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Zhang H, Tian Y, Xu C, Chen M, Xiang Z, Gu L, Xue H, Xu Q. Crosstalk between gut microbiotas and fatty acid metabolism in colorectal cancer. Cell Death Discov 2025; 11:78. [PMID: 40011436 DOI: 10.1038/s41420-025-02364-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 01/30/2025] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
Colorectal cancer (CRC) is the third most common malignancy globally and the second leading cause of cancer-related mortality. Its development is a multifactorial and multistage process influenced by a dynamic interplay between gut microbiota, environmental factors, and fatty acid metabolism. Dysbiosis of intestinal microbiota and abnormalities in microbiota-associated metabolites have been implicated in colorectal carcinogenesis, highlighting the pivotal role of microbial and metabolic interactions. Fatty acid metabolism serves as a critical nexus linking dietary patterns with gut microbial activity, significantly impacting intestinal health. In CRC patients, reduced levels of short-chain fatty acids (SCFAs) and SCFA-producing bacteria have been consistently observed. Supplementation with SCFA-producing probiotics has demonstrated tumor-suppressive effects, while therapeutic strategies aimed at modulating SCFA levels have shown potential in enhancing the efficacy of radiation therapy and immunotherapy in both preclinical and clinical settings. This review explores the intricate relationship between gut microbiota, fatty acid metabolism, and CRC, offering insights into the underlying mechanisms and their potential translational applications. Understanding this interplay could pave the way for novel diagnostic, therapeutic, and preventive strategies in the management of CRC.
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Affiliation(s)
- Hao Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Yuan Tian
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Chunjie Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Miaomiao Chen
- Department of Radiology, Huashan Hospital, National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200040, PR China
| | - Zeyu Xiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Lei Gu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
| | - Hanbing Xue
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Qing Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
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Kim MJ, Song MH, Ji YS, Park JW, Shin YK, Kim SC, Kim G, Cho B, Park H, Ku JL, Jeong SY. Cell free supernatants of Bifidobacterium adolescentis and Bifidobacterium longum suppress the tumor growth in colorectal cancer organoid model. Sci Rep 2025; 15:935. [PMID: 39762302 PMCID: PMC11704243 DOI: 10.1038/s41598-024-83048-5] [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: 05/10/2024] [Accepted: 12/11/2024] [Indexed: 01/11/2025] Open
Abstract
The probiotic gut microbiome and its metabolites are pivotal in regulating host metabolism, inflammation, and immunity. Host genetics, colonization at birth, the host lifestyle, and exposure to diseases and drugs determine microbial composition. Dysbiosis and disruption of homeostasis in the beneficial microbiome have been reported to be involved in the tumorigenesis and progression of colorectal cancer (CRC). However, the influence of bacteria-secreted metabolites on CRC growth is yet to be fully elucidated. In this study, we compared the microbial composition of CRC patients to healthy controls to identify distinct patterns of microbiota-derived metabolites in CRC patients. Metagenomic analysis demonstrated that beneficial bacteria strains; Blautia producta, Bifidobacterium adolescentis, and Bifidobacterium longum decreased, while Parabacteroides distasonis and Bacteroides ovatus were more prevalent in the CRC patient group. Treatment of cancer organoid lines with microbial culture supernatants from Blautia producta, Bifidobacterium adolescentis, and Bifidobacterium longum showed remarkable inhibition of cancer growth. This study demonstrates that the bacterial metabolites depleted in CRC patients may inhibit cancer growth and highlights the effects of microbiome-derived metabolites on CRC growth.
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Affiliation(s)
- Min Jung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea
| | - Myoung-Hyun Song
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea
- Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
| | - Yo-Sep Ji
- Holzapfel Effective Microbes (HEM) Pharma, Handong Global University, Pohang, Gyungbuk, Republic of Korea
| | - Ji Won Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea
| | - Young-Kyoung Shin
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea
- Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
| | - Soon-Chan Kim
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea
- Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
- Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
| | - Gihyeon Kim
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
| | - Beomki Cho
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
| | - Hansoo Park
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
| | - Ja-Lok Ku
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea.
- Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
- Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
| | - Seung-Yong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
- Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea.
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Sepehr A, Miri ST, Aghamohammad S, Rahimirad N, Milani M, Pourshafie MR, Rohani M. Health benefits, antimicrobial activities, and potential applications of probiotics: A review. Medicine (Baltimore) 2024; 103:e32412. [PMID: 39969286 PMCID: PMC11688011 DOI: 10.1097/md.0000000000032412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 12/02/2022] [Indexed: 02/20/2025] Open
Abstract
Gut microbiota and its metabolic activities can influence the physiology and pathology of the human body. It is well established that alterations in the balance of living microbiota can contribute to various health problems, such as inflammatory bowel disease and autoimmune disorders. Probiotics administered in sufficient quantities as functional food ingredients provide health benefits to hosts. They help to maintain the stability and composition of the gut microbiota and provide resistance to infection by pathogens. The most important probiotic bacteria are Lactobacillus spp. and Bifidobacteria spp., which protect the intestine through various mechanisms such as the production of organic acids and bacteriocins. Scientific and clinical research has demonstrated that probiotics play a role in modulating immune response and preventing cancer and chronic inflammatory diseases, especially in the gastrointestinal tract. This article summarizes the potential health benefits, antimicrobial activities, and purposes for which probiotics can be used as functional foods to improve human health.
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Affiliation(s)
- Amin Sepehr
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Seyedeh Tina Miri
- Department of Microbiology, Islamic Azad University Science and Research Branch, Tehran, Iran
| | | | - Nazanin Rahimirad
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mahnaz Milani
- Department of Microbiology, Islamic Azad University Science and Research Branch, Tehran, Iran
| | | | - Mahdi Rohani
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
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Alan Y, Keskin AO, Sönmez M. Probiotic and functional characterization of newly isolated Lactiplantibacillus plantarum strains from human breast milk and proliferative inhibition potential of metabolites. Enzyme Microb Technol 2024; 182:110545. [PMID: 39546820 DOI: 10.1016/j.enzmictec.2024.110545] [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: 08/13/2024] [Revised: 10/10/2024] [Accepted: 11/05/2024] [Indexed: 11/17/2024]
Abstract
Four Lactiplantibacillus plantarum strains newly isolated and identified from human breast milk in Türkiye, have probiotic, functional and proliferative inhibition potential of metabolites against colon cancer cell lines were evaluated. In simulated gastric and intestinal media, all strains exhibited strong probiotic character by showing resistance, although decreasing with time and concentration. The strains were sensitive to penicillin G, rifampin and chloramphenicol and showed antibacterial effect on all pathogenic bacteria. Citric acid, malic acid, tartaric acid, pyruvic acid and fumaric acid were not detected in the strains, while the highest amount of acetic acid was detected. The quantitative-qualitative analysis and structural characterization of exopolysaccharide (EPS) was confirmed and it was determined that the strains synthesized similar amounts. Compared to standard antioxidants, the strains showed less DPPH activity and similar ABTS activity. High amounts of metabolites of the strains showed good antiproliferative effect on Caco-2, while lower amounts showed good antiproliferative effect on the HT-29 cell line. When all the data were considered, it was determined that the strains were close to each other, but the YAAS 23 strain showed slightly better properties. In conclusion, breast milk is a unique environment harboring beneficial bacteria such as L. plantarum for human health.
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Affiliation(s)
- Yusuf Alan
- Department of Medical Services and Techniques, Bitlis Eren University, Bitlis, Türkiye.
| | - Ali-Osman Keskin
- Department of Biology, Institute of Science, Muş Alparslan University, Muş, Türkiye
| | - Mehmet Sönmez
- Department of Biology, Institute of Science, Muş Alparslan University, Muş, Türkiye
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Xu Y, Wu X, Li Y, Liu X, Fang L, Jiang Z. Probiotics and the Role of Dietary Substrates in Maintaining the Gut Health: Use of Live Microbes and Their Products for Anticancer Effects against Colorectal Cancer. J Microbiol Biotechnol 2024; 34:1933-1946. [PMID: 39210613 PMCID: PMC11540615 DOI: 10.4014/jmb.2403.03056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 07/19/2024] [Accepted: 07/28/2024] [Indexed: 09/04/2024]
Abstract
The gut microbiome is an important and the largest endocrine organ linked to the microbes of the GI tract. The bacterial, viral and fungal communities are key regulators of the health and disease status in a host at hormonal, neurological, immunological, and metabolic levels. The useful microbes can compete with microbes exhibiting pathogenic behavior by maintaining resistance against their colonization, thereby maintaining eubiosis. As diagnostic tools, metagenomic, proteomic and genomic approaches can determine various microbial markers in clinic for early diagnosis of colorectal cancer (CRC). Probiotics are live non-pathogenic microorganisms such as lactic acid bacteria, Bifidobacteria, Firmicutes and Saccharomyces that can help maintain eubiosis when administered in appropriate amounts. In addition, the type of dietary intake contributes substantially to the composition of gut microbiome. The use of probiotics has been found to exert antitumor effects at preclinical levels and promote the antitumor effects of immunotherapeutic drugs at clinical levels. Also, modifying the composition of gut microbiota by Fecal Microbiota Transplantation (FMT), and using live lactic acid producing bacteria such as Lactobacillus, Bifidobacteria and their metabolites (termed postbiotics) can contribute to immunomodulation of the tumor microenvironment. This can lead to tumor-preventive effects at early stages and antitumor effects after diagnosis of CRC. To conclude, probiotics are presumably found to be safe to use in humans and are to be studied further to promote their appliance at clinical levels for management of CRC.
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Affiliation(s)
- Yi Xu
- Phase I Clinical Cancer Trial Center, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, P.R. China
| | - Xiahui Wu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Yan Li
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Xuejie Liu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Lijian Fang
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Ziyu Jiang
- Phase I Clinical Cancer Trial Center, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, P.R. China
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
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Varada VV, Kumar S, Balaga S, Thanippilly AJ, Pushpadass HA, M RH, Jangir BL, Tyagi N, Samanta AK. Oral delivery of electrohydrodynamically encapsulated Lactiplantibacillus plantarum CRD7 modulates gut health, antioxidant activity, and cytokines-related inflammation and immunity in mice. Food Funct 2024; 15:10761-10781. [PMID: 39390885 DOI: 10.1039/d4fo02732a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Abstract
The current study aimed to evaluate the effects of L. plantarum CRD7 on performance and gut health biomarkers in a Swiss albino mouse model. The results showed that supplementation with non-encapsulated (NLP) and electrohydrodyanamically encapsulated L. plantarum CRD7 (ELP) for four weeks significantly increased (P < 0.05) body weight and weekly feed intake of mice. Specifically, these interventions strengthened the gut barrier functions, as evidenced by the increased expression of tight junction proteins (claudin-1, ZO-1, and occludin), inhibiting pro-inflammatory factors (TNF-α, MCP-1, and IL-6), and promoting short-chain fatty acid production. Histopathological examination revealed no probiotic-related adverse effects in liver and intestinal tissues. Furthermore, ELP and NLP possess the ability to regulate immunity and antioxidant capacity in mice. Notably, the supplementation of ELP modified the gut microbiota by promoting beneficial bacteria (Lactobacillus and Bifibacterium) and suppressing pathogenic bacteria (E. coli and C. perfringens), thereby restoring a balanced gut microbiota. Taken together, oral delivery of encapsulated L. plantarum CRD7 can modify the composition of the gut microbiota, fortify the intestinal barrier functions, maintain the gastrointestinal equilibrium, and augment the immune and antioxidant capacity. This comprehensive study provides valuable insights for the potential application of encapsulated probiotic products in food and feed formulations aimed at alleviating gut diseases.
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Affiliation(s)
- Vinay Venkatesh Varada
- Rumen Biotechnology Lab., Animal Nutrition Division, ICAR-National Dairy Research Institute, Karnal-132001, Haryana, India.
| | - Sachin Kumar
- Rumen Biotechnology Lab., Animal Nutrition Division, ICAR-National Dairy Research Institute, Karnal-132001, Haryana, India.
| | - Sravani Balaga
- Rumen Biotechnology Lab., Animal Nutrition Division, ICAR-National Dairy Research Institute, Karnal-132001, Haryana, India.
| | - Antony Johnson Thanippilly
- Rumen Biotechnology Lab., Animal Nutrition Division, ICAR-National Dairy Research Institute, Karnal-132001, Haryana, India.
| | - Heartwin A Pushpadass
- Dairy Engineering Section, ICAR-National Dairy Research Institute, Southern Regional Station, Bengaluru, India.
| | - Rashmi H M
- Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal-132001, Haryana, India.
| | - Babu Lal Jangir
- Department of Veterinary Pathology, College of Veterinary Sciences, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar-125004, India.
| | - Nitin Tyagi
- Rumen Biotechnology Lab., Animal Nutrition Division, ICAR-National Dairy Research Institute, Karnal-132001, Haryana, India.
| | - Ashish Kumar Samanta
- Rumen Biotechnology Lab., Animal Nutrition Division, ICAR-National Dairy Research Institute, Karnal-132001, Haryana, India.
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7
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Sudaarsan ASK, Ghosh AR. Appraisal of postbiotics in cancer therapy. Front Pharmacol 2024; 15:1436021. [PMID: 39372197 PMCID: PMC11449718 DOI: 10.3389/fphar.2024.1436021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 09/05/2024] [Indexed: 10/08/2024] Open
Abstract
Cancer remains a multifactorial disease with an increased mortality rate around the world for the past several decades. Despite advancements in treatment strategies, lower survival rates, drug-associated side effects, and drug resistance create a need for novel anticancer agents. Ample evidence shows that imbalances in the gut microbiota are associated with the formation of cancer and its progression. Altering the gut microbiota via probiotics and their metabolites has gained attention among the research community as an alternative therapy to treat cancer. Probiotics exhibit health benefits as well as modulate the immunological and cellular responses in the host. Apart from probiotics, their secreted products like bacteriocins, exopolysaccharides, short-chain fatty acids, conjugated linoleic acid, peptidoglycan, and other metabolites are found to possess anticancer activity. The beneficiary role of these postbiotic compounds is widely studied for characterizing their mechanism and mode of action that reduces cancer growth. The present review mainly focuses on the postbiotic components that are employed against cancer with their reported mechanism of action. It also describes recent research works carried out so far with specific strain and anticancer activity of derived compounds both in vitro and in vivo, validating that the probiotic approach would pave an alternative way to reduce the burden of cancer.
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Li Q, Liu D, Liang M, Zhu Y, Yousaf M, Wu Y. Mechanism of probiotics in the intervention of colorectal cancer: a review. World J Microbiol Biotechnol 2024; 40:306. [PMID: 39160377 DOI: 10.1007/s11274-024-04112-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 08/13/2024] [Indexed: 08/21/2024]
Abstract
The human microbiome interacts with the host mainly in the intestinal lumen, where putrefactive bacteria are suggested to promote colorectal cancer (CRC). In contrast, probiotics and their isolated components and secreted substances, display anti-tumor properties due to their ability to modulate gut microbiota composition, promote apoptosis, enhance immunity, resist oxidation and alter metabolism. Probiotics help to form a solid intestinal barrier against damaging agents via altering the gut microbiota and preventing harmful microbes from colonization. Probiotic strains that specifically target essential proteins involved in the process of apoptosis can overcome CRC resistance to apoptosis. They can increase the production of anti-inflammatory cytokines, essential in preventing carcinogenesis, and eliminate cancer cells by activating T cell-mediated immune responses. There is a clear indication that probiotics optimize the antioxidant system, decrease radical generation, and detect and degrade potential carcinogens. In this review, the pathogenic mechanisms of pathogens in CRC and the recent insights into the mechanism of probiotics in CRC prevention and therapy are discussed to provide a reference for the actual application of probiotics in CRC.
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Affiliation(s)
- Qinqin Li
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Dongmei Liu
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
| | - Minghua Liang
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Yichao Zhu
- Laboratory of Cell Engineering, Research Unit of Cell Death Mechanism, Beijing Institute of Biotechnology, Chinese Academy of Medical Sciences (2021RU008), Beijing, 100071, China
| | - Muhammad Yousaf
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Yaping Wu
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
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Gad AI, Orabi MM, Abou-Taleb KA, Abdelghani DY, Amin SA. In vitro digestive system simulation and anticancer activity of soymilk fermented by probiotics and synbiotics immobilised on agro-industrial residues. Sci Rep 2024; 14:18518. [PMID: 39122808 PMCID: PMC11316043 DOI: 10.1038/s41598-024-68086-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/19/2024] [Indexed: 08/12/2024] Open
Abstract
In this study, a variety of probiotic strains, including Lactiplantibacillus plantarum, Lacticaseibacillus casei, Lactobacillus acidophilus, Streptococcus thermophilus, Bifidobacterium longum, Limosilactobacillus reuteri, Lactobacillus delbrueckii subsp. bulgaricus, Lacticaseibacillus rhamnosus, and Bifidobacterium bifidum, were utilized for soymilk fermentation both as free cells and as synbiotics on agro-industrial residuals such as okara, whey protein, banana peels, apple pomace, sugarcane bagasse, orange peels, and lemon peels. Among these, Lacticaseibacillus rhamnosus emerged as the most significant strain for soymilk fermentation, exhibiting a viability of 10.47 log cfu/mL, a pH of 4.41, total acidity of 1.12%, and organic acid contents (lactic and acetic acid) of 11.20 and 7.50 g/L, respectively. As a synbiotic Lacticaseibacillus rhamnosus immobilised on okara, showed even more impressive results, with a viability of 12.98 log cfu/mL, a pH of 4.31, total acidity of 1.27%, and organic acid contents of 13.90 and 9.30 g/L, respectively. Over a 12-h fermentation period, cell viability values increased by 10.47-fold in free cells and 11.19-fold in synbiotics. Synbiotic supplementation of fermented soymilk proved more beneficial than free cells in terms of viability, acidity, and organic acid content. Furthermore, when synbiotic fermented soymilk was freeze-dried to simulate the digestive system in vitro, synbiotics and freeze-dried cells demonstrated superior gastrointestinal tract survival compared to free cells. Both the probiotic bacteria and the synbiotics exhibited cytotoxicity against colon and liver cancer cell lines, with half-maximal inhibitory concentrations ranging from 41.96 to 61.52 μL/well.
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Affiliation(s)
- Abdallah I Gad
- Agricultural Microbiology Department, Faculty of Agriculture, Ain Shams University, Hadayek Shobra, P.O. Box 68, Cairo, 11241, Egypt
| | - Mona M Orabi
- Agricultural Microbiology Department, Faculty of Agriculture, Ain Shams University, Hadayek Shobra, P.O. Box 68, Cairo, 11241, Egypt
| | - Khadiga A Abou-Taleb
- Agricultural Microbiology Department, Faculty of Agriculture, Ain Shams University, Hadayek Shobra, P.O. Box 68, Cairo, 11241, Egypt.
| | - Dina Y Abdelghani
- Department of Special Food and Nutrition, Agriculture Research Center, Food Technology Research Institute, Giza, Egypt.
| | - Shimaa A Amin
- Agricultural Microbiology Department, Faculty of Agriculture, Ain Shams University, Hadayek Shobra, P.O. Box 68, Cairo, 11241, Egypt
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Yadav D, Sainatham C, Filippov E, Kanagala SG, Ishaq SM, Jayakrishnan T. Gut Microbiome-Colorectal Cancer Relationship. Microorganisms 2024; 12:484. [PMID: 38543535 PMCID: PMC10974515 DOI: 10.3390/microorganisms12030484] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 02/10/2024] [Accepted: 02/13/2024] [Indexed: 11/12/2024] Open
Abstract
Traditionally, the role of gut dysbiosis was thought to be limited to pathologies like Clostridioides difficile infection, but studies have shown its role in other intestinal and extraintestinal pathologies. Similarly, recent studies have surfaced showing the strong potential role of the gut microbiome in colorectal cancer, which was traditionally attributed mainly to sporadic or germline mutations. Given that it is the third most common cancer and the second most common cause of cancer-related mortality, 78 grants totaling more than USD 28 million have been granted to improve colon cancer management since 2019. Concerted efforts by several of these studies have identified specific bacterial consortia inducing a proinflammatory environment and promoting genotoxin production, causing the induction or progression of colorectal cancer. In addition, changes in the gut microbiome have also been shown to alter the response to cancer chemotherapy and immunotherapy, thus changing cancer prognosis. Certain bacteria have been identified as biomarkers to predict the efficacy of antineoplastic medications. Given these discoveries, efforts have been made to alter the gut microbiome to promote a favorable diversity to improve cancer progression and the response to therapy. In this review, we expand on the gut microbiome, its association with colorectal cancer, and antineoplastic medications. We also discuss the evolving paradigm of fecal microbiota transplantation in the context of colorectal cancer management.
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Affiliation(s)
- Devvrat Yadav
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Chiranjeevi Sainatham
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Evgenii Filippov
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Sai Gautham Kanagala
- Department of Internal Medicine, NYC Health + Hospital/Metropolitan, New York, NY 10029, USA
| | - Syed Murtaza Ishaq
- Department of Internal Medicine, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Baltimore, MD 21215, USA (E.F.); (S.M.I.)
| | - Thejus Jayakrishnan
- Division of Hematology and Oncology, Cleveland Clinic, Cleveland, OH 44195, USA
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11
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Zaib S, Hayat A, Khan I. Probiotics and their Beneficial Health Effects. Mini Rev Med Chem 2024; 24:110-125. [PMID: 37291788 DOI: 10.2174/1389557523666230608163823] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 05/10/2023] [Accepted: 05/17/2023] [Indexed: 06/10/2023]
Abstract
Probiotics are living microorganisms that are present in cultured milk and fermented food. Fermented foods are a rich source for the isolation of probiotics. They are known as good bacteria. They have various beneficial effects on human health including antihypertensive effects, antihypercholesterolemic effects, prevention of bowel disease, and improving the immune system. Microorganisms including bacteria, yeast, and mold are used as probiotics but the major microorganisms that are used as probiotics are bacteria from the genus Lactobacillus, Lactococcus, Streptococcus, and Bifidobacterium. Probiotics are beneficial in the prevention of harmful effects. Recently, the use of probiotics for the treatment of various oral and skin diseases has also gained significant attention. Clinical studies indicate that the usage of probiotics can alter gut microbiota composition and provoke immune modulation in a host. Due to their various health benefits, probiotics are attaining more interest as a substitute for antibiotics or anti-inflammatory drugs leading to the growth of the probiotic market.
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Affiliation(s)
- Sumera Zaib
- Department of Basic and Applied Chemistry, Faculty of Sciences and Technology, University of Central Punjab, Lahore, 54590, Pakistan
| | - Aqsa Hayat
- Department of Basic and Applied Chemistry, Faculty of Sciences and Technology, University of Central Punjab, Lahore, 54590, Pakistan
| | - Imtiaz Khan
- Department of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131, Princess Street, Manchester M1 7DN, United Kingdom
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12
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Abbasi A, Rad AH, Maleki LA, Kafil HS, Baghbanzadeh A. Antigenotoxicity and Cytotoxic Potentials of Cell-Free Supernatants Derived from Saccharomyces cerevisiae var. boulardii on HT-29 Human Colon Cancer Cell Lines. Probiotics Antimicrob Proteins 2023; 15:1583-1595. [PMID: 36588138 DOI: 10.1007/s12602-022-10039-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2022] [Indexed: 01/03/2023]
Abstract
Microbial-derived postbiotics are of interest recently due to their lower side effects than chemotherapy for cancer treatment and prevention. This study aimed to investigate the potential antigenotoxic and cytotoxic effects of cell-free-supernatant (CFS) postbiotics derived from Saccharomyces boulardii by applying SOS chromotest and MTT assay on HT-29 cell lines. Also, further cellular pathway-related assays such as cell cycle, DAPI, and annexin V-FITC/PI staining were performed. Real-time PCR was utilized to assess the expression levels of some genes involved in apoptosis. Based on the outcomes, the CFSs of S. boulardii showed significant antigenotoxic effects (20-60%, P < 0.05), decreased cell viability (with the significant IC50 values of 33.82, 22.68, and 27.67 µg/mL after 24, 48, and 72 h respectively), suppressed the initial (G0/G1) phase of the cell's division, influenced the nucleus of the treated cells, induced apoptosis, and increased the expression of Caspas3 and PTEN genes after 48 h, while the RelA and Bcl-XL genes indicated diminished expression in treated HT-29 cells. Consequently, CFS postbiotics of S. boulardii exhibited significant antigenotoxic and cytotoxic effects and induced apoptosis responses in HT-29 cancer cells. The results of this investigation lead us to recommend that the CFS postbiotics generated from Saccharomyces cerevisiae var. boulardii be taken into consideration as a potential anticancer agent or in the design of supplementary medications to treat and prevent colon cancers.
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Affiliation(s)
- Amin Abbasi
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aziz Homayouni Rad
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | | | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Baghbanzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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13
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Meng R, Zeng M, Ji Y, Huang X, Xu M. The potential role of gut microbiota outer membrane vesicles in colorectal cancer. Front Microbiol 2023; 14:1270158. [PMID: 38029123 PMCID: PMC10661380 DOI: 10.3389/fmicb.2023.1270158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 10/02/2023] [Indexed: 12/01/2023] Open
Abstract
Colorectal cancer (CRC) is a common malignant digestive tract tumor in colorectal regions. Considerable evidence now shows that the gut microbiota have essential roles in CRC occurrence and development. Most Gram-negative bacteria release outer membrane vesicles (OMVs) via outer membrane blistering, which contain specific cargoes which interact with host cells via intercellular communications, host immune regulation, and gut microbiota homeostasis. Studies have also shown that OMVs selectively cluster near tumor cells, thus cancer treatment strategies based on OMVs have attracted considerable research attention. However, little is known about the possible impact of gut microbiota OMVs in CRC pathophysiology. Therefore, in this review, we summarize the research progress on molecular composition and function of OMV, and review the microbial dysbiosis in CRC. We then focus on the potential role of gut microbiota OMVs in CRC. Finally, we examine the clinical potential of OMVs in CRC treatment, and their main advantages and challenges in tumor therapy.
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Affiliation(s)
- Ran Meng
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Minmin Zeng
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ying Ji
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xinxiang Huang
- Department of Biochemistry and Molecular Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Min Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
- Institute of Digestive Diseases, Jiangsu University, Zhenjiang, Jiangsu, China
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14
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Sharma D, Gajjar D, Seshadri S. Understanding the role of gut microfloral bifidobacterium in cancer and its potential therapeutic applications. MICROBIOME RESEARCH REPORTS 2023; 3:3. [PMID: 38455077 PMCID: PMC10917622 DOI: 10.20517/mrr.2023.51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/28/2023] [Accepted: 10/30/2023] [Indexed: 03/09/2024]
Abstract
Gut microbiota research has gained a tremendous amount of attention from the scientific community because of its contribution to gut homeostasis, human health, and various pathophysiological conditions. The early colonizer of the human gut, i.e., bifidobacteria, has emerged as an efficient probiotic in various diseased conditions, including cancer. This review explores the pros and cons of Bifidobacterium in various malignancies and various therapeutic strategies. We have illustrated the controversial role of bifidobacteria participating in various malignancies as well as described the current knowledge regarding its use in anticancer therapies. Ultimately, this article also addresses the need for further extensive research in elucidating the mechanism of how bifidobacteria is involved and is indirectly affecting the tumor microenvironment. Exhaustive and large-scale research is also required to solve the controversial questions regarding the involvement of bifidobacteria in cancer research.
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Affiliation(s)
| | | | - Sriram Seshadri
- Institute of Science, Nirma University, 382481 Ahmedabad, Gujarat, India
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15
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Bahuguna A, Dubey SK. Overview of the Mechanistic Potential of Probiotics and Prebiotics in Cancer Chemoprevention. Mol Nutr Food Res 2023; 67:e2300221. [PMID: 37552810 DOI: 10.1002/mnfr.202300221] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/15/2023] [Indexed: 08/10/2023]
Abstract
Despite of strides in modern cancer therapeutic strategies, there has not been a successful cure for it until now and prognostic side effects and substantial toxicity to chemotherapy and subsequent homeostatic imbalance remains a major concern for professionals in this field. The significance of the human microbiome in the pathogenesis of cancer is being recognized, documented, and established worldwide. Probiotics and prebiotics are some of the most extensively researched approaches to modulate the microbiota for therapeutic purposes, and research on their potential to prevent and treat cancer has sparked an immense amount of interest. The characteristics of probiotics and prebiotics allow for an array of efficient applications in cancer preventive measures. Probiotics can also be administered coupled with chemotherapy and surgery to alleviate their side effects and help promote the effectiveness of chemotherapeutic drugs. Besides showing promising results they are accompanied by potential risks and controversies that may eventually result in clinical repercussions. This review emphasizes the mechanistic potential and oncosuppressive effects of probiotic and prebiotics through maintenance of intestinal barrier function, modifying innate immune system, immunomodulation, intestinal microbiota metabolism, inhibition of host cell proliferation, preventing pathogen colonization, and exerting selective cytotoxicity against tumor cells.
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Affiliation(s)
- Ananya Bahuguna
- Department of Biochemistry, C.B.S.H., G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India
| | - Shiv Kumar Dubey
- Department of Biochemistry, C.B.S.H., G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India
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16
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Zeighamy Alamdary S, Halimi S, Rezaei A, Afifirad R. Association between Probiotics and Modulation of Gut Microbial Community Composition in Colorectal Cancer Animal Models: A Systematic Review (2010-2021). THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2023; 2023:3571184. [PMID: 37719797 PMCID: PMC10505085 DOI: 10.1155/2023/3571184] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 07/09/2023] [Accepted: 07/21/2023] [Indexed: 09/19/2023]
Abstract
Background Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies and is considered the third major cause of mortality globally. Probiotics have been shown to protect against the CRC cascade in numerous studies. Aims The goal of this systematic review was to gather the preclinical studies that examined the impact of probiotics on the alteration of gut microbiota profiles (bacterial communities) and their link to colorectal carcinogenesis as well as the potential processes involved. Methods The search was performed using Scopus, Web of Science, and PubMed databases. Five parameters were used to develop search filters: "probiotics," "prebiotics," "synbiotics," "colorectal cancer," and "animal model." Results Of the 399 full texts that were screened, 33 original articles met the inclusion criteria. According to the current findings, probiotics/synbiotics could significantly attenuate aberrant crypt foci (ACF) formation, restore beneficial bacteria in the microbiota population, increase short-chain fatty acids (SCFAs), and change inflammatory marker expression. Conclusions The present systematic review results indicate that probiotics could modulate the gut microbial composition and immune regulation to combat/inhibit CRC in preclinical models. However, where the evidence is more limited, it is critical to transfer preclinical research into clinical data.
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Affiliation(s)
| | - Shahnaz Halimi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Rezaei
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Roghayeh Afifirad
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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17
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Shakhpazyan N, Mikhaleva L, Bedzhanyan A, Gioeva Z, Sadykhov N, Mikhalev A, Atiakshin D, Buchwalow I, Tiemann M, Orekhov A. Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets. Biomedicines 2023; 11:2361. [PMID: 37760801 PMCID: PMC10525158 DOI: 10.3390/biomedicines11092361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 07/31/2023] [Accepted: 08/21/2023] [Indexed: 09/29/2023] Open
Abstract
Colorectal cancer (CRC) is a major health burden worldwide and is the third most common type of cancer. The early detection and diagnosis of CRC is critical to improve patient outcomes. This review explores the intricate interplay between the tumor microenvironment, stromal interactions, and the progression and metastasis of colorectal cancer. The review begins by assessing the gut microbiome's influence on CRC development, emphasizing its association with gut-associated lymphoid tissue (GALT). The role of the Wnt signaling pathway in CRC tumor stroma is scrutinized, elucidating its impact on disease progression. Tumor budding, its effect on tumor stroma, and the implications for patient prognosis are investigated. The review also identifies conserved oncogenic signatures (COS) within CRC stroma and explores their potential as therapeutic targets. Lastly, the seed and soil hypothesis is employed to contextualize metastasis, accentuating the significance of both tumor cells and the surrounding stroma in metastatic propensity. This review highlights the intricate interdependence between CRC cells and their microenvironment, providing valuable insights into prospective therapeutic approaches targeting tumor-stroma interactions.
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Affiliation(s)
- Nikolay Shakhpazyan
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Liudmila Mikhaleva
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Arkady Bedzhanyan
- Department of Abdominal Surgery and Oncology II (Coloproctology and Uro-Gynecology), Petrovsky National Research Center of Surgery, 119435 Moscow, Russia;
| | - Zarina Gioeva
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Nikolay Sadykhov
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Alexander Mikhalev
- Department of Hospital Surgery No. 2, Pirogov Russian National Research Medical University, 117997 Moscow, Russia;
| | - Dmitri Atiakshin
- Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples’ Friendship University of Russia, 117198 Moscow, Russia;
- Research Institute of Experimental Biology and Medicine, Burdenko Voronezh State Medical University, 394036 Voronezh, Russia
| | - Igor Buchwalow
- Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples’ Friendship University of Russia, 117198 Moscow, Russia;
- Institute for Hematopathology, 22547 Hamburg, Germany;
| | | | - Alexander Orekhov
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
- Institute for Atherosclerosis Research, 121096 Moscow, Russia
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18
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Thoda C, Touraki M. Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment. Microorganisms 2023; 11:1898. [PMID: 37630458 PMCID: PMC10456921 DOI: 10.3390/microorganisms11081898] [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: 06/30/2023] [Revised: 07/14/2023] [Accepted: 07/24/2023] [Indexed: 08/27/2023] Open
Abstract
Colorectal cancer (CRC) is a multifactorial disease with increased morbidity and mortality rates globally. Despite advanced chemotherapeutic approaches for the treatment of CRC, low survival rates due to the regular occurrence of drug resistance and deleterious side effects render the need for alternative anticancer agents imperative. Accumulating evidence supports that gut microbiota imbalance precedes the establishment of carcinogenesis, subsequently contributing to cancer progression and response to anticancer therapy. Manipulation of the gut microbiota composition via the administration of probiotic-derived bioactive compounds has gradually attained the interest of scientific communities as a novel therapeutic strategy for CRC. These compounds encompass miscellaneous metabolic secreted products of probiotics, including bacteriocins, short-chain fatty acids (SCFAs), lactate, exopolysaccharides (EPSs), biosurfactants, and bacterial peptides, with profound anti-inflammatory and antiproliferative properties. This review provides a classification of postbiotic types and a comprehensive summary of the current state of research on their biological role against CRC. It also describes how their intricate interaction with the gut microbiota regulates the proper function of the intestinal barrier, thus eliminating gut dysbiosis and CRC development. Finally, it discusses the future perspectives in precision-medicine approaches as well as the challenges of their synthesis and optimization of administration in clinical studies.
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Affiliation(s)
| | - Maria Touraki
- Laboratory of General Biology, Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, 54 124 Thessaloniki, Greece;
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19
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Liang JQ, Zeng Y, Lau EYT, Sun Y, Huang Y, Zhou T, Xu Z, Yu J, Ng SC, Chan FKL. A Probiotic Formula for Modulation of Colorectal Cancer Risk via Reducing CRC-Associated Bacteria. Cells 2023; 12:cells12091244. [PMID: 37174650 PMCID: PMC10177585 DOI: 10.3390/cells12091244] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 04/17/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (B. adolescentis, B. longum, and B. bifidum) based on the identification of bacterial species that showed significant correlations with CRC-related bacteria including Fusobacterium nucleatum (Fn), Lachnoclostridium sp. m3, Clostridium hathewayi (Ch), and Bacteroides clarus (Bc). We co-cultured Fn with each bifidobacterium or the combined formula and examined the growth of Fn by qPCR. The three individual bifidobacteria significantly inhibited the growth of Fn compared to the control treatment (24~65% inhibition; all p < 0.001). The combination of the three bifidobacteria showed a greater inhibitory effect on Fn growth (70% inhibition) than the individual bifidobacteria (all p < 0.05). We further examined the effect of the probiotic formula in a pilot study of 72 subjects (40 on probiotics; 32 with no intervention) for 4 weeks and followed them up for 12 weeks. The relative fecal abundances of the bifidobacteria in the formula and the CRC-related markers (Fn, m3, Ch, and Bc) were quantitated by qPCR before and after the intervention, and the combined CRC risk score (4Bac; Fn, m3, Ch, and Bc) was evaluated. Subjects with probiotics intervention showed significantly increased abundances of the bifidobacteria from week 2 to week 5 compared to baseline (p < 0.05), and the abundances dropped to baseline levels after the cessation of the intervention. There were significant decreases in the levels of CRC-related markers (Fn and m3) and the CRC risk score (4Bac) from week 2 to week 12 compared to baseline levels (p < 0.05) in the intervention group but not in the control group. A novel probiotic formula containing B. adolescentis, B. longum, and B. bifidum was effective in inhibiting the growth of F. nucleatum in vitro and improving the gut microbial environment against CRC development.
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Affiliation(s)
- Jessie Qiaoyi Liang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yao Zeng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Effie Yin Tung Lau
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yuting Sun
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China
| | - Yao Huang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Tingyu Zhou
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Zhilu Xu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Microbiota I-Center (MagIC), Hong Kong, China
| | - Jun Yu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Microbiota I-Center (MagIC), Hong Kong, China
| | - Francis Ka Leung Chan
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Microbiota I-Center (MagIC), Hong Kong, China
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Lv H, Tao F, Peng L, Chen S, Ren Z, Chen J, Yu B, Wei H, Wan C. In Vitro Probiotic Properties of Bifidobacterium animalis subsp. lactis SF and Its Alleviating Effect on Non-Alcoholic Fatty Liver Disease. Nutrients 2023; 15:nu15061355. [PMID: 36986084 PMCID: PMC10053994 DOI: 10.3390/nu15061355] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 02/20/2023] [Accepted: 03/06/2023] [Indexed: 03/15/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with many influencing factors. With the increasing role of the gut–liver axis in various liver diseases, research on the prevention and treatment of NAFLD with probiotics is increasing. In the present study, a Bifidobacterium animalis subsp. strain, B. lactis SF, was isolated from the feces of healthy infants and characterized by sequencing of the 16S rDNA. A systematic probiotic evaluation was carried out, and a diet-induced mouse model was constructed to study the effect and mechanism of B. lactis SF on diet-induced NAFLD. Results show that B. lactis SF has excellent gastrointestinal fluid tolerance and intestinal colonization, and strong antibacterial and antioxidant capabilities. In vivo, B. lactis SF modulated intestinal flora, restored the intestinal barrier, and inhibited LPS entrance into the portal circulation, which subsequently inhibited the TLR4/NF-κB and modulated the PI3K-Akt/AMPK signaling pathway, attenuated the inflammatory response, and reduced lipid accumulation. In addition, B. lactis SF attenuated oxidative stress and further alleviated autophagy, resulting in an ameliorative effect on NAFLD. Therefore, our study provides a new dietary method for the treatment of NAFLD.
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Affiliation(s)
- Huihui Lv
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Feiyue Tao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Lingling Peng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Shufang Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Zhongyue Ren
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Jiahui Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Bo Yu
- Jiangxi-OAI Joint Research Institute, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China;
| | - Hua Wei
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
- Jiangxi-OAI Joint Research Institute, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China;
| | - Cuixiang Wan
- Jiangxi-OAI Joint Research Institute, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China;
- Correspondence: ; Tel.: +86-791-8833-4578; Fax: +86-791-8833-3708
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21
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Pandey H, Tang DWT, Wong SH, Lal D. Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities. Cancers (Basel) 2023; 15:cancers15030866. [PMID: 36765824 PMCID: PMC9913759 DOI: 10.3390/cancers15030866] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer to the ~40 trillion microorganisms that inhabit the human gut. Advances in next-generation sequencing technologies and metagenomics have provided new insights into the gut microbial ecology and have helped in linking gut microbiota to CRC. Many studies carried out in humans and animal models have emphasized the role of certain gut bacteria, such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, in the onset and progression of CRC. Metagenomic studies have opened up new avenues for the application of gut microbiota in the diagnosis, prevention, and treatment of CRC. This review article summarizes the role of gut microbiota in CRC development and its use as a biomarker to predict the disease and its potential therapeutic applications.
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Affiliation(s)
- Himani Pandey
- Redcliffe Labs, Electronic City, Noida 201301, India
| | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Correspondence: (S.H.W.); (D.L.)
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India
- Correspondence: (S.H.W.); (D.L.)
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22
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Thekkekkara D, Manjula SN, Mishra N, Bhatt S, Shilpi S. Synbiotics in the Management of Breast Cancer. SYNBIOTICS FOR THE MANAGEMENT OF CANCER 2023:289-304. [DOI: 10.1007/978-981-19-7550-9_14] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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23
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Nami Y, Hejazi S, Geranmayeh MH, Shahgolzari M, Yari Khosroushahi A. Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention. Eur J Cancer Prev 2023; 32:30-47. [PMID: 36134612 DOI: 10.1097/cej.0000000000000738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest & West Region, Agricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)
| | - Salva Hejazi
- Department of Medicine, Student Research Committee, Tabriz University of Medical Sciences
| | - Mohammad Hossein Geranmayeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Biotechnology Research Center, Tabriz University of Medical Sciences
| | - Ahmad Yari Khosroushahi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Jha SK, Pandey S, Karn A, Panthi VK. Synbiotics in Gastroesophageal Cancer. SYNBIOTICS FOR THE MANAGEMENT OF CANCER 2023:305-314. [DOI: 10.1007/978-981-19-7550-9_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Quazi S. Anti-cancer activity of human gastrointestinal bacteria. Med Oncol 2022; 39:220. [PMID: 36175586 DOI: 10.1007/s12032-022-01771-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 06/14/2022] [Indexed: 06/16/2023]
Abstract
Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human's gastrointestinal tract can create immune response against inflammation and also can develop diseases, including cancer. The bacteria of the gastrointestinal tract of human can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.
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Affiliation(s)
- Sameer Quazi
- GenLab Biosolutions Private Limited, Bangalore, 560043, Karnataka, India.
- Department of Biomedical Sciences, School of Life Sciences, Anglia Ruskin University, Cambridge, UK.
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Chen YC, Chuang CH, Miao ZF, Yip KL, Liu CJ, Li LH, Wu DC, Cheng T, Lin CY, Wang JY. Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer. Front Oncol 2022; 12:955313. [PMID: 36212420 PMCID: PMC9539537 DOI: 10.3389/fonc.2022.955313] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 08/19/2022] [Indexed: 12/19/2022] Open
Abstract
Studies have reported the effects of the gut microbiota on colorectal cancer (CRC) chemotherapy, but few studies have investigated the association between gut microbiota and targeted therapy. This study investigated the role of the gut microbiota in the treatment outcomes of patients with metastatic CRC (mCRC). We enrolled 110 patients with mCRC and treated them with standard cancer therapy. Stool samples were collected before administering a combination of chemotherapy and targeted therapy. Patients who had a progressive disease (PD) or partial response (PR) for at least 12 cycles of therapy were included in the study. We further divided these patients into anti-epidermal growth factor receptor (cetuximab) and anti-vascular endothelial growth factor (bevacizumab) subgroups. The gut microbiota of the PR group and bevacizumab-PR subgroup exhibited significantly higher α-diversity. The β-diversity of bacterial species significantly differed between the bevacizumab-PR and bevacizumab-PD groups (P = 0.029). Klebsiella quasipneumoniae exhibited the greatest fold change in abundance in the PD group than in the PR group. Lactobacillus and Bifidobacterium species exhibited higher abundance in the PD group. The abundance of Fusobacterium nucleatum was approximately 32 times higher in the PD group than in the PR group. A higher gut microbiota diversity was associated with more favorable treatment outcomes in the patients with mCRC. Bacterial species analysis of stool samples yielded heterogenous results. K. quasipneumoniae exhibited the greatest fold change in abundance among all bacterial species in the PD group. This result warrants further investigation especially in a Taiwanese population.
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Affiliation(s)
- Yen-Cheng Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | - Zhi-Feng Miao
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kwan-Ling Yip
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Jung Liu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ling-Hui Li
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Deng-Chyang Wu
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tian−Lu Cheng
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Yen Lin
- Institute of Information Science, Academia Sinica, Taipei, Taiwan
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan
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Alan Y, Savcı A, Koçpınar EF, Ertaş M. Postbiotic metabolites, antioxidant and anticancer activities of probiotic Leuconostoc pseudomesenteroides strains in natural pickles. Arch Microbiol 2022; 204:571. [PMID: 35997840 DOI: 10.1007/s00203-022-03180-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 08/02/2022] [Accepted: 08/08/2022] [Indexed: 11/26/2022]
Abstract
In this study, five strains of Leuconostoc pseudomesenteroides were thought to have probiotic properties and anticancer activity isolated from natural pickles and identified by performing the 16S rRNA sequence analysis. The probiotic properties, postbiotic amounts, the capacity to adhere to the L-929, HT-29 and Caco-2 cell lines, the effects of postbiotic and bacterial extracts on cell viability and biochemical activities were investigated in the strains. In the results, Leu. pseudomesenteroides Y6 strain was detected to have the best resistance to the stomach and intestinal environments, and the quantities of postbiotic metabolites are similar to each other. The bacterial adhesion capacities were found to be in the range of 1.66-8.5%. Furthermore, postbiotic metabolites of all isolates had good anticancer activity (27.67-86.05%) and the activity of bacterial extractions increased depending on concentration. Leu. pseudomesenteroides Y4 and Y6 strains generally showed better activity than controls and all strains were strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavengers in the antioxidant studies. In conclusion, the Y6 strain, which had the best probiotic feature, was found to show significantly good biological activity. It is thought that this isolate will be supported by new in vivo studies and eventually be brought to the food and health industry.
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Affiliation(s)
- Yusuf Alan
- Department of Molecular Biology and Genetics, Faculty of Science, Muş Alparslan University, 49250, Muş, Turkey
| | - Ahmet Savcı
- Department of Molecular Biology and Genetics, Faculty of Science, Muş Alparslan University, 49250, Muş, Turkey
| | - Enver Fehim Koçpınar
- Department of Medical Loboratory Techniques, Vocational School of Health Services, Muş Alparslan University, 49250, Muş, Turkey
| | - Metin Ertaş
- Department of Plant and Animal Production, Vocational School of Yuksekova, Hakkari University, 30300, Hakkari, Turkey.
- Biological Diversity Application and Research Center, Hakkari University, 30000, Hakkari, Turkey.
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Ali A, Ara A, Kashyap MK. Gut microbiota: Role and Association with Tumorigenesis in Different Malignancies. Mol Biol Rep 2022; 49:8087-8107. [PMID: 35543828 DOI: 10.1007/s11033-022-07357-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/01/2022] [Accepted: 03/10/2022] [Indexed: 02/07/2023]
Abstract
The microbiota has been associated with different cancer and may vary from patient to patient. A specific microbial strain can alter the progression of cancer and therapeutic outcome in response to anti-cancer therapy. The variations in microbiota contributed due to the individual microbiome of the microorganism are responsible for diverse clinical outcomes. The expansion of microbiota subpopulation during dysbiosis can lead to toxin production, inducing inflammation and cancer. The microbiota can be a dual-edged sword because it can be tumor-suppressive or oncogenic in the case of the gut. The transition of cancer cells from early to late-stage also impacts the composition of the microbiota, and this alteration could change the behavior of cancer. Multi-omics platforms derived data from an individual's multi-dimensional data (DNA, mRNA, microRNA, protein, metabolite, microbiota, and microbiome), i.e., individualome, to exploit it for personalized tailored treatment for different cancers in a precise manner. A number of studies suggest the importance of microbiota and its add-in suitability to existing treatment options for different malignancies. Furthermore, in vitro, and in vivo studies and cancer clinical trials suggest that probiotics have driven modulation of gut microbiota and other sites discourage the aggressive behavior and progression of different cancers.
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Affiliation(s)
- Altamas Ali
- Department of Biosciences, Jamia Millia Islamia (A central University), Jamia Nagar, 110025, New Delhi, India
| | - Anam Ara
- Department of Biosciences, Jamia Millia Islamia (A central University), Jamia Nagar, 110025, New Delhi, India
| | - Manoj Kumar Kashyap
- Amity Stem Cell Institute/Amity Medical School, Amity University Haryana, Amity Education Valley, Panchgaon (Manesar), Gurugram, HR, 122413, India.
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Kvakova M, Kamlarova A, Stofilova J, Benetinova V, Bertkova I. Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy. World J Gastroenterol 2022; 28:3370-3382. [PMID: 36158273 PMCID: PMC9346452 DOI: 10.3748/wjg.v28.i27.3370] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/22/2022] [Accepted: 06/16/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a leading cause of human mortality worldwide. As conventional anticancer therapy not always being effective, there is growing interest in innovative “drug-free” cancer treatments or interventions that improve the efficacy of established therapy. CRC is associated with microbiome alterations, a process known as dysbiosis that involves depletion and/or enrichment of particular gut bacterial species and their metabolic functions. Supplementing patient treatment with traditional probiotics (with or without prebiotics), next-generation probiotics (NGP), or postbiotics represents a potentially effective and accessible complementary anticancer strategy by restoring gut microbiota composition and/or by signaling to the host. In this capacity, restoration of the gut microbiota in cancer patients can stabilize and enhance intestinal barrier function, as well as promote anticarcinogenic, anti-inflammatory, antimutagenic or other biologically important biochemical pathways that show high specificity towards tumor cells. Potential benefits of traditional probiotics, NGP, and postbiotics include modulating gut microbiota composition and function, as well as the host inflammatory response. Their application in CRC prevention is highlighted in this review, where we consider supportive in vitro, animal, and clinical studies. Based on emerging research, NGP and postbiotics hold promise in establishing innovative treatments for CRC by conferring physiological functions via the production of dominant natural products and metabolites that provide new host-microbiota signals to combat CRC. Although favorable results have been reported, further investigations focusing on strain and dose specificity are required to ensure the efficacy and safety of traditional probiotics, NGP, and postbiotics in CRC prevention and treatment.
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Affiliation(s)
- Monika Kvakova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Anna Kamlarova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Jana Stofilova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Veronika Benetinova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Izabela Bertkova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
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Role of a mixed probiotic product, VSL#3, in the prevention and treatment of colorectal cancer. Eur J Pharmacol 2022; 930:175152. [PMID: 35835181 DOI: 10.1016/j.ejphar.2022.175152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/03/2022] [Accepted: 07/07/2022] [Indexed: 12/09/2022]
Abstract
Colorectal cancer (CRC) is a multifactorial disease. The incidence of this type of cancer in younger patients has increased in recent years, and more strategies are needed to prevent and delay the progression of CRC. Probiotics play an adjunctive role in the prevention and treatment of CRC and can not only prevent the onset and delay the progression of disease but also reduce the side effects after the application of anti-cancer drugs. The anti-cancer effect of individual probiotics has been extensively studied, and the exact curative effect of various probiotics has been found, but the anti-cancer effect of mixed probiotics is still not well summarized. In this review, we discuss the positive effects of mixed probiotics on CRC and the related mechanisms of action, especially VSL#3 (VSL Pharmaceuticals, Inc., Gaithersburg, MD, USA), thus providing new ideas for the treatment of CRC. Moreover, we suggest the need to search for more therapeutic possibilities, especially via the research and application of synbiotics and postbiotics.
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Nanodrug-loaded Bifidobacterium bifidum conjugated with anti-death receptor antibody for tumor-targeted photodynamic and sonodynamic synergistic therapy. Acta Biomater 2022; 146:341-356. [PMID: 35580829 DOI: 10.1016/j.actbio.2022.05.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 05/04/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022]
Abstract
Using bacteria for tumor-targeted therapy has attracted much attention in recent years. However, how to improve the targeted delivery and cancer therapy efficacy is an important but challenging scientific issue. Herein, a drug delivery system using a probiotic as a carrier was developed for tumor-targeted photodynamic and sonodynamic synergistic therapy. In this system, chlorin e6 (Ce6) nanoparticles (NPs) were prepared and incorporated into B. bifidum, followed by the conjugation of anti-death receptor 5 antibody (anti-DR5 Ab). Interestingly, B. bifidum under 671 nm laser or ultrasound (US) irradiation could generate reactive oxygen species (ROS), and Ce6-B. bifidum-anti-DR5 Ab obtained could target hypoxic regions in tumor with high efficiency after intravenous injection. The ROS level generated by Ce6-B. bifidum-anti-DR5 Ab under both laser and US irradiation was much higher than the combined ROS generated separately using a laser and US for the same probiotics. The cytotoxicity and laryngeal tumor growth-inhibiting efficiency of Ce6-B. bifidum-anti-DR5 Ab under both laser and US irradiation were significant higher than the values obtained using laser or US irradiation alone, which demonstrated the synergistic effect on tumor growth. B. bifidum could be eliminated from the body without exerting harmful effects on mouse health. This strategy is a platform that can be extended to treat other solid tumors. STATEMENT OF SIGNIFICANCE: Using bacteria as drug delivery carriers will show unique advantages. However, how to improve the targeted delivery efficiency and tumor inhibiting capacity is a challenging scientific issue. Herein, a delivery system using a probiotic as carrier was developed for tumor-targeted therapy. In this delivery system, chlorin e6 nanoparticles were prepared and then incorporated into living Bifidobacterium bifidum (B.bifidum), followed by the conjugation of anti-death receptor 5 antibody. This delivery system could efficiently target to mouse tumors, accumulate the hypoxic areas and inhibit the tumor growth through the photodynamic and sonodynamic synergistic effect. Our results will provide a platform for B.bifidum-mediated tumor targeted therapy.
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Liu H, Zhang K, Liu P, Xu X, Zhou Y, Gan L, Yao L, Li B, Chen T, Fang N. Improvement Effect of Bifidobacterium animalis subsp. lactis MH-02 in Patients Receiving Resection of Colorectal Polyps: A Randomized, Double-Blind, Placebo-Controlled Trial. Front Immunol 2022; 13:940500. [PMID: 35833120 PMCID: PMC9271559 DOI: 10.3389/fimmu.2022.940500] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 06/01/2022] [Indexed: 11/24/2022] Open
Abstract
Background Postoperative symptoms, bowel dysfunction and recurrence are common problems after resection of colorectal polyps. We aimed to evaluate the efficacy of Bifidobacterium in the postoperative patients. Methods In this single-center, randomized, double-blind, placebo-controlled trial, adults (≥ 18 years) undergoing endoscopic resection of colorectal polyps were treated with probiotics (Bifidobacterium animalis subsp. lactis MH-02, 2 × 109 colony-forming units per packet) or placebo once daily for 7 days. The primary clinical endpoint was a reduction in the mean total postoperative symptoms score within 7 days postoperatively. Secondary clinical endpoints were the single symptom scores, time to recovery of bowel function, and changes in the intestinal microbiota. This study is registered with the number ChiCTR2100046687. Results A total of 100 individuals were included (48 in probiotic group and 52 in placebo group). No difference was seen in the mean scores between the two groups (0.29 vs. 0.43, P = 0.246). Colorectal polyps size (P = 0.008) and preoperative symptoms (P = 0.032) were influential factors for the primary endpoint. Besides, MH-02 alleviated difficult defecation (P = 0.045), and reduced the time to recovery of bowel function (P = 0.032). High-throughput analysis showed that MH-02 can help restore the diversity of intestinal microbiota, and increased the relative abundance of Bifidobacterium, Roseburia, Gemmiger, Blautia and Ruminococcus, while reduced the relative abundance of Clostridium at genus level (P < 0.05). Conclusion In this prospective trial, MH-02 showed efficacy in patients with resection of colorectal polyps, particularly in the recovery of bowel function, and the changes in the intestinal microbiota may provide evidence for further exploration of the therapeutic mechanisms.
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Affiliation(s)
- Hui Liu
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Kaige Zhang
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Peng Liu
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Xuan Xu
- Huankui Academy, Nanchang University, Nanchang, China
| | - Yuyang Zhou
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Lihong Gan
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Ling Yao
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Bin Li
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Tingtao Chen
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China
- *Correspondence: Tingtao Chen, ; Nian Fang,
| | - Nian Fang
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
- *Correspondence: Tingtao Chen, ; Nian Fang,
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Gut Microbial Profile in Patients with Pancreatic Cancer. Jundishapur J Microbiol 2022. [DOI: 10.5812/jjm-122386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: Pancreatic cancer is a lethal tumor with a poor prognosis. The connection between pancreatic cancer and gut microbiota is less reported. Objectives: This study analyzed microbial characteristics in patients with pancreatic cancer from the tropical area of China and explored the potential impact of the characteristic microflora on pancreatic cancer. Methods: Stool samples and blood test indices of participants were collected in Hainan, China. Metagenomic sequencing was used to analyze the gut microbiota characteristics. The R corrplot package was used to analyze the correlation between gut microbiota and blood test indices. Results: The microbial community in pancreatic cancer were clustered together and significantly separated from controls. The Simpson index was increased significantly in pancreatic cancer compared to controls. The abundances of butyrate-producing bacteria (Anaerostipes hadrus, Lachnoclostridium phocaeense, and Romboutsia ilealis), Bifidobacteria, and [Eubacterium] eligens were significantly decreased, while Fusobacterium, Enterobacter, and Enterococcus were significantly increased in pancreatic cancer. Prevotella copri may have a vital role in the bacterial interaction network. Pathways connected to metabolism, environment (bacterial secretion system), genetic information (protein export and ribosome), and human diseases (infectious diseases and drug resistance) were increased in the pancreatic cancer group. Butyrate-producing bacteria (butyrate-producing bacterium SS3/4, A. hadrus, R. intestinalis, and Faecalibacterium prausnitzii) and Bifidobacteria were significantly negatively correlated with the neutrophil-to-lymphocyte ratio. Conclusions: The gut microbiome was distinct in patients with pancreatic cancer from the tropical area of China. Changes in intestinal flora abundance and metabolic pathways may play an essential role in the occurrence and development of pancreatic cancer.
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Patil A, Munot N, Patwekar M, Patwekar F, Ahmad I, Alraey Y, Alghamdi S, Kabrah A, Dablool AS, Islam F. Encapsulation of Lactic Acid Bacteria by Lyophilisation with Its Effects on Viability and Adhesion Properties. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:4651194. [PMID: 35668781 PMCID: PMC9166943 DOI: 10.1155/2022/4651194] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 05/09/2022] [Indexed: 12/03/2022]
Abstract
Lactobacillus (LAB) genera are considered important functional food but are found to have a short shelf life. In this study, two LAB, Lactobacillus plantarum (Lp) and Lactobacillus rhamnosus (Lr), were isolated from sheep's milk, and whole-genome sequencing was carried out by using 16s rRNA Illumina Nextseq, the Netherlands. The LAB were encapsulated by the lyophilisation technique using different lyoprotective pharmaceutical excipients. This process was carried out using a freeze dryer (U-TECH, Star Scientific Instruments, India). Shelf-life determination was carried out by a 12-month study using the viability survival factor (Vsf). The in vitro cell adhesion technique was carried out by using the red snapper fish along with autoaggregation and cell surface hydrophobicity as vital probiotic properties. It was observed that Lp has a significantly higher (P < 0.001) Vsf of 7.2, while Lr has a Vsf of 7 (P < 0.05) when both are encapsulated with 10% maltodextrin + 5% sucrose kept at 4°C for 12 months. The result demonstrated that Lp had significantly high (P < 0.05) cell adhesion, 96% ± 1.2 autoaggregation, and 6% cell surface hydrophobicity as compared to Lr. Moreover, this study demonstrated that lyophilised LAB with lyoprotective excipients enhances shelf life without any changes in probiotic properties when kept at 4°C exhibiting all its probiotic properties.
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Affiliation(s)
| | - Neha Munot
- Vishwakarma University, Pune, Maharastra, India
| | | | | | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Yasser Alraey
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Saad Alghamdi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ahmed Kabrah
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Anas S. Dablool
- Department of Public Health, Health Sciences College, Al Leith, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
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Effects of Resistant Dextrin from Potato Starch on the Growth Dynamics of Selected Co-Cultured Strains of Gastrointestinal Bacteria and the Activity of Fecal Enzymes. Nutrients 2022; 14:nu14102158. [PMID: 35631299 PMCID: PMC9144799 DOI: 10.3390/nu14102158] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 05/16/2022] [Accepted: 05/20/2022] [Indexed: 02/04/2023] Open
Abstract
Preparations of resistant dextrins have become an interesting topic of research due to their properties, which bear resemblance those of prebiotics, e.g., the improvement of metabolic parameters, increased efficiency of the immune system and induction of vitamin production. The aim of this study was to investigate the effects of the resistant dextrin produced from potato starch on the growth dynamics of typical gastrointestinal microbiota and the activity of fecal enzymes in order to assess a possible exhibition of prebiotic properties. In the study, in vitro cultivation of co-cultures of Lactobacillus, Bifidobacterium, E. coli, Enterococcus, Clostridium and Bacteroides spp. was conducted on media enriched with the resistant dextrin. The CFU/mL for each strain was measured in time periods of 24, 48, 72, 96 and 168 h. Furthermore, the activities of α-glucosidase, α-galactosidase, β-glucosidase, β-galactosidase and β-glucuronidase were determined using spectrophotometric methods at a wavelength of 400 nm. The results show that the resistant dextrin can be utilized as a source of carbon for the growth of intestinal bacteria. Moreover, the results revealed that, after 168 h of cultivation, it enhances the viability of probiotic strains of Lactobacillus and Bifidobacterium spp. and decreases the growth of other intestinal strains (Clostridium, Escherichia coli, Enterococcus and Bacteroides), which is demonstrated by a high Prebiotic Index (p < 0.05). Furthermore, there was no significant change in the pH of the cultures; however, the pace of the pH decrease during the cultivation was slower in the case of culture with resistant dextrin. Furthermore, it was revealed that usage of the resistant dextrin as a medium additive noticeably lowered the activities of β-glucosidase and β-glucuronidase compared to the control (p < 0.05), whereas the activities of the other fecal enzymes were affected to a lesser degree. The resistant dextrins derived from potato starch are a suitable prebiotic candidate as they promote the growth of beneficial strains of gut bacteria and improve health markers, such as the activity of fecal enzymes. Nevertheless, additional in vivo research is necessary to further assess the suspected health-promoting properties.
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Doublier S, Cirrincione S, Scardaci R, Botta C, Lamberti C, Di Giuseppe F, Angelucci S, Rantsiou K, Cocolin L, Pessione E. Putative probiotics decrease cell viability and enhance chemotherapy effectiveness in human cancer cells: role of butyrate and secreted proteins. Microbiol Res 2022; 260:127012. [DOI: 10.1016/j.micres.2022.127012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/16/2022] [Accepted: 03/16/2022] [Indexed: 12/29/2022]
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Bacteria and bacterial derivatives as delivery carriers for immunotherapy. Adv Drug Deliv Rev 2022; 181:114085. [PMID: 34933064 DOI: 10.1016/j.addr.2021.114085] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 11/16/2021] [Accepted: 12/14/2021] [Indexed: 02/08/2023]
Abstract
There is growing interest in the role of microorganisms in human health and disease, with evidence showing that new types of biotherapy using engineered bacterial therapeutics, including bacterial derivatives, can address specific mechanisms of disease. The complex interactions between microorganisms and metabolic/immunologic pathways underlie many diseases with unmet medical needs, suggesting that targeting these interactions may improve patient treatment. Using tools from synthetic biology and chemical engineering, non-pathogenic bacteria or bacterial products can be programmed and designed to sense and respond to environmental signals to deliver therapeutic effectors. This review describes current progress in biotherapy using live bacteria and their derivatives to achieve therapeutic benefits against various diseases.
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Waziri A, Bharti C, Aslam M, Jamil P, Mirza MA, Javed MN, Pottoo U, Ahmadi A, Alam MS. Probiotics for the Chemoprotective Role against the Toxic Effect of Cancer Chemotherapy. Anticancer Agents Med Chem 2022; 22:654-667. [PMID: 33992067 DOI: 10.2174/1871520621666210514000615] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/10/2020] [Accepted: 01/05/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Chemo- and radiation therapy-based clinical management of different types of cancers is associated with toxicity and several side effects. Therefore, there is always an unmet need to explore agents that reduce such risk factors. Among these, natural products have attracted much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. METHODS Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. RESULTS Apart from excellent anti-cancer abilities, probiotics alleviate toxicity & side effects of chemotherapeutics, with a high degree of safety and efficiency. CONCLUSION Preclinical and clinical evidence suggests that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.
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Affiliation(s)
- Aafrin Waziri
- University School of Biotechnology, Guru Gobind Singh Indraprastha University, Delhi, India
| | - Charu Bharti
- School of Medical and Allied Sciences, K.R. Mangalam University, Sohna Road, Gurgaon, Haryana-122103, India
| | - Mohammed Aslam
- Faculty of Pharmacy, AL Hawash Private University, Homs, Syria
| | - Parween Jamil
- Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
| | - Mohd Aamir Mirza
- Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
| | - Md Noushad Javed
- Department of Pharmacy, SMAS, KR Mangalam University, Gurugram, India
- Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
| | - Uzma Pottoo
- Department of Food Science & Technology, School of Applied Sciences & Technology, University of Kashmir, J.K., India
| | - Amirhossein Ahmadi
- Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Md Sabir Alam
- NIMS Institute of Pharmacy, NIMS University, NH-11C, Delhi - Jaipur Expy, Shobha Nagar, Jaipur, Rajasthan India
- SGT College of Pharmacy, SGT University, Gurgaon-Badli Road Chandu, Budhera, Gurugram, Haryana 122505, India
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Davoodvandi A, Fallahi F, Tamtaji OR, Tajiknia V, Banikazemi Z, Fathizadeh H, Abbasi-Kolli M, Aschner M, Ghandali M, Sahebkar A, Taghizadeh M, Mirzaei H. An Update on the Effects of Probiotics on Gastrointestinal Cancers. Front Pharmacol 2021; 12:680400. [PMID: 34992527 PMCID: PMC8724544 DOI: 10.3389/fphar.2021.680400] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 11/26/2021] [Indexed: 12/28/2022] Open
Abstract
Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.
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Affiliation(s)
- Amirhossein Davoodvandi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Farzaneh Fallahi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Omid Reza Tamtaji
- Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Vida Tajiknia
- Department of Surgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zarrin Banikazemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hadis Fathizadeh
- Department of Laboratory Sciences, Sirjan Faculty of Medicine Sciences, Sirjan, Iran
| | - Mohammad Abbasi-Kolli
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Maryam Ghandali
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Taghizadeh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Dey P, Chaudhuri SR, Efferth T, Pal S. The intestinal 3M (microbiota, metabolism, metabolome) zeitgeist - from fundamentals to future challenges. Free Radic Biol Med 2021; 176:265-285. [PMID: 34610364 DOI: 10.1016/j.freeradbiomed.2021.09.026] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/18/2021] [Accepted: 09/30/2021] [Indexed: 12/12/2022]
Abstract
The role of the intestine in human health and disease has historically been neglected and was mostly attributed to digestive and absorptive functions. In the past two decades, however, discoveries related to human nutrition and intestinal host-microbe reciprocal interaction have established the essential role of intestinal health in the pathogenesis of chronic diseases and the overall wellbeing. That transfer of gut microbiota could be a means of disease phenotype transfer has revolutionized our understanding of chronic disease pathogenesis. This narrative review highlights the major concepts related to intestinal microbiota, metabolism, and metabolome (3M) that have facilitated our fundamental understanding of the association between the intestine, and human health and disease. In line with increased interest of microbiota-dependent modulation of human health by dietary phytochemicals, we have also discussed the emerging concepts beyond the phytochemical bioactivities which emphasizes the integral role of microbial metabolites of parent phytochemicals at extraintestinal tissues. Finally, this review concludes with challenges and future prospects in defining the 3M interactions and has emphasized the fact that, it takes 'guts' to stay healthy.
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Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India.
| | - Saumya Ray Chaudhuri
- Council of Scientific and Industrial Research (CSIR), Institute of Microbial Technology, Chandigarh, India
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Sirshendu Pal
- Mukherjee Hospital, Mitra's Clinic and Nursing Home, Siliguri, West Bengal, India
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Miknevicius P, Zulpaite R, Leber B, Strupas K, Stiegler P, Schemmer P. The Impact of Probiotics on Intestinal Mucositis during Chemotherapy for Colorectal Cancer: A Comprehensive Review of Animal Studies. Int J Mol Sci 2021; 22:9347. [PMID: 34502251 PMCID: PMC8430988 DOI: 10.3390/ijms22179347] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/26/2021] [Accepted: 08/21/2021] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females (incidence 16.4/10,000) and the third in males (incidence 23.4/10,000) worldwide. Surgery, chemotherapy (CTx), radiation therapy (RTx), or a combined treatment of those are the current treatment modalities for primary CRC. Chemotherapeutic drug-induced gastrointestinal (GIT) toxicity mainly presents as mucositis and diarrhea. Preclinical studies revealed that probiotic supplementation helps prevent CTx-induced side effects by reducing oxidative stress and proinflammatory cytokine production and promoting crypt cell proliferation. Moreover, probiotics showed significant results in preventing the loss of body weight (BW) and reducing diarrhea. However, further clinical studies are needed to elucidate the exact doses and most promising combination of strains to reduce or prevent chemotherapy-induced side effects. The aim of this review is to overview currently available literature on the impact of probiotics on CTx-induced side effects in animal studies concerning CRC treatment and discuss the potential mechanisms based on experimental studies' outcomes.
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Affiliation(s)
- Povilas Miknevicius
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerpl. 2, 8036 Graz, Austria; (P.M.); (R.Z.); (B.L.); (P.S.)
- Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania;
| | - Ruta Zulpaite
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerpl. 2, 8036 Graz, Austria; (P.M.); (R.Z.); (B.L.); (P.S.)
- Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania;
| | - Bettina Leber
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerpl. 2, 8036 Graz, Austria; (P.M.); (R.Z.); (B.L.); (P.S.)
| | - Kestutis Strupas
- Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania;
| | - Philipp Stiegler
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerpl. 2, 8036 Graz, Austria; (P.M.); (R.Z.); (B.L.); (P.S.)
| | - Peter Schemmer
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerpl. 2, 8036 Graz, Austria; (P.M.); (R.Z.); (B.L.); (P.S.)
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Probiotics: A Promising Candidate for Management of Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13133178. [PMID: 34202265 PMCID: PMC8268640 DOI: 10.3390/cancers13133178] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/20/2021] [Accepted: 06/21/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the World's third most frequently diagnosed cancer type. It accounted for about 9.4% mortality out of the total incidences of cancer in the year 2020. According to estimated facts by World Health Organization (WHO), by 2030, 27 million new CRC cases, 17 million deaths, and around 75 million people living with the disease will appear. The facts and evidence that establish a link between the intestinal microflora and the occurrence of CRC are quite intuitive. Current shortcomings of chemo- and radiotherapies and the unavailability of appropriate treatment strategies for CRC are becoming the driving force to search for an alternative approach for the prevention, therapy, and management of CRC. Probiotics have been used for a long time due to their beneficial health effects, and now, it has become a popular candidate for the preventive and therapeutic treatment of CRC. The probiotics adopt different strategies such as the improvement of the intestinal barrier function, balancing of natural gut microflora, secretion of anticancer compounds, and degradation of carcinogenic compounds, which are useful in the prophylactic treatment of CRC. The pro-apoptotic ability of probiotics against cancerous cells makes them a potential therapeutic candidate against cancer diseases. Moreover, the immunomodulatory properties of probiotics have created interest among researchers to explore the therapeutic strategy by activating the immune system against cancerous cells. The present review discusses in detail different strategies and mechanisms of probiotics towards the prevention and treatment of CRC.
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Faghfoori Z, Faghfoori MH, Saber A, Izadi A, Yari Khosroushahi A. Anticancer effects of bifidobacteria on colon cancer cell lines. Cancer Cell Int 2021; 21:258. [PMID: 33980239 PMCID: PMC8114702 DOI: 10.1186/s12935-021-01971-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 05/05/2021] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and has uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using it as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines. METHODS The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method. RESULTS The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes. CONCLUSIONS In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.
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Affiliation(s)
- Zeinab Faghfoori
- Food (Salt) Safety Research Center, School of Nutrition and Food Sciences, Semnan University of Medical Sciences, Semnan, Iran
| | - Mohammad Hasan Faghfoori
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Amir Saber
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technologies, Kermanshah University of Medical Sciences, Isar Sq., next to Farabi Hospital, P.O. Box 6719851351, Kermanshah, Iran.
| | - Azimeh Izadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmad Yari Khosroushahi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
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Vrzáčková N, Ruml T, Zelenka J. Postbiotics, Metabolic Signaling, and Cancer. Molecules 2021; 26:molecules26061528. [PMID: 33799580 PMCID: PMC8000401 DOI: 10.3390/molecules26061528] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/05/2021] [Accepted: 03/09/2021] [Indexed: 12/19/2022] Open
Abstract
Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and even though the prognosis of patients is improving, it is still poor in the substantial part of the cases. The preventable nature of cancer and the importance of a complex multi-level approach in anticancer therapy motivate the search for novel avenues of establishing the anticancer environment in the human body. This review summarizes the principal findings demonstrating the usefulness of both natural and synthetic sources of postbotics in the prevention and therapy of cancer. Specifically, the effects of crude cell-free supernatants, the short-chain fatty acid butyrate, lactic acid, hydrogen sulfide, and β-glucans are described. Contradictory roles of postbiotics in healthy and tumor tissues are highlighted. In conclusion, the application of postbiotics is an efficient complementary strategy to combat cancer.
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The Western Dietary Pattern Combined with Vancomycin-Mediated Changes to the Gut Microbiome Exacerbates Colitis Severity and Colon Tumorigenesis. Nutrients 2021; 13:nu13030881. [PMID: 33803094 PMCID: PMC8000903 DOI: 10.3390/nu13030881] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/01/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023] Open
Abstract
Previous work by our group using a mouse model of inflammation-associated colorectal cancer (CAC) showed that the total Western diet (TWD) promoted colon tumor development. Others have also shown that vancomycin-mediated changes to the gut microbiome increased colorectal cancer (CRC). Therefore, the objective of this study was to determine the impact of vancomycin on colon tumorigenesis in the context of a standard mouse diet or the TWD. A 2 × 2 factorial design was used, in which C57Bl/6J mice were fed either the standard AIN93G diet or TWD and with vancomycin in the drinking water or not. While both the TWD and vancomycin treatments independently increased parameters associated with gut inflammation and tumorigenesis compared to AIN93G and plain water controls, mice fed the TWD and treated with vancomycin had significantly increased tumor multiplicity and burden relative to all other treatments. Vancomycin treatment significantly decreased alpha diversity and changed the abundance of several taxa at the phylum, family, and genus levels. Conversely, basal diet had relatively minor effects on the gut microbiome composition. These results support our previous research that the TWD promotes colon tumorigenesis and suggest that vancomycin-induced changes to the gut microbiome are associated with higher tumor rates.
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Khan AA, Nema V, Khan Z. Current status of probiotics for prevention and management of gastrointestinal cancers. Expert Opin Biol Ther 2021; 21:413-422. [PMID: 33034210 DOI: 10.1080/14712598.2021.1828858] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 09/23/2020] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Gastrointestinal cancers contribute to a significant number of cancer- associated mortality. The gastrointestinal tract harbors a multitude of microorganisms, known as the microbiota. Recently, the microbiota is considered to be an accessory organ resulting in several health benefits. The microbiota is involved in almost all aspects of an individual ranging from managing behavior to controlling metabolism, immune status and the response to a disease. Researchers are observing the modulation of microbiota in almost every disease, including cancer. Probiotics are microorganisms that can help to alter the host microbiota toward a healthy state thus providing benefits from many diseases including cancer. AREAS COVERED We explored the current status of the use of probiotics in cancer patients. Although probiotic bacteria can provide significant benefits to individuals suffering from cancer, the number of cancer-specific clinical products containing probiotics is not comparable to research studies showing their benefits. The lack of available products is due to several factors including a lack of risk assessment data of beneficial probiotics in cancer patients. EXPERT OPINION Laboratory investigations indicate a huge potential of probiotics for the prevention and management of gastrointestinal cancer, but more clinical studies are required to support their application in clinical settings.
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Affiliation(s)
- Abdul Arif Khan
- Division of Microbiology, Indian Council of Medical Research-National AIDS Research Institute, Pune, Maharashtra, India
| | - Vijay Nema
- Division of Molecular Biology, Indian Council of Medical Research-National AIDS Research Institute, Pune, Maharashtra, India
| | - Zakir Khan
- Department of Biomedical Sciences, Pathology and Laboratory Medicine, Cedars- Sinai Medical Centre, Los Angeles, USA
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Rai N, Singh AK, Keshri PK, Barik S, Kamble SC, Singh SK, Kumar R, Mishra P, Kotiya D, Gautam V. Probiotics for Management of Gastrointestinal Cancers. PROBIOTIC RESEARCH IN THERAPEUTICS 2021:191-209. [DOI: 10.1007/978-981-15-8214-1_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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The Role of Probiotics in Cancer Prevention. Cancers (Basel) 2020; 13:cancers13010020. [PMID: 33374549 PMCID: PMC7793079 DOI: 10.3390/cancers13010020] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/17/2020] [Accepted: 12/21/2020] [Indexed: 12/23/2022] Open
Abstract
Simple Summary Cancer is considered one of the leading causes of human mortality in the world and is the subject of much research. The risk of developing cancer depends on genetic factors, as well as the body’s immune status. The intestinal microbiome plays very important role in maintaining homeostasis in the human body. Probiotics have gained increasing medical significance due to the beneficial effect on the human body associated with the prevention and support of the treatment of many chronic diseases, including cancer in the absence of side effects. The aim of this review was to summarize the knowledge about the effect of probiotic microorganisms in the prevention of cancer. There is a lot of evidence that the use of probiotics can play an important role in cancer prevention and support anti-cancer therapies. Abstract The gut microbiome can play important role in maintaining homeostasis in the human body. An imbalance in the gut microbiome can lead to pro-inflammatory immune responses and the initiation of disease processes, including cancer. The research results prove some strains of probiotics by modulating intestinal microbiota and immune response can be used for cancer prevention or/and as adjuvant treatment during anticancer chemotherapy. This review presents the latest advances in research into the effectiveness of probiotics in the prevention and treatment support of cancer. The described issues concern to the anticancer activity of probiotic microorganisms and their metabolites. In addition, we described the potential mechanisms of probiotic chemoprevention and the advisability of using probiotics.
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Badgeley A, Anwar H, Modi K, Murphy P, Lakshmikuttyamma A. Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives. Biochim Biophys Acta Rev Cancer 2020; 1875:188494. [PMID: 33346129 DOI: 10.1016/j.bbcan.2020.188494] [Citation(s) in RCA: 119] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 12/11/2020] [Accepted: 12/13/2020] [Indexed: 02/07/2023]
Abstract
Bacteria present in probiotics, particularly the common Lactobacillus and Bifidobacterium microbes, have been found to induce anti-cancer action by enhancing cancer cell apoptosis and protecting against oxidative stress. Probiotics supplements also decrease the cancer-producing microorganism Fusobacterium. Studies have demonstrated that gut microbiota modifies the effect of chemo/radiation therapy. Gut microbes not only enhance the action of chemotherapy drugs but also reduce the side effects of these medications. Additionally, gut microbes reduce immunotherapy toxicity, in particular, the presence of Bacteroidetes or Bifidobacterium decreases the development of colitis by ipilimumab therapy. Probiotics supplements containing Bifidobacterium also reduce chemotherapy-induced mucositis and radiation-induced diarrhea. This review focused on elucidating the mechanism behind the anti-cancer action of Bifidobacterium species. Available studies have revealed Bifidobacterium species decrease cancer cell proliferation via the inhibition of growth factor signaling as well as inducing mitochondrial-mediated apoptosis. Moreover, Bifidobacterium species reduce the adverse effects of chemo/immuno/radiation therapy by inhibiting proinflammatory cytokines. Further clinical studies are needed to identify the powerful and suitable Bifidobacterium strain for the development of adjuvant therapy to support chemo/immuno/radiation therapy.
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Affiliation(s)
- Aja Badgeley
- Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Hina Anwar
- Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Karan Modi
- Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Paige Murphy
- Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Ashakumary Lakshmikuttyamma
- Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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Samanta S. Potential Impacts of Prebiotics and Probiotics in Cancer Prevention. Anticancer Agents Med Chem 2020; 22:605-628. [PMID: 33305713 DOI: 10.2174/1871520621999201210220442] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 09/15/2020] [Accepted: 10/26/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cancer is a serious problem throughout the world. The pathophysiology of cancer is multifactorial and is also related to gut microbiota. Intestinal microbes are the useful resident of the healthy human. They play various aspects of human health including nutritional biotransformation, flushing of the pathogens, toxin neutralization, immune response, and onco-suppression. Disruption in the interactions among the gut microbiota, intestinal epithelium, and the host immune system are associated with gastrointestinal disorders, neurodegenerative diseases, metabolic syndrome, and cancer. Probiotic bacteria (Lactobacillus spp., Bifidobacterium spp.) have been regarded as beneficial to health and shown to play a significant role in immunomodulation and displayed preventive role against obesity, diabetes, liver disease, inflammatory bowel disease, tumor progression, and cancer. OBJECTIVE The involvement of gut microorganisms in cancer development and prevention has been recognized as a balancing factor. The events of dysbiosis emphasize metabolic disorder and carcinogenesis. The gut flora potentiates immunomodulation and minimizes the limitations of usual chemotherapy. The significant role of prebiotics and probiotics on the improvement of immunomodulation and antitumor properties has been considered. METHODS I had reviewed the literature on the multidimensional activities of prebiotics and probiotics from the NCBI website database PubMed, Springer Nature, Science Direct (Elsevier), Google Scholar database to search relevant articles. Specifically, I had focused on the role of prebiotics and probiotics in immunomodulation and cancer prevention. RESULTS Prebiotics are the nondigestible fermentable sugars that selectively influence the growth of probiotic organisms that exert immunomodulation over the cancerous growth. The oncostatic properties of bacteria are mediated through the recruitment of cytotoxic T cells, natural killer cells, and oxidative stress-induced apoptosis in the tumor microenvironment. Moreover, approaches have also been taken to use probiotics as an adjuvant in cancer therapy. CONCLUSION The present review has indicated that dysbiosis is the crucial factor in many pathological situations including cancer. Applications of prebiotics and probiotics exhibit the immune-surveillance as oncostatic effects. These events increase the possibilities of new therapeutic strategies for cancer prevention.
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Affiliation(s)
- Saptadip Samanta
- Department of Physiology, Midnapore College, Midnapore, Paschim Medinipur, 721101, West Bengal,. India
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