and Neural Network at 0.811 and 0.436, respectively. In this context, we have discovered the influence of delivery mode on infant gut microbial communities. Along the human lifespan, we also applied microDELTA to a Chinese traveler cohort, a Hadza hunter-gatherer cohort and an elderly cohort. Results revealed the association between long-term dietary shifts during travel and adult gut microbial communities, the seasonal cycling of gut microbial communities for the Hadza hunter-gatherers, and the distinctive microbial pattern of elderly gut microbial communities. In summary, microDELTA can largely solve the issues in tracing the life trajectory of the human microbial communities and generate accurate and flexible models for a broad spectrum of microbial-based longitudinal researches.
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Affiliation(s)
- Haohong Zhang
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of AI Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
| | - Hui Chong
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of AI Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
| | - Qingyang Yu
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of AI Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
| | - Yuguo Zha
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of AI Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
| | - Mingyue Cheng
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of AI Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
| | - Kang Ning
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of AI Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
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19
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Nami Y, Hejazi S, Geranmayeh MH, Shahgolzari M, Yari Khosroushahi A. Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention. Eur J Cancer Prev 2023; 32:30-47. [PMID: 36134612 DOI: 10.1097/cej.0000000000000738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest & West Region, Agricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)
| | - Salva Hejazi
- Department of Medicine, Student Research Committee, Tabriz University of Medical Sciences
| | - Mohammad Hossein Geranmayeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Biotechnology Research Center, Tabriz University of Medical Sciences
| | - Ahmad Yari Khosroushahi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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20
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Ullah H, Zada H, Khan F, Hayat S, Rahim F, Hussain A, Manzoor A, Wadood A, Ayub K, Rehman AU, Sarfaraz S. Benzimidazole bearing thiourea analogues: Synthesis, β-glucuronidase inhibitory potential and their molecular docking study. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.133941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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21
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Jafari M, Laraqui A, Baba W, Benmokhtar S, Zaitouni SE, Ali AA, Bounaim A, Moujahid M, Tanz R, Mahfoud T, Sbitti Y, Annaz HE, Abi R, Tagajdid MR, Kochri SE, Lahlou IA, Hsaini HE, Belayachi L, Benjouad A, Ichou M, En-Nya A, Ennibi K. Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa. BMC Cancer 2022; 22:1142. [PMID: 36344948 PMCID: PMC9639273 DOI: 10.1186/s12885-022-10235-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 10/11/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk. METHODS: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia. RESULTS: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). CONCLUSION KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.
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Affiliation(s)
- Meryem Jafari
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco.
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco.
| | - Abdelilah Laraqui
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Walid Baba
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Soukaina Benmokhtar
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Sara El Zaitouni
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Abdelmounaim Ait Ali
- Department of Digestive Surgery, Faculty of Medicine and Pharmacy, Mohammed V Military Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Ahmed Bounaim
- Department of Digestive Surgery, Faculty of Medicine and Pharmacy, Mohammed V Military Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Mountassir Moujahid
- Department of Digestive Surgery, Faculty of Medicine and Pharmacy, Mohammed V Military Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Rachid Tanz
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Tarik Mahfoud
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Yassir Sbitti
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Hicham El Annaz
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Rachid Abi
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Mohamed Rida Tagajdid
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Safae El Kochri
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Idriss Amine Lahlou
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Houda El Hsaini
- International Faculty of Dental Medicine, College of Health Sciences, International University in Rabat, Rabat, Morocco
| | - Lamiae Belayachi
- International Faculty of Dental Medicine, College of Health Sciences, International University in Rabat, Rabat, Morocco
| | - Abdelaziz Benjouad
- International Faculty of Dental Medicine, College of Health Sciences, International University in Rabat, Rabat, Morocco
| | - Mohammed Ichou
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Amina En-Nya
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Khalid Ennibi
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
- Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
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Saeed M, Shoaib A, Kandimalla R, Javed S, Almatroudi A, Gupta R, Aqil F. Microbe-based therapies for colorectal cancer: Advantages and limitations. Semin Cancer Biol 2022; 86:652-665. [PMID: 34020027 DOI: 10.1016/j.semcancer.2021.05.018] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 04/06/2021] [Accepted: 05/14/2021] [Indexed: 01/27/2023]
Abstract
Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.
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Affiliation(s)
- Mohd Saeed
- Department of Biology, College of Sciences, University of Hail, Hail, Saudi Arabia
| | - Ambreen Shoaib
- Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Raghuram Kandimalla
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
| | - Shamama Javed
- Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia
| | - Ramesh Gupta
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
| | - Farrukh Aqil
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
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Mishra S, Amatya SB, Salmi S, Koivukangas V, Karihtala P, Reunanen J. Microbiota and Extracellular Vesicles in Anti-PD-1/PD-L1 Therapy. Cancers (Basel) 2022; 14:cancers14205121. [PMID: 36291904 PMCID: PMC9600290 DOI: 10.3390/cancers14205121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 10/07/2022] [Accepted: 10/13/2022] [Indexed: 12/04/2022] Open
Abstract
Simple Summary Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 have emerged as contemporary treatments for a variety of cancers. However, the efficacy of antibody-based ICIs could be further enhanced. Microbiota have been demonstrated to be among the vital factors governing cancer progression and response to therapy in patients. Bacteria secrete extracellular vesicles carrying bioactive metabolites within their cargo that can cross physiological barriers, selectively accumulate near tumor cells, and alter the tumor microenvironment. Extracellular vesicles, particularly those derived from bacteria, could thus be of promising assistance in refining the treatment outcomes for anti-PD-1/PD-L1 therapy. The potentiality of microbiota-derived extracellular vesicles in improving the currently used treatments and presenting new therapeutic avenues for cancer has been featured in this review. Abstract Cancer is a deadly disease worldwide. In light of the requisite of convincing therapeutic methods for cancer, immune checkpoint inhibition methods such as anti-PD-1/PD-L1 therapy appear promising. Human microbiota have been exhibited to regulate susceptibility to cancer as well as the response to anti-PD-1/PD-L1 therapy. However, the probable contribution of bacterial extracellular vesicles (bEVs) in cancer pathophysiology and treatment has not been investigated much. bEVs illustrate the ability to cross physiological barriers, assemble around the tumor cells, and likely modify the tumor microenvironment (EVs). This systematic review emphasizes the correlation between cancer-associated extracellular vesicles, particularly bEVs and the efficacy of anti-PD-1/PD-L1 therapy. The clinical and pharmacological prospective of bEVs in revamping the contemporary treatments for cancer has been further discussed.
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Affiliation(s)
- Surbhi Mishra
- Biocenter Oulu & Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
| | - Sajeen Bahadur Amatya
- Biocenter Oulu & Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
| | - Sonja Salmi
- Biocenter Oulu & Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
| | - Vesa Koivukangas
- Department of Surgery, Oulu University Hospital, University of Oulu, 90014 Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital, University of Oulu, 90014 Oulu, Finland
| | - Peeter Karihtala
- Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, 00029 Helsinki, Finland
| | - Justus Reunanen
- Biocenter Oulu & Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
- Correspondence:
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Zha Y, Chong H, Yang P, Ning K. Microbial Dark Matter: from Discovery to Applications. GENOMICS, PROTEOMICS & BIOINFORMATICS 2022; 20:867-881. [PMID: 35477055 PMCID: PMC10025686 DOI: 10.1016/j.gpb.2022.02.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/28/2021] [Accepted: 03/22/2022] [Indexed: 01/12/2023]
Abstract
With the rapid increase of the microbiome samples and sequencing data, more and more knowledge about microbial communities has been gained. However, there is still much more to learn about microbial communities, including billions of novel species and genes, as well as countless spatiotemporal dynamic patterns within the microbial communities, which together form the microbial dark matter. In this work, we summarized the dark matter in microbiome research and reviewed current data mining methods, especially artificial intelligence (AI) methods, for different types of knowledge discovery from microbial dark matter. We also provided case studies on using AI methods for microbiome data mining and knowledge discovery. In summary, we view microbial dark matter not as a problem to be solved but as an opportunity for AI methods to explore, with the goal of advancing our understanding of microbial communities, as well as developing better solutions to global concerns about human health and the environment.
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Affiliation(s)
- Yuguo Zha
- MOE Key Laboratory of Molecular Biophysics, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Hui Chong
- MOE Key Laboratory of Molecular Biophysics, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Pengshuo Yang
- MOE Key Laboratory of Molecular Biophysics, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Kang Ning
- MOE Key Laboratory of Molecular Biophysics, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Center of Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
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25
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Taniya MA, Chung HJ, Al Mamun A, Alam S, Aziz MA, Emon NU, Islam MM, Hong STS, Podder BR, Ara Mimi A, Aktar Suchi S, Xiao J. Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation. Front Cell Infect Microbiol 2022; 12:915701. [PMID: 35937689 PMCID: PMC9355470 DOI: 10.3389/fcimb.2022.915701] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 06/22/2022] [Indexed: 12/14/2022] Open
Abstract
Autism spectrum disorder (ASD) is a neurological disorder that affects normal brain development. The recent finding of the microbiota-gut-brain axis indicates the bidirectional connection between our gut and brain, demonstrating that gut microbiota can influence many neurological disorders such as autism. Most autistic patients suffer from gastrointestinal (GI) symptoms. Many studies have shown that early colonization, mode of delivery, and antibiotic usage significantly affect the gut microbiome and the onset of autism. Microbial fermentation of plant-based fiber can produce different types of short-chain fatty acid (SCFA) that may have a beneficial or detrimental effect on the gut and neurological development of autistic patients. Several comprehensive studies of the gut microbiome and microbiota-gut-brain axis help to understand the mechanism that leads to the onset of neurological disorders and find possible treatments for autism. This review integrates the findings of recent years on the gut microbiota and ASD association, mainly focusing on the characterization of specific microbiota that leads to ASD and addressing potential therapeutic interventions to restore a healthy balance of gut microbiome composition that can treat autism-associated symptoms.
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Affiliation(s)
- Masuma Afrin Taniya
- Department of Life Sciences, School of Environment and Life Science, Independent University, Dhaka, Bangladesh
| | - Hea-Jong Chung
- Gwanju Center, Korea Basic Science Institute, Gwanju, South Korea
| | - Abdullah Al Mamun
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Safaet Alam
- Drugs and Toxins Research Division, BCSIR Laboratories, Rajshahi, Bangladesh Council of Scientific and Industrial Research, Rajshahi, Bangladesh
| | - Md. Abdul Aziz
- Department of Pharmacy, Faculty of Pharmacy and Health Sciences, State University of Bangladesh, Dhaka, Bangladesh
| | - Nazim Uddin Emon
- Department of Pharmacy, Faculty of Science and Engineering, International Islamic University Chittagong, Chattogram, Bangladesh
| | - Md. Minarul Islam
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, South Korea
| | - Seong-T shool Hong
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, South Korea
| | - Bristy Rani Podder
- Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh
| | - Anjuman Ara Mimi
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Suzia Aktar Suchi
- Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, South Korea
| | - Jian Xiao
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
- Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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26
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Zhang X, Yang G, Chen Y, Mu Z, Zhou H, Zhang L. Resveratrol pre-treatment alleviated caerulein-induced acute pancreatitis in high-fat diet-feeding mice via suppressing the NF-κB proinflammatory signaling and improving the gut microbiota. BMC Complement Med Ther 2022; 22:189. [PMID: 35842665 PMCID: PMC9288014 DOI: 10.1186/s12906-022-03664-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 06/09/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND hyperlipidemia acute pancreatitis (HTG-AP) is a major hidden danger affecting human health, however, whether there is a protective effect of resveratrol on HTG-AP is unclear. Therefore our study was aimed to investigate the preventive effect and the underlying mechanism of resveratrol in the HTG-AP mice model. METHODS This research was divided into two parts. In the first part, mice were adaptively fed with normal chow or HFD for 6 weeks. From the second week, resveratrol-treated mice were in intragastric administration with resveratrol (45 mg/kg/d) for 4 weeks. In the second part, the procedures were the same as the first part. After the last intragastric administration with resveratrol, all mice were intraperitoneal injections of cerulean. RESULTS We found resveratrol effectively inhibited pancreatic pathological injury in the HFD, AP, and HTG-AP mice. Resveratrol reduced the LPS, IL-6, TNF-α, and MCP-1 expressions in the HFD mice. Resveratrol also reduced TNF-α, MDA, and MCP-1 expressions and increased SOD and T-AOC expressions in the AP and HTG-AP mice. Furthermore, resveratrol suppressed the NF-κB pro-inflammatory signaling pathway in pancreatic tissues in the AP and HTG-AP mice. Moreover, resveratrol improved the gut microbiota in the HFD mice. CONCLUSION The resveratrol pre-treatment could attenuate pancreas injury, inflammation, and oxidative stress in the HTG-AP mice, via restraining the NF-κB signaling pathway and regulating gut microbiota. Therefore, Our study proved that the resveratrol pre-treatment had a preventive effect on HTG-AP.
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Affiliation(s)
- Xiaoying Zhang
- School of Basic Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Guodong Yang
- Department of Gastroenterology and Hepatology, Affiliated Hospital of North Sichuan Medical College, No.63, Cultural Rd., Shunqing Dist, Nanchong, 637000, Sichuan Province, China.
| | - Yulin Chen
- North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Zhao Mu
- North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Haiyue Zhou
- North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Luoyao Zhang
- North Sichuan Medical College, Nanchong, 637000, Sichuan, China
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Effects of Resistant Dextrin from Potato Starch on the Growth Dynamics of Selected Co-Cultured Strains of Gastrointestinal Bacteria and the Activity of Fecal Enzymes. Nutrients 2022; 14:nu14102158. [PMID: 35631299 PMCID: PMC9144799 DOI: 10.3390/nu14102158] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 05/16/2022] [Accepted: 05/20/2022] [Indexed: 02/04/2023] Open
Abstract
Preparations of resistant dextrins have become an interesting topic of research due to their properties, which bear resemblance those of prebiotics, e.g., the improvement of metabolic parameters, increased efficiency of the immune system and induction of vitamin production. The aim of this study was to investigate the effects of the resistant dextrin produced from potato starch on the growth dynamics of typical gastrointestinal microbiota and the activity of fecal enzymes in order to assess a possible exhibition of prebiotic properties. In the study, in vitro cultivation of co-cultures of Lactobacillus, Bifidobacterium, E. coli, Enterococcus, Clostridium and Bacteroides spp. was conducted on media enriched with the resistant dextrin. The CFU/mL for each strain was measured in time periods of 24, 48, 72, 96 and 168 h. Furthermore, the activities of α-glucosidase, α-galactosidase, β-glucosidase, β-galactosidase and β-glucuronidase were determined using spectrophotometric methods at a wavelength of 400 nm. The results show that the resistant dextrin can be utilized as a source of carbon for the growth of intestinal bacteria. Moreover, the results revealed that, after 168 h of cultivation, it enhances the viability of probiotic strains of Lactobacillus and Bifidobacterium spp. and decreases the growth of other intestinal strains (Clostridium, Escherichia coli, Enterococcus and Bacteroides), which is demonstrated by a high Prebiotic Index (p < 0.05). Furthermore, there was no significant change in the pH of the cultures; however, the pace of the pH decrease during the cultivation was slower in the case of culture with resistant dextrin. Furthermore, it was revealed that usage of the resistant dextrin as a medium additive noticeably lowered the activities of β-glucosidase and β-glucuronidase compared to the control (p < 0.05), whereas the activities of the other fecal enzymes were affected to a lesser degree. The resistant dextrins derived from potato starch are a suitable prebiotic candidate as they promote the growth of beneficial strains of gut bacteria and improve health markers, such as the activity of fecal enzymes. Nevertheless, additional in vivo research is necessary to further assess the suspected health-promoting properties.
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Fornasaro S, Esposito A, Florian F, Pallavicini A, De Leo L, Not T, Lagatolla C, Mezzarobba M, Di Silvestre A, Sergo V, Bonifacio A. Spectroscopic investigation of faeces with surface-enhanced Raman scattering: a case study with coeliac patients on gluten-free diet. Anal Bioanal Chem 2022; 414:3517-3527. [PMID: 35258650 PMCID: PMC9018641 DOI: 10.1007/s00216-022-03975-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/07/2022] [Accepted: 02/10/2022] [Indexed: 11/06/2022]
Abstract
Surface-enhanced Raman scattering (SERS) spectra of faecal samples can be obtained by adding AuNP to their methanol extracts according to the reported protocol, and display bands that are due to bilirubin-like species but also to xanthine and hypoxanthine, two metabolic products secreted by gut bacteria. A total of 27 faecal samples from three different groups, i.e. coeliac patients (n = 9), coeliac patients on gluten-free diet (n = 10) and a control group (n = 8), were characterized with both SERS spectroscopy and 16S rRNA sequencing analysis. Significant differences are present between SERS spectra of coeliac patients and those on gluten-free diet, with a marked increase in the relative intensity of both xanthine and hypoxanthine for the latter. Interestingly, these differences do not correlate with bacterial composition as derived from 16S rRNA sequencing.
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Affiliation(s)
- Stefano Fornasaro
- Raman Spectroscopy Laboratory, Department of Engineering and Architecture, University of Trieste, P.le Europa 1, 34100, Trieste, Italy
| | - Alessandro Esposito
- Raman Spectroscopy Laboratory, Department of Engineering and Architecture, University of Trieste, P.le Europa 1, 34100, Trieste, Italy
| | - Fiorella Florian
- Department of Life Sciences, University of Trieste, Via Edoardo Weiss 2, 34128, Trieste, TS, Italy
| | - Alberto Pallavicini
- Department of Life Sciences, University of Trieste, Via Edoardo Weiss 2, 34128, Trieste, TS, Italy
| | - Luigina De Leo
- Institute for Maternal Child Health-IRCCS "Burlo Garofolo" Trieste, via dell'Istria 65/1, 34100, Trieste, Italy
| | - Tarcisio Not
- Institute for Maternal Child Health-IRCCS "Burlo Garofolo" Trieste, via dell'Istria 65/1, 34100, Trieste, Italy
| | - Cristina Lagatolla
- Department of Life Sciences, University of Trieste, Via Edoardo Weiss 2, 34128, Trieste, TS, Italy
| | - Marica Mezzarobba
- Department of Life Sciences, University of Trieste, Via Edoardo Weiss 2, 34128, Trieste, TS, Italy
| | - Alessia Di Silvestre
- Raman Spectroscopy Laboratory, Department of Engineering and Architecture, University of Trieste, P.le Europa 1, 34100, Trieste, Italy
| | - Valter Sergo
- Raman Spectroscopy Laboratory, Department of Engineering and Architecture, University of Trieste, P.le Europa 1, 34100, Trieste, Italy
| | - Alois Bonifacio
- Raman Spectroscopy Laboratory, Department of Engineering and Architecture, University of Trieste, P.le Europa 1, 34100, Trieste, Italy.
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Yu T, Ji L, Lou L, Ye S, Fang X, Li C, Jiang F, Gao H, Lou Y, Li X. Fusobacterium nucleatum Affects Cell Apoptosis by Regulating Intestinal Flora and Metabolites to Promote the Development of Colorectal Cancer. Front Microbiol 2022; 13:841157. [PMID: 35369440 PMCID: PMC8971960 DOI: 10.3389/fmicb.2022.841157] [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: 12/22/2021] [Accepted: 02/23/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND/AIMS Intestinal flora, especially Fusobacterium nucleatum (Fn), can affect the development of colorectal cancer (CRC). In this study, we examined the composition of intestinal flora and their metabolites in the tissues, serum and feces of CRC patients. MATERIALS AND METHODS CRC tissues, adjacent normal colonic tissues, fecal and serum samples were collected from CRC patients who received surgical treatment between January 2018 and January 2020. Fecal and serum samples were collected from healthy individuals for comparison. In addition, fecal samples were collected from BALB/c female mice. SW480, a human CRC cell line, was utilized for in vitro studies. The experiments involved 1H-NMR-based metabolomics analysis, targeted and untargeted mass spectrometry analysis, and intestinal flora 16S rDNA V4 region sequencing. RESULTS The abundance of Bacteroides and propionic acid concentration were decreased and that of Lactobacillus and lactic acid concentration were increased in CRC tissues. In addition, the abundances of Ruminococcus, Prevotella, and Sutterell were decreased in CRC patients. The levels of leucine and isoleucine were decreased in the serum and tumor tissues of CRC patients. Aspartate, glutamate and glutathione levels were elevated in the tissues of CRC patients only. The serum glutamine, tyrosine, valine, alanine, and histidine levels were decreased significantly. Lactic acid inhibited and propionic acid promoted apoptosis among SW480 CRC cells. CONCLUSION Fn affected the apoptosis of CRC cells and promoted the progression of CRC by affecting the distribution of intestinal flora, which altered the concentrations of metabolites such as lactic acid, propionic acid. Intestinal flora could regulate amino acid metabolism.
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Affiliation(s)
- Tingting Yu
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Ling Ji
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Liqin Lou
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Shiqing Ye
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Xiaoting Fang
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Chen Li
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Feizhao Jiang
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hongchang Gao
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Yongliang Lou
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Xiang Li
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
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Kumarasamy V, Atroosh WM, Anbazhagan D, Abdalla MMI, Azzani M. Association of Blastocystis hominis with colorectal cancer: A systematic review of in vitro and in vivo evidences. World J Gastrointest Oncol 2022; 14:734-745. [PMID: 35321272 PMCID: PMC8919012 DOI: 10.4251/wjgo.v14.i3.734] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/16/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recently, there have been several findings that showed intestinal colonisation of Blastocystis hominis (Blastocystis) as a risk factor to the worsening of colorectal cancer (CRC). However, studies have shown controversial results in the pathogenicity of Blastocystis.
AIM To review systematically the evidence available on the association between CRC and Blastocystis and the prevalence of Blastocystis in CRC patients and to investigate cytopathic and immunological effects of Blastocystis in in vitro and in vivo studies.
METHODS PRISMA guidelines were utilised in conducting this systematic review. Original articles published before February 2, 2020 were included. PubMed, Science Direct, Scopus and Google scholar databases were searched. Manual searching was carried out to find articles missed during the online search.
RESULTS Out of 12 studies selected for this systematic review, seven studies confirmed the prevalence of Blastocystis and found it to be between 2%-28% in CRC patients, whereby subtype 1 and subtype 3 were predominantly seen. A total of four studies employing in vitro human colorectal carcinoma cell line study models showed significant cytopathic and immunological effects of Blastocystis. In addition, one in vivo experimental animal model study showed that there was a significant effect of infection with Blastocystis on exacerbation of colorectal carcinogenesis.
CONCLUSION Blastocystis is a commonly identified microorganism in CRC patients. These studies have provided supportive data that Blastocystis could exacerbate existing CRC via alteration in host immune response and increased oxidative damage. Future studies of CRC and Blastocystis should attempt to determine the various stages of CRC that are most likely to be associated with Blastocystis and its relationship with other intestinal bacteria.
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Affiliation(s)
- Vinoth Kumarasamy
- Department of Microbiology and Parasitology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom 42610, Selangor, Malaysia
- Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang 43000, Selangor, Malaysia
| | - Wahib Mohammed Atroosh
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Wilayah Persekutuan, Malaysia
- Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, University of Aden, Aden 00, Yemen
| | - Deepa Anbazhagan
- Department of Microbiology and Parasitology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom 42610, Selangor, Malaysia
| | | | - Meram Azzani
- Department of Community Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom 42610, Selangor, Malaysia
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Doublier S, Cirrincione S, Scardaci R, Botta C, Lamberti C, Di Giuseppe F, Angelucci S, Rantsiou K, Cocolin L, Pessione E. Putative probiotics decrease cell viability and enhance chemotherapy effectiveness in human cancer cells: role of butyrate and secreted proteins. Microbiol Res 2022; 260:127012. [DOI: 10.1016/j.micres.2022.127012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/16/2022] [Accepted: 03/16/2022] [Indexed: 12/29/2022]
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Gastrointestinal Microbiota Dysbiosis Associated with SARS-CoV-2 Infection in Colorectal Cancer: The Implication of Probiotics. GASTROENTEROLOGY INSIGHTS 2022. [DOI: 10.3390/gastroent13010006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The complexity of coronavirus disease 2019 (COVID-19)’s pathophysiology is such that microbial dysbiosis in the lung and gastrointestinal (GI) microbiota may be involved in its pathogenic process. GI microbiota dysbiosis has been associated with respiratory disorders, including COVID-19, as well as sporadic colorectal cancer (CRC) through imbalanced microbiota and compromised immune response. It is pertinent to understand the possible role of probiotics in stabilizing the microbial environment and maintaining the integrity of the respiratory and GI tracts in SARS-CoV-2 induced dysbiosis and colorectal carcinogenesis. The long-term implication of SARS-CoV-2 in GI dysbiosis via microbiota-gut-lung cross-talk could increase the risk of new CRC diagnosis or worsen the condition of previously diagnosed individuals. Recent knowledge shows that the immune-modulatory response to probiotics is shifting the beneficial use of probiotics towards the treatment of various diseases. In this review, we highlight the potential impact of probiotics on SARS-CoV-2 infection associated with CRC through microbiota imbalance in COVID-19 patients.
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ADIYOGA R, ARIEF II, BUDIMAN C, ABIDIN Z. In vitro anticancer potentials of Lactobacillus plantarum IIA-1A5 and Lactobacillus acidophilus IIA-2B4 extracts against WiDr human colon cancer cell line. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.87221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Wan C, Wu K, Lu X, Fang F, Li Y, Zhao Y, Li S, Gao J. Integrative Analysis of the Gut Microbiota and Metabolome for In Vitro Human Gut Fermentation Modeling. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:15414-15424. [PMID: 34889098 DOI: 10.1021/acs.jafc.1c04259] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
This study aimed to find the best in vitro fermentation method by integrative analysis of the gut microbiota and metabolome. We selected five different media: brain heart infusion broth, Luria-Bertani broth, Mueller-Hinton broth, anaerobe basal broth, and anaerobic medium base (AMB). After in vitro fermentation, the gut microbiota and metabolites were analyzed at different culture times. The results showed that different culture media have different effects on the bacterial community structure and metabolites. The integrative analysis of gut microbiota and metabolism also proved that AMB medium is effective in keeping a stable bacterial community structure and producing less metabolites and short-chain fatty acids by simulating the nutrient-poor microenvironment in the human gut during in vitro fermentation. Thus, culturing with AMB medium for 48 h is the most suitable in vitro model for human gut microbiota fermentation, which provides an alternative approach for diet and health research.
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Affiliation(s)
- Chu Wan
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Kaizhang Wu
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Xingyu Lu
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Fang Fang
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Yaqian Li
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Yumin Zhao
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Shubo Li
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Jie Gao
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
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Ullah H, Ahmad S, Khan F, Taha M, Rahim F, Sarfraz M, Aziz A, Wadood A. Synthesis, in-vitro and in-silico studies of triazinoindole bearing bis-Schiff base as β-glucuronidase inhibitors. J Mol Struct 2021. [DOI: 10.1016/j.molstruc.2021.131003] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Habib S, Swaby AM, Gaisawat MB, Kubow S, Agellon LB. A novel, scalable, and modular bioreactor design for dynamic simulation of the digestive tract. Biotechnol Bioeng 2021; 118:4338-4346. [PMID: 34297349 DOI: 10.1002/bit.27902] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 06/01/2021] [Accepted: 07/14/2021] [Indexed: 11/06/2022]
Abstract
In vitro gut model systems permit the growth of gut microbes outside their natural habitat and are essential to the study of gut microbiota. Systems available today are limited by a lack of scalability and flexibility in the mode of operation. Here, we describe the development of a versatile bioreactor module that can be easily adjusted for culture size and capable of sensing and controlling of environmental parameters such as pH control of culture medium, rate of influx and efflux of the culture medium, and aerobic/anaerobic atmosphere. Bioreactor modules can be operated as single units or linked in series to construct a model of a digestive tract with multiple compartments to allow the growth of microbiota in vitro. We tested the growth of synthetic and natural bacterial communities in a multicompartment continuous dynamic culture model simulation of the mammalian gut. The distal compartments of a sterile system inoculated with the synthetic bacterial community at the proximal module attained a stable bacterial density by 24 h, and all the genera present in the inoculum were firmly established in the distal modules simulating the large intestine at 5 days of continuous culture. A natural bacterial community simultaneously inoculated into the distal modules attained a stable bacterial composition at the phylum level by Day 7 of continuous culture. The findings illustrate the utility of the system to culture mixed bacterial communities which can be used to study the collective biological activities of the cultured microbiota in the absence of host influence.
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Affiliation(s)
- Salam Habib
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
| | - Anikka M Swaby
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
| | - Mohd B Gaisawat
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
| | - Stan Kubow
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
| | - Luis B Agellon
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
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Fang CY, Chen JS, Hsu BM, Hussain B, Rathod J, Lee KH. Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers. Microorganisms 2021; 9:microorganisms9081548. [PMID: 34442626 PMCID: PMC8401100 DOI: 10.3390/microorganisms9081548] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 12/12/2022] Open
Abstract
Despite advances in the characterization of colorectal cancer (CRC), it still faces a poor prognosis. There is growing evidence that gut microbiota and their metabolites potentially contribute to the development of CRC. Thus, microbial dysbiosis and their metabolites associated with CRC, based on stool samples, may be used to advantage to provide an excellent opportunity to find possible biomarkers for the screening, early detection, prevention, and treatment of CRC. Using 16S rRNA amplicon sequencing coupled with statistical analysis, this study analyzed the cause–effect shift of the microbial taxa and their metabolites that was associated with the fecal gut microbiota of 17 healthy controls, 21 polyps patients, and 21 cancer patients. The microbial taxonomic shift analysis revealed striking differences among the healthy control, polyps and cancer groups. At the phylum level, Synergistetes was reduced significantly in the polyps group compared to the healthy control and cancer group. Additionally, at the genus level and in association with the cancer group, a total of 12 genera were highly enriched in abundance. In contrast, only Oscillosprira was significantly higher in abundance in the healthy control group. Comparisons of the polyps and cancer groups showed a total of 18 significantly enriched genera. Among them, 78% of the genera associated with the cancer group were in higher abundance, whereas the remaining genera showed a higher abundance in the polyps group. Additionally, the comparison of healthy control and polyp groups showed six significantly abundant genera. More than 66% of these genera showed a reduced abundance in the polyps group than in healthy controls, whereas the remaining genera were highly abundant in the polyps group. Based on tumor presence and absence, the abundance of Olsenella and Lactobacillus at the genus level was significantly reduced in the patient group compared to healthy controls. The significant microbial function prediction revealed an increase in the abundance of metabolites in the polyps and cancer groups compared to healthy controls. A correlation analysis revealed a higher contribution of Dorea in the predicted functions. This study showed dysbiosis of gut microbiota at the taxonomic level and their metabolic functions among healthy subjects and in two stages of colorectal cancer, including adenoma and adenocarcinoma, which might serve as potential biomarkers for the early diagnosis and treatment of CRC.
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Affiliation(s)
- Chuan-Yin Fang
- Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 621, Taiwan;
| | - Jung-Sheng Chen
- Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan;
| | - Bing-Mu Hsu
- Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi 621, Taiwan;
- Center for Innovative on Aging Society (CIRAS), National Chung Cheng University, Chiayi 621, Taiwan
- Correspondence: ; Tel.: +886-52720411 (ext. 66218)
| | - Bashir Hussain
- Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi 621, Taiwan;
- Department of Biomedical Sciences, National Chung Cheng University, Chiayi 621, Taiwan
| | - Jagat Rathod
- Department of Earth Sciences, National Cheng Kung University, Tainan 701, Taiwan;
| | - Kuo-Hsin Lee
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan;
- School of Medicine, I-Shou University, Kaohsiung 824, Taiwan
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Chang VC, Cotterchio M, De P, Tinmouth J. Risk factors for early-onset colorectal cancer: a population-based case-control study in Ontario, Canada. Cancer Causes Control 2021; 32:1063-1083. [PMID: 34120288 PMCID: PMC8416813 DOI: 10.1007/s10552-021-01456-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 05/30/2021] [Indexed: 02/06/2023]
Abstract
Purpose There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC). Methods A population-based case–control study was conducted in Ontario, Canada during 2018–2019. EO-CRC cases aged 20–49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47–3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02–3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57–5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01–3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31–0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39–0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11–0.76) were each associated with a reduced risk. Conclusion Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons. Supplementary Information The online version contains supplementary material available at 10.1007/s10552-021-01456-8.
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Affiliation(s)
- Vicky C Chang
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada.
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
| | - Michelle Cotterchio
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Prithwish De
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
| | - Jill Tinmouth
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
- Department of Medicine, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
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Kim J, Lee HK. The Role of Gut Microbiota in Modulating Tumor Growth and Anticancer Agent Efficacy. Mol Cells 2021; 44:356-362. [PMID: 33972463 PMCID: PMC8175145 DOI: 10.14348/molcells.2021.0032] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/19/2021] [Accepted: 03/20/2021] [Indexed: 02/08/2023] Open
Abstract
An increasing number of studies have revealed an interaction between gut microbiota and tumors. The enrichment of specific bacteria strains in the intestines has been found to modulate tumor growth and influence the mechanisms of tumor treatment. Various bacteria are involved in modulating the effects of chemotherapeutic drugs currently used to treat patients with cancer, and they affect not only gastrointestinal tract tumors but also distant organ tumors. In addition, changes in the gut microbiota are known to be involved in the antitumor immune response as well as the modulation of the intestinal immune system. As a result, the gut microbiota plays an important role in modulating the efficacy of immune checkpoint inhibitors. Therefore, gut microbiota could be considered as an adjuvant treatment option with other cancer treatment or as another marker for predicting treatment response. In this review, we examine how gut microbiota affects cancer treatments.
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Affiliation(s)
- Jaeho Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
| | - Heung Kyu Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
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Shen W, Sun J, Li Z, Yao F, Lin K, Jiao X. Food intake and its effect on the species and abundance of intestinal flora in colorectal cancer and healthy individuals. Korean J Intern Med 2021; 36:568-583. [PMID: 33167104 PMCID: PMC8137414 DOI: 10.3904/kjim.2019.373] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 07/01/2019] [Accepted: 07/05/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIM It is known that an imbalance in the intestinal f lora plays a crucial role in colorectal cancer (CRC), but the effect of food consumption patterns on the types of intestinal flora remains to be clarified. We aimed to analyze the associations between food intake and intestinal flora in healthy and CRC individuals. METHODS Food intake data were recorded using the Food Frequency Questionnaire (FFQ). The composition and diversity of the intestinal flora detected by 16S rRNA gene sequencing, and the data were analyzed by R version 3.1.1 software. RESULTS Higher intake of red meat or pickled foods, and lower intake of white meat, fruits, vegetables, beans, nuts were found in the CRC group compared with the healthy group. Higher levels of Fusobacteria and Proteobacteria, and lower levels of Firmicutes were observed in the CRC group. Partial correlation analysis revealed that the intake of fruits, beans, and nuts was negatively correlated with Proteobacteria and Fusobacteria, but pickled food was positively correlated with Fusobacteria (p < 0.05). Fish, beans, and nuts intake was negatively correlated with Escherichia (p = 0.01). Multiple regression analysis revealed that vegetable oil (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.13 to 0.82), vegetables (OR, 0.26; 95% CI, 0.10 to 0.64), eggs (OR, 0.26; 95% CI, 0.10 to 0.69), pickled foods (OR, 21.02; 95% CI, 6.02 to 73.45), and red meat (OR, 4.23; 95% CI, 1.68 to 10.60) had an impact on CRC risk. CONCLUSION The species and abundance of intestinal flora varies between CRC and healthy individuals and may be affected by their food preference.
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Affiliation(s)
- Weitao Shen
- The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Jiayu Sun
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, China
| | - Zhiyang Li
- The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Fen Yao
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, China
| | - Kaihuang Lin
- The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Xiaoyang Jiao
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, China
- Correspondence to Xiaoyang Jiao, Ph.D. Department of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Rd, 515041, Guangdong, China Tel +86-754-88900497 Fax: +86-754-88900410 E-mail:
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Raheem A, Liang L, Zhang G, Cui S. Modulatory Effects of Probiotics During Pathogenic Infections With Emphasis on Immune Regulation. Front Immunol 2021; 12:616713. [PMID: 33897683 PMCID: PMC8060567 DOI: 10.3389/fimmu.2021.616713] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 02/12/2021] [Indexed: 12/11/2022] Open
Abstract
In order to inhibit pathogenic complications and to enhance animal and poultry growth, antibiotics have been extensively used for many years. Antibiotics applications not only affect target pathogens but also intestinal beneficially microbes, inducing long-lasting changes in intestinal microbiota associated with diseases. The application of antibiotics also has many other side effects like, intestinal barrier dysfunction, antibiotics residues in foodstuffs, nephropathy, allergy, bone marrow toxicity, mutagenicity, reproductive disorders, hepatotoxicity carcinogenicity, and antibiotic-resistant bacteria, which greatly compromise the efficacy of antibiotics. Thus, the development of new antibiotics is necessary, while the search for antibiotic alternatives continues. Probiotics are considered the ideal antibiotic substitute; in recent years, probiotic research concerning their application during pathogenic infections in humans, aquaculture, poultry, and livestock industry, with emphasis on modulating the immune system of the host, has been attracting considerable interest. Hence, the adverse effects of antibiotics and remedial effects of probiotics during infectious diseases have become central points of focus among researchers. Probiotics are live microorganisms, and when given in adequate quantities, confer good health effects to the host through different mechanisms. Among them, the regulation of host immune response during pathogenic infections is one of the most important mechanisms. A number of studies have investigated different aspects of probiotics. In this review, we mainly summarize recent discoveries and discuss two important aspects: (1) the application of probiotics during pathogenic infections; and (2) their modulatory effects on the immune response of the host during infectious and non-infectious diseases.
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Affiliation(s)
- Abdul Raheem
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Lin Liang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Guangzhi Zhang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Shangjin Cui
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
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Zou Y, Xue W, Lin X, Lv M, Luo G, Dai Y, Sun H, Liu SW, Sun CH, Hu T, Xiao L. Butyribacter intestini gen. nov., sp. nov., a butyric acid-producing bacterium of the family Lachnospiraceae isolated from human faeces, and reclassification of Acetivibrio ethanolgignens as Acetanaerobacter ethanolgignens gen. nov., comb. nov. Syst Appl Microbiol 2021; 44:126201. [PMID: 33892267 DOI: 10.1016/j.syapm.2021.126201] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 03/11/2021] [Accepted: 03/18/2021] [Indexed: 12/19/2022]
Abstract
A novel, non-motile, Gram-stain-positive, non-spore-forming, obligate anaerobic bacterium, designated strain TF01-11T, was isolated from human faeces. The isolate was characterized by phylogenetic and phenotypic properties, as well as by determination of its whole genome sequence. The growth temperature and pH ranges were 30-42 °C and 6.0-8.5, respectively. The end products of glucose fermentation were butyric acid and a small amount of acetic acid. The genome was estimated to be 3.61 Mbp with G + C content of 36.8 mol%. Genes related to biosynthesis of diaminopimelic acid, polar lipids, polyamines, teichoic and lipoteichoic acids were present. The predominant fatty acids were C16:0 (37.9%), C14:0 (16.4%), C13:0 OH/iso-C15:1H (11.1%) and C18:1ω9c (10.6%). Phylogenetic analyses based on 16S rRNA gene sequences demonstrated that the isolate was a member of family Lachnospiraceae, with the highest sequence similarity to the type strain of Roseburia intestinalis DSM 14610T (92.2%), followed by Acetivibrio ethanolgignens ATCC 33324T (92.0%). The average nucleotide identity (ANI) and average amino acid identity (AAI) values between strain TF01-11T and these closest relatives were less than 70.5% and 52.3%. Based on results of phenotypic characteristics and genotypic properties presented in this study, strain TF01-11T represents a novel species in a new genus, for which the name Butyribacter intestini gen. nov., sp. nov. is proposed. The type strain of the type species is TF01-11T (CGMCC 1.5203T = DSM 105140T). In addition, Acetivibrio ethanolgignens is proposed to be reclassified as Acetanaerobacter ethanolgignens gen. nov., comb. nov.
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Affiliation(s)
- Yuanqiang Zou
- BGI-Shenzhen, Shenzhen 518083, China; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen, Denmark; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, China; Qingdao-Europe Advanced Institute for Life Sciences, BGI-Shenzhen, Qingdao 266555, China.
| | | | - Xiaoqian Lin
- BGI-Shenzhen, Shenzhen 518083, China; School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, China
| | - Mei Lv
- BGI-Shenzhen, Shenzhen 518083, China
| | | | - Ying Dai
- BGI-Shenzhen, Shenzhen 518083, China
| | | | - Shao-Wei Liu
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Cheng-Hang Sun
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | | | - Liang Xiao
- BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, China; Qingdao-Europe Advanced Institute for Life Sciences, BGI-Shenzhen, Qingdao 266555, China; BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, China.
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43
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Yenuganti VR, Yadala R, Azad R, Singh S, Chiluka V, Ahire J, Reddanna P. In vitro evaluation of anticancer effects of different probiotic strains on HCT-116 cell line. J Appl Microbiol 2021; 131:1958-1969. [PMID: 33694215 DOI: 10.1111/jam.15060] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/11/2021] [Accepted: 03/08/2021] [Indexed: 12/16/2022]
Abstract
AIM Since the evolution of man, microbes are associated with humans, playing a vital role in the maintenance of good health. However, an imbalance in the gut microbial ecosystem is associated with several diseases including colorectal cancer (CRC). The supplementation with probiotics has been proven to be beneficial in improving CRC. In this study, we have evaluated the anticancer effects of 11 probiotic strains on human colorectal carcinoma cell line (HCT-116). METHODS AND RESULTS In this study, HCT-116 cells were treated with various concentrations (0·5, 5, 10, 20 and 200 million CFU per ml) of probiotic strains. The viability was analysed using a MTT assay and IC50 values were determined. Besides this, we evaluated the expression of multiple genes involved in the apoptosis and stress tolerance by real-time PCR. Lactobacillus reuteri (UBLRu-87), Saccharomyces boulardii (Unique-28), Bacillus clausii (UBBC-07), Bacillus coagulans (Unique-IS2), Streptococcus salivarius (UBSS-01), Lactobacillus fermentum (UBLF-31), Lactobacillus salivarius (UBLS-22), Bifidobacterium bifidum (UBBB-55) and Lactobacillus plantarum (UBLP-40) exhibited potent cytotoxicity on HCT 116 cells. Furthermore, UBLF-31 and Unique-28 induced the expression of CJUN, CFOS and CASP-9, and downregulated the expression of BCL6. UBLRu-87 and UBBB-55 induced the expression of CJUN, CFOS and CASP-9 but not BCL-6. UBLP-40, UBBC-07, UBLS-22, and Unique-IS2 induced the expression of CJUN and CASP-9 and downregulated the expression of BCL-6. CONCLUSION These studies indicate the anticancer effects of selected probiotic strains by inducing apoptosis. SIGNIFICANCE AND IMPACT OF THE STUDY The probiotic strains with the anticancer effects identified in this study can be proposed as potential candidates in the treatment of CRCs.
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Affiliation(s)
- V R Yenuganti
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India
| | - R Yadala
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India
| | - R Azad
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India
| | - S Singh
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India
| | - V Chiluka
- Department of Biological Sciences, School of Applied Sciences, Kalinga Institute of Industrial Technology, Bhubaneswar, Odisha, India
| | - J Ahire
- Centre for Research & Development, Unique Biotech Ltd, Hyderabad, Telangana, India
| | - P Reddanna
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India
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Abstract
High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has led to US and international guidelines recommending aspirin for the primary prevention of CRC in specific populations. In this review, we summarize key questions that require addressing prior to broader adoption of aspirin-based chemoprevention, review recent evidence related to the benefits and harms of aspirin use among specific populations, and offer a rationale for precision prevention approaches. We specifically consider the mechanistic implications of evidence showing differences in aspirin's effects according to age, the potential role of modifiable mechanistic biomarkers for personalizing prevention, and emerging evidence that the gut microbiota may offer novel aspirin-associated preventive targets to reduce high-risk neoplasia.
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Affiliation(s)
- David A Drew
- Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA; ,
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA; ,
- Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
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Li X, Huang J, Yu T, Fang X, Lou L, Xin S, Ji L, Jiang F, Lou Y. Fusobacterium nucleatum Promotes the Progression of Colorectal Cancer Through Cdk5-Activated Wnt/β-Catenin Signaling. Front Microbiol 2021; 11:545251. [PMID: 33488528 PMCID: PMC7815597 DOI: 10.3389/fmicb.2020.545251] [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: 05/14/2020] [Accepted: 11/25/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/AIMS Growing evidence supports the direct link of Fusobacterium nucleatum with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of F. nucleatum on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/β-catenin signaling pathway. MATERIALS AND METHODS CRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for in vitro mechanistic investigations. RESULTS The abundance of F. nucleatum was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. In vitro investigations revealed that F. nucleatum significantly enhanced the proliferation and migration of CRC cells. Furthermore, F. nucleatum significantly induced the expression of Cdk5 and activation of the Wnt/β-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of F. nucleatum on cellular processes and Wnt/β-catenin signaling in relation to the progression of CRC. CONCLUSION The results of this study demonstrate that F. nucleatum orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/β-catenin signaling to modulate CRC progression. Thus, in-depth investigations of F. nucleatum-associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.
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Affiliation(s)
- Xiang Li
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Jiepeng Huang
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Tingting Yu
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Xiaoting Fang
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Liqin Lou
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Shijun Xin
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
| | - Ling Ji
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Feizhao Jiang
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yongliang Lou
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
- Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou, China
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Dilek ON, Kar H, Acar T. Prophylactic Appendectomy. PROPHYLACTIC SURGERY 2021:181-191. [DOI: 10.1007/978-3-030-66853-2_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Pitchumoni CS. Colorectal Cancer. GERIATRIC GASTROENTEROLOGY 2021:1963-1989. [DOI: 10.1007/978-3-030-30192-7_80] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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The Role of Probiotics in Cancer Prevention. Cancers (Basel) 2020; 13:cancers13010020. [PMID: 33374549 PMCID: PMC7793079 DOI: 10.3390/cancers13010020] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/17/2020] [Accepted: 12/21/2020] [Indexed: 12/23/2022] Open
Abstract
Simple Summary Cancer is considered one of the leading causes of human mortality in the world and is the subject of much research. The risk of developing cancer depends on genetic factors, as well as the body’s immune status. The intestinal microbiome plays very important role in maintaining homeostasis in the human body. Probiotics have gained increasing medical significance due to the beneficial effect on the human body associated with the prevention and support of the treatment of many chronic diseases, including cancer in the absence of side effects. The aim of this review was to summarize the knowledge about the effect of probiotic microorganisms in the prevention of cancer. There is a lot of evidence that the use of probiotics can play an important role in cancer prevention and support anti-cancer therapies. Abstract The gut microbiome can play important role in maintaining homeostasis in the human body. An imbalance in the gut microbiome can lead to pro-inflammatory immune responses and the initiation of disease processes, including cancer. The research results prove some strains of probiotics by modulating intestinal microbiota and immune response can be used for cancer prevention or/and as adjuvant treatment during anticancer chemotherapy. This review presents the latest advances in research into the effectiveness of probiotics in the prevention and treatment support of cancer. The described issues concern to the anticancer activity of probiotic microorganisms and their metabolites. In addition, we described the potential mechanisms of probiotic chemoprevention and the advisability of using probiotics.
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Heinzinger LR, Johnson A, Wurster JI, Nilson R, Penumutchu S, Belenky P. Oxygen and Metabolism: Digesting Determinants of Antibiotic Susceptibility in the Gut. iScience 2020; 23:101875. [PMID: 33354661 PMCID: PMC7744946 DOI: 10.1016/j.isci.2020.101875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Microbial metabolism is a major determinant of antibiotic susceptibility. Environmental conditions that modify metabolism, notably oxygen availability and redox potential, can directly fine-tune susceptibility to antibiotics. Despite this, relatively few studies have discussed these modifications within the gastrointestinal tract and their implication on in vivo drug activity and the off-target effects of antibiotics in the gut. In this review, we discuss the environmental and biogeographical complexity of the gastrointestinal tract in regard to oxygen availability and redox potential, addressing how the heterogeneity of gut microhabitats may modify antibiotic activity in vivo. We contextualize the current literature surrounding oxygen availability and antibiotic efficacy and discuss empirical treatments. We end by discussing predicted patterns of antibiotic activity in prominent microbiome taxa, given gut heterogeneity, oxygen availability, and polymicrobial interactions. We also propose additional work required to fully elucidate the role of oxygen metabolism on antibiotic susceptibility in the context of the gut.
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Affiliation(s)
- Lauren R. Heinzinger
- Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA
| | - Angus Johnson
- Department of Biological Science, Binghamton University, Binghamton, NY 13902, USA
| | - Jenna I. Wurster
- Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
| | - Rachael Nilson
- Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
| | - Swathi Penumutchu
- Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
| | - Peter Belenky
- Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
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50
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da Silva Duarte V, dos Santos Cruz BC, Tarrah A, Sousa Dias R, de Paula Dias Moreira L, Lemos Junior WJF, Fidélis Silva LC, Rocha Santana G, Licursi de Oliveira L, Gouveia Peluzio MDC, Mantovani HC, Corich V, Giacomini A, de Paula SO. Chemoprevention of DMH-Induced Early Colon Carcinogenesis in Male BALB/c Mice by Administration of Lactobacillus Paracasei DTA81. Microorganisms 2020; 8:microorganisms8121994. [PMID: 33327620 PMCID: PMC7765108 DOI: 10.3390/microorganisms8121994] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/08/2020] [Accepted: 12/09/2020] [Indexed: 12/26/2022] Open
Abstract
We evaluated the effects of the probiotic candidate Lactobacillus paracasei DTA81 (DTA81) on liver oxidative stress, colonic cytokine profile, and gut microbiota in mice with induced early colon carcinogenesis (CRC) by 1,2-dimethylhydrazine (DMH). Animals were divided into four different groups (n = 6) and received the following treatments via orogastric gavage for 8 weeks: Group skim milk (GSM): 300 mg/freeze-dried skim milk/day; Group L. paracasei DTA81 (DTA81): 3 × 109 colony-forming units (CFU)/day; Group Lactobacillus rhamnosus GG (LGG): 3 × 109 CFU/day; Group non-intervention (GNI): 0.1 mL/water/day. A single DMH dose (20 mg/kg body weight) was injected intraperitoneally (i.p), weekly, in all animals (seven applications in total). At the end of the experimental period, DTA81 intake reduced hepatic levels of carbonyl protein and malondialdehyde (MDA). Moreover, low levels of the pro-inflammatory cytokines Interleukin-6 (IL-6) and IL-17, as well as a reduced expression level of the proliferating cell nuclear antigen (PCNA) were observed in colonic homogenates. Lastly, animals who received DTA81 showed an intestinal enrichment of the genus Ruminiclostridium and increased concentrations of caecal acetic acid and total short-chain fatty acids. In conclusion, this study indicates that the administration of the probiotic candidate DTA81 can have beneficial effects on the initial stages of CRC development.
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Affiliation(s)
- Vinícius da Silva Duarte
- Department of Agronomy Food Natural Resources Animals and Environment, University of Padova, Viale dell’Universitá, 16, 35020 Legnaro (PD), Italy; (V.d.S.D.); (A.T.); (L.d.P.D.M.); (V.C.)
- Department of Microbiology, Av. Peter Henry Rolfs, s/n, Campus Universitário, Universidade Federal de Viçosa, 36570-900 Vicosa, Brazil; (L.C.F.S.); (H.C.M.)
| | - Bruna Cristina dos Santos Cruz
- Department of Nutrition and Health, Av. Peter Henry Rolfs, s/n, Campus Universitário, Universidade Federal de Vicosa, 36570-900 Vicosa, Brazil; (B.C.d.S.C.); (M.d.C.G.P.)
| | - Armin Tarrah
- Department of Agronomy Food Natural Resources Animals and Environment, University of Padova, Viale dell’Universitá, 16, 35020 Legnaro (PD), Italy; (V.d.S.D.); (A.T.); (L.d.P.D.M.); (V.C.)
| | - Roberto Sousa Dias
- Department of General Biology, Av. Peter Henry Rolfs, s/n, Campus Universitario, Universidade Federal de Vicosa, 36570-900 Vicosa, Brazil; (R.S.D.); (G.R.S.); (L.L.d.O.)
| | - Luiza de Paula Dias Moreira
- Department of Agronomy Food Natural Resources Animals and Environment, University of Padova, Viale dell’Universitá, 16, 35020 Legnaro (PD), Italy; (V.d.S.D.); (A.T.); (L.d.P.D.M.); (V.C.)
| | | | - Lívia Carneiro Fidélis Silva
- Department of Microbiology, Av. Peter Henry Rolfs, s/n, Campus Universitário, Universidade Federal de Viçosa, 36570-900 Vicosa, Brazil; (L.C.F.S.); (H.C.M.)
| | - Gabriele Rocha Santana
- Department of General Biology, Av. Peter Henry Rolfs, s/n, Campus Universitario, Universidade Federal de Vicosa, 36570-900 Vicosa, Brazil; (R.S.D.); (G.R.S.); (L.L.d.O.)
| | - Leandro Licursi de Oliveira
- Department of General Biology, Av. Peter Henry Rolfs, s/n, Campus Universitario, Universidade Federal de Vicosa, 36570-900 Vicosa, Brazil; (R.S.D.); (G.R.S.); (L.L.d.O.)
| | - Maria do Carmo Gouveia Peluzio
- Department of Nutrition and Health, Av. Peter Henry Rolfs, s/n, Campus Universitário, Universidade Federal de Vicosa, 36570-900 Vicosa, Brazil; (B.C.d.S.C.); (M.d.C.G.P.)
| | - Hilario Cuquetto Mantovani
- Department of Microbiology, Av. Peter Henry Rolfs, s/n, Campus Universitário, Universidade Federal de Viçosa, 36570-900 Vicosa, Brazil; (L.C.F.S.); (H.C.M.)
| | - Viviana Corich
- Department of Agronomy Food Natural Resources Animals and Environment, University of Padova, Viale dell’Universitá, 16, 35020 Legnaro (PD), Italy; (V.d.S.D.); (A.T.); (L.d.P.D.M.); (V.C.)
| | - Alessio Giacomini
- Department of Agronomy Food Natural Resources Animals and Environment, University of Padova, Viale dell’Universitá, 16, 35020 Legnaro (PD), Italy; (V.d.S.D.); (A.T.); (L.d.P.D.M.); (V.C.)
- Correspondence: (A.G.); (S.O.d.P.); Tel.: +39-328-0390077 (A.G.); +55-31-3612-5016 (S.O.d.P.)
| | - Sérgio Oliveira de Paula
- Department of General Biology, Av. Peter Henry Rolfs, s/n, Campus Universitario, Universidade Federal de Vicosa, 36570-900 Vicosa, Brazil; (R.S.D.); (G.R.S.); (L.L.d.O.)
- Correspondence: (A.G.); (S.O.d.P.); Tel.: +39-328-0390077 (A.G.); +55-31-3612-5016 (S.O.d.P.)
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