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Sadri M, Shafaghat Z, Roozbehani M, Hoseinzadeh A, Mohammadi F, Arab FL, Minaeian S, Fard SR, Faraji F. Effects of Probiotics on Liver Diseases: Current In Vitro and In Vivo Studies. Probiotics Antimicrob Proteins 2025; 17:1688-1710. [PMID: 39739162 DOI: 10.1007/s12602-024-10431-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2024] [Indexed: 01/02/2025]
Abstract
Various types of liver or hepatic diseases cause the death of about 2 million people worldwide every year, of which 1 million die from the complications of cirrhosis and another million from hepatocellular carcinoma and viral hepatitis. Currently, the second most common solid organ transplant is the liver, and the current rate represents less than 10% of global transplant requests. Hence, finding new approaches to treat and prevent liver diseases is essential. In liver diseases, the interaction between the liver, gut, and immune system is crucial, and probiotics positively affect the human microbiota. Probiotics are a non-toxic and biosafe alternative to synthetic chemical compounds. Health promotion by lowering cholesterol levels, stimulating host immunity, the natural gut microbiota, and other functions are some of the activities of probiotics, and their metabolites, including bacteriocins, can exert antimicrobial effects against a broad range of pathogenic bacteria. The present review discusses the available data on the results of preclinical and clinical studies on the effects of probiotic administration on different types of liver diseases.
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Affiliation(s)
- Maryam Sadri
- Department of Immunology, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Shafaghat
- Department of Immunology, Iran University of Medical Sciences, Tehran, Iran
| | - Mona Roozbehani
- Vaccine Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Akram Hoseinzadeh
- Cancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Fatemeh Mohammadi
- Department of Immunology, School of Medicine, Mashhad University of Medicine Sciences, Mashhad, Iran
| | - Fahimeh Lavi Arab
- Department of Immunology, School of Medicine, Mashhad University of Medicine Sciences, Mashhad, Iran
| | - Sara Minaeian
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medicine Sciences, Tehran, Iran
| | - Soheil Rahmani Fard
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medicine Sciences, Tehran, Iran
| | - Fatemeh Faraji
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medicine Sciences, Tehran, Iran.
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Ray D, Bose P, Mukherjee S, Roy S, Kaity S. Recent drug delivery systems targeting the gut-brain-microbiome axis for the management of chronic diseases. Int J Pharm 2025; 680:125776. [PMID: 40425058 DOI: 10.1016/j.ijpharm.2025.125776] [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: 02/25/2025] [Revised: 05/14/2025] [Accepted: 05/24/2025] [Indexed: 05/29/2025]
Abstract
In recent years, the study of microorganisms and the brain has become increasingly connected. The gut-brain-microbiome axis (GBMA), a bi-directional communication system, is the key part of how the body's bacteria and the brain interact. This system can influence the brain and behaviour. Changes in this relationship have been linked to various mental and physical health conditions. The immune system, tryptophan metabolism, the vagus nerve, and the enteric nervous system all facilitate connections between the gut and brain. Microbes produce Peptidoglycans, branched-chain amino acids, and short-chain fatty acids, which are involved in this communication. Studies suggest the gut microbiome may be involved in conditions like autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Researchers are exploring the gut-brain connection to cure a variety of disorders, such as neurological disorders, cancers, metabolic problems, and liver diseases. Developing novel drug delivery systems is a key focus in GBMA for therapeutic targeting at various disease pathways. Notable platforms attracting significant interest include silica nanoparticle-based delivery systems for probiotic spores, composite hydrogels formulated from protein isolates and citrus pectin, and biomimetic nanosystems designed for targeted therapeutic delivery. This review summarizes different methods of delivering drugs and using dietary interventions to target the GBMA and treat these conditions in a less invasive way. By understanding how the gut and brain communicate, scientists aim to develop new and more effective therapies for these complex chronic diseases.
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Affiliation(s)
- Debjani Ray
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Piyas Bose
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Saptarshi Mukherjee
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Subhadeep Roy
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India
| | - Santanu Kaity
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India.
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3
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Ren S, Zhang Y, Wang X, Su J, Wang X, Yuan Z, He X, Guo S, Chen Y, Deng S, Wu X, Li M, Du F, Zhao Y, Shen J, Hu W, Li X, Xiao Z. Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma. Front Immunol 2025; 16:1526967. [PMID: 40070843 PMCID: PMC11893557 DOI: 10.3389/fimmu.2025.1526967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.
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Affiliation(s)
- Siqi Ren
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yinping Zhang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xingyue Wang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Jiahong Su
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xiang Wang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zijun Yuan
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xinyu He
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Sipeng Guo
- Research and Experiment Center, Sichuan College of Traditional Chinese Medicine, Mianyang, China
| | - Yu Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Shuai Deng
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Wei Hu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Xiaobing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Research and Experiment Center, Sichuan College of Traditional Chinese Medicine, Mianyang, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Gulin Traditional Chinese Medicine Hospital, Luzhou, China
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Zhang N, Ye S, Wang X, Wang K, Zhong F, Yao F, Liu J, Huang B, Xu F, Wang X. Hepatic Symbiotic Bacterium L. reuteri FLRE5K1 Inhibits the Development and Progression of Hepatocellular Carcinoma via Activating the IFN-γ/CXCL10/CXCR3 Pathway. Probiotics Antimicrob Proteins 2024; 16:1158-1171. [PMID: 37289406 DOI: 10.1007/s12602-023-10098-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/25/2023] [Indexed: 06/09/2023]
Abstract
Symbiotic bacteria participate in the formation of the structure and function of the tissues and organs in which they live, and play an essential role in maintaining the balance between health and disease. Lactobacillus reuteri FLRE5K1 was isolated from the liver of healthy mice and proved to be a probiotic with anti-melanoma activity in previous studies. The relationship between hepatic symbiotic probiotics and hepatocellular carcinoma (HCC) has not been reported yet. In the present study, L. reuteri FLRE5K1 was initially confirmed to successfully enter the liver after being administered by gavage, and the efficacy of probiotic feeding on HCC and its potential mechanism of inhibiting tumor progression were investigated by an orthotopic liver cancer model established. The results showed that L. reuteri FLRE5K1 significantly reduced the tumor formation rate and inhibited tumor growth in mice. From the perspective of mechanism, activation of the IFN-γ/CXCL10/CXCR3 pathway, as well as its positive feedback on the secretion of IFN-γ, induced the polarization of Th0 cell to Th1 cells and inhibited the differentiation of Tregs, which played a key role in the inhibitory effect of L. reuteri FLRE5K1 on the development and progression of HCC.
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Affiliation(s)
- Nan Zhang
- Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Shuiwen Ye
- Department of Blood Transfusion, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Xinlu Wang
- Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Kang Wang
- Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Fangmin Zhong
- Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Fangyi Yao
- Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Jing Liu
- Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Bo Huang
- Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China
| | - Feng Xu
- Jiangxi-Oai Joint Research Institute, Nanchang University, Nanchang, 330047, Jiangxi, China.
| | - Xiaozhong Wang
- Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330047, Jiangxi, China.
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5
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Aghaei F, Arabzadeh E, Mahmoodzadeh Hosseini H, Shirvani H. Exercise Training and Probiotic Lacticaseibacillus rhamnosus GG Reduce Tetracycline-Induced Liver Oxidative Stress and Inflammation in Rats with Hepatic Steatosis. Probiotics Antimicrob Proteins 2023; 15:1393-1405. [PMID: 36169882 DOI: 10.1007/s12602-022-09994-6] [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] [Accepted: 09/19/2022] [Indexed: 10/25/2022]
Abstract
Lifestyle modification with regular exercise can improve metabolic diseases by reducing lipid profile and inflammation. Probiotics have been recently recommended not only for gastrointestinal diseases but also for metabolic and even degenerative diseases. Therefore, in the present study, the effect of high-intensity interval training (HIIT) and Lacticaseibacillus rhamnosus strain GG (LGG) as a probiotic on tetracycline-induced hepatic steatosis in an animal model was evaluated. Eighty male Wistar rats were randomly divided into eight groups (n = 10 in each group): control, LGG, HIIT, LGG + HIIT, tetracycline-induced (TTC), TTC + LGG, TTC + HIIT, and TTC + LGG + HIIT. The rats are treated by intraperitoneal injection (IP) with 140 mg kg-1 tetracycline, an antibiotic previously known to induce steatosis. The exercise training groups performed HIIT 5 days/week for 5 weeks, and 107 CFU/ml of Lacticaseibacillus rhamnosus GG was gavaged for the LGG groups 5 days/week for 5 weeks. Fatty droplets in the hepatocyte were considered with Oil Red staining. TTC-receiving rats have more lipid accumulation and larger lipid droplets in the liver compared to healthy animals. The two-way ANOVA showed that the interaction of LGG and HIIT significantly decreased LDL, cholesterol, and triglyceride in the healthy rats (p < 0.05). In TTC-receiving rats, the interaction of LGG and HIIT significantly increased HDL and SOD and significantly decreased triglyceride, ALP, AST, and ALT (p < 0.05). The consumption of probiotic LGG, along with HIIT with control of lipid profile and liver enzymes and improvement of the oxidative capacity, neutralizes the damage of TTC to liver tissue. Therefore, this protocol can be recommended for people with hepatic steatosis.
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Affiliation(s)
- Fariba Aghaei
- Faculty of Physical Education and Sport Sciences, Karaj Branch, Islamic Azad University, Alborz, Iran
| | - Ehsan Arabzadeh
- Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hamideh Mahmoodzadeh Hosseini
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hossein Shirvani
- Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Stanic B, Milošević N, Sukur N, Samardzija Nenadov D, Fa Nedeljkovic S, Škrbić S, Andric N. An in silico toxicogenomic approach in constructing the aflatoxin B1-mediated regulatory network of hub genes in hepatocellular carcinoma. Toxicol Mech Methods 2023; 33:552-562. [PMID: 36978281 DOI: 10.1080/15376516.2023.2196686] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 03/17/2023] [Accepted: 03/18/2023] [Indexed: 03/30/2023]
Abstract
Aflatoxin B1 (AFB1) can cause hepatocellular carcinoma (HCC) through a mutagenic mode of action but can also lead to global changes in gene expression; however, the AFB1 network of molecular pathways involved in HCC is not known. Here, we used toxicogenomic data from human liver cells exposed to AFB1 to infer the network of AFB1-responsive molecular pathways involved in HCC. The following computational tools: STRING, MCODE, cytoHubba, iRegulon, kinase enrichment tool KEA3, and DAVID were used to identify protein-protein interaction network, hub genes, transcription factors (TFs), upstream kinases, and biological processes (BPs). Predicted molecular events were validated with an external dataset, whereas the hub genes in HCC were validated using the UALCAN database. The results revealed an association between AFB1 and the hub genes involved in the cell cycle. We identified TFs that regulate the hub genes and linked them with upstream kinases including cyclin-dependent kinases, mitogen-activated protein kinase 1, and AKT. This approach enabled the construction of the AFB1-mediated regulatory network consisting of upstream kinases, TFs, hub genes, and BPs, thus revealing the signaling hierarchy and information flow that may contribute to AFB1-induced HCC. This could be a useful tool in predicting the molecular mechanisms involved in chemical-induced diseases when available toxicogenomic data exist.
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Affiliation(s)
- Bojana Stanic
- Department of Biology and Ecology, University of Novi Sad, Novi Sad, Serbia
| | - Nemanja Milošević
- Department of Mathematics and Informatics, University of Novi Sad, Novi Sad, Serbia
| | - Nataša Sukur
- Department of Mathematics and Informatics, University of Novi Sad, Novi Sad, Serbia
| | | | | | - Srđan Škrbić
- Department of Mathematics and Informatics, University of Novi Sad, Novi Sad, Serbia
| | - Nebojsa Andric
- Department of Biology and Ecology, University of Novi Sad, Novi Sad, Serbia
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Sadiq A, Arshad MS, Amjad RB, Munir H, Rohi M, Khalid W, Nadeem MT, Suleria HAR. Impact of gamma irradiation and guava leaf extract on the quality and storage stability of chicken patties. Food Sci Nutr 2023; 11:4485-4501. [PMID: 37576041 PMCID: PMC10420856 DOI: 10.1002/fsn3.3174] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 11/24/2022] [Accepted: 11/26/2022] [Indexed: 08/15/2023] Open
Abstract
The current investigation was carried out to evaluate the impact of gamma irradiation and guava leaf extract (GLE) on chicken meat patties. The effects of treatments on chicken meat patties were determined by physicochemical, stability (oxidative and microbial), and antioxidant status during different packaging (aerobic and vacuum) at storage intervals (0, 5, and 10 days). The changes in physicochemical parameters of chicken patties were observed on various treatments, storage intervals, and different packaging. The TBARS and POV were found to increase significantly (p < .05) on 2 kGy and with the passage of storage time. The results of microbial load in samples were found to decrease on gamma irradiation with and without GLE. The antioxidant profile in chicken patties was with respect to control. Slight changes were seen in sensory parameters on different treatments at storage intervals. It is concluded that gamma irradiation eliminated the microbes and different concentrations of GLE improve the stability and antioxidant profile of chicken patties.
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Affiliation(s)
- Anam Sadiq
- Department of Food Science, Faculty of Life SciencesGovernment College UniversityFaisalabadPakistan
| | - Muhammad Sajid Arshad
- Department of Food Science, Faculty of Life SciencesGovernment College UniversityFaisalabadPakistan
| | | | - Haroon Munir
- Department of Food Science, Faculty of Life SciencesGovernment College UniversityFaisalabadPakistan
| | - Madiha Rohi
- Department of Food Science and TechnologyGovernment College Women University FaisalabadFaisalabadPakistan
| | - Waseem Khalid
- University Institute of Food Science and TechnologyThe University of LahoreLahorePakistan
| | - Muhammad Tahir Nadeem
- Department of Food Science, Faculty of Life SciencesGovernment College UniversityFaisalabadPakistan
- Grand Asian University SialkotSialkotPakistan
| | - Hafiz Ansar Rasul Suleria
- School of Agriculture and Food, Faculty of Veterinary and Agricultural SciencesThe University of MelbourneParkvilleVic.Australia
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Szopa K, Szajnar K, Pawlos M, Znamirowska-Piotrowska A. Probiotic Fermented Goat's and Sheep's Milk: Effect of Type and Dose of Collagen on Survival of Four Strains of Probiotic Bacteria during Simulated In Vitro Digestion Conditions. Nutrients 2023; 15:3241. [PMID: 37513662 PMCID: PMC10384213 DOI: 10.3390/nu15143241] [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: 06/15/2023] [Revised: 06/28/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Microbial tolerance of digestive stresses depends not only on the bacterial strain but also on the structure and physicochemical properties of the supply chain and the foods that contain it. In the present study, we aimed to evaluate the effects of the type of milk (ovine, caprine) and the type and dose of collagen on the viability of four probiotic strains, Lacticaseibacillus paracasei L-26, Lacticaseibacillus casei 431, Lactobacillus acidophilus LA-5, and Lacticaseibacillus rhamnosus Lr-32, during in vitro gastrointestinal digestion. The highest survival rate under simulated in vitro digestion conditions compared to the number of cells before digestion was found in two strains, L. casei and L. paracasei, where survival rates were greater than 50% in each batch. The survival rate of the L. rhamnosus strain ranged from 41.05% to 64.23%. In caprine milk fermented by L. acidophilus, a higher survival rate was found in milk with 1.5% hydrolysate than the control, by about 6%. Survival of the L. rhamnosus strain was favorably affected by the 3% addition of bovine collagen in caprine milk, which increased survival by about 14% compared to the control sample. Adding 3% of hydrolysate to sheep's and goat's milk enhanced the survival of the L. rhamnosus strain by 3% and 19%, respectively. This study reports that fermented caprine and ovine milk may be suitable matrices for the probiotic supply of commercial dairy starter cultures and promote gut homeostasis.
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Affiliation(s)
- Kamil Szopa
- Department of Dairy Technology, Institute of Food Technology and Nutrition, University of Rzeszow, Ćwiklińskiej 2D, 35601 Rzeszow, Poland
| | - Katarzyna Szajnar
- Department of Dairy Technology, Institute of Food Technology and Nutrition, University of Rzeszow, Ćwiklińskiej 2D, 35601 Rzeszow, Poland
| | - Małgorzata Pawlos
- Department of Dairy Technology, Institute of Food Technology and Nutrition, University of Rzeszow, Ćwiklińskiej 2D, 35601 Rzeszow, Poland
| | - Agata Znamirowska-Piotrowska
- Department of Dairy Technology, Institute of Food Technology and Nutrition, University of Rzeszow, Ćwiklińskiej 2D, 35601 Rzeszow, Poland
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Youn HY, Kim HJ, Kim DH, Jang YS, Kim H, Seo KH. Gut microbiota modulation via short-term administration of potential probiotic kefir yeast Kluyveromyces marxianus A4 and A5 in BALB/c mice. Food Sci Biotechnol 2023; 32:589-598. [PMID: 36911334 PMCID: PMC9992467 DOI: 10.1007/s10068-023-01268-3] [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: 09/21/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 02/16/2023] Open
Abstract
Kefir yeast, Kluyveromyces marxianus, has been evaluated for its potential probiotic properties-survivability, non-pathogenicity, and antioxidant and anti-microbial activities. However, host gut microbiota modulation of kefir yeasts remains unclear. Here, we compared kefir yeast strains K. marxianus A4 (Km A4) and K. marxianus A5 (Km A5) with Saccharomyces boulardii ATCC MYA-796 (Sb MYA-796) by investigating their adherence to colorectal adenocarcinoma (Caco-2) cells and gut microbiota modulation in BALB/c mice. The kefir yeast strains exhibited higher intestinal cell adhesion than Sb MYA-796 (p < 0.05). Bacteroidetes, Bacteroidales, and Bacteroides were more abundant in the 1 × 108 CFU/mL of Km A4 treatment group than in the control group (p < 0.05). Moreover, 1 × 108 CFU/mL of Km A5 increased Corynebacteriales and Corynebacterium compared to the 1 × 108 CFU/mL of Km A4 treatment group (p < 0.01). The results showed that Km A4 and Km A5 had good Caco-2 cell adhesion ability and modulated gut microbiota upon short-term administration in healthy mice. Supplementary Information The online version contains supplementary material available at 10.1007/s10068-023-01268-3.
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Affiliation(s)
- Hye-Young Youn
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Hyeon-Jin Kim
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Dong-Hyeon Kim
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Yong-Seok Jang
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
| | - Hyunsook Kim
- Department of Food & Nutrition, College of Human Ecology, Hanyang University, Seoul, 04763 Republic of Korea
| | - Kun-Ho Seo
- Center for One Health, Department of Veterinary Public Health, College of Veterinary Medicine, Konkuk University, Seoul, 05029 Republic of Korea
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10
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Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol 2023; 14:1133308. [PMID: 36845131 PMCID: PMC9950271 DOI: 10.3389/fimmu.2023.1133308] [Citation(s) in RCA: 108] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 02/02/2023] [Indexed: 02/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the third leading cause of tumor-related mortality worldwide. In recent years, the emergency of immune checkpoint inhibitor (ICI) has revolutionized the management of HCC. Especially, the combination of atezolizumab (anti-PD1) and bevacizumab (anti-VEGF) has been approved by the FDA as the first-line treatment for advanced HCC. Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing to drug resistance and frequent recurrence. The tumor microenvironment (TME) of HCC is a complex and structured mixture characterized by abnormal angiogenesis, chronic inflammation, and dysregulated extracellular matrix (ECM) remodeling, collectively contributing to the immunosuppressive milieu that in turn prompts HCC proliferation, invasion, and metastasis. The tumor microenvironment coexists and interacts with various immune cells to maintain the development of HCC. It is widely accepted that a dysfunctional tumor-immune ecosystem can lead to the failure of immune surveillance. The immunosuppressive TME is an external cause for immune evasion in HCC consisting of 1) immunosuppressive cells; 2) co-inhibitory signals; 3) soluble cytokines and signaling cascades; 4) metabolically hostile tumor microenvironment; 5) the gut microbiota that affects the immune microenvironment. Importantly, the effectiveness of immunotherapy largely depends on the tumor immune microenvironment (TIME). Also, the gut microbiota and metabolism profoundly affect the immune microenvironment. Understanding how TME affects HCC development and progression will contribute to better preventing HCC-specific immune evasion and overcoming resistance to already developed therapies. In this review, we mainly introduce immune evasion of HCC underlying the role of immune microenvironment, describe the dynamic interaction of immune microenvironment with dysfunctional metabolism and the gut microbiome, and propose therapeutic strategies to manipulate the TME in favor of more effective immunotherapy.
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Affiliation(s)
| | | | | | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Greco G, Zeppa SD, Agostini D, Attisani G, Stefanelli C, Ferrini F, Sestili P, Fimognari C. The Anti- and Pro-Tumorigenic Role of Microbiota and Its Role in Anticancer Therapeutic Strategies. Cancers (Basel) 2022; 15:190. [PMID: 36612186 PMCID: PMC9818275 DOI: 10.3390/cancers15010190] [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: 11/15/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 12/31/2022] Open
Abstract
Human gut microbiota physiologically and actively participates as a symbiont to a wide number of fundamental biological processes, such as absorption and metabolism of nutrients, regulation of immune response and inflammation; gut microbiota plays also an antitumor role. However, dysbiosis, resulting from a number of different situations-dysmicrobism, infections, drug intake, age, diet-as well as from their multiple combinations, may lead to tumorigenesis and is associated with approximately 20% of all cancers. In a diagnostic, prognostic, therapeutic, and epidemiological perspective, it is clear that the bifaceted role of microbiota needs to be thoroughly studied and better understood. Here, we discuss the anti- and pro-tumorigenic potential of gut and other microbiota districts along with the causes that may change commensal bacteria from friend to foes.
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Affiliation(s)
- Giulia Greco
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy
| | - Sabrina Donati Zeppa
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Deborah Agostini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Giuseppe Attisani
- Department for Life Quality Studies, University of Bologna, 47921 Rimini, Italy
| | - Claudio Stefanelli
- Department for Life Quality Studies, University of Bologna, 47921 Rimini, Italy
| | - Fabio Ferrini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Piero Sestili
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Carmela Fimognari
- Department for Life Quality Studies, University of Bologna, 47921 Rimini, Italy
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12
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Kowalczyk M, Znamirowska-Piotrowska A, Buniowska-Olejnik M, Pawlos M. Sheep Milk Symbiotic Ice Cream: Effect of Inulin and Apple Fiber on the Survival of Five Probiotic Bacterial Strains during Simulated In Vitro Digestion Conditions. Nutrients 2022; 14:nu14214454. [PMID: 36364717 PMCID: PMC9655080 DOI: 10.3390/nu14214454] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 10/17/2022] [Accepted: 10/20/2022] [Indexed: 01/24/2023] Open
Abstract
We conducted a study to determine the survival of bacterial cells under in vitro digestion. For this purpose, ice cream mixes were prepared: control, with 4% inulin, 2.5% inulin and 1.5% apple fiber and 4% apple fiber. Each inoculum (pH = 4.60 ± 0.05), containing 9 log cfu g-1 bacteria, at 5% (w/w) was added to the ice cream mixes (Lacticaseibacilluscasei 431, Lactobacillus acidophilus LA-5, Lacticaseibacillus paracasei L-26, Lacticaseibacillusrhamnosus, Bifidobacterium animalis ssp. lactis BB-12) and fermentation was carried out to pH 4.60 ± 0.05. The in vitro digestion method simulated the stages of digestion that occur in the mouth, stomach and small intestine under optimal controlled conditions (pH value, time and temperature). At each stage of digestion, the survival rate of probiotic bacteria was determined using the plate-deep method. As expected, in the oral stage, there was no significant reduction in the viability of the probiotic bacteria in any ice cream group compared to their content before digestion. In the stomach stage, Bifidobacterium animalis ssp. lactis BB-12 strain had the highest viable counts (8.48 log cfu g-1) among the control samples. Furthermore, a 4% addition of inulin to ice cream with Bifidobacterium BB-12 increased gastric juice tolerance and limited strain reduction by only 16.7% compared to the number of bacterial cells before digestion. Regarding ice cream samples with Bifidobacterium BB-12, replacing part of the inulin with apple fiber resulted in increased survival at the stomach stage and a low reduction in the bacterial population of only 15.6% compared to samples before digestion. At the stomach stage, the positive effect of the addition of inulin and apple fiber was also demonstrated for ice cream samples with Lacticaseibacilluscasei 431 (9.47 log cfu g-1), Lactobacillus acidophilus LA-5 (8.06 log cfu g-1) and Lacticaseibacillus paracasei L-26 (5.79 log cfu g-1). This study showed the highest sensitivity to simulated gastric stress for ice cream samples with Lacticaseibacillusrhamnosus (4.54 log cfu g-1). Our study confirmed that the 4% addition of inulin to ice cream increases the survival rate of L. casei and Bifidobacterium BB-12 in simulated intestinal juice with bile by 0.87 and 2.26 log cfu g-1, respectively. The highest viable count in the small intestine stage was observed in ice cream with L. acidophilus. The addition of inulin increased the survival of L. rhamnosus by 10.8% and Bifidobacterium BB-12 by about 22% under conditions of simulated in vitro digestion compared to their control samples. The survival rates of L. casei and L. paracasei were also highly affected by the 4% addition of apple fiber, where the increase under gastrointestinal passage conditions was determined to range from 7.86-11.26% compared to their control counterparts. In comparison, the lowest survival rate was found in the control ice cream with L. rhamnosus (47.40%). In our study at the intestinal stage, only five ice cream groups: a sample with 4% inulin and L. acidophilus, a control sample with Bifidobacterium BB12, a sample with 2.5% inulin and 1.5% apple fiber with Bifidobacterium BB12, a control sample with L. rhamnosus, a sample with 4% fiber and L. rhamnosus reported bacterial cell counts below 6 log cfu g-1 but higher than 5 log cfu g-1. However, in the remaining ice cream groups, viable counts of bacterial cells ranged from 6.11 to 8.88 log cfu g-1, ensuring a therapeutic effect. Studies have clearly indicated that sheep milk ice cream could provide a suitable matrix for the delivery of probiotics and prebiotics and contribute to intestinal homeostasis. The obtained results have an applicative character and may play an essential role in developing new functional sheep milk ice cream.
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Role of Intestinal Microbes in Chronic Liver Diseases. Int J Mol Sci 2022; 23:ijms232012661. [PMID: 36293518 PMCID: PMC9603943 DOI: 10.3390/ijms232012661] [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: 08/31/2022] [Revised: 10/15/2022] [Accepted: 10/19/2022] [Indexed: 11/07/2022] Open
Abstract
With the recent availability and upgrading of many emerging intestinal microbes sequencing technologies, our research on intestinal microbes is changing rapidly. A variety of investigations have found that intestinal microbes are essential for immune system regulation and energy metabolism homeostasis, which impacts many critical organs. The liver is the first organ to be traversed by the intestinal portal vein, and there is a strong bidirectional link between the liver and intestine. Many intestinal factors, such as intestinal microbes, bacterial composition, and intestinal bacterial metabolites, are deeply involved in liver homeostasis. Intestinal microbial dysbiosis and increased intestinal permeability are associated with the pathogenesis of many chronic liver diseases, such as alcoholic fatty liver disease (AFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic hepatitis B (CHB), chronic hepatitis C (CHC), autoimmune liver disease (AIH) and the development of hepatocellular carcinoma (HCC). Intestinal permeability and dysbacteriosis often lead to Lipopolysaccharide (LPS) and metabolites entering in serum. Then, Toll-like receptors activation in the liver induces the exposure of the intestine and liver to many small molecules with pro-inflammatory properties. And all of these eventually result in various liver diseases. In this paper, we have discussed the current evidence on the role of various intestinal microbes in different chronic liver diseases. As well as potential new therapeutic approaches are proposed in this review, such as antibiotics, probiotics, and prebiotics, which may have an improvement in liver diseases.
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Zoghi A, Todorov SD, Khosravi-Darani K. Potential application of probiotics in mycotoxicosis reduction in mammals and poultry. Crit Rev Toxicol 2022; 52:731-741. [PMID: 36757083 DOI: 10.1080/10408444.2023.2168176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
Mycotoxins in feedstuffs are considered as a principal worry by food safety authorities worldwide because most of them can be transferred from the feed to food commodities of animal origin, and further consumed by humans. Therefore, effective alternatives for the reduction of the impact of mycotoxins need to be applied in the feed production industry. Applications of beneficial microorganisms (probiotics) can be alternative and applied as feed additives in order to reduce or eliminate the toxic effects of mycotoxins on animals. The aim of this article is to provide information on the role of beneficial microorganisms (probiotics) and point out their role in the reduction of the effect of mycotoxin toxicity in farming animals (mammals and poultry). The objective was to provide a summary of the existing knowledge based on the application of different strains belonging to the group of lactic acid bacteria (LAB) or yeasts that are already or can be future employed in the feed industry, in order to reduce mycotoxicosis presence in mammals and poultry exposed to mycotoxin-contaminated feed. Moreover, an overview of mycotoxins toxicity in mammals and poultry will be presented, and furthermore, the role of the beneficial microorganisms (including probiotics) in the reduction of mycotoxins toxicity (aflatoxicosis, deoxynivalenol, zearalenone, ochratoxin A, and fumonisin toxicities) will be described in detail.
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Affiliation(s)
- Alaleh Zoghi
- Department of Food Science and Technology, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Svetoslav Dimitrov Todorov
- Department of Advanced Convergence, ProBacLab, Handong Global University, Pohang, Gyeongbuk, Republic of Korea
| | - Kianoush Khosravi-Darani
- Department of Food Science and Technology, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice. Sci Rep 2022; 12:16206. [PMID: 36171333 PMCID: PMC9519992 DOI: 10.1038/s41598-022-20296-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 09/12/2022] [Indexed: 11/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), a hepatic characteristic of metabolic syndrome, received significant attention in clinical settings. The multiple-hit theory is one of the proposed mechanisms of NAFLD, and gut dysbiosis is considered a hit. Thus, controlling gut microbiota is a potential target in the management of NAFLD, and probiotics can be used as a treatment agent for NAFLD. The current study aimed to investigate the efficacy of probiotics against nonalcoholic steatohepatitis in a hepatocyte-specific PTEN knockout mouse model that mimics the characteristics of human NAFLD. Probiotics were administered to male knockout mice for 8 or 40 weeks. Next, we assessed hepatic inflammation, fibrosis, carcinogenesis, and oxidative stress. Probiotics were found to reduce serum transaminase levels, NAFLD activity score, and the gene expression of pro-inflammatory cytokines. In addition, they decreased liver fibrosis grade, which was examined via Sirius red staining, gene expression of fibrotic markers, and hydroxyproline. Furthermore, probiotics suppressed the number of liver tumors, particular in HCC. Probiotics reduced oxidative stresses, including glutathione levels, and anti-oxidative stress marker, which may be an underlying mechanism for their beneficial effects. In conclusion, probiotics treatment had beneficial effects against NAFLD and carcinogenesis in hepatocyte-specific PTEN knockout mice.
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16
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Utilization of autochthonous lactic acid bacteria attaining safety attributes, probiotic properties, and hypocholesterolemic potential in the production of a functional set yogurt. BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 2022. [DOI: 10.1016/j.bcab.2022.102448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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17
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Zhang T, Zhang R, Zhao G, Liu W, Pan L, Tong Y, Jiang M, Zhang H, Xiao Z, Pandol SJ, Fu X, Han YP, Zheng X. Plant green pigment of chlorophyllin attenuates inflammatory bowel diseases by suppressing autophagy activation in mice. Am J Physiol Gastrointest Liver Physiol 2022; 323:G102-G113. [PMID: 35638642 PMCID: PMC9291423 DOI: 10.1152/ajpgi.00291.2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are intestinal complications characterized by chronic inflammation, autophagy abnormality, and lysosomal stress, which are derived from genetic predisposition and environmental risk factors. It is generally precepted that dietary green vegetable is beneficial for physiological homeostasis. In this study, we found that dextran sulfate sodium (DSS)-induced colitis and altered intestinal epithelia in mice were attenuated by oral administration of chlorophyllin (CHL), a water-soluble derivate of chlorophyll. In DSS-treated mice, autophagy was persistently activated in intestinal tissues and associated with bowel disorders. Conversely, supplement of CHL in diet or gavage suppressed intestinal inflammation, downregulated autophagy flux in intestinal tissue, and relieved endoplasmic reticulum stress. In vitro studies show that CHL could activate Akt and mTOR pathways, leading to downregulation of autophagic and lysosomal flux. Thus, consumption of green vegetables and chlorophyllin may be beneficial for IBD recovery in part through alleviation of inflammation and autolysosomal flux.NEW & NOTEWORTHY Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disease, while the etiology remains poorly understood. Dietary composition and lifestyle are crucial for pathogenesis and progression of IBD. In this study, we observed that autophagy in the intestinal tissue was persistently activated in IBD mice. Chlorophyllin (CHL), a water-soluble derivate of chlorophyll, can attenuate colitis by regulating autophagy and inflammation. Thus, consumption of green vegetables and chlorophyllin may be beneficial for IBD recovery.
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Affiliation(s)
- Tianci Zhang
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Ruofei Zhang
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Guangfu Zhao
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Wei Liu
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Liwei Pan
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Ying Tong
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Mingshan Jiang
- 2Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hu Zhang
- 2Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhixiong Xiao
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Stephen J. Pandol
- 3Department of Medicine, Cedar-Sinai Medical Center, Los Angeles, California
| | - Xiansheng Fu
- 4The Division of Gastroenterology, The First Associated Hospital of the Chengdu Medical Collage, Chengdu, China
| | - Yuan-Ping Han
- 1The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Xiaofeng Zheng
- 5Department of Endocrinology and Metabolism, Center for Diabetes and
Metabolism Research, West China Hospital, Sichuan University, Chengdu, China
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18
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Qin H, Yuan B, Huang W, Wang Y. Utilizing Gut Microbiota to Improve Hepatobiliary Tumor Treatments: Recent Advances. Front Oncol 2022; 12:924696. [PMID: 35924173 PMCID: PMC9339707 DOI: 10.3389/fonc.2022.924696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022] Open
Abstract
Hepatobiliary tumors, which include cholangiocarcinoma, hepatocellular carcinoma (HCC), and gallbladder cancer, are common cancers that have high morbidity and mortality rates and poor survival outcomes. In humans, the microbiota is comprised of symbiotic microbial cells (10-100 trillion) that belong to the bacterial ecosystem mainly residing in the gut. The gut microbiota is a complicated group that can largely be found in the intestine and has a dual role in cancer occurrence and progression. Previous research has focused on the crucial functions of the intestinal microflora as the main pathophysiological mechanism in HCC development. Intestinal bacteria produce a broad range of metabolites that exhibit a variety of pro- and anticarcinogenic effects on HCC. Therefore, probiotic alteration of the gut microflora could promote gut flora balance and help prevent the occurrence of HCC. Recent evidence from clinical and translational studies suggests that fecal microbiota transplant is one of the most successful therapies to correct intestinal bacterial imbalance. We review the literature describing the effects and mechanisms of the microbiome in the gut in the context of HCC, including gut bacterial metabolites, probiotics, antibiotics, and the transplantation of fecal microbiota, and discuss the potential influence of the microbiome environment on cholangiocarcinoma and gallbladder cancer. Our findings are expected to reveal therapeutic targets for the prevention of hepatobiliary tumors, and the development of clinical treatment strategies, by emphasizing the function of the gut microbiota.
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Affiliation(s)
- Hao Qin
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Baowen Yuan
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Huang
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- *Correspondence: Wei Huang, ; Yan Wang,
| | - Yan Wang
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- *Correspondence: Wei Huang, ; Yan Wang,
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19
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Russo E, Fiorindi C, Giudici F, Amedei A. Immunomodulation by probiotics and prebiotics in hepatocellular carcinoma. World J Hepatol 2022; 14:372-385. [PMID: 35317185 PMCID: PMC8891667 DOI: 10.4254/wjh.v14.i2.372] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/21/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent primary malignancy in patients suffering from chronic liver diseases and cirrhosis. Recent attention has been paid to the involvement of the gut-liver axis (GLA) in HCC pathogenesis. This axis results from a bidirectional, anatomical and functional relationship between the gastrointestinal system and the liver. Moreover, the complex network of interactions between the intestinal microbiome and the liver plays a crucial role in modulation of the HCC-tumor microenvironment, contributing to the pathogenesis of HCC by exposing the liver to pathogen-associated molecular patterns, such as bacterial lipopolysaccharides, DNA, peptidoglycans and flagellin. Indeed, the alteration of gut microflora may disturb the intestinal barrier, bringing several toll-like receptor ligands to the liver thus activating the inflammatory response. This review explores the new therapeutic opportunities that may arise from novel insights into the mechanisms by which microbiota immunomodulation, represented by probiotics, and prebiotics, affects HCC through the GLA.
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Affiliation(s)
- Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy
| | - Camila Fiorindi
- Department of Health Professions, Dietary Production Line and Nutrition, University Hospital of Careggi, Florence 50134, Italy
| | - Francesco Giudici
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy.
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20
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Devi P, Khan A, Chattopadhyay P, Garg A, Pandey R. Gut Microbiota and the Liver: Interaction Shaping Interactome. COMPREHENSIVE GUT MICROBIOTA 2022:400-411. [DOI: 10.1016/b978-0-12-819265-8.00080-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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21
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Microbiome-based therapeutics: Opportunity and challenges. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2022; 191:229-262. [DOI: 10.1016/bs.pmbts.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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22
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Amedei A, Gitto S, Campani C, Marra F. Probiotics and the gut-liver axis. PROBIOTICS 2022:467-481. [DOI: 10.1016/b978-0-323-85170-1.00003-8] [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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23
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Gastrointestinal cancers: the role of microbiota in carcinogenesis and the role of probiotics and microbiota in anti-cancer therapy efficacy. Cent Eur J Immunol 2021; 45:476-487. [PMID: 33658894 PMCID: PMC7882408 DOI: 10.5114/ceji.2020.103353] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 09/24/2019] [Indexed: 02/06/2023] Open
Abstract
The gut epithelium is a habitat of a variety of microorganisms, including bacteria, fungi, viruses and Archaea. With the advent of sophisticated molecular techniques and bioinformatics tools, more information on the composition and thus function of gut microbiota was revealed. The gut microbiota as an integral part of the intestinal barrier has been shown to be involved in shaping the mucosal innate and adaptive immune response and to provide protection against pathogens. Consequently, a set of biochemical signals exchanged within microbes and communication between the microbiota and the host have opened a new way of thinking about cancer biology. Probiotics are living organisms which administered in adequate amounts may bring health benefits and have the potential to be an integral part of the prevention/treatment strategies in clinical approaches. Here we provide a comprehensive review of data linking gut microbiota to cancer pathogenesis and its clinical course. We focus on gastrointestinal cancers, such as gastric, colorectal, pancreatic and liver cancer.
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Manibalan S, Thirukumaran K, Varshni M, Shobana A, Achary A. Report on biopharmaceutical profile of recent biotherapeutics and insilco docking studies on target bindings of known aptamer biotherapeutics. Biotechnol Genet Eng Rev 2021; 36:57-80. [PMID: 33393433 DOI: 10.1080/02648725.2020.1858395] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Accumulated Toxicity, disease recurrence and drug resistivity problems have been observed due to the synthetic and semisynthetic therapeutic practices, which alternatively led to focus on Bio-therapeutics production than xenobiotics. Quick plasma clearance and high potency are the reasons for trending research with huge pharma market of numerous Bio-therapeutics than ever before. Researchers proved that most of the nano and micro Bio-therapeutics have multiple beneficial therapeutic effects. We have analyzed the past, and present scenario of some notable clinically approved Bio-therapeutics to identify the future formulation needs with advanced techniques. Protein-related drugs are the foremost Bio-therapeutics such as antibodies, enzymes, and short, fragmented polypeptides show aggregation properties during storage, naked peptide moieties are resisted by the polar cell membrane, and also the antidrug antibodies were reported. Even though Nucleic acid nano-bodies are excellent target binders than proteins, they had only a few minutes of half-life. Maintaining homogeneousness upon storage of Bio-therapeutics is still a significant challenge in industrial-scale formulation. Notably, plant systems are identified as most useful cost-effective hosts to produce human enzymes than animal systems without any possible viral loads. Irrespective of numerous advancements in routes of administration and additives, subcutaneous is still a golden one to achieve better dynamics. Additionally, the interactions and effective bonds made by each class of well-known aptamer biotherapeutics which are considered as future drugs were studied.
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Affiliation(s)
- Subramaniyan Manibalan
- Center for Research, Department of Biotechnology, Kamaraj College of Engineering and Technology , Madurai, India
| | - Kandasamy Thirukumaran
- Center for Research, Department of Biotechnology, Kamaraj College of Engineering and Technology , Madurai, India
| | - Mathimaran Varshni
- Center for Research, Department of Biotechnology, Kamaraj College of Engineering and Technology , Madurai, India
| | - Ayyasamy Shobana
- Center for Research, Department of Biotechnology, Kamaraj College of Engineering and Technology , Madurai, India
| | - Anant Achary
- Center for Research, Department of Biotechnology, Kamaraj College of Engineering and Technology , Madurai, India
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25
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Hayes M, Ferruzzi MG. Update on the bioavailability and chemopreventative mechanisms of dietary chlorophyll derivatives. Nutr Res 2020; 81:19-37. [DOI: 10.1016/j.nutres.2020.06.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 04/24/2020] [Accepted: 06/11/2020] [Indexed: 12/30/2022]
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26
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Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review. Int J Mol Sci 2020; 21:ijms21175999. [PMID: 32825440 PMCID: PMC7504062 DOI: 10.3390/ijms21175999] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/14/2020] [Accepted: 08/19/2020] [Indexed: 12/24/2022] Open
Abstract
Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.
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Aminlari L, Shekarforoush SS, Hosseinzadeh S, Nazifi S, Sajedianfard J, Eskandari MH. Effect of Probiotics Bacillus coagulans and Lactobacillus plantarum on Lipid Profile and Feces Bacteria of Rats Fed Cholesterol-Enriched Diet. Probiotics Antimicrob Proteins 2020; 11:1163-1171. [PMID: 30368715 DOI: 10.1007/s12602-018-9480-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The aim of this study was to investigate the effect of Lactobacillus plantarum and Bacillus coagulans on serum lipid profile and lowering potential of probiotic in hypercholesterolemic rats. Twenty-eight male Wistar rats were divided into four groups as follows: (1) control group, fed standard commercial diet; (2) HC group, fed high-cholesterol diet; (3) HC + LP group, fed high-cholesterol diet and gavaging of L. plantarum; and (4) HC + BC group fed high-cholesterol diet and gavaging of B. coagulans. After 28 and 50 days, serum lipid profile; serum ALT and AST; the body and organ weights; fecal total count; Enterobacteriaceae, L. plantarum, and B. coagulans counts; and blood glucose tolerance were measured. We observed that levels of triglyceride, cholesterol, LDL, VLDL, and atherogenic index in serum were significantly lower in the HC + probiotic groups. Also, serum ALT and AST were significantly decreased in probiotic-treated groups. In addition, we found that feeding of a high-cholesterol diet for 50 days produced significant increases in the body weight, in addition to the fact that the administration of L. plantarum and B. coagulans has considerably reduced the body weight gain. B. coagulans and L. plantarum can survive passing through the upper-gastrointestinal tract after oral feeding to the rats and colonized in their colon. These bacteria could be exploited as a potential biotherapeutic remedy to reduce TC, TG, LDL, VLDL, and atherogenic index in hypercholesterolemic condition.
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Affiliation(s)
- Ladan Aminlari
- Department of Food Hygiene and Public Health, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Seyed Shahram Shekarforoush
- Department of Food Hygiene and Public Health, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
| | - Saeid Hosseinzadeh
- Department of Food Hygiene and Public Health, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Saeed Nazifi
- Department of Clinical Study, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Javad Sajedianfard
- Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Mohammad Hadi Eskandari
- Department of Food Science and Technology, College of Agriculture, Shiraz University, Shiraz, Iran
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Elsalem L, Jum'ah AA, Alfaqih MA, Aloudat O. The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives. Clin Exp Gastroenterol 2020; 13:151-185. [PMID: 32440192 PMCID: PMC7211962 DOI: 10.2147/ceg.s243337] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.
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Affiliation(s)
- Lina Elsalem
- Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmad A Jum'ah
- Department of Conservative Dentistry, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Osama Aloudat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
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29
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Yang W, Sui J, Ma Y, Simon TG, Chong D, Meyerhardt JA, Willett WC, Giovannucci EL, Chan AT, Zhang X. A prospective study of dairy product intake and the risk of hepatocellular carcinoma in U.S. men and women. Int J Cancer 2020; 146:1241-1249. [PMID: 31116416 PMCID: PMC6872903 DOI: 10.1002/ijc.32423] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 04/20/2019] [Accepted: 05/09/2019] [Indexed: 12/27/2022]
Abstract
Although increasing dairy product intake has been associated with risk of several cancers, epidemiological studies on hepatocellular carcinoma are sparse and have yielded inconsistent results. We prospectively assessed the associations of dairy products (total, milk, butter, cheese and yogurt) and their major components (calcium, vitamin D, fats and protein) with the risk of hepatocellular carcinoma development among 51,418 men and 93,427 women in the Health Professionals Follow-Up Study and the Nurses' Health Study. Diets were collected at baseline and updated every 4 years using validated food frequency questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression model. During up to 32 years of follow-up, a total of 164 hepatocellular carcinoma cases were documented. After adjustment for most known hepatocellular carcinoma risk factors, higher total dairy product intake was associated with an increased risk of hepatocellular carcinoma (highest vs. lowest tertile, HR = 1.85, 95% CI: 1.19-2.88; ptrend = 0.009). For the same comparison, we observed significant positive associations of high-fat dairy (HR = 1.81, 95% CI: 1.19-2.76; ptrend = 0.008) and butter (HR = 1.58, 95% CI: 1.06-2.36; ptrend = 0.04) with hepatocellular carcinoma risk. There was a nonsignificant inverse association between yogurt intake and hepatocellular carcinoma risk (HR = 0.72, 95% CI: 0.49-1.05; ptrend = 0.26). Our data suggest that higher intake of high-fat dairy foods was associated with higher, whereas higher yogurt consumption might be associated with lower risk of developing hepatocellular carcinoma among U.S. men and women.
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Affiliation(s)
- Wanshui Yang
- Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, P.R. China
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Jing Sui
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of public Health, Southeast University, Nanjing, Jiangsu, P.R. China
| | - Yanan Ma
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- School of Public Health, China Medical University, Shenyang, Liaoning, P.R. China
| | - Tracey G. Simon
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Dawn Chong
- National Cancer Centre Singapore, Singapore
| | - Jeffrey A. Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Walter C. Willett
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Edward L. Giovannucci
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T. Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Cimbalo A, Alonso-Garrido M, Font G, Manyes L. Toxicity of mycotoxins in vivo on vertebrate organisms: A review. Food Chem Toxicol 2020; 137:111161. [PMID: 32014537 DOI: 10.1016/j.fct.2020.111161] [Citation(s) in RCA: 114] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 01/21/2020] [Accepted: 01/22/2020] [Indexed: 12/31/2022]
Abstract
Mycotoxins are considered to be a major risk factor affecting human and animal health as they are one of the most dangerous contaminants of food and feed. This review aims to compile the research developed up to date on the toxicological effects that mycotoxins can induce on human health, through the examination of a selected number of studies in vivo. AFB1 shows to be currently the most studied mycotoxin in vivo, followed by DON, ZEA and OTA. Scarce data was found for FBs, PAT, CIT, AOH and Fusarium emerging mycotoxins. The majority of them concerned the investigation of immunotoxicity, whereas the rest consisted in the study of genotoxicity, oxidative stress, hepatotoxicity, cytotoxicity, teratogenicity and neurotoxicity. In order to assess the risk, a wide range of different techniques have been employed across the reviewed studies: qPCR, ELISA, IHC, WB, LC-MS/MS, microscopy, enzymatic assays, microarray and RNA-Seq. In the last decade, the attention has been drawn to immunologic and transcriptomic aspects of mycotoxins' action, confirming their toxicity at molecular level. Even though, more in vivo studies are needed to further investigate their mechanism of action on human health.
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Affiliation(s)
- A Cimbalo
- Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Avinguda Vicent Andrés Estellés S/n, 46100, Burjassot, Spain.
| | - M Alonso-Garrido
- Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Avinguda Vicent Andrés Estellés S/n, 46100, Burjassot, Spain
| | - G Font
- Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Avinguda Vicent Andrés Estellés S/n, 46100, Burjassot, Spain
| | - L Manyes
- Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Avinguda Vicent Andrés Estellés S/n, 46100, Burjassot, Spain
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Zhou A, Tang L, Zeng S, Lei Y, Yang S, Tang B. Gut microbiota: A new piece in understanding hepatocarcinogenesis. Cancer Lett 2020; 474:15-22. [PMID: 31917160 DOI: 10.1016/j.canlet.2020.01.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/18/2019] [Accepted: 01/03/2020] [Indexed: 02/07/2023]
Abstract
The gut microbiota forms a symbiotic relationship with the host and benefits the body in many critical aspects of life. However, immune system defects, alterations in the gut microbiota and environmental changes can destroy this symbiotic relationship and may lead to diseases, including cancer. Due to the anatomic and functional connection of the gut and liver, increasing studies show the important role of the gut microbiota in the carcinogenesis of hepatocellular carcinoma (HCC). In this manuscript, we review the available evidence and analyze some potential mechanisms of the gut microbiota, including bacterial dysbiosis, lipopolysaccharide (LPS), and genotoxins, in the progression and promotion of HCC. Furthermore, we discuss the possible therapeutic applications of probiotics, chemotherapy modulation, immunotherapy, targeted drugs and fecal microbiota transplantation (FMT) in targeting the gut microbiota.
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Affiliation(s)
- An Zhou
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Li Tang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Shuo Zeng
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Yuanyuan Lei
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
| | - Bo Tang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
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Acham M, Wesselius A, van Osch FHM, Yu EYW, van den Brandt PA, White E, Adami HO, Weiderpass E, Brinkman M, Giles GG, Milne RL, Zeegers MP. Intake of milk and other dairy products and the risk of bladder cancer: a pooled analysis of 13 cohort studies. Eur J Clin Nutr 2020; 74:28-35. [PMID: 31209273 DOI: 10.1038/s41430-019-0453-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 05/03/2019] [Accepted: 06/02/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Inconsistent associations between milk and other dairy product consumption and bladder cancer (BC) have been reported. We aimed to investigate possible associations with BC risk for total and individual dairy products by bringing together the world's data on this topic. METHODS Thirteen cohort studies, included in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study, provided data for 3590 BC cases and 593,637 non-cases. Associations between milk and other dairy product consumption and BC risk were investigated using Cox proportional hazard regression analyses stratified by study center and adjusted for potential confounders. RESULTS Overall, total 'other' dairy product consumption was not associated with BC risk (HR comparing highest with lowest tertile: 0.97 (95% CI: 0.87-1.07; ptrend = 0.52) and likewise no association was observed for either liquid milk, processed milk, cream, cheese or icecream. However, an inverse association was observed between yoghurt consumption and BC risk when comparing those in the moderate (25-85 g/day) and high categories (>85 g/day) with non-consumers, with multivariate HR of 0.85 (95% CI: 0.75-0.96) and 0.88 (95% CI: 0.78-0.98), respectively. CONCLUSIONS We found no evidence of association between either total or individual dairy products and BC risk, but suggestive evidence that consumption of yoghurt may be associated with a decreased risk.
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Affiliation(s)
- Merab Acham
- Department of Complex Genetics and Epidemiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, The Netherlands, Maastricht University, Maastricht, The Netherlands
| | - Anke Wesselius
- Department of Complex Genetics and Epidemiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, The Netherlands, Maastricht University, Maastricht, The Netherlands.
| | - Frits H M van Osch
- Department of Complex Genetics and Epidemiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, The Netherlands, Maastricht University, Maastricht, The Netherlands
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | - Evan Yi-Wen Yu
- Department of Complex Genetics and Epidemiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, The Netherlands, Maastricht University, Maastricht, The Netherlands
| | - Piet A van den Brandt
- Department of Epidemiology, Schools for Oncology and Developmental Biology and Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Emily White
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Hans-Olov Adami
- Department of Medical Epidemiology and Biostatistics, Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden
- Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Elisabete Weiderpass
- Department of Medical Epidemiology and Biostatistics, Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden
- Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
- Genetic Epidemiology Group, Folkhälsan Research Center and Faculty of Medicine, Helsinki University, Helsinki, Finland
- Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Maree Brinkman
- Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia
| | - Graham G Giles
- Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway
- Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Roger L Milne
- Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway
- Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia
- School of Public Health and Preventive Medicine, Monash University Faculty of Medicine, Nursing & Health Sciences, Melbourne, VIC, Australia
| | - Maurice P Zeegers
- Department of Complex Genetics and Epidemiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, The Netherlands, Maastricht University, Maastricht, The Netherlands
- CAPHRI School for Public Health and Primary Care, University of Maastricht, Maastricht, The Netherlands
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Nagano T, Otoshi T, Hazama D, Kiriu T, Umezawa K, Katsurada N, Nishimura Y. Novel cancer therapy targeting microbiome. Onco Targets Ther 2019; 12:3619-3624. [PMID: 31190864 PMCID: PMC6526180 DOI: 10.2147/ott.s207546] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 04/10/2019] [Indexed: 12/23/2022] Open
Abstract
In the human intestinal tract, there are more than 100 trillion symbiotic bacteria, which form the gut microbiota. Approximately 70% of the human immune system is in the intestinal tract, which prevents infection by pathogenic bacteria. When the intestinal microbiota is disturbed, causing dysbiosis, it can lead to obesity, diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, autism spectrum disorder and cancer. Recent metabolomics analyses have also made the association between the microbiota and carcinogenesis clear. Here, we review the current evidence on the association between the microbiota and gastric, bladder, hepatobiliary, pancreatic, lung and colorectal cancer. Moreover, several animal studies have revealed that probiotics seem to be effective for the prevention of carcinogenesis to some extent. In this review, we focused on this relationship between the microbiota and cancer, and considered how to prevent cancer using strategies involving the gut microbiota.
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Affiliation(s)
- Tatsuya Nagano
- Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Takehiro Otoshi
- Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Daisuke Hazama
- Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Tatsunori Kiriu
- Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Kanoko Umezawa
- Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Naoko Katsurada
- Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Yoshihiro Nishimura
- Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
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34
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Role of Gut Microbiota in Hepatocarcinogenesis. Microorganisms 2019; 7:microorganisms7050121. [PMID: 31060311 PMCID: PMC6560397 DOI: 10.3390/microorganisms7050121] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/23/2019] [Accepted: 05/03/2019] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulates over decades. Observations from recent studies have accounted for the involvement of the gut–liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis can cause the intestinal microbiome to serve as the main source of portal-vein endotoxins, such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on clinical as well as animal studies involving the gut microbiota, with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, which represent key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.
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Abstract
Liver cancer is the sixth most common cancer worldwide, and the third most common cause of cancer-related death. Hepatocellular carcinoma (HCC), which accounts for more than 90% of primary liver cancers, is an important public health problem. In addition to cirrhosis caused by hepatitis B viral (HBV) or hepatitis C viral (HCV) infection, non-alcoholic fatty liver disease (NAFLD) is becoming a major risk factor for liver cancer because of the prevalence of obesity. Non-alcoholic steatohepatitis (NASH) will likely become the leading indication for liver transplantation in the future. It is well recognized that gut microbiota is a key environmental factor in the pathogenesis of liver disease and cancer. The interplay between gut microbiota and liver disease has been investigated in animal and clinical studies. In this article, we summarize the roles of gut microbiota in the development of liver disease as well as gut microbiota-targeted therapies.
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Affiliation(s)
- Lijun Wang
- Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA,The College of Life Science, Yangtze University, Jingzhou, Hubei, China
| | - Yu-Jui Yvonne Wan
- Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA,Corresponding author. Department of medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA. (Y.-J.Y. Wan)
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Milosevic I, Vujovic A, Barac A, Djelic M, Korac M, Radovanovic Spurnic A, Gmizic I, Stevanovic O, Djordjevic V, Lekic N, Russo E, Amedei A. Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Int J Mol Sci 2019; 20:395. [PMID: 30658519 PMCID: PMC6358912 DOI: 10.3390/ijms20020395] [Citation(s) in RCA: 330] [Impact Index Per Article: 55.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Revised: 01/13/2019] [Accepted: 01/14/2019] [Indexed: 02/06/2023] Open
Abstract
The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called "the new virtual metabolic organ", makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of "ancient" microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.
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Affiliation(s)
- Ivana Milosevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Ankica Vujovic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Aleksandra Barac
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Marina Djelic
- Faculty of Medicine, Universisty of Belgrade; Institute of Medical Physiology "Rihard Burijan", 11000 Belgrade, Serbia.
| | - Milos Korac
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Aleksandra Radovanovic Spurnic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Ivana Gmizic
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Olja Stevanovic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Vladimir Djordjevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Clinic for Digestive Surgery, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Nebojsa Lekic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Clinic for Digestive Surgery, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
- Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50134 Florence, Italy.
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Ren T, You Y, Luo Y, Wang Y, Liu X. Hypocholesterolemic Effects of Capsaicinoids and Lactobacillus plantarum
Swun5815 Combined by Inhibiting Cholesterol Synthesis and Increasing Bile Acid and Sterols Excretion on Ovariectomized Rats. J Food Sci 2018; 83:2247-2256. [DOI: 10.1111/1750-3841.14285] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 05/16/2018] [Accepted: 06/15/2018] [Indexed: 11/28/2022]
Affiliation(s)
- Ting Ren
- College of Food Science; Southwest Univ.; Chongqing 400715 China
- Southeast Chongqing Acad. of Agricultural Sciences; Chongqing 408000 P. R. China
| | - Yuming You
- College of Food Science; Southwest Univ.; Chongqing 400715 China
- College of Forestry and Life Science; Chongqing Univ. of Arts and Sciences; Chongqing 402160 China
| | - Yuanli Luo
- Southeast Chongqing Acad. of Agricultural Sciences; Chongqing 408000 P. R. China
| | - Yuanwei Wang
- College of Food Science; Southwest Univ.; Chongqing 400715 China
| | - Xiong Liu
- College of Food Science; Southwest Univ.; Chongqing 400715 China
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Ghavami A, Roshanravan N, Alipour S, Barati M, Mansoori B, Ghalichi F, Nattagh-Eshtivan E, Ostadrahimi A. Assessing the Effect of High Performance Inulin Supplementation via KLF5 mRNA Expression in Adults with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trail. Adv Pharm Bull 2018; 8:39-47. [PMID: 29670837 PMCID: PMC5896394 DOI: 10.15171/apb.2018.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 02/17/2018] [Accepted: 03/03/2018] [Indexed: 12/14/2022] Open
Abstract
Purpose: The worldwide prevalence of metabolic disorders such as diabetes is increasing rapidly. Currently, the complications of diabetes are the major health concern. The aim of this study was to investigate the effect of high performance (HP) inulin supplementation on glucose homeostasis via KLF5 mRNA expression in adults with type 2 diabetes. Methods: In the present clinical trial conducted for a duration of 6 weeks, 46 volunteers diabetic patients referring to diabetes clinic in Tabriz, Iran, were randomly assigned into intervention (n= 23, consuming 10 gr/d HP inulin) and control groups (n= 23, consuming 10 gr/ d starch). We assessed glycemic and anthropometric indices, blood lipids and plasmatic level of miR-375 as well as KLF5 mRNA expression before and after the intervention. Results: Findings indicated that inulin supplementation significantly decreased fasting plasma glucose (FPG) in comparison to the placebo group (P<0.001). Also Intra-group and between group results showed that inulin supplementation resulted in significant decrease in KLF5 mRNA expression in peripheral blood mononuclear cells (PBMCs) (Fold change: 0.61± 0.11; P-value= 0.001) and significant increase in plasmatic level of miR-375 (Fold change: 3.75± 0.70; P-value=0.004). Conclusion: Considering the improvements of FPG level in diabetic patients, it seems that HP inulin supplementation may be beneficial in controlling diabetes via the expression of some genes. However, further studies are needed to achieve concise conclusions.
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Affiliation(s)
- Abed Ghavami
- Department of Nutrition, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Roshanravan
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shahriar Alipour
- Department of Molecular Medicine, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Meisam Barati
- Department of Nutrition, School of Nutrition, Shahid beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Mansoori
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Faezeh Ghalichi
- Department of Nutrition, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elyas Nattagh-Eshtivan
- Department of Nutrition, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Ostadrahimi
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Abstract
Hepatocellular carcinoma (HCC), the most common primary liver cancer, is one of the dreaded complications of chronic liver disease. Recent experimental and clinical studies have revealed that the alteration of gut-liver axis plays a pivotal role in the onset of chronic liver diseases, including HCC. Altered gut microbiota and endotoxemia are increasingly recognized as critical components in promoting the progression of chronic liver diseases to HCC. Probiotics have been suggested as a novel, safe and cost-effective approach to prevent or treat HCC. Mechanisms by which probiotics exerts their anti-cancer effects include their ability to bind carcinogens, modulation of gut microbiota, improvement of intestinal barrier function, and immunomodulation. This review summarizes the literature findings of the changes in gut microbiota linked to HCC, and discusses the possible therapeutic implications of probiotics for HCC.
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Affiliation(s)
- Murphy L Y Wan
- School of Biological Sciences, Faculty of Science, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Hani El-Nezami
- School of Biological Sciences, Faculty of Science, The University of Hong Kong, Pokfulam, Hong Kong, China.,Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
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Chiocchetti GM, Jadán-Piedra C, Monedero V, Zúñiga M, Vélez D, Devesa V. Use of lactic acid bacteria and yeasts to reduce exposure to chemical food contaminants and toxicity. Crit Rev Food Sci Nutr 2018; 59:1534-1545. [PMID: 29337587 DOI: 10.1080/10408398.2017.1421521] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Chemical contaminants that are present in food pose a health problem and their levels are controlled by national and international food safety organizations. Despite increasing regulation, foods that exceed legal limits reach the market. In Europe, the number of notifications of chemical contamination due to pesticide residues, mycotoxins and metals is particularly high. Moreover, in many parts of the world, drinking water contains high levels of chemical contaminants owing to geogenic or anthropogenic causes. Elimination of chemical contaminants from water and especially from food is quite complex. Drastic treatments are usually required, which can modify the food matrix or involve changes in the forms of cultivation and production of the food products. These modifications often make these treatments unfeasible. In recent years, efforts have been made to develop strategies based on the use of components of natural origin to reduce the quantity of contaminants in foods and drinking water, and to reduce the quantity that reaches the bloodstream after ingestion, and thus, their toxicity. This review provides a summary of the existing literature on strategies based on the use of lactic acid bacteria or yeasts belonging to the genus Saccharomyces that are employed in food industry or for dietary purposes.
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Affiliation(s)
- Gabriela Matuoka Chiocchetti
- a Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC) , C/ Agustín Escardino 7 - Paterna (Valencia) , Spain
| | - Carlos Jadán-Piedra
- a Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC) , C/ Agustín Escardino 7 - Paterna (Valencia) , Spain
| | - Vicente Monedero
- a Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC) , C/ Agustín Escardino 7 - Paterna (Valencia) , Spain
| | - Manuel Zúñiga
- a Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC) , C/ Agustín Escardino 7 - Paterna (Valencia) , Spain
| | - Dinoraz Vélez
- a Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC) , C/ Agustín Escardino 7 - Paterna (Valencia) , Spain
| | - Vicenta Devesa
- a Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC) , C/ Agustín Escardino 7 - Paterna (Valencia) , Spain
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Putta S, Yarla NS, Lakkappa DB, Imandi SB, Malla RR, Chaitanya AK, Chari BP, Saka S, Vechalapu RR, Kamal MA, Tarasov VV, Chubarev VN, Siva Kumar K, Aliev G. Probiotics: Supplements, Food, Pharmaceutical Industry. THERAPEUTIC, PROBIOTIC, AND UNCONVENTIONAL FOODS 2018:15-25. [DOI: 10.1016/b978-0-12-814625-5.00002-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Athari Nik Azm S, Djazayeri A, Safa M, Azami K, Djalali M, Sharifzadeh M, Vafa M. Probiotics improve insulin resistance status in an experimental model of Alzheimer's disease. Med J Islam Repub Iran 2017; 31:103. [PMID: 29951404 PMCID: PMC6014785 DOI: 10.14196/mjiri.31.103] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 12/18/2017] [Indexed: 12/22/2022] Open
Abstract
Background: Nowadays, Alzheimer's disease (AD) is considered as Type 3 diabetes in which insulin resistance is the common cause of both diseases. Disruption of insulin signaling cascade and insulin resistance can induce AD; and central insulin resistance causes systemic alterations in serum insulin, FBS levels, and lipid profile. Studies have shown that probiotics (Lactobacillus and Bifidobacterium species) can be used as a nutritional approach to improve these metabolic changes. We assessed the probiotic effect (4 species of Lactobacillus and Bifidobacterium) on insulin resistance biomarkers in an experimental model of AD. Methods: A total of 60 rats were divided into 5 groups: (1) a control group without surgical and dietary intervention; (2) a controlprobiotics group receiving probiotics for 8 weeks, but not receiving any surgical intervention; (3) a group receiving a sham operation in which PBS was injected intrahippocampus but without dietary intervention; (4) an Alzheimer group for which Amyloid-ß (Aß) 1- 42 was injected intrahippocampus but without dietary intervention; (5) and an Alzheimer-probiotics group for which Aß1-42 was injected intrahippocampus and given 2g probiotics for 8 weeks. The FBS levels and lipid profile were measured by a calorimetric method, insulin levels were detected by an ELISA kit, and HOMA-IR was calculated using a formula. ANOVA (one way analysis of variance followed by Bonferroni comparisons post hoc) was used to compare all the variables between groups. Results: Serum glucose, insulin levels, and HOMA-IR index increased in the Alzheimer group compared to the control (p<0.001), while probiotics decreased only insulin level and HOMA-IR index in AP group compared to Alzheimer group (p<0.001). Also, TG levels increased in the Alzheimer group (p<0.001), but no significant difference was detected between Alzheimer and Alzheimerprobiotics group. Conclusion: It seems that probiotics play an effective role in controlling glycemic status of Alzheimer's disease.
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Affiliation(s)
- Somayeh Athari Nik Azm
- Department of Community Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Abolghassem Djazayeri
- Department of Community Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Majid Safa
- Cellular and Molecular Research Center and Hematology Department, School of Allied Medical Science, Iran University of Medical Sciences, Tehran, Iran
| | - Kian Azami
- Department of Pharmacology, Pharmaceutical Science Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Djalali
- Department of Cellular-Molecular Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sharifzadeh
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Vafa
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
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Keshari AK, Singh AK, Kumar U, Raj V, Rai A, Kumar P, Kumar D, Maity B, Nath S, Prakash A, Saha S. 5H-benzo[h]thiazolo[2,3-b]quinazolines ameliorate NDEA-induced hepatocellular carcinogenesis in rats through IL-6 downregulation along with oxidative and metabolic stress reduction. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:2981-2995. [PMID: 29075102 PMCID: PMC5648320 DOI: 10.2147/dddt.s143075] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
5H-benzo[h]thiazolo[2,3-b]quinazoline scaffold is known to have an antitumor effect on certain types of malignancies; however, its effect on hepatocellular carcinoma (HCC) remains unclear. Previously, we reported p-toluenesulfonic acid-promoted syntheses, molecular modeling and in vitro antitumor activity of 5H-benzo[h]thiazolo[2,3-b]quinazoline against human hepatoma (Hep-G2) cells where compounds 4A and 6A were found to be potent inhibitors among the series. In continuation to our previous effort to develop novel therapeutic strategies for HCC treatment, here we investigated the in vivo antitumor activity and the mechanism underlying the effects of 4A and 6A in N-nitrosodiethylamine (NDEA)-induced HCC using male Wistar rats. NDEA was administered weekly intraperitoneally at a dose of 100 mg/kg for 6 weeks. Various physiological and morphological changes, oxidative parameters, liver marker enzymes and cytokines were assessed to evaluate the antitumor effect of 4A and 6A. In addition, proton nuclear magnetic resonance-based serum metabolomics were performed to analyze the effects of 4A and 6A against HCC-induced metabolic alterations. Significant tumor incidences with an imbalance in carcinogen metabolizing enzymes and cellular redox status were observed in carcinogenic rats. Tumor inhibitory effects of 4A and 6A were noted by histopathology and biochemical profiles in NDEA-induced hepatic cancer. Compounds 4A and 6A had a potential role in normalizing the elevated levels of inflammatory mediators such as interleukin-1β (IL-1β), IL-2, IL-6 and IL-10. At molecular level, the real-time quantitative reverse-transcribed polymerase chain reaction analysis revealed that 4A and 6A attenuated the IL-6 gene overexpression in hepatic cancer. Further, orthogonal partial least squares discriminant analysis scores plot demonstrated a significant separation of 4A and 6A-treated groups from carcinogen control group. Both the compounds have potential to restore the imbalanced metabolites due to HCC, signifying promising hepatoprotective activities. All these findings suggested that 4A and 6A could be potential drug candidates to treat HCC.
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Affiliation(s)
- Amit K Keshari
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University
| | - Ashok K Singh
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University
| | - Umesh Kumar
- Centre of Biomedical Research, SGPGIMS Campus
| | - Vinit Raj
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University
| | - Amit Rai
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University
| | - Pranesh Kumar
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University
| | | | | | - Sneha Nath
- Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
| | - Anand Prakash
- Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
| | - Sudipta Saha
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University
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Riaz Rajoka MS, Shi J, Zhu J, Shao D, Huang Q, Yang H, Jin M. Capacity of lactic acid bacteria in immunity enhancement and cancer prevention. Appl Microbiol Biotechnol 2017; 101:35-45. [PMID: 27888334 DOI: 10.1007/s00253-016-8005-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 11/09/2016] [Accepted: 11/11/2016] [Indexed: 02/06/2023]
Abstract
Lactic acid bacteria are associated with the human gastrointestinal tract. They are important for maintaining the balance of microflora in the human gut. An increasing number of published research reports in recent years have denoted the importance of producing interferon-gamma and IgA for treatment of disease. These agents can enhance the specific and nonspecific immune systems that are dependent on specific bacterial strains. The mechanisms of these effects were revealed in this investigation, where the cell walls of these bacteria were modulated by the cytokine pathways, while the whole bacterial cell mediated the host cell immune system and regulated the production of tumor necrosis factors and interleukins. A supplement of highly active lactic acid bacteria strains provided significant potential to enhance host's immunity, offering prevention from many diseases including some cancers. This review summarizes the current understanding of the function of lactic acid bacteria immunity enhancement and cancer prevention.
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Affiliation(s)
- Muhammad Shahid Riaz Rajoka
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Junling Shi
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China.
| | - Jing Zhu
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Dongyan Shao
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Qingsheng Huang
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Hui Yang
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Mingliang Jin
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
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Probiotics and Liver Disease: Where Are We Now and Where Are We Going? J Clin Gastroenterol 2016; 50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S188-S190. [PMID: 27741172 DOI: 10.1097/mcg.0000000000000712] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Probiotics are live, nonpathogenic bacteria capable of colonizing the colonic mucosa. The most common probiotics include strains of Lactobacillus or Bifidobacteria, which are part of the normal gastrointestinal microbiota. Initial studies of selected probiotic species have suggested potential efficacy in several gastrointestinal diseases including inflammatory bowel diseases (particularly pouchitis), antibiotic-related diarrhea, Clostridium difficile toxin-induced colitis, infectious diarrhea, irritable bowel syndrome, and allergy. The so-called "gut-liver axis" involves complex interaction between the liver parenchyma and gut microbiota. There is growing evidence to suggest that alteration in gut microbial components may affect the liver and can be a precipitating cofactor in development and modulating of chronic liver damage through ethanol, production of ammonia and endotoxin. This may allow for a better understanding of its role in the pathogenesis of verities of liver diseases and help to identify a microbial target for prevention and treatment of such diseases. This paper discusses the growing evidence that highlights the relationship between gut microbiota and development, prevention and treatment of numbers of liver diseases.
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Abstract
In nutraceutical science, the ingestible live microbes 'probiotics' are regarded for their ability to confer multiplicity of health benefits on the consumers. Wide spectrum impact of these friendly microbes on the host health has been proved very frequently. They have been confirmed to boost immunity, aid in digestion, eliminate pathogens, curb inflammatory bowel diseases, moderate side effects of antibiotic therapy, lower cholesterol and blood glycemic index and produce vitamins. This review, however, focuses on the incipient, but promising area of probiotic diet-based prevention and remedy of cancer. Researchers are in universal agreement with the critical role of probiotics in getting rid of mutagens, delaying the onset of tumors, alleviating the side effects, pepping up chemotherapy, easing the postoperative complications, foiling remission and lifting the spirit of survivors. The key findings in the emerging roles of probiotics in onco-care have been summarized; the biological pathways discussed and anticipated developments in coming times are presented.
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Kumar M, Nagpal R, Hemalatha R, Yadav H, Marotta F. Probiotics and Prebiotics for Promoting Health. PROBIOTICS, PREBIOTICS, AND SYNBIOTICS 2016:75-85. [DOI: 10.1016/b978-0-12-802189-7.00006-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kumar M, Hemalatha R, Nagpal R, Singh B, Parasannanavar D, Verma V, Kumar A, Marotta F, Catanzaro R, Cuffari B, Jain S, Bissi L, Yadav H. PROBIOTIC APPROACHES FOR TARGETING INFLAMMATORY BOWEL DISEASE: AN UPDATE ON ADVANCES AND OPPORTUNITIES IN MANAGING THE DISEASE. INTERNATIONAL JOURNAL OF PROBIOTICS & PREBIOTICS 2016; 11:99-116. [PMID: 31452650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 09/28/2022]
Abstract
Various commensal enteric and pathogenic bacteria may be involved in the pathogenesis of inflammatory bowel diseases (IBDs), a chronic condition with a pathogenic background that involves both immunogenetic and environmental factors. IBDs comprising of Crohn's disease, and ulcerative colitis, and pauchitis are chronic inflammatory conditions, and known for causing disturbed homeostatic balance among the intestinal immune compartment, gut epithelium and microbiome. An increasing trend of IBDs in incidence, prevalence, and severity has been reported during recent years. Probiotic strains have been reported to manage the IBDs and related pathologies, and hence are current hot topics of research for their potential to manage metabolic diseases as well as various immunopathologies. However, the probiotics industry will need to undergo a transformation, with increased focus on stringent manufacturing guidelines and high-quality clinical trials. This article reviews the present state of art of role of probiotic bacteria in reducing inflammation and strengthening the host immune system with reference to the management of IBDs. We infer that t healthcare will move beyond its prevailing focus on human physiology, and embrace the superorganism as a paradigm to understand and ameliorate IBDs.
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Affiliation(s)
- Manoj Kumar
- Department of Microbiology and Immunology, National Institute of Nutrition, Hyderabad
| | - Rajkumar Hemalatha
- Department of Microbiology and Immunology, National Institute of Nutrition, Hyderabad
| | - Ravinder Nagpal
- Probiotics Research Laboratory, Graduate School of Medicine, Juntendo University, Tokyo
| | - Birbal Singh
- Indian Veterinary Research Institute, Regional Station, Palampur, India
| | - Devraj Parasannanavar
- Department of Microbiology and Immunology, National Institute of Nutrition, Hyderabad
| | - Vinod Verma
- Centre of Biotechnology, Nehru Science Complex, University of Allahabad, Allahabad, India
| | - Ashok Kumar
- Department of Zoology, M.L.K. Post-Graduate College, Balrampur (U.P.), India
| | - Francesco Marotta
- ReGenera Research Group for Aging Intervention & MMC-Milano Medical, Milano, Italy
| | - Roberto Catanzaro
- Department of Internal Medicine, University of Catania, Catania, Italy
| | - Biagio Cuffari
- Department of Internal Medicine, University of Catania, Catania, Italy
| | - Shalini Jain
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Laura Bissi
- ReGenera Research Group for Aging Intervention & MMC-Milano Medical, Milano, Italy
| | - Hariom Yadav
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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Nagpal R, Kumar M, Yadav AK, Hemalatha R, Yadav H, Marotta F, Yamashiro Y. Gut microbiota in health and disease: an overview focused on metabolic inflammation. Benef Microbes 2015; 7:181-194. [PMID: 26645350 DOI: 10.3920/bm2015.0062] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In concern to the continuously rising global prevalence of obesity, diabetes and associated diseases, novel preventive and therapeutic approaches are urgently required. However, to explore and develop such innovative strategies, a meticulous comprehension of the biological basis of these diseases is extremely important. Past decade has witnessed an enormous amount of research investigation and advancement in the field of obesity, diabetes and metabolic syndrome, with the gut microbiota receiving a special focus in the triangle of nutrition, health and diseases. In particular, the role of gut microbiota in health and diseases has been one of the most vigorous and intriguing field of recent research; however, much still remains to be elucidated about its precise role in host metabolism and immune functions and its implication in the onset, progression as well as in the amelioration of metabolic ailments. Recent investigations have suggested a significant contribution of the gut microbiota in the regulation and impairment of energy homeostasis, thereby causing metabolic disorders, such as metabolic endotoxemia, insulin resistance and type 2 diabetes. Numerous inflammatory biomarkers have been found to be associated with obesity, diabetes and risk of other associated adverse outcomes, thereby suggesting that a persistent low-grade inflammatory response is a potential risk factor. In this milieu, this review intends to discuss potential evidences supporting the disturbance of the gut microbiota balance and the intestinal barrier permeability as a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.
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Affiliation(s)
- R Nagpal
- 1 Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
| | - M Kumar
- 2 Department of Microbiology and Immunology, National Institute of Nutrition, 500 007 Hyderabad, India
| | - A K Yadav
- 2 Department of Microbiology and Immunology, National Institute of Nutrition, 500 007 Hyderabad, India
| | - R Hemalatha
- 2 Department of Microbiology and Immunology, National Institute of Nutrition, 500 007 Hyderabad, India
| | - H Yadav
- 3 Clinical Research Centre, Diabetes, Endocrinology and Obesity Branch, NIDDK, NIH, Bethesda, MD 20892-2560, USA
| | - F Marotta
- 4 ReGenera Research Group for Aging Intervention, Via Moisé Loira 75, 20144 Milan, Italy
| | - Y Yamashiro
- 1 Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
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50
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Chávez-Tapia NC, González-Rodríguez L, Jeong M, López-Ramírez Y, Barbero-Becerra V, Juárez-Hernández E, Romero-Flores JL, Arrese M, Méndez-Sánchez N, Uribe M. Current evidence on the use of probiotics in liver diseases. J Funct Foods 2015; 17:137-151. [DOI: 10.1016/j.jff.2015.05.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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