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Zhong B, Zhao Y, Gao L, Yang G, Gao Y, Li F, Li S. Anticancer Effects of Weizmannia coagulans MZY531 Postbiotics in CT26 Colorectal Tumor-Bearing Mice by Regulating Apoptosis and Autophagy. Life (Basel) 2024; 14:1334. [PMID: 39459634 PMCID: PMC11509727 DOI: 10.3390/life14101334] [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: 09/14/2024] [Revised: 10/08/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024] Open
Abstract
Weizmannia coagulans has been shown to have anticancer properties. However, there is limited research on the effects of postbiotic W. coagulans on colorectal cancer cell proliferation. Additionally, the exact mechanisms through which it influences apoptosis- and autophagy-related signaling pathways are yet to be thoroughly elucidated. This study explored the role of W. coagulans MZY531 as a postbiotic in inhibiting tumor growth by modulating apoptosis and autophagy in tumor cells. During the experimental period in the model group, tumors proliferated, tumor markers increased significantly, and immunofluorescence results showed that caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling were significantly decreased. Conversely, supplementation with W. coagulans MZY531 postbiotics significantly reduced the levels of tumor markers carcinoembryonic antigen, colon cancer antigen, and extracellular protein kinase A and promoted cell apoptosis by increasing the caspase-3-positive count and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in tumor tissue. Mechanistically, W. coagulans MZY531 postbiotics inhibit tumor growth through the modulation of the Bax/Bcl-2/caspase-3 and JAK2/STAT3 apoptosis pathways and PI3K/AKT/mTOR and TGF-β/SMAD4 cell autophagy pathways. W. coagulans MZY531 postbiotics had a more significant effect than that of W. coagulans MZY531 alone. Probiotics are expected to become effective natural functional foods for the treatment of colorectal cancer.
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Affiliation(s)
- Bao Zhong
- Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China; (B.Z.); (Y.Z.); (L.G.); (G.Y.); (Y.G.)
- College of Food Science and Nutritional Engineering, Jilin Agriculture Science and Technology University, Jilin 132101, China;
| | - Yujuan Zhao
- Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China; (B.Z.); (Y.Z.); (L.G.); (G.Y.); (Y.G.)
| | - Lei Gao
- Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China; (B.Z.); (Y.Z.); (L.G.); (G.Y.); (Y.G.)
| | - Ge Yang
- Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China; (B.Z.); (Y.Z.); (L.G.); (G.Y.); (Y.G.)
| | - Yansong Gao
- Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China; (B.Z.); (Y.Z.); (L.G.); (G.Y.); (Y.G.)
| | - Fenglin Li
- College of Food Science and Nutritional Engineering, Jilin Agriculture Science and Technology University, Jilin 132101, China;
| | - Shengyu Li
- Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China; (B.Z.); (Y.Z.); (L.G.); (G.Y.); (Y.G.)
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Zhang H, Fu L, Leiliang X, Qu C, Wu W, Wen R, Huang N, He Q, Cheng Q, Liu G, Cheng Y. Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response. Cancer Commun (Lond) 2024; 44:1130-1167. [PMID: 39087354 PMCID: PMC11483591 DOI: 10.1002/cac2.12597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 06/25/2024] [Accepted: 07/13/2024] [Indexed: 08/02/2024] Open
Abstract
The intratumoral microbiome (TM) refers to the microorganisms in the tumor tissues, including bacteria, fungi, viruses, and so on, and is distinct from the gut microbiome and circulating microbiota. TM is strongly associated with tumorigenesis, progression, metastasis, and response to therapy. This paper highlights the current status of TM. Tract sources, adjacent normal tissue, circulatory system, and concomitant tumor co-metastasis are the main origin of TM. The advanced techniques in TM analysis are comprehensively summarized. Besides, TM is involved in tumor progression through several mechanisms, including DNA damage, activation of oncogenic signaling pathways (phosphoinositide 3-kinase [PI3K], signal transducer and activator of transcription [STAT], WNT/β-catenin, and extracellular regulated protein kinases [ERK]), influence of cytokines and induce inflammatory responses, and interaction with the tumor microenvironment (anti-tumor immunity, pro-tumor immunity, and microbial-derived metabolites). Moreover, promising directions of TM in tumor therapy include immunotherapy, chemotherapy, radiotherapy, the application of probiotics/prebiotics/synbiotics, fecal microbiome transplantation, engineered microbiota, phage therapy, and oncolytic virus therapy. The inherent challenges of clinical application are also summarized. This review provides a comprehensive landscape for analyzing TM, especially the TM-related mechanisms and TM-based treatment in cancer.
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Affiliation(s)
- Hao Zhang
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
| | - Li Fu
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
- Department of GastroenterologyThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
| | - Xinwen Leiliang
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
| | - Chunrun Qu
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanP. R. China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanP. R. China
| | - Wantao Wu
- Department of OncologyXiangya HospitalCentral South UniversityChangshaHunanP. R. China
| | - Rong Wen
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
| | - Ning Huang
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
| | - Qiuguang He
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
| | - Quan Cheng
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanP. R. China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanP. R. China
| | - Guodong Liu
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
| | - Yuan Cheng
- Department of NeurosurgeryThe Second Affiliated HospitalChongqing Medical UniversityChongqingP. R. China
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Wang Y, Meng L, Liu X. Capecitabine-associated gastrointestinal ulceration, haemorrhage, and obstruction: a pharmacovigilance analysis based on the FAERS. Front Pharmacol 2024; 15:1412938. [PMID: 38948471 PMCID: PMC11211585 DOI: 10.3389/fphar.2024.1412938] [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: 04/06/2024] [Accepted: 06/03/2024] [Indexed: 07/02/2024] Open
Abstract
Background Capecitabine has been reported to be associated with severe gastrointestinal (GI) adverse drug reactions (gastrointestinal ulceration, haemorrhage, and obstruction). However, statistical correlations have not been demonstrated, and specific GI adverse drug reactions, such as GI obstruction, are not listed on its label. Aim We aimed to determine the associations between capecitabine and GI ulceration, haemorrhage, or obstruction among patients with breast cancer by examining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods We performed disproportionality analysis of GI ulceration, haemorrhage, and obstruction by evaluating the reporting odds ratio (ROR) and the information component (IC) with their 95% confidence intervals (CIs). Results We identified 279 patients with capecitabine-associated GI ulceration, haemorrhage, or obstruction reported between 1 January 2004 and 31 December 2020. One-fourth of the cases of GI ulceration, haemorrhage, or obstruction resulted in death. Capecitabine as a drug class had disproportionately high reporting rates for GI ulceration [ROR 1.94 (1.71-2.21); IC 0.80 (0.60-0.99)], haemorrhage [ROR 2.27 (1.86-2.76); IC 0.99 (0.69-1.28)], and obstruction [ROR 2.19 (1.63-2.95); IC 0.96 (0.51-1.40)]. Conclusion Pharmacovigilance research on the FAERS has revealed a slight increase in reports of GI ulceration, haemorrhage, and obstruction in capecitabine users, which may cause serious or deadly consequences. In addition to the adverse reactions described in the package insert, close attention should be paid to GI obstruction to avoid discontinuation or life-threatening outcomes.
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Affiliation(s)
- Yuwei Wang
- Department of Radiation Oncology, The Cancer Hospital of Chongqing University, Chongqing, China
| | - Long Meng
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao Liu
- Department of Gastrointestinal Surgery, The Fifth People’s Hospital of Chongqing, Chongqing, China
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Abaturov A, Babуch V. Drug regulation of microRNA. CHILD`S HEALTH 2024; 18:572-583. [DOI: 10.22141/2224-0551.18.8.2023.1657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The scientific review provides the mechanisms of drug regulation of microRNA in the human body. To write the article, information was searched using Scopus, Web of Science, MEDLINE, PubMed, Google Scholar, Embase, Global Health, The Cochrane Library databases. To restore the reduced functional activity of microRNAs, replacement therapy is used, with modified synthetic analogs of endogenous microRNAs, and drugs that enhance the production of the body’s own microRNAs. The authors state that numerous studies have confirmed the effectiveness of miRNA replacement therapy. It is known that there are several groups of drugs among miRNA inhibitors: anti-miRNA oligonucleotides, miRNA traps, miRNA mimics that prevent miRNA binding; peptide nucleic acids, small-molecule inhibitors. The authors suggest that the expression of drug-metabolizing enzymes is controlled by nuclear receptors and transcription factors, epigenetic regulation such as DNA methylation and histone acetylation, and post-translational modification. It is emphasized that ursodeoxycholic acid modulates the expression of some miRNAs. It is known that probiotic bacteria can modulate the expression level of miRNA genes. The use of probiotics is accompanied by a change in the expression of numerous genes of the body involved in the regulation of the inflammatory response, allergic reactions, metabolism and other biological processes. Thus, modern science is intensively studying the potential of using drugs that restore miRNA content or inhibit miRNA activity for the therapy of miRNA-dependent conditions. The results of scientific research confirmed the therapeutic effect of ursodeoxycholic acid and probiotic preparations due to the effect on the activity of miRNA generation in hepatobiliary diseases. Therefore, the introduction into clinical practice of drugs than can modulate the content and expression of specific miRNAs will certainly open new perspectives in the treatment of patients with hepatobiliary diseases.
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Khaleel SM, Shanshal SA, Khalaf MM. The Role of Probiotics in Colorectal Cancer: A Review. J Gastrointest Cancer 2023; 54:1202-1211. [PMID: 36622515 DOI: 10.1007/s12029-022-00903-2] [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: 12/18/2022] [Indexed: 01/10/2023]
Abstract
PURPOSE Globally, cancer is among the principal causes of death, and the incidence of colorectal cancer is increasing annually around the world, and it is currently ranked third most diagnosed cancer type. Despite the development in the treatment procedures for colorectal cancer including chemotherapy, surgery, immunotherapy and radiotherapy, the death rates from this cancer type are still elevated due to the adverse effects associated with treatment that may affect patients' quality of life. Recently, the global interest in probiotics research has grown with significant positive results. METHODS: This review discusses the role of probiotics in normal colorectal physiology and cancer. RESULTS Probiotics will become an essential part in the prevention and management of colorectal cancer in the near future as they are expected to provide a solution to the problems associated with cancer treatment. Probiotics' properties open the way for multiple effective uses in colorectal cancer prevention strategies. Additionally, probiotics can reduce the problems associated with chemotherapy and surgery when used synergistically. Probiotics can also increase the efficacy of chemotherapeutic medications. Targeted drug delivery and TRAIL collaboration techniques are other effective and promising methods that involve probiotics. CONCLUSIONS Probiotics have properties that make them useful in the management and prevention of colorectal cancer and can provide new avenue to reduce the occurrence of this malignancy and enhance the patients' quality of life.
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Affiliation(s)
- Shahad M Khaleel
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Mosul, Mosul, Iraq
| | - Sadeel A Shanshal
- Department of Clinical Pharmacy, College of Pharmacy, University of Mosul, Mosul, Nineveh, Iraq.
| | - Musab M Khalaf
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Mosul, Mosul, Iraq
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Thet D, Areepium N, Siritientong T. Effects of Probiotics on Chemotherapy-induced Diarrhea. Nutr Cancer 2023; 75:1811-1821. [PMID: 37908158 DOI: 10.1080/01635581.2023.2267779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 11/02/2023]
Abstract
Chemotherapy-induced diarrhea (CID) is a common adverse event in cancer patients, which, unless treated, may lead to drug discontinuation and treatment failure. Some probiotics such as Lactobacillus, Bifidobacterium, and Saccharomyces species have been gaining clinical attention in alleviating chemotherapy-induced adverse events including diarrhea. This comprehensive review provides an overview and discusses preventive approaches of probiotics with respect to CID in several types of cancers. The potential mechanisms of probiotics may comprise regulation of intestinal microbiota, modulation of immune functions, or reduction of proinflammatory cytokines. The efficacy and safety precautions of probiotics in immunocompromised cancer patients are discussed. The non-pharmacological strategy using probiotics could reduce the use of anti-diarrheal or antibiotic agents. Some individuals experienced shorter length of hospital stay, better gastrointestinal function, and reduced incidence of chemotherapy dose reduction after probiotic administration. Nonetheless, some studies failed to report the benefits of probiotics in certain patients. This review also highlights preventive protocols and therapeutic implications by considering the potential influencing factors, particularly types of probiotic strains, dosages of probiotics, duration of their administration, patients' tolerability, and variations in probiotic effects over the cancer stages.
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Affiliation(s)
- Daylia Thet
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Nutthada Areepium
- Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Tippawan Siritientong
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
- Metabolomics for Life Sciences Research Unit, Chulalongkorn University, Bangkok, Thailand
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Summer M, Ali S, Fiaz U, Tahir HM, Ijaz M, Mumtaz S, Mushtaq R, Khan R, Shahzad H, Fiaz H. Therapeutic and immunomodulatory role of probiotics in breast cancer: A mechanistic review. Arch Microbiol 2023; 205:296. [PMID: 37486419 DOI: 10.1007/s00203-023-03632-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 07/03/2023] [Accepted: 07/09/2023] [Indexed: 07/25/2023]
Abstract
Breast cancer has become the most prevalent and noxious type of malignancy around the globe (Giaquinto et al., 2022). Multiple clinical strategies including chemotherapy, radiotherapy, and immunotherapy have been in practice to manage breast cancer. Besides the protective roles of conventional remedial approaches, and non-reversible and deteriorative impacts like healthy cell damage, organ failure, etc., the world scientific community is in a continuous struggle to find some alternative biocompatible and comparatively safe solutions. Among novel breast cancer management/treatment options, the role of probiotics has become immensely important. The current review encompasses the prevalence statistics of breast cancer across the globe concerning developed and undeveloped counties, intestinal microbiota linkage with breast cancer, and association of breast microbiome with breast carcinoma. Furthermore, this review also narrates the role of probiotics against breast cancer and their mode of action. In Vivo and In Vitro studies under breast cancer research regarding probiotics are mechanistically explained. The current review systematically explains the immunomodulatory role of probiotics to prevent breast cancer. Last, but not the least, current review concludes the use of probiotics in the treatment of breast cancer through various mechanisms and future recommendations for molecular basis studies.
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Affiliation(s)
- Muhammad Summer
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan
| | - Shaukat Ali
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan.
| | - Umaima Fiaz
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan
| | - Hafiz Muhammad Tahir
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan
| | - Muhammad Ijaz
- Department of Veterinary Medicine, University of Veterinary and Animal Sciences Lahore, Lahore, Pakistan
| | - Shumaila Mumtaz
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan
| | - Rabia Mushtaq
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan
| | - Rida Khan
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan
| | - Hafsa Shahzad
- Department of Zoology, Government College University Lahore, Lahore, 54000, Pakistan
| | - Hashim Fiaz
- Department of Medicine and Surgery, Ammer-ul-din Medical College Lahore, Lahore, Pakistan
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Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol 2023; 14:1133308. [PMID: 36845131 PMCID: PMC9950271 DOI: 10.3389/fimmu.2023.1133308] [Citation(s) in RCA: 108] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 02/02/2023] [Indexed: 02/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the third leading cause of tumor-related mortality worldwide. In recent years, the emergency of immune checkpoint inhibitor (ICI) has revolutionized the management of HCC. Especially, the combination of atezolizumab (anti-PD1) and bevacizumab (anti-VEGF) has been approved by the FDA as the first-line treatment for advanced HCC. Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing to drug resistance and frequent recurrence. The tumor microenvironment (TME) of HCC is a complex and structured mixture characterized by abnormal angiogenesis, chronic inflammation, and dysregulated extracellular matrix (ECM) remodeling, collectively contributing to the immunosuppressive milieu that in turn prompts HCC proliferation, invasion, and metastasis. The tumor microenvironment coexists and interacts with various immune cells to maintain the development of HCC. It is widely accepted that a dysfunctional tumor-immune ecosystem can lead to the failure of immune surveillance. The immunosuppressive TME is an external cause for immune evasion in HCC consisting of 1) immunosuppressive cells; 2) co-inhibitory signals; 3) soluble cytokines and signaling cascades; 4) metabolically hostile tumor microenvironment; 5) the gut microbiota that affects the immune microenvironment. Importantly, the effectiveness of immunotherapy largely depends on the tumor immune microenvironment (TIME). Also, the gut microbiota and metabolism profoundly affect the immune microenvironment. Understanding how TME affects HCC development and progression will contribute to better preventing HCC-specific immune evasion and overcoming resistance to already developed therapies. In this review, we mainly introduce immune evasion of HCC underlying the role of immune microenvironment, describe the dynamic interaction of immune microenvironment with dysfunctional metabolism and the gut microbiome, and propose therapeutic strategies to manipulate the TME in favor of more effective immunotherapy.
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Affiliation(s)
| | | | | | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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The role of microbiota in colorectal cancer. Folia Microbiol (Praha) 2022; 67:683-691. [PMID: 35534716 DOI: 10.1007/s12223-022-00978-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 05/02/2022] [Indexed: 11/04/2022]
Abstract
Cancer is one of the most important causes of death throughout the world, and the mortality rate is increasing significantly due to the aging of the population. One of the most common types of cancer is colorectal cancer (CRC). Human microbial ecosystems use metabolism to make important impacts on the body physiology. An intensive literature review was made to investigate the correlations between human gut microbiota and the incidence of CRC. The results of these studies show that there are differences in the composition of microbiota between CRC patients and normal people and the microorganisms in CRC patients are very different from healthy individuals. Therefore, changes in the microbiome can be used as a biomarker for the early detection of CRC. On the other hand, the intestinal flora is may be act as a powerful weapon against CRC in the future.
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Luo W, Guo S, Zhou Y, Zhao J, Wang M, Sang L, Chang B, Wang B. Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy. Front Microbiol 2022; 13:873160. [PMID: 35572649 PMCID: PMC9092458 DOI: 10.3389/fmicb.2022.873160] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/05/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota is gaining increasing attention, and the concept of the "gut-liver axis" is gradually being recognized. Leaky gut resulting from injury and/or inflammation can cause the translocation of flora to the liver. Microbiota-associated metabolites and components mediate the activation of a series of signalling pathways, thereby playing an important role in the development of hepatocellular carcinoma (HCC). For this reason, targeting the gut microbiota in the diagnosis, prevention, and treatment of HCC holds great promise. In this review, we summarize the gut microbiota and the mechanisms by which it mediates HCC development, and the characteristic alterations in the gut microbiota during HCC pathogenesis. Furthermore, we propose several strategies to target the gut microbiota for the prevention and treatment of HCC, including antibiotics, probiotics, faecal microbiota transplantation, and immunotherapy.
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Affiliation(s)
- Wenyu Luo
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- The Second Clinical College, China Medical University, Shenyang, China
| | - Shiqi Guo
- The Second Clinical College, China Medical University, Shenyang, China
| | - Yang Zhou
- The Second Clinical College, China Medical University, Shenyang, China
| | - Jingwen Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lixuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Bingyuan Wang
- Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
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Antiparasitic Action of Lactobacillus casei ATCC 393 and Lactobacillus paracasei CNCM Strains in CD-1 Mice Experimentally Infected with Trichinella britovi. Pathogens 2022; 11:pathogens11030296. [PMID: 35335620 PMCID: PMC8949586 DOI: 10.3390/pathogens11030296] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 02/17/2022] [Accepted: 02/23/2022] [Indexed: 11/17/2022] Open
Abstract
Nematodes of the genus Trichinella are among the most widespread parasites of domestic and wild omnivores and predatory animals. The present study aimed to evaluate the antiparasitic effect of Lactobacillus casei ATCC 393 (original) and L. paracasei CNCM in CD-1 mice experimentally infected with Trichinella britovi. Four groups of 20 mice (10 females and 10 males/group) were used, with two control (C) groups and two experimental (E) groups, in which each animal received a daily oral dose of 100 µL of 105 CFU/mL probiotics in Ringer’s solution. On day 7, all mice (except the negative control group) were infected orally with Trichinella (100 larvae/animal) as well as the two probiotics. On day 9 post-infection (p.i.), 10 mice/group were euthanized, and the presence of adult parasites in the intestinal content and wall was tested. On day 32 p.i., 10 mice/group were euthanized, then trichinoscopy and artificial digestion were performed to assess the muscle infection with T. britovi. On day 9 p.i., the experimental group pretreated with L. casei ATCC 393 (6.3 ± 3.03) showed a significantly lower number of adult parasites in the intestinal wall compared with the positive control group (24.6 ± 4.78). Additionally, a significantly lower adult parasite count in the intestinal wall was registered in female mice pretreated with L. paracasei CNCM (7.4 ± 4.71) compared to female mice from the positive control (29.0 ± 5.17). No statistically relevant results were obtained concerning the male mice or the data obtained at 32 days p.i., irrespective of mice gender.
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12
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Ojeda-Linares CI, Solís-García IA, Casas A. Constructing Micro-Landscapes: Management and Selection Practices on Microbial Communities in a Traditional Fermented Beverage. Front Ecol Evol 2022. [DOI: 10.3389/fevo.2022.821268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Colonche is a traditional beverage produced in Mexico by the fermentation of fruits of several cacti species. In the Meridional Central Plateau region of Mexico, where this study was conducted, it is mainly produced with fruits of Opuntia streptacantha; there, the producers perform spontaneous fermentation and/or fermentations through inoculums. Several factors can change the microbial community structure and dynamics through the fermentation process, but little attention has been directed to evaluate what type and extent of change the human practices have over the microbial communities. This study aims to assess the microbiota under spontaneous and inoculated fermentation techniques, the microorganisms present in the inoculums and containers, and the changes of microbiota during the process of producing colonche with different techniques. We used next-generation sequencing of the V3-V4 regions of the 16S rRNA gene and the ITS2, to characterize bacterial and fungal diversity associated with the different fermentation techniques. We identified 701 bacterial and 203 fungal amplicon sequence variants (ASVs) belonging to 173 bacterial and 187 fungal genera. The alpha and beta diversity analysis confirmed that both types of fermentation practices displayed differences in richness, diversity, and community structure. Richness of bacteria in spontaneous fermentation (0D = 136 ± 0.433) was higher than in the inoculated samples (0D = 128 ± 0.929), while fungal richness in the inoculated samples (0D = 32 ± 0.539) was higher than in spontaneous samples (0D = 19 ± 0.917). We identified bacterial groups like Lactobacillus, Leuconostoc, Pediococcus and the Saccharomyces yeast shared in ferments managed with different practices; these organisms are commonly related to the quality of the fermentation process. We identified that clay pots, where spontaneous fermentation is carried out, have an outstanding diversity of fungal and bacterial richness involved in fermentation, being valuable reservoirs of microorganisms for future fermentations. The inoculums displayed the lowest richness and diversity of bacterial and fungal communities suggesting unconscious selection on specific microbial consortia. The beta diversity analysis identified an overlap in microbial communities for both types of fermentation practices, which might reflect a shared composition of microorganisms occurring in the Opuntia streptacantha substrate. The variation in the spontaneous bacterial community is consistent with alpha diversity data, while fungal communities showed less differences among treatments, probably due to the high abundance and dominance of Saccharomyces. This information illustrates how traditional management guides selection and may drive changes in the microbial consortia to produce unique fermented beverages through specific fermentation practices. Although further studies are needed to analyze more specifically the advantages of each fermentation type over the quality of the product, our current analysis supports the role of traditional knowledge driving it and the relevance of plans for its conservation.
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Dairy Lactic Acid Bacteria and Their Potential Function in Dietetics: The Food-Gut-Health Axis. Foods 2021; 10:foods10123099. [PMID: 34945650 PMCID: PMC8701325 DOI: 10.3390/foods10123099] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/29/2021] [Accepted: 12/03/2021] [Indexed: 12/23/2022] Open
Abstract
Fermented dairy products are the good source of different species of live lactic acid bacteria (LAB), which are beneficial microbes well characterized for their health-promoting potential. Traditionally, dietary intake of fermented dairy foods has been related to different health-promoting benefits including antimicrobial activity and modulation of the immune system, among others. In recent years, emerging evidence suggests a contribution of dairy LAB in the prophylaxis and therapy of non-communicable diseases. Live bacterial cells or their metabolites can directly impact physiological responses and/or act as signalling molecules mediating more complex communications. This review provides up-to-date knowledge on the interactions between LAB isolated from dairy products (dairy LAB) and human health by discussing the concept of the food–gut-health axis. In particular, some bioactivities and probiotic potentials of dairy LAB have been provided on their involvement in the gut–brain axis and non-communicable diseases mainly focusing on their potential in the treatment of obesity, cardiovascular diseases, diabetes mellitus, inflammatory bowel diseases, and cancer.
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Singh D, Khan MA, Siddique HR. Therapeutic implications of probiotics in microbiota dysbiosis: A special reference to the liver and oral cancers. Life Sci 2021; 285:120008. [PMID: 34606851 DOI: 10.1016/j.lfs.2021.120008] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/20/2021] [Accepted: 09/28/2021] [Indexed: 02/07/2023]
Abstract
The microbiota plays an important role in maintaining the body's homeostasis. Imbalance in the microbiota is referred to as microbiota dysbiosis. Microbiota dysbiosis leads to pro-inflammatory immune response and progression of cancer- one of the leading causes of mortality globally. Accumulating evidence suggest the role of microbiota-dysbiosis in the liver and oral carcinogenesis and the therapeutic role of probiotic strains against these diseases. Probiotics are active microbial strains that have recently gained clinical importance due to their beneficial effects on the human body associated with the prevention and treatment of different diseases, including cancer. Multiple researchers have reported the use of probiotic strains in the modulation of microbiota and immune responses for cancer prevention and management. Clinical trials have also highlighted the efficacy of probiotic strains in reducing the side effects of microbiota dysbiosis related to cancer. In this context, the probiotic-mediated modulation to reverse microbiota dysbiosis is now considered one of the possible novel strategies for cancer prevention and management. In this article, we review the association between microbiota dysbiosis and liver/oral cancer. This review highlights the research advances on the anti-cancer activity of probiotic strains and their metabolites in the management of liver and oral cancers.
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Affiliation(s)
- Deepti Singh
- Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Mohammad Afsar Khan
- Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Hifzur R Siddique
- Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
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15
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Saracino MP, Vila CC, Baldi PC, González Maglio DH. Searching for the one(s): Using Probiotics as Anthelmintic Treatments. Front Pharmacol 2021; 12:714198. [PMID: 34434110 PMCID: PMC8381770 DOI: 10.3389/fphar.2021.714198] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/22/2021] [Indexed: 12/29/2022] Open
Abstract
Helminths are a major health concern as over one billion people are infected worldwide and, despite the multiple efforts made, there is still no effective human vaccine against them. The most important drugs used nowadays to control helminth infections belong to the benzimidazoles, imidazothiazoles (levamisole) and macrocyclic lactones (avermectins and milbemycins) families. However, in the last 20 years, many publications have revealed increasing anthelmintic resistance in livestock which is both an economical and a potential health problem, even though very few have reported similar findings in human populations. To deal with this worrying limitation of anthelmintic drugs, alternative treatments based on plant extracts or probiotics have been developed. Probiotics are defined by the Food and Agriculture Organization as live microorganisms, which, when consumed in adequate amounts, confer a health benefit to the host. It has been proven that probiotic microbes have the ability to exert an immunomodulatory effect both at the mucosa and the systemic level. The immune response against gastrointestinal helminths is characterized as a type 2 response, with high IgE levels, increased numbers and/or activity of Th2 cells, type 2 innate lymphoid cells, eosinophils, basophils, mast cells, and alternatively activated macrophages. The oral administration of probiotics may contribute to controlling gastrointestinal helminth infections since it has been demonstrated that these microorganisms stimulate dendritic cells to elicit a type 2 or regulatory immune response, among other effects on the host immune system. Here we review the current knowledge about the use of probiotic bacteria as anthelmintic therapy or as a complement to traditional anthelmintic treatments. Considering all research papers reviewed, we may conclude that the effect generated by probiotics on helminth infection depends not only on the parasite species, their stage and localization but also on the administration scheme.
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Affiliation(s)
- Maria Priscila Saracino
- Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Cecilia Celeste Vila
- Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Pablo César Baldi
- Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Daniel Horacio González Maglio
- Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
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16
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Temraz S, Nassar F, Kreidieh F, Mukherji D, Shamseddine A, Nasr R. Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome. Int J Mol Sci 2021; 22:ijms22157800. [PMID: 34360566 PMCID: PMC8346024 DOI: 10.3390/ijms22157800] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 06/30/2021] [Accepted: 06/30/2021] [Indexed: 02/06/2023] Open
Abstract
Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.
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Affiliation(s)
- Sally Temraz
- Department of Internal Medicine, Hematology/Oncology Division, American University of Beirut Medical Center, Riad El Solh, Beirut 1107 2020, Lebanon; (F.N.); (F.K.); (D.M.); (A.S.)
- Correspondence: (S.T.); (R.N.)
| | - Farah Nassar
- Department of Internal Medicine, Hematology/Oncology Division, American University of Beirut Medical Center, Riad El Solh, Beirut 1107 2020, Lebanon; (F.N.); (F.K.); (D.M.); (A.S.)
| | - Firas Kreidieh
- Department of Internal Medicine, Hematology/Oncology Division, American University of Beirut Medical Center, Riad El Solh, Beirut 1107 2020, Lebanon; (F.N.); (F.K.); (D.M.); (A.S.)
| | - Deborah Mukherji
- Department of Internal Medicine, Hematology/Oncology Division, American University of Beirut Medical Center, Riad El Solh, Beirut 1107 2020, Lebanon; (F.N.); (F.K.); (D.M.); (A.S.)
| | - Ali Shamseddine
- Department of Internal Medicine, Hematology/Oncology Division, American University of Beirut Medical Center, Riad El Solh, Beirut 1107 2020, Lebanon; (F.N.); (F.K.); (D.M.); (A.S.)
| | - Rihab Nasr
- Department of Anatomy, Cell Biology and Physiology, American University of Beirut Medical Center, Riad El Solh, Beirut 1107 2020, Lebanon
- Correspondence: (S.T.); (R.N.)
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17
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Tang G, Zhang L. Update on Strategies of Probiotics for the Prevention and Treatment of Colorectal Cancer. Nutr Cancer 2020; 74:27-38. [PMID: 33356609 DOI: 10.1080/01635581.2020.1865420] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In recent years, with the further research on probiotics, probiotics may become an indispensable part in the prevention and treatment of colorectal cancer (CRC) in the future. As one of the most common cancer, the incidence of CRC is still rising in developing countries. Nowadays, there are lacking in prevention methods with low side effect. Surgery and chemotherapy, as the main treatment of CRC, bring many complications and affect the quality of life of patients. Probiotics has provided new ideas to solve these problems. Probiotics have anti-inflammatory, immune-enhancing, tumor-suppressing and other beneficial effects. Probiotics may provide some safe and effective prevention strategies for CRC. In addition, probiotics can also reduce the complications of surgery and chemotherapy, and improve the effectiveness of chemotherapy. Target administration with probiotics or probiotics cooperated with TRAIL to treat CRC. This article aims to review the mechanisms of probiotics for the prevention and treatment of CRC, as well as specific ways to use probiotics, in order to provide more new strategies for the prevention and treatment of CRC in the future, and reduce the incidence of and improve the quality of life of patients.
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Affiliation(s)
- Gang Tang
- Department of Clinical Medicine, Chongqing Medical University, Chongqing, China
| | - Linyu Zhang
- Department of Clinical Medicine, Chongqing Medical University, Chongqing, China
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18
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Yu Q, Wu L, Ji J, Feng J, Dai W, Li J, Wu J, Guo C. Gut Microbiota, Peroxisome Proliferator-Activated Receptors, and Hepatocellular Carcinoma. J Hepatocell Carcinoma 2020; 7:271-288. [PMID: 33150145 PMCID: PMC7605923 DOI: 10.2147/jhc.s277870] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 10/10/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. HCC incidence rate is sixth and mortality is fourth worldwide. However, HCC pathogenesis and molecular mechanisms remain unclear. The incidence of HCC is associated with genetic, environmental, and metabolic factors. The role of gut microbiota in the pathogenesis of HCC has attracted researchers' attention because of anatomical and functional interactions between liver and intestine. Studies have demonstrated the involvement of gut microbiota in the development of HCC and chronic liver diseases, such as alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and liver cirrhosis. Peroxisome proliferator-activated receptors (PPARs) are a group of receptors with diverse biological functions. Natural and synthetic PPAR agonists show potential for treatment of NAFLD, liver fibrosis, and HCC. Recent studies have demonstrated that PPARs take part in gut microbiota inhabitation and adaptation. This manuscript reviews the role of gut microbiota in the development of HCC and precancerous diseases, the role of PPARs in modulation of gut microbiota and HCC, and potential of gut microbiota for HCC diagnosis and treatment.
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Affiliation(s)
- Qiang Yu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University School of Medicine, Shanghai200060, People’s Republic of China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai200072, People’s Republic of China
| | - Liwei Wu
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai200072, People’s Republic of China
| | - Jie Ji
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai200072, People’s Republic of China
| | - Jiao Feng
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai200072, People’s Republic of China
| | - Weiqi Dai
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University School of Medicine, Shanghai200060, People’s Republic of China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai200072, People’s Republic of China
- Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai200336, People’s Republic of China
| | - Jingjing Li
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University School of Medicine, Shanghai200060, People’s Republic of China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai200072, People’s Republic of China
| | - Jianye Wu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University School of Medicine, Shanghai200060, People’s Republic of China
| | - Chuanyong Guo
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University School of Medicine, Shanghai200060, People’s Republic of China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai200072, People’s Republic of China
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Zhou A, Tang L, Zeng S, Lei Y, Yang S, Tang B. Gut microbiota: A new piece in understanding hepatocarcinogenesis. Cancer Lett 2020; 474:15-22. [PMID: 31917160 DOI: 10.1016/j.canlet.2020.01.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/18/2019] [Accepted: 01/03/2020] [Indexed: 02/07/2023]
Abstract
The gut microbiota forms a symbiotic relationship with the host and benefits the body in many critical aspects of life. However, immune system defects, alterations in the gut microbiota and environmental changes can destroy this symbiotic relationship and may lead to diseases, including cancer. Due to the anatomic and functional connection of the gut and liver, increasing studies show the important role of the gut microbiota in the carcinogenesis of hepatocellular carcinoma (HCC). In this manuscript, we review the available evidence and analyze some potential mechanisms of the gut microbiota, including bacterial dysbiosis, lipopolysaccharide (LPS), and genotoxins, in the progression and promotion of HCC. Furthermore, we discuss the possible therapeutic applications of probiotics, chemotherapy modulation, immunotherapy, targeted drugs and fecal microbiota transplantation (FMT) in targeting the gut microbiota.
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Affiliation(s)
- An Zhou
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Li Tang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Shuo Zeng
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Yuanyuan Lei
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
| | - Bo Tang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
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20
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Bohlul E, Hasanlou F, Taromchi AH, Nadri S. TRAIL-expressing recombinant Lactococcus lactis induces apoptosis in human colon adenocarcinoma SW480 and HCT116 cells. J Appl Microbiol 2019; 126:1558-1567. [PMID: 30815963 DOI: 10.1111/jam.14237] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 01/31/2019] [Accepted: 02/22/2019] [Indexed: 12/21/2022]
Abstract
AIMS We investigated the ability of Lactococcus lactis, a species generally regarded as safe, to express tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) protein. The expressed protein was either cell wall anchored or secreted, and it was assessed whether this could induce apoptosis in human colon adenocarcinoma cell lines SW480 and HCT116. METHODS AND RESULTS Constructs were designed to produce either secreted or cell wall-anchored forms of human TRAIL cloned into pNZ7021 expression vector. The expression by L. lactis was confirmed by Western blotting and immunofluorescence. Induction of cell death was evaluated by coculturing transformants producing either form of TRAIL protein with the two cell lines followed by MTT assay. Gene expression of apoptosis genes, Bax and Bcl2, was assessed by qPCR. The viability of SW480 and HCT116 cells treated with recombinant L. lactis was significantly reduced. A significant change was observed in the ratio of Bax/Bcl2 expression in HCT116 cells only following treatment with the supernatant of recombinant L. lactis containing secreted TRAIL. CONCLUSION Recombinant L. lactis producing TRAIL protein can induce apoptosis in human colon adenocarcinoma cell lines SW480 and HCT116. SIGNIFICANCE AND IMPACT OF THE STUDY The use of recombinant probiotics that produce anticancer compounds is a promising option for combating cancer cells.
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Affiliation(s)
- E Bohlul
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - F Hasanlou
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - A H Taromchi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.,Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - S Nadri
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.,Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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21
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Yu L, Liu L, Wang F, Zhou F, Xiang Y, Huang S, Yin G, Zhuo Y, Ma Z, Zhang Q, Yu Z. Higher frequency of dairy intake is associated with a reduced risk of breast cancer: Results from a case-control study in Northern and Eastern China. Oncol Lett 2019; 17:2737-2744. [PMID: 30854047 PMCID: PMC6365923 DOI: 10.3892/ol.2019.9898] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Accepted: 12/31/2018] [Indexed: 11/24/2022] Open
Abstract
The association between dairy intake and breast cancer risk has not been well investigated, especially in the Chinese population. This study aimed to examine the association between the weekly frequency of dairy intake and the risk of breast cancer among women in Northern and Eastern China, and to investigate whether the association varied by hormone receptor status. A total of 1,286 cases of breast cancer and 1,461 controls were enrolled in this study. Dairy intake was obtained using a food-frequency questionnaire (FFQ). Frequency of dairy intake per week was divided into four categories (<1 day/week, 1–2 days/week, 3–4 days/week and 5–7 days/week). Unconditional multivariate logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). Stratified analyses were performed by residence, age, and education level. Separate analyses were also conducted for different estrogen receptor (ER) and progesterone receptor (PR) status. This analysis revealed that weekly frequency of dairy intake was strongly inversely associated with breast cancer risk, with an adjusted OR for intake 5–7 days/week of 0.53 (95% CI=0.39–0.72, P<0.001 for trend). In the stratified analyses, women who consumed dairy 5–7 days/week had a lower risk of breast cancer in urban areas (OR=0.45, 95% CI=0.30–0.66, P<0.001 for trend), in the group 45–59 years old (OR=0.39, 95% CI=0.26–0.60, P<0.001 for trend), and in the group educated to senior high school or above (OR=0.39, 95% CI=0.25–0.59, P<0.001 for trend). There was an inverse association between the weekly frequency of dairy intake and the risk of ER+, PR+, and ER+PR+ breast cancer (all P<0.001 for trend). These results indicated that the weekly frequency of dairy intake was inversely associated with the risk of breast cancer among women in Northern and Eastern China.
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Affiliation(s)
- Lixiang Yu
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Liyuan Liu
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Fei Wang
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Fei Zhou
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Yujuan Xiang
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Shuya Huang
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Gengshen Yin
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Yingjie Zhuo
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Zhongbing Ma
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Qiang Zhang
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China
| | - Zhigang Yu
- Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong 250033, P.R. China.,Suzhou Institute, Shandong University, Suzhou, Jiangsu 215123, P.R. China
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De Almeida CV, de Camargo MR, Russo E, Amedei A. Role of diet and gut microbiota on colorectal cancer immunomodulation. World J Gastroenterol 2019; 25:151-162. [PMID: 30670906 PMCID: PMC6337022 DOI: 10.3748/wjg.v25.i2.151] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 12/20/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and it is characterized by genetic and epigenetic alterations, as well as by inflammatory cell infiltration among malignant and stromal cells. However, this dynamic infiltration can be influenced by the microenvironment to promote tumor proliferation, survival and metastasis or cancer inhibition. In particular, the cancer microenvironment metabolites can regulate the inflammatory cells to induce a chronic inflammatory response that can be a predisposing condition for CRC retention. In addition, some nutritional components might contribute to a chronic inflammatory condition by regulating various immune and inflammatory pathways. Besides that, diet strongly modulates the gut microbiota composition, which has a key role in maintaining gut homeostasis and is associated with the modulation of host inflammatory and immune responses. Therefore, diet has a fundamental role in CRC initiation, progression and prevention. In particular, functional foods such as probiotics, prebiotics and symbiotics can have a potentially positive effect on health beyond basic nutrition and have anti-inflammatory effects. In this review, we discuss the influence of diet on gut microbiota composition, focusing on its role on gut inflammation and immunity. Finally, we describe the potential benefits of using probiotics and prebiotics to modulate the host inflammatory response, as well as its application in CRC prevention and treatment.
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Affiliation(s)
| | - Marcela Rodrigues de Camargo
- Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry, São Paulo University, Bauru-Sao Paulo 17012901, Brazil
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50139, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), Florence 50139, Italy
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23
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Van Zyl WF, Deane SM, Dicks LMT. In vivo bioluminescence imaging of the spatial and temporal colonization of lactobacillus plantarum 423 and enterococcus mundtii ST4SA in the intestinal tract of mice. BMC Microbiol 2018; 18:171. [PMID: 30376820 PMCID: PMC6208077 DOI: 10.1186/s12866-018-1315-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 10/14/2018] [Indexed: 12/23/2022] Open
Abstract
Background Lactic acid bacteria (LAB) are major inhabitants and part of the normal microflora of the gastrointestinal tract (GIT) of humans and animals. Despite substantial evidence supporting the beneficial properties of LAB, only a few studies have addressed the migration and colonization of probiotic bacteria in the GIT. The reason for this is mostly due to the limitations, or lack of, efficient reporter systems. Here we describe the development and application of a non-invasive in vivo bioluminescence reporter system to study, in real-time, the spatial and temporal persistence of Lactobacillus plantarum 423 and Enterococcus mundtii ST4SA in the intestinal tract of mice. Results This study reports on the application of the firefly luciferase gene (ffluc) from Photinus pyralis to develop luciferase-expressing L. plantarum 423 and E. mundtii ST4SA, using a Lactococcus lactis NICE system on a high copy number plasmid (pNZ8048) and strong constitutive lactate dehydrogenase gene promoters (Pldh and STldh). The reporter system was used for in vivo and ex vivo monitoring of both probiotic LAB strains in the GIT of mice after single and multiple oral administrations. Enterococcus mundtii ST4SA reached the large intestine 45 min after gavage, while L. plantarum 423 reached the cecum/colon after 90 min. Both strains predominantly colonized the cecum and colon after five consecutive daily administrations. Enterococcus mundtii ST4SA persisted in faeces at higher numbers and for more days compared to L. plantarum 423. Conclusions Our findings demonstrate the efficiency of a high-copy number vector, constitutive promoters and bioluminescence imaging to study the colonization and persistence of L. plantarum 423 and E. mundtii ST4SA in the murine GIT. The system allowed us to differentiate between intestinal transit times of the two strains in the digestive tract. This is the first report of bioluminescence imaging of a luciferase-expressing E. mundtii strain to study colonization dynamics in the murine model. The bioluminescence system developed in this study may be used to study the in vivo colonization dynamics of other probiotic LAB. Electronic supplementary material The online version of this article (10.1186/s12866-018-1315-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Winschau F Van Zyl
- Department of Microbiology, Stellenbosch University, Private Bag X1, Matieland, Stellenbosch, 7600, South Africa
| | - Shelly M Deane
- Department of Microbiology, Stellenbosch University, Private Bag X1, 7 Matieland, Stellenbosch, 7602, South Africa
| | - Leon M T Dicks
- Department of Microbiology, Stellenbosch University, Private Bag X1, 7 Matieland, Stellenbosch, 7602, South Africa.
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El Sheikha AF, Hu DM. Molecular techniques reveal more secrets of fermented foods. Crit Rev Food Sci Nutr 2018; 60:11-32. [DOI: 10.1080/10408398.2018.1506906] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Aly Farag El Sheikha
- Jiangxi Agricultural University, Jiangxi Key Laboratory for Conservation and Utilization of Fungal Resources, Nanchang, China
- McMaster University, Department of Biology, Hamilton, Ontario, Canada
- Minufiya University, Faculty of Agriculture, Department of Food Science and Technology, Shibin El Kom, Minufiya Government, Egypt
| | - Dian-Ming Hu
- Jiangxi Agricultural University, Jiangxi Key Laboratory for Conservation and Utilization of Fungal Resources, Nanchang, China
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Abstract
Hepatocellular carcinoma (HCC), the most common primary liver cancer, is one of the dreaded complications of chronic liver disease. Recent experimental and clinical studies have revealed that the alteration of gut-liver axis plays a pivotal role in the onset of chronic liver diseases, including HCC. Altered gut microbiota and endotoxemia are increasingly recognized as critical components in promoting the progression of chronic liver diseases to HCC. Probiotics have been suggested as a novel, safe and cost-effective approach to prevent or treat HCC. Mechanisms by which probiotics exerts their anti-cancer effects include their ability to bind carcinogens, modulation of gut microbiota, improvement of intestinal barrier function, and immunomodulation. This review summarizes the literature findings of the changes in gut microbiota linked to HCC, and discusses the possible therapeutic implications of probiotics for HCC.
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Affiliation(s)
- Murphy L Y Wan
- School of Biological Sciences, Faculty of Science, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Hani El-Nezami
- School of Biological Sciences, Faculty of Science, The University of Hong Kong, Pokfulam, Hong Kong, China.,Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
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De Moreno De Leblanc A, Chaves S, Perdigón G. Effect of Yoghurt on the Cytokine Profile using a Murine Model of Intestinal Inflammation. EUR J INFLAMM 2017. [DOI: 10.1177/1721727x0900700206] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are important problems in industrialized countries. The complete aetiology of both diseases is still unknown but likely involves genetic, environmental and immunological factors. The aim of this work is to study the anti-inflammatory mechanisms reported for yoghurt in a colon cancer model in order to evaluate its usefulness in the treatment of intestinal inflammation such as Crohn's disease. A trinitrobenzenesulfonic acid (TNBS)-induced colitis model was used. The influence of yoghurt feeding was studied before and after TNBS inoculation. The effect on the intestinal microbiota and on the host immune response was evaluated. IgA-producing cells and cells positive for specific cytokines (IL-12, IL-17, IFNγ and IL-10) were analyzed. Yoghurt administration diminished the severity of inflammation in the TNBS-inoculated mice. This effect occurred mainly through IL-10, which was increased in the intestinal tissues throughout the study, and by the decrease observed in IL-17 and IL-12 levels. In addition to this immunomodulatory capacity, another mechanism by which yoghurt could exert the anti-inflammatory activity observed in our model would be through beneficial changes in the intestinal microbiota (increases in the bifidobacteria and lactobacilli populations). These changes in the intestinal microbiota could also be considered one of the causes of the intestinal inflammation reduction. These results show that yoghurt administration modulated the immune response, inducing down regulation of the inflammatory cytokines produced by the immune cells involved in the inflammatory process. The protective effect
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Affiliation(s)
| | - S. Chaves
- Centro de Referenda para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán
- Cátedra de Inmunología, Facultad de Bioquimíca, Química y Farmacia, Universidad Nacional de Tucumán, Argentina
| | - G. Perdigón
- Centro de Referenda para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán
- Cátedra de Inmunología, Facultad de Bioquimíca, Química y Farmacia, Universidad Nacional de Tucumán, Argentina
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Effects of oral Lactobacillus administration on antioxidant activities and CD4+CD25+forkhead box P3 (FoxP3)+ T cells in NZB/W F1 mice. Br J Nutr 2017; 118:333-342. [PMID: 28901888 DOI: 10.1017/s0007114517002112] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by a dysregulation of the immune system, which causes inflammation responses, excessive oxidative stress and a reduction in the number of cluster of differentiation (CD)4+CD25+forkhead box P3 (FoxP3)+ T cells. Supplementation with certain Lactobacillus strains has been suggested to be beneficial in the comprehensive treatment of SLE. However, little is known about the effect and mechanism of certain Lactobacillus strains on SLE. To investigate the effects of Lactobacillus on SLE, NZB/W F1 mice were orally gavaged with Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263). Supplementation with GMNL-32, GMNL-89 and GMNL-263 significantly increased antioxidant activity, reduced IL-6 and TNF-α levels and significantly decreased the toll-like receptors/myeloid differentiation primary response gene 88 signalling in NZB/W F1 mice. Notably, supplementation with GMNL-263, but not GMNL-32 and GMNL-89, in NZB/W F1 mice significantly increased the differentiation of CD4+CD25+FoxP3+ T cells. These findings reveal beneficial effects of GMNL-32, GMNL-89 and GMNL-263 on NZB/W F1 mice and suggest that these specific Lactobacillus strains can be used as part of a comprehensive treatment of SLE patients.
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Madempudi RS, Kalle AM. Antiproliferative Effects ofBacillus coagulansUnique IS2 in Colon Cancer Cells. Nutr Cancer 2017; 69:1062-1068. [DOI: 10.1080/01635581.2017.1359317] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
| | - Arunasree M. Kalle
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India
- UICC-ACSBI Visiting Scholar, Department of Environmental Health Sciences, Laboratory of Human Environmental Epigenomes, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
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Lactobacillus paracasei GMNL-32, Lactobacillus reuteri GMNL-89 and L. reuteri GMNL-263 ameliorate hepatic injuries in lupus-prone mice. Br J Nutr 2017; 117:1066-1074. [PMID: 28502277 DOI: 10.1017/s0007114517001039] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Probiotics are known to regulate host immunity by interacting with systemic and mucosal immune cells as well as intestinal epithelial cells. Supplementation with certain probiotics has been reported to be effective against various disorders, including immune-related diseases. However, little is known about the effectiveness of Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263) in the management of autoimmune diseases, especially systemic lupus erythematosus (SLE). NZB/W F1 mice, which are a lupus-prone animal model, were orally gavaged with GMNL-32, GMNL-89 or GMNL-263 to investigate the effects of these Lactobacillus strains on liver injuries in NZB/W F1 mice. The results thus obtained reveal that supplementary GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice ameliorates hepatic apoptosis and inflammatory indicators, such as matrix metalloproteinase-9 activity and C-reactive protein and inducible nitric oxide synthase expressions. In addition, supplementation with GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice reduced the expressions of hepatic IL-1β, IL-6 and TNF-α proteins by suppressing the mitogen-activated protein kinase and NF-κB signalling pathways. These findings, presented here for the first time, reveal that GMNL-32, GMNL-89 and GMNL-263 mitigate hepatic inflammation and apoptosis in lupus-prone mice and may support an alternative remedy for liver disorders in cases of SLE.
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Tamang JP, Shin DH, Jung SJ, Chae SW. Functional Properties of Microorganisms in Fermented Foods. Front Microbiol 2016; 7:578. [PMID: 27199913 PMCID: PMC4844621 DOI: 10.3389/fmicb.2016.00578] [Citation(s) in RCA: 244] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Accepted: 04/08/2016] [Indexed: 12/25/2022] Open
Abstract
Fermented foods have unique functional properties imparting some health benefits to consumers due to presence of functional microorganisms, which possess probiotics properties, antimicrobial, antioxidant, peptide production, etc. Health benefits of some global fermented foods are synthesis of nutrients, prevention of cardiovascular disease, prevention of cancer, gastrointestinal disorders, allergic reactions, diabetes, among others. The present paper is aimed to review the information on some functional properties of the microorganisms associated with fermented foods and beverages, and their health-promoting benefits to consumers.
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Affiliation(s)
- Jyoti P. Tamang
- Department of Microbiology, School of Life Sciences, Sikkim UniversityGangtok, India
| | - Dong-Hwa Shin
- Shindonghwa Food Research InstituteJeonju, South Korea
- Clinical Trial Center for Functional Foods, Chonbuk National University HospitalJeonju, South Korea
| | - Su-Jin Jung
- Clinical Trial Center for Functional Foods, Chonbuk National University HospitalJeonju, South Korea
| | - Soo-Wan Chae
- Clinical Trial Center for Functional Foods, Chonbuk National University HospitalJeonju, South Korea
- Division of Pharmacology, Chonbuk National University Medical SchoolJeonju, South Korea
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31
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Antiobesity effect of Pediococcus pentosaceus LP28 on overweight subjects: a randomized, double-blind, placebo-controlled clinical trial. Eur J Clin Nutr 2016; 70:582-7. [PMID: 26956126 DOI: 10.1038/ejcn.2016.17] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 12/06/2015] [Accepted: 12/22/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND/OBJECTIVES The population of the obese is increasing worldwide. Prevention and improvement of obesity are indispensable for decreasing the risk of metabolic disorders. We have recently shown that obesity and fatty liver are reduced by a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28), in high-fat diet-induced obese mice. The aim of the present clinical study is to prove that LP28 is effective for reducing body fat and body weight, as shown in the experiment using mice. SUBJECTS/METHODS The clinical trial was carried out as a double-blind, randomized, placebo-controlled study comprising 62 subjects (20-70 years of age, BMI 25-30 kg/m(2)). These subjects were randomly assigned to three groups that received living LP28, heat-killed LP28 or a placebo powder, administered orally once a day for 12 weeks. RESULTS Heat-killed LP28 reduced BMI (0.45 kg/m(2), 95% CI (0.04, 0.86), P=0.035), body fat percentage (1.11%, (0.39, 1.82), P=0.002), body fat mass (1.17 kg (0.43, 1.92), P=0.004) and waist circumference (2.84 cm (0.74, 4.93), P=0.009) when compared with a placebo group. Fasting plasma glucose, HbA1c, fasting insulin, HOMA-IR and serum lipids levels did not change by either living LP28 or heat-killed LP28 intake. CONCLUSIONS Heat-killed LP28 displays an antiobesity effect that reduces BMI, body fat and waist circumference, suggesting that the plant-derived lactic acid bacterium LP28 would be a promising preventive of metabolic syndrome.
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Abstract
In nutraceutical science, the ingestible live microbes 'probiotics' are regarded for their ability to confer multiplicity of health benefits on the consumers. Wide spectrum impact of these friendly microbes on the host health has been proved very frequently. They have been confirmed to boost immunity, aid in digestion, eliminate pathogens, curb inflammatory bowel diseases, moderate side effects of antibiotic therapy, lower cholesterol and blood glycemic index and produce vitamins. This review, however, focuses on the incipient, but promising area of probiotic diet-based prevention and remedy of cancer. Researchers are in universal agreement with the critical role of probiotics in getting rid of mutagens, delaying the onset of tumors, alleviating the side effects, pepping up chemotherapy, easing the postoperative complications, foiling remission and lifting the spirit of survivors. The key findings in the emerging roles of probiotics in onco-care have been summarized; the biological pathways discussed and anticipated developments in coming times are presented.
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Erdman SE, Poutahidis T. Gut bacteria and cancer. Biochim Biophys Acta Rev Cancer 2015; 1856:86-90. [PMID: 26050963 DOI: 10.1016/j.bbcan.2015.05.007] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 05/24/2015] [Indexed: 02/07/2023]
Abstract
Microbiota on the mucosal surfaces of the gastrointestinal (GI) tract greatly outnumbers the cells in the human body. Effects of antibiotics indicate that GI tract bacteria may be determining the fate of distal cancers. Recent data implicate dysregulated host responses to enteric bacteria leading to cancers in extra-intestinal sites. Together these findings point to novel anti-cancer strategies aimed at promoting GI tract homeostasis.
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Affiliation(s)
- Susan E Erdman
- Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States.
| | - Theofilos Poutahidis
- Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States; Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, 54124, Greece
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34
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Eom JE, Ahn WG, Her S, Moon GS. Construction of bioluminescent Lactobacillus casei CJNU 0588 for murine whole body imaging. Food Sci Biotechnol 2015. [DOI: 10.1007/s10068-015-0077-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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35
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Aragón F, Perdigón G, LeBlanc ADMD. Modification in the diet can induce beneficial effects against breast cancer. World J Clin Oncol 2014; 5:455-464. [PMID: 25114859 PMCID: PMC4127615 DOI: 10.5306/wjco.v5.i3.455] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 05/15/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
The population tends to consume foods that in addition to their nutritional values can offer some benefits to their health. There are many epidemiological evidences and research studies in animal models suggesting that diet plays an important role in breast cancer prevention or progression. This review summarized some of the relevant researches about nutrition and cancer during the last years, especially in breast cancer. The analysis of probiotics and fermented products containing lactic acid bacteria in cancer prevention and/or treatment was especially discussed. It was observed that a balance of fatty acids similar to those of traditional Mediterranean diet, the consumption of fruits and vegetables, dietary fiber intake, vitamin supplementation are, along with the intake of probiotic products, the most extensively studied by the negative association to breast cancer risk. The consumption of probiotics and fermented products containing lactic acid bacteria was associated to reduce breast cancer risk in some epidemiological studies. The use of animal models showed the modulation of the host’s immune response as one of the important effects associated to the benefices observed with most probiotics. However; future assays in human are very important before the medical community can accept the addition of probiotic or fermented milks containing lactic acid bacteria as supplements for cancer patients.
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36
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The immunopotentiating effects of shark-derived protein hydrolysate. Nutrition 2014; 30:706-12. [DOI: 10.1016/j.nut.2013.10.025] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 09/30/2013] [Accepted: 10/24/2013] [Indexed: 11/20/2022]
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Lakritz JR, Poutahidis T, Levkovich T, Varian BJ, Ibrahim YM, Chatzigiagkos A, Mirabal S, Alm EJ, Erdman SE. Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice. Int J Cancer 2014; 135:529-40. [PMID: 24382758 PMCID: PMC4131439 DOI: 10.1002/ijc.28702] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Accepted: 12/23/2013] [Indexed: 12/16/2022]
Abstract
Recent studies suggest health benefits including protection from cancer after eating fermented foods such as probiotic yogurt, though the mechanisms are not well understood. Here we tested mechanistic hypotheses using two different animal models: the first model studied development of mammary cancer when eating a Westernized diet, and the second studied animals with a genetic predilection to breast cancer. For the first model, outbred Swiss mice were fed a Westernized chow putting them at increased risk for development of mammary tumors. In this Westernized diet model, mammary carcinogenesis was inhibited by routine exposure to Lactobacillus reuteri ATCC-PTA-6475 in drinking water. The second model was FVB strain erbB2 (HER2) mutant mice, genetically susceptible to mammary tumors mimicking breast cancers in humans, being fed a regular (non-Westernized) chow diet. We found that oral supplement with these purified lactic acid bacteria alone was sufficient to inhibit features of mammary neoplasia in both models. The protective mechanism was determined to be microbially-triggered CD4+CD25+ lymphocytes. When isolated and transplanted into other subjects, these L. reuteri-stimulated lymphocytes were sufficient to convey transplantable anti-cancer protection in the cell recipient animals. These data demonstrate that host immune responses to environmental microbes significantly impact and inhibit cancer progression in distal tissues such as mammary glands, even in genetically susceptible mice. This leads us to conclude that consuming fermentative microbes such as L. reuteri may offer a tractable public health approach to help counteract the accumulated dietary and genetic carcinogenic events integral in the Westernized diet and lifestyle.
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Affiliation(s)
- Jessica R Lakritz
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
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Bazzan AJ, Newberg AB, Cho WC, Monti DA. Diet and nutrition in cancer survivorship and palliative care. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2013; 2013:917647. [PMID: 24288570 PMCID: PMC3832963 DOI: 10.1155/2013/917647] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/06/2013] [Revised: 09/07/2013] [Accepted: 09/18/2013] [Indexed: 02/07/2023]
Abstract
The primary goal of palliative cancer care is typically to relieve suffering and improve quality of life. Most approaches to diet in this setting have focused only on eating as many calories as possible to avoid cachexia. However, as the concept of palliative care has evolved to include all aspects of cancer survivorship and not just end of life care, there is an increasing need to thoughtfully consider diet and nutrition approaches that can impact not only quality of life but overall health outcomes and perhaps even positively affect cancer recurrence and progression. In this regard, there has been a recent emphasis in the literature on nutrition and cancer as an important factor in both quality of life and in the pathophysiology of cancer. Hence, the primary purpose of this paper is to review the current data on diet and nutrition as it pertains to a wide range of cancer patients in the palliative care setting.
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Affiliation(s)
- Anthony J. Bazzan
- Myrna Brind Center of Integrative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Andrew B. Newberg
- Myrna Brind Center of Integrative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
| | - Daniel A. Monti
- Myrna Brind Center of Integrative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Park JE, Oh SH, Cha YS. Lactobacillus plantarum LG42 isolated from gajami sik-hae decreases body and fat pad weights in diet-induced obese mice. J Appl Microbiol 2013; 116:145-56. [PMID: 24131682 DOI: 10.1111/jam.12354] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Revised: 09/10/2013] [Accepted: 09/15/2013] [Indexed: 12/24/2022]
Abstract
AIMS This study investigated the antiobesity effect of lactic acid bacteria (Lactobacillus plantarum LG42) isolated from gajami sik-hae. METHODS AND RESULTS Male C57BL/6J mice were divided into four groups (n = 10); NDC (normal diet & DW), HDC (high-fat diet & DW), LGLAB (high-fat diet & Lactobacillus plantarum LG42, 1 × 10(7) CFU per mouse), HGLAB (high-fat diet & L. plantarum LG42, 1 × 10(9) CFU per mouse). After 12 weeks, GLAB supplemented groups showed lower body weight, with a significant reduction in epididymal and back fat. Serum and hepatic triglyceride, serum insulin and leptin levels were significantly lowered in GLAB supplemented groups. The hepatic mRNA expression of PPARα and CPT-I were significantly increased in GLAB groups, whereas the level of ACC, SREBP-1 and LXRα were significantly decreased in GLAB groups compared with HDC group. Additionally, GLAB reduces the expression of PPARγ in the epididymal adipose tissue resulting in inhibition of genes regulated by PPARγ. CONCLUSION These results suggest that the Lactobacillus plantarum LG42 has antiobesity effects in high-fat-diet-induced obese mice. SIGNIFICANCE AND IMPACT OF THE STUDY These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.
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Affiliation(s)
- J-E Park
- Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, Korea; Jeonju Makgeolli Research Center, Chonbuk National University, Jeonju, Korea
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Oral Lactobacillus reuteri GMN-32 treatment reduces blood glucose concentrations and promotes cardiac function in rats with streptozotocin-induced diabetes mellitus. Br J Nutr 2013; 111:598-605. [PMID: 24001238 DOI: 10.1017/s0007114513002791] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 10⁷ colony-forming units (cfu)/d) and 3040 mg/l (with 10⁹ cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats.
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Bhat AR, Irorere VU, Bartlett T, Hill D, Kedia G, Morris MR, Charalampopoulos D, Radecka I. Bacillus subtilis natto: a non-toxic source of poly-γ-glutamic acid that could be used as a cryoprotectant for probiotic bacteria. AMB Express 2013; 3:36. [PMID: 23829836 PMCID: PMC3720193 DOI: 10.1186/2191-0855-3-36] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Accepted: 07/03/2013] [Indexed: 11/19/2022] Open
Abstract
It is common practice to freeze dry probiotic bacteria to improve their shelf life. However, the freeze drying process itself can be detrimental to their viability. The viability of probiotics could be maintained if they are administered within a microbially produced biodegradable polymer - poly-γ-glutamic acid (γ-PGA) - matrix. Although the antifreeze activity of γ-PGA is well known, it has not been used for maintaining the viability of probiotic bacteria during freeze drying. The aim of this study was to test the effect of γ-PGA (produced by B. subtilis natto ATCC 15245) on the viability of probiotic bacteria during freeze drying and to test the toxigenic potential of B. subtilis natto. 10% γ-PGA was found to protect Lactobacillus paracasei significantly better than 10% sucrose, whereas it showed comparable cryoprotectant activity to sucrose when it was used to protect Bifidobacterium breve and Bifidobacterium longum. Although γ-PGA is known to be non-toxic, it is crucial to ascertain the toxigenic potential of its source, B. subtilis natto. Presence of six genes that are known to encode for toxins were investigated: three component hemolysin (hbl D/A), three component non-haemolytic enterotoxin (nheB), B. cereus enterotoxin T (bceT), enterotoxin FM (entFM), sphingomyelinase (sph) and phosphatidylcholine-specific phospholipase (piplc). From our investigations, none of these six genes were present in B. subtilis natto. Moreover, haemolytic and lecithinase activities were found to be absent. Our work contributes a biodegradable polymer from a non-toxic source for the cryoprotection of probiotic bacteria, thus improving their survival during the manufacturing process.
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Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology. Nutrients 2013; 5:1869-912. [PMID: 23760057 PMCID: PMC3725482 DOI: 10.3390/nu5061869] [Citation(s) in RCA: 313] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 05/08/2013] [Accepted: 05/09/2013] [Indexed: 12/13/2022] Open
Abstract
Probiotics are beneficial microbes that confer a realistic health benefit on the host, which in combination with prebiotics, (indigestible dietary fibre/carbohydrate), also confer a health benefit on the host via products resulting from anaerobic fermentation. There is a growing body of evidence documenting the immune-modulatory ability of probiotic bacteria, it is therefore reasonable to suggest that this is potentiated via a combination of prebiotics and probiotics as a symbiotic mix. The need for probiotic formulations has been appreciated for the health benefits in "topping up your good bacteria" or indeed in an attempt to normalise the dysbiotic microbiota associated with immunopathology. This review will focus on the immunomodulatory role of probiotics and prebiotics on the cells, molecules and immune responses in the gut mucosae, from epithelial barrier to priming of adaptive responses by antigen presenting cells: immune fate decision-tolerance or activation? Modulation of normal homeostatic mechanisms, coupled with findings from probiotic and prebiotic delivery in pathological studies, will highlight the role for these xenobiotics in dysbiosis associated with immunopathology in the context of inflammatory bowel disease, colorectal cancer and hypersensitivity.
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Kumar M, Nagpal R, Verma V, Kumar A, Kaur N, Hemalatha R, Gautam SK, Singh B. Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr Rev 2012; 71:23-34. [PMID: 23282249 DOI: 10.1111/j.1753-4887.2012.00542.x] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Dietary interventions for preventing colon cancer have recently attracted increased attention from researchers and clinicians. The probiotics have emerged as potential therapeutic agents but are also regarded as healthy dietary supplements for nutrition and health applications. The probiotic metabolome may interfere with various cellular and molecular processes, including the onset and progression of colon cancer. Probiotic metabolites may lead to the modulation of diverse cellular signal transduction and metabolic pathways. The gut microbial metabolites (organic acids, bacteriocins, peptides, etc.) have been noted to interact with multiple key targets in various metabolic pathways that regulate cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis, and metastasis. Progress in this field suggests that epigenetic alterations will be widely used in the near future to manage colon cancer. The present review provides insights into the molecular basis of the therapeutic applications and the chemopreventive activities of certain probiotic metabolites, with emphasis on the interaction between these metabolites and the molecular signaling cascades that are considered to be epigenetic targets in preventing colon cancer.
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Affiliation(s)
- Manoj Kumar
- Department of Microbiology and Immunology, National Institute of Nutrition, Hyderabad, India.
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Rupa P, Mine Y. Recent advances in the role of probiotics in human inflammation and gut health. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:8249-8256. [PMID: 22897745 DOI: 10.1021/jf301903t] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
The gastrointestinal (GI) tract provides residence to an astounding number of bacterial species, which have profound effects on host biology, function, physiology, and immune response. Discovery of "symbiosis factors" from symbionts that facilitate the peaceful coexistence of microbiota and the host immune system are of interest. Symbionts synthesize immunomodulatory molecules that guide maturation of the immune system and have pivotal roles in many biological processes; however, individuals differ in the makeup of their GI microbiota, which is influenced by many external and internal factors such as diet, antibiotic use, and host genetics, which in turn influences health and disease outcomes. Various endogenous, genetic, and environmental factors influence GI development including species composition and health status of neonates, resulting in interactions that occur between the bacteria and the host. Mechanisms of probiotics involved in homeostasis of a balanced immune system have been inconclusive. The probable mechanism of action may be postulated as direct competition between pathogenic bacteria in the gut and/or immune modulation. This review focuses on probiotics in health and disease prevention, especially the biological importance of intestinal regulation of inflammatory processes that may be beneficial in a multitude of disorders both inside and outside the GI tract.
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Affiliation(s)
- Prithy Rupa
- Department of Food Science, University of Guelph , Guelph, Ontario, Canada N1G 2W1
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Espeche Turbay MB, de Moreno de LeBlanc A, Perdigón G, Savoy de Giori G, Hebert EM. β-Casein hydrolysate generated by the cell envelope-associated proteinase of Lactobacillus delbrueckii ssp. lactis CRL 581 protects against trinitrobenzene sulfonic acid-induced colitis in mice. J Dairy Sci 2012; 95:1108-18. [PMID: 22365194 DOI: 10.3168/jds.2011-4735] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2011] [Accepted: 09/17/2011] [Indexed: 11/19/2022]
Abstract
Lactobacillus delbrueckii ssp. lactis CRL 581, a thermophilic lactic acid bacterium used as a starter culture for the manufacture of several fermented dairy products, possesses an efficient proteolytic system that is able to release a series of potentially bioactive peptides (i.e., antihypertensive and phosphopeptides) from α- and β-caseins. Considering the potential beneficial health effects of the peptides released by L. delbrueckii ssp. lactis CRL 581 from milk proteins, the aim of this work was to analyze the anti-mutagenic and anti-inflammatory properties of the casein hydrolysates generated by the cell envelope-associated proteinase of this bacterium. The ability of α- and β-casein hydrolysates to suppress the mutagenesis of a direct-acting mutagen 4-nitroquinoline-N-oxide on Salmonella typhimurium TA 98 and TA 100 increased concomitantly with the time of casein hydrolysis. The anti-inflammatory effect of the β-casein hydrolysate was evaluated using a trinitrobenzene sulfonic acid (TNBS)-induced Crohn's disease murine model. The hydrolysate was administered to mice 10 d before the intrarectal inoculation of TNBS. The mice that received β-casein hydrolysate previously to TNBS showed decreased mortality rates, faster recovery of initial body weight loss, less microbial translocation to the liver, decreased β-glucuronidase and myeloperoxidase activities in the gut, and decreased colonic macroscopic and microscopic damage compared with the animals that did not receive this hydrolysate. In addition, β-casein hydrolysate exerted a beneficial effect on acute intestinal inflammation by increased interleukin 10 and decreased IFN-γ production in the gut. Our findings are consistent with the health-promoting attributes of the milk products fermented by L. delbrueckii ssp. lactis CRL 581 and open up new opportunities for developing novel functional foods.
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Affiliation(s)
- M B Espeche Turbay
- Centro de Referencia para Lactobacilos-Consejo Nacional de Investigaciones Científicas y Técnicas, Chacabuco 145, 4000 San Miguel de Tucumán, Argentina
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Zhao X, Higashikawa F, Noda M, Kawamura Y, Matoba Y, Kumagai T, Sugiyama M. The obesity and fatty liver are reduced by plant-derived Pediococcus pentosaceus LP28 in high fat diet-induced obese mice. PLoS One 2012; 7:e30696. [PMID: 22363472 PMCID: PMC3281851 DOI: 10.1371/journal.pone.0030696] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Accepted: 12/24/2011] [Indexed: 12/24/2022] Open
Abstract
We evaluated the effect of an oral administration of a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28), on metabolic syndrome by using high fat diet-induced obese mice. The obese mice were divided into 2 groups and fed either a high fat or regular diet for 8 weeks. Each group was further divided into 3 groups, which took LP28, another plant-derived Lactobacillus plantarum SN13T (SN13T) or no lactic acid bacteria (LAB). The lean control mice were fed a regular diet without inducing obesity prior to the experiment. LP28 reduced body weight gain and liver lipid contents (triglyceride and cholesterol), in mice fed a high fat diet for 8 weeks (40%, 54%, and 70% less than those of the control group without LAB, and P = 0.018, P<0.001, and P = 0.021, respectively), whereas SN13T and the heat treated LP28 at 121°C for 15 min were ineffective. Abdominal visceral fat in the high fat diet mice fed with LP28 was also lower than that without LAB by 44%, although it was not significant but borderline (P = 0.076). The sizes of the adipocytes and the lipid droplets in the livers were obviously decreased. A real-time PCR analyses showed that lipid metabolism-related genes, such as CD36 (P = 0.013), SCD1 encoding stearoyl-CoA desaturase 1 (not significant but borderline, P = 0.066), and PPARγ encoding peroxisome proliferator-activated receptor gamma (P = 0.039), were down-regulated by taking LP28 continuously, when compared with those of the control group. In conclusion, LP28 may be a useful LAB strain for the prevention and reduction of the metabolic syndrome.
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Affiliation(s)
- Xingrong Zhao
- Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Fumiko Higashikawa
- Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Masafumi Noda
- Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Yusuke Kawamura
- Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasuyuki Matoba
- Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Takanori Kumagai
- Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Masanori Sugiyama
- Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
- * E-mail:
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Foo NP, Ou Yang H, Chiu HH, Chan HY, Liao CC, Yu CK, Wang YJ. Probiotics prevent the development of 1,2-dimethylhydrazine (DMH)-induced colonic tumorigenesis through suppressed colonic mucosa cellular proliferation and increased stimulation of macrophages. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:13337-13345. [PMID: 22049926 DOI: 10.1021/jf203444d] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Probiotics modulate immunity and inhibit colon carcinogenesis in experimental models, but these effects largely depend on the bacterial strain, and the precise mechanisms are not well understood. Therefore, we studied the effect of Bifidobacterium longum and/or Lactobacillus gasseri on the development of 1,2-dimethylhydrazine (DMH)-induced colonic precancerous lesions and tumors in mice while delineating the possible mechanisms involved. The results suggest that dietary consumption of probiotics (B. longum and L. gasseri) resulted in a significant inhibition of DMH-induced aberrant crypt foci (ACF) formation in male ICR mice. Long-term (24 weeks) dietary consumption of probiotics resulted in a reduction of colon tumor multiplicity and the size of the tumors. Administration of B. longum and L. gasseri suppressed the rate of colonic mucosa cellular proliferation in a manner correlating with the inhibition of tumor induction by DMH. In addition, the phagocytic activity of peritoneal macrophages was significantly increased in the DMH-treated mice that were fed various doses of B. longum, but not with L. gasseri or combined probiotics (B. longum + L. gasseri). We also found that L. gasseri significantly increased the proliferation of RAW264.7 macrophage cells through an increase in S phase DNA synthesis, which was related to the up-regulation of proliferating cell nuclear antigen (PCNA) and cyclin A. Taken together, these results demonstrate the in vivo chemopreventive efficacy and the immune stimulating mechanisms of dietary probiotics against DMH-induced colonic tumorigenesis.
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Affiliation(s)
- Ning-Ping Foo
- Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan
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Wirfält E, Li C, Manjer J, Ericson U, Sonestedt E, Borgquist S, Landberg G, Olsson H, Gullberg B. Food Sources of Fat and Sex Hormone Receptor Status of Invasive Breast Tumors in Women of the Malmö Diet and Cancer Cohort. Nutr Cancer 2011; 63:722-33. [DOI: 10.1080/01635581.2011.570897] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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LeBlanc JG, del Carmen S, Miyoshi A, Azevedo V, Sesma F, Langella P, Bermúdez-Humarán LG, Watterlot L, Perdigon G, de Moreno de LeBlanc A. Use of superoxide dismutase and catalase producing lactic acid bacteria in TNBS induced Crohn's disease in mice. J Biotechnol 2010; 151:287-93. [PMID: 21167883 DOI: 10.1016/j.jbiotec.2010.11.008] [Citation(s) in RCA: 126] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2010] [Revised: 11/08/2010] [Accepted: 11/15/2010] [Indexed: 01/06/2023]
Abstract
Reactive oxygen species are involved in various aspects of intestinal inflammation and tumor development. Decreasing their levels using antioxidant enzymes, such as catalase (CAT) or superoxide dismutase (SOD) could therefore be useful in the prevention of certain diseases. Lactic acid bacteria (LAB) are ideal candidates to deliver these enzymes in the gut. In this study, the anti-inflammatory effects of CAT or SOD producing LAB were evaluated using a trinitrobenzenesulfonic acid (TNBS) induced Crohn's disease murine model. Engineered Lactobacillus casei BL23 strains producing either CAT or SOD, or the native strain were given to mice before and after intrarectal administration of TNBS. Animal survival, live weight, intestinal morphology and histology, enzymatic activities, microbial translocation to the liver and cytokines released in the intestinal fluid were evaluated. The mice that received CAT or SOD-producing LAB showed a faster recovery of initial weight loss, increased enzymatic activities in the gut and lesser extent of intestinal inflammation compared to animals that received the wild-type strain or those that did not receive bacterial supplementation. Our findings suggest that genetically engineered LAB that produce antioxidant enzymes could be used to prevent or decrease the severity of certain intestinal pathologies.
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Affiliation(s)
- Jean Guy LeBlanc
- Centro de Referencia para Lactobacilos (CERELA-CONICET), Chacabuco 145, San Miguel de Tucumán, Tucumán T4000ILC, Argentina.
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50
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Abstract
Lactic acid bacteria are present in many foods such as yoghurt and are frequently used as probiotics to improve some biological functions of the host. Many researchers have evaluated the effects of yoghurt and lactic acid bacteria against diseases such as cancer and intestinal inflammation. The preventive effect of probiotics on intestinal carcinogenesis may be associated with changes in the intestinal microbiota, suppressing the growth of bacteria that convert procarcinogens into carcinogens. Other mechanisms could be related to the immune response modulation and have been evaluated using milks fermented with lactic acid bacteria in chemically induced colon cancer and hormone-dependent breast cancer models. We demonstrated, using a murine colon cancer model, that yoghurt consumption inhibited tumour growth by decreasing the inflammatory response by increasing IL-10-secreting cells, cellular apoptosis and diminishing procarcinogenic enzymes. Milk fermented with Lactobacillus helveticus R389 delayed breast tumour growth by decreasing IL-6 and increasing IL-10 in serum and in the mammary glands and tumour-infiltrating immune cells. Previous results obtained with yoghurt administration in a colon cancer model led us to analyse its effect on a trinitrobenzenesulfonic acid-induced intestinal inflammation model in mice. Yoghurt was able to attenuate the symptoms of acute inflammation by reducing inflammatory cytokines, and increasing regulatory cytokine IL-10-producing cells, leading to desirable changes of the intestinal microbiota. It was demonstrated, by using murine models, that the consumption of fermented milks can modulate the immune system and can maintain it in a state of surveillance, which could affront different pathologies such as cancer and intestinal inflammation.
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