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Koller AM, Săsăran MO, Mărginean CO. Small Intestinal Bacterial Overgrowth and Pediatric Obesity-A Systematic Review. Nutrients 2025; 17:1499. [PMID: 40362809 PMCID: PMC12073544 DOI: 10.3390/nu17091499] [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: 04/01/2025] [Revised: 04/26/2025] [Accepted: 04/26/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: Childhood obesity is a growing global concern linked to metabolic disorders such as nonalcoholic fatty liver disease (NAFLD). Small intestinal bacterial overgrowth (SIBO) may exacerbate these conditions by promoting systemic inflammation and metabolic dysfunction. This review evaluates the prevalence of SIBO in obese children, its association with inflammatory and metabolic markers, and the efficacy of diagnostic and therapeutic strategies. Methods: A systematic search of PubMed, Scopus, and Web of Science (2010-present) was conducted using Boolean operators: ('small intestinal bacterial overgrowth' OR 'SIBO') AND 'prevalence' AND ('low-grade inflammatory markers' OR 'metabolic status') AND 'gut microbiome' AND 'dysbiosis' AND 'obese children'. Results: The data show that SIBO is frequently observed in obese pediatric populations and is associated with gut dysbiosis, impaired nutrient absorption, and reduced production of short-chain fatty acids. These changes contribute to increased intestinal permeability, endotoxemia, and chronic low-grade inflammation. Several microbial taxa have been proposed as biomarkers and therapeutic targets. Diagnostic inconsistencies persist, but treatments such as probiotics, prebiotics, dietary interventions, and selective antibiotics show potential, pending further validation. Conclusions: Early identification and treatment of SIBO with tailored strategies may help reduce metabolic complications and improve outcomes in children with obesity.
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Affiliation(s)
- Ana Maria Koller
- Doctoral School, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Maria Oana Săsăran
- Department of Pediatrics 3, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania
| | - Cristina Oana Mărginean
- Department of Pediatrics 1, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
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Velasco-Aburto S, Llama-Palacios A, Sánchez MC, Ciudad MJ, Collado L. Nutritional Approach to Small Intestinal Bacterial Overgrowth: A Narrative Review. Nutrients 2025; 17:1410. [PMID: 40362719 PMCID: PMC12073203 DOI: 10.3390/nu17091410] [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: 03/17/2025] [Revised: 04/19/2025] [Accepted: 04/22/2025] [Indexed: 05/15/2025] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is a functional digestive disorder whose incidence has been acknowledged by several medical associations, such as the American Gastroenterological Association. It is estimated that between 14% and 40% of patients diagnosed with irritable bowel syndrome also have SIBO, highlighting the importance of accurate diagnosis to enable effective treatment plans. Nutrition and diet therapy play a pivotal role in SIBO management, not only in alleviating symptoms but also in preventing relapses. The objective of this review is to gather updated information on dietary management for SIBO to define the role of the dietitian and determine the most suitable nutritional therapy based on scientific evidence. The review will encompass various strategies, ranging from specific diets to dietary supplements, as well as the potential contribution of dietary treatment to improving SIBO.
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Affiliation(s)
- Sol Velasco-Aburto
- Department of Medicine, Faculty of Medicine, University Complutense, 28040 Madrid, Spain; (S.V.-A.); (A.L.-P.); (M.C.S.)
| | - Arancha Llama-Palacios
- Department of Medicine, Faculty of Medicine, University Complutense, 28040 Madrid, Spain; (S.V.-A.); (A.L.-P.); (M.C.S.)
- GINTRAMIS Research Group (Translational Research Group on Microbiota and Health), Faculty of Medicine, University Complutense, 28040 Madrid, Spain
| | - María Carmen Sánchez
- Department of Medicine, Faculty of Medicine, University Complutense, 28040 Madrid, Spain; (S.V.-A.); (A.L.-P.); (M.C.S.)
- GINTRAMIS Research Group (Translational Research Group on Microbiota and Health), Faculty of Medicine, University Complutense, 28040 Madrid, Spain
| | - María José Ciudad
- Department of Medicine, Faculty of Medicine, University Complutense, 28040 Madrid, Spain; (S.V.-A.); (A.L.-P.); (M.C.S.)
- GINTRAMIS Research Group (Translational Research Group on Microbiota and Health), Faculty of Medicine, University Complutense, 28040 Madrid, Spain
| | - Luis Collado
- Department of Medicine, Faculty of Medicine, University Complutense, 28040 Madrid, Spain; (S.V.-A.); (A.L.-P.); (M.C.S.)
- GINTRAMIS Research Group (Translational Research Group on Microbiota and Health), Faculty of Medicine, University Complutense, 28040 Madrid, Spain
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3
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Yao B, Wei W, Zhang H. Efficacy of probiotics or synbiotics supplementation on chemotherapy-induced complications and gut microbiota dysbiosis in gastrointestinal cancer: a systematic review and meta-analysis. Eur J Clin Nutr 2024:10.1038/s41430-024-01542-5. [PMID: 39562823 DOI: 10.1038/s41430-024-01542-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 10/30/2024] [Accepted: 11/05/2024] [Indexed: 11/21/2024]
Abstract
This study aimed to systematically review the clinical efficacy of probiotics or synbiotics supplementation in the treatment of chemotherapy-induced complications and gut microbiota dysbiosis in patients with gastrointestinal cancer. A literature search was performed systematically using PubMed, Embase, Cochrane, Web of Science, Wanfang Data, and CNKI for randomized controlled trials of probiotics or synthetic supplementation on chemotherapy-induced complications and gut microbiota dysbiosis in gastrointestinal cancer up to December 2023. The outcome measures included chemotherapy-related complications and the the incidence of gut microbiotas. Fifteen studies were finally eligible for meta-analysis, involving 1356 patients. Meta-analysis results showed that the the incidence rates of chemotherapy-related complications such as nausea and vomiting [RR = 0.61, 95% CI (0.46,0.82), P = 0.0008] and diarrhea [RR = 0.47, 95% CI (0.32,0.68), P < 0.001] were significantly reduced after probiotic intervention. The number of intestinal flora changed significantly after intervention, such as bifidobacterium [SMD = 1.33, 95% CI (0.52,2.31), P = 0.001], Escherichia coli [SMD = -0.82, 95% CI (-1.26, -0.38), P = 0.0003], and the difference was statistically significant. Probiotics or synbiotics supplementation can reduce chemotherapy-induced complications in patients with gastrointestinal cancer and regulate the number of gut microbiotas to balance the intestinal microecology of the body.
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Affiliation(s)
- Bei Yao
- First school of clinical medicine, Shandong Traditional Chinese Medicine University, Jinan Shandong, 250014, China
| | - Wei Wei
- Acupuncture rehabilitation Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, GuangDong, 510006, China
| | - Huiping Zhang
- Oncology department, Jinan Hospital of Traditional Chinese Medicine, Jinan Shandong, 250012, China.
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4
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Li YK, Mou FY, Qian XX. Therapeutic efficacy of a probiotic preparation on idiopathic halitosis: a retrospective observational study. J Breath Res 2024; 19:016005. [PMID: 39496205 DOI: 10.1088/1752-7163/ad8e7e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 11/04/2024] [Indexed: 11/06/2024]
Abstract
Idiopathic halitosis is an unusual condition of unclear causes, which has never been thoroughly investigated. We aimed to explore the role of small intestinal bacterial overgrowth (SIBO) in the pathogenesis of idiopathic halitosis, and to evaluate the therapeutic efficacy of a probiotic preparation on this condition. This retrospective observational study included 162 idiopathic halitosis patients and 198 healthy controls (HCs). Halitosis was diagnosed using the organoleptic test, and idiopathic halitosis was diagnosed by excluding known causes. SIBO was identified through the hydrogen/methane lactulose breath test, and accordingly, patients were identified as SIBO-positive or SIBO-negative. Idiopathic halitosis patients were treated with the probiotic preparationBifidobacteriumtriple viable capsule for two months, followed by re-evaluation of halitosis and SIBO. This study found that all cases of idiopathic halitosis were extra-oral. The SIBO positivity rate in idiopathic halitosis patients was significantly higher than that in HCs (74.69% [121/162] vs 3.03% [6/198],P< 0.001), with an odds ratio of 94.44% (95% CI: 39.99%-211.35%). After treatment, 80.17% (97/121) of the SIBO-positive patients became SIBO-negative. Moreover, 87.60% (106/121) of the SIBO-positive patients experienced improved halitosis, a rate significantly higher than that observed in SIBO-negative patients (2.75%, 3/41) (P< 0.001). In addition, 98.97% (96/97) of the post-treatment SIBO-negative patients experienced improved halitosis, a rate significantly higher than that of post-treatment sustained SIBO-positive patients (41.67%, 10/24) (P< 0.001). Our findings suggest that idiopathic halitosis is an extra-oral condition which mostly originates from the small intestine. SIBO is one of its underlying causes. The probiotic preparation can effectively improve idiopathic halitosis, probably through its impact on SIBO.
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Affiliation(s)
- Ye Kan Li
- Department of Stomatology, Minhang Hospital, Fudan University, Shanghai, People's Republic of China
| | - Fu Yuan Mou
- Department of Stomatology, Minhang Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xiao Xian Qian
- Halitosis Clinic and Department of Gastroenterology, Minhang Hospital, Fudan University, Shanghai, People's Republic of China
- No.3 Internal Medicine Department, People's Hospital of Daguan County, Daguan, Zhaotong, Yunnan Province, People's Republic of China
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Lim NR, Lim S, Chung WC. A Study on the Glucose Breath Test Positivity Rate and Occurrence of Small Intestine Bacterial Overgrowth-Related Symptoms Caused by Long-Term Use of Proton Pump Inhibitor (PPI) Versus Potassium-Competitive Acid Blocker (P-CAB) in Elderly Patients: SIBO Between PPI and P-CAB. Adv Pharmacol Pharm Sci 2024; 2024:6069151. [PMID: 39502577 PMCID: PMC11537742 DOI: 10.1155/2024/6069151] [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: 02/13/2024] [Revised: 09/22/2024] [Accepted: 10/04/2024] [Indexed: 11/08/2024] Open
Abstract
Background/Aims: Long-term acid suppression with proton pump inhibitors (PPI) leads to hypochlorhydria and facilitates the growth of bacterial flora in the small intestine. Novel acid-suppressants called potassium-competitive acid blockers (P-CABs) seem to be superior to PPIs. However, data on the risk of small intestinal bacterial overgrowth (SIBO) in patients taking P-CABs are limited. Method: We retrospectively analyzed a consecutive series of patients with long-term acid-suppressant (PPIs or P-CABs) use for gastroesophageal reflux disease or nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. All of them underwent endoscopic examinations and Helicobacter pylori testing and took PPIs or P-CABs for at least 3 months. Glucose hydrogen breath tests (GBT) were performed to check for SIBO, and newly developed SIBO-related symptoms including bloating, postprandial discomfort, diarrheas, and constipation, were evaluated. Results: A total of 142 patients were enrolled. Six patients were excluded due to equivocal Helicobacter pylori infection results. The frequency of positive GBTs was 31.7% (25/79) for PPI and 22.8% (13/57) for P-CAB use (p=0.15). Regarding GBT positivity, age-related factor was found to be significant in multivariate analysis (p=0.02). The results of multivariate analysis in cases of SIBO-related symptoms showed that GBT positivity and PPI use were significant (p < 0.01). Conclusion: Long-term use of gastric acid suppressants resulted in positive GBT in approximately 30% of patients, and the risk was particularly high in elderly patients. The occurrence of SIBO-related symptoms was significant in long-term use of PPIs and in patients with positive GBT.
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Affiliation(s)
- Na Rae Lim
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Saenal Lim
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Woo Chul Chung
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea, Seoul, Republic of Korea
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Pan Y, Li J, Fan Z, Chen Y, Huang X, Wu D. New Insights into Chronic Pancreatitis: Potential Mechanisms Related to Probiotics. Microorganisms 2024; 12:1760. [PMID: 39338435 PMCID: PMC11434092 DOI: 10.3390/microorganisms12091760] [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: 08/08/2024] [Revised: 08/22/2024] [Accepted: 08/23/2024] [Indexed: 09/30/2024] Open
Abstract
Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), the facilitation of short-chain fatty acids' (SCFAs) production, and the activation of glucagon-like peptide-1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we discuss research in other disease models that have used probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.
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Affiliation(s)
- Yingyu Pan
- Department of Gastroenterology, State Key Laborotary of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jianing Li
- Department of Gastroenterology, State Key Laborotary of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Zhengyang Fan
- Department of Gastroenterology, State Key Laborotary of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yonghao Chen
- Department of Gastroenterology, State Key Laborotary of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiaoxuan Huang
- Department of Gastroenterology, State Key Laborotary of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Dong Wu
- Department of Gastroenterology, State Key Laborotary of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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7
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Mares CR, Săsăran MO, Mărginean CO. The relationship between small intestinal bacterial overgrowth and constipation in children - a comprehensive review. Front Cell Infect Microbiol 2024; 14:1431660. [PMID: 38994003 PMCID: PMC11236546 DOI: 10.3389/fcimb.2024.1431660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 06/12/2024] [Indexed: 07/13/2024] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations.
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Affiliation(s)
- Cristina Roxana Mares
- Department of Pediatrics, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mures, Târgu Mures, Romania
| | - Maria Oana Săsăran
- Department of Pediatrics 3, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mures, Târgu Mures, Romania
| | - Cristina Oana Mărginean
- Department of Pediatrics 1, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mures, Târgu Mures, Romania
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Roszkowska P, Klimczak E, Ostrycharz E, Rączka A, Wojciechowska-Koszko I, Dybus A, Cheng YH, Yu YH, Mazgaj S, Hukowska-Szematowicz B. Small Intestinal Bacterial Overgrowth (SIBO) and Twelve Groups of Related Diseases-Current State of Knowledge. Biomedicines 2024; 12:1030. [PMID: 38790992 PMCID: PMC11117733 DOI: 10.3390/biomedicines12051030] [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: 03/24/2024] [Revised: 05/01/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024] Open
Abstract
The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.
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Affiliation(s)
- Paulina Roszkowska
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Emilia Klimczak
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Ewa Ostrycharz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Doctoral School, University of Szczecin, st. A. Mickiewicz 16, 71-412 Szczecin, Poland
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
| | - Aleksandra Rączka
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Iwona Wojciechowska-Koszko
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Andrzej Dybus
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Yeong-Hsiang Cheng
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Yu-Hsiang Yu
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Szymon Mazgaj
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Beata Hukowska-Szematowicz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
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Rau S, Gregg A, Yaceczko S, Limketkai B. Prebiotics and Probiotics for Gastrointestinal Disorders. Nutrients 2024; 16:778. [PMID: 38542689 PMCID: PMC10975713 DOI: 10.3390/nu16060778] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 01/03/2025] Open
Abstract
The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.
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Affiliation(s)
| | | | | | - Berkeley Limketkai
- Vatche & Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA; (S.R.); (A.G.); (S.Y.)
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10
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Khan Z, Mehan S, Saifi MA, Das Gupta G, Narula AS, Kalfin R. Proton Pump Inhibitors and Cognitive Health: Review on Unraveling the Dementia Connection and Co-morbid Risks. Curr Alzheimer Res 2024; 20:739-757. [PMID: 38424433 PMCID: PMC11107432 DOI: 10.2174/0115672050289946240223050737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/28/2024] [Accepted: 01/31/2024] [Indexed: 03/02/2024]
Abstract
Dementia, an international health issue distinguished by the impairment of daily functioning due to cognitive decline, currently affects more than 55 million people worldwide, with the majority residing in low-income and middle-income countries. Globally, dementia entails significant economic burdens in 2019, amounting to a cost of 1.3 trillion US dollars. Informal caregivers devote considerable hours to providing care for those affected. Dementia imposes a greater caregiving and disability-adjusted life-year burden on women. A recent study has established a correlation between prolonged Proton Pump Inhibitor (PPI) usage and dementia, in addition to other neurodegenerative conditions. PPIs are frequently prescribed to treat peptic ulcers and GERD (gastroesophageal reflux disease) by decreasing stomach acid secretion. They alleviate acid-related symptoms through the inhibition of acid-secreting H+-K+ ATPase. In a number of observational studies, cognitive decline and dementia in the elderly have been linked to the use of PPIs. The precise mechanism underlying this relationship is unknown. These drugs might also alter the pH of brain cells, resulting in the accumulation of amyloid-beta (Aβ) peptides and the development of Alzheimer's disease (AD). Despite the compelling evidence supporting the association of PPIs with dementia, the results of studies remain inconsistent. The absence of a correlation between PPI use and cognitive decline in some studies emphasizes the need for additional research. Chronic PPI use can conceal underlying conditions, including cancer, celiac disease, vitamin B12 deficiency, and renal injury, highlighting dementia risk and the need for further investigations on cognitive health.
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Affiliation(s)
- Zuber Khan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India;
| | - Sidharth Mehan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India;
| | - Mohd. Anas Saifi
- Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi-110062, India;
| | - Ghanshyam Das Gupta
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India;
| | - Acharan S. Narula
- Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USA;
| | - Reni Kalfin
- Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, Sofia 1113, Bulgaria;
- Department of Healthcare, South-West University “NeofitRilski”, Ivan Mihailov St. 66, Blagoevgrad 2700, Bulgaria
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11
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Maslennikov R, Alieva A, Poluektova E, Zharikov Y, Suslov A, Letyagina Y, Vasileva E, Levshina A, Kozlov E, Ivashkin V. Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota. World J Gastroenterol 2023; 29:4236-4251. [PMID: 37545638 PMCID: PMC10401661 DOI: 10.3748/wjg.v29.i27.4236] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/25/2023] [Accepted: 06/21/2023] [Indexed: 07/13/2023] Open
Abstract
Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Yana Letyagina
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Ekaterina Vasileva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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12
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Yu J. Bifidobacterium triple viable powder/capsule: How effective it is against gastrointestinal diseases? J Gastroenterol Hepatol 2023. [PMID: 37414587 DOI: 10.1111/jgh.16283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/08/2023]
Affiliation(s)
- Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
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13
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Kiecka A, Szczepanik M. Proton pump inhibitor-induced gut dysbiosis and immunomodulation: current knowledge and potential restoration by probiotics. Pharmacol Rep 2023:10.1007/s43440-023-00489-x. [PMID: 37142877 PMCID: PMC10159235 DOI: 10.1007/s43440-023-00489-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/06/2023]
Abstract
Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs), esophagitis, peptic ulcer disease (PUD), Zollinger-Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), non-ulcer dyspepsia, and Helicobacter pylori eradication therapy. The drugs have the effect of inhibiting acid production in the stomach. According to research, PPIs can affect the composition of gut microbiota and modulate the immune response. Recently, there has been a problem with the over-prescription of such drugs. Although PPIs do not have many side effects, their long-term use can contribute to small intestinal bacterial overgrowth (SIBO) or C. difficile and other intestinal infections. Probiotic supplementation during PPIs therapy may provide some hope in the reduction of emerging therapy side effects. This review aims to present the most important effects of long-term PPI use and provides critical insights into the role of probiotic intervention in PPI therapy.
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Affiliation(s)
- Aneta Kiecka
- Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, Kopernika 7a, 31-034, Kraków, Poland.
| | - Marian Szczepanik
- Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, Kopernika 7a, 31-034, Kraków, Poland
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14
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Sintusek P, Mutalib M, Thapar N. Gastroesophageal reflux disease in children: What's new right now? World J Gastrointest Endosc 2023; 15:84-102. [PMID: 37034973 PMCID: PMC10080553 DOI: 10.4253/wjge.v15.i3.84] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/15/2023] [Accepted: 02/08/2023] [Indexed: 03/16/2023] Open
Abstract
Gastroesophageal reflux (GER) in children is very common and refers to the involuntary passage of gastric contents into the esophagus. This is often physiological and managed conservatively. In contrast, GER disease (GERD) is a less common pathologic process causing troublesome symptoms, which may need medical management. Apart from abnormal transient relaxations of the lower esophageal sphincter, other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense, impaired esophageal and gastric motility and clearance, as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia. The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation. Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD. The following review focuses on up-to-date information regarding of the pathogenesis, diagnostic evaluation and management of GERD in children.
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Affiliation(s)
- Palittiya Sintusek
- Thai Pediatric Gastroenterology, Hepatology and Immunology Research Unit (TPGHAI), Division of Gastroenterology, Department of Pediatrics, King Chulalongkorn Memorial Hospital and Thai Red Cross, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Bangkok, Thailand
| | - Mohamed Mutalib
- Department of Paediatric Gastroenterology, Pediatric and Gastroenterology Services, Evelina London Children’s Hospital, London SE1 7EH, United Kingdom
| | - Nikhil Thapar
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Queensland 4101, Australia
- School of Medicine, University of Queensland, Brisbane, Queensland 4006, Australia
- Woolworths Centre for Child Nutrition Research, Queensland University of Technology, Brisbane, Queensland 4101, Australia
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15
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Nami Y, Hejazi S, Geranmayeh MH, Shahgolzari M, Yari Khosroushahi A. Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention. Eur J Cancer Prev 2023; 32:30-47. [PMID: 36134612 DOI: 10.1097/cej.0000000000000738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest & West Region, Agricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)
| | - Salva Hejazi
- Department of Medicine, Student Research Committee, Tabriz University of Medical Sciences
| | - Mohammad Hossein Geranmayeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Biotechnology Research Center, Tabriz University of Medical Sciences
| | - Ahmad Yari Khosroushahi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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16
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Koyande N, Gangopadhyay M, Thatikonda S, Rengan AK. The role of gut microbiota in the development of colorectal cancer: a review. Int J Colorectal Dis 2022; 37:1509-1523. [PMID: 35704091 DOI: 10.1007/s00384-022-04192-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/21/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE Colorectal cancer (CRC) is the cancer of the colon and rectum. Recent research has found a link between CRC and human gut microbiota. This review explores the effect of gut microbiota on colorectal carcinogenesis and the development of chemoresistance. METHODS A literature overview was performed to identify the gut microbiota species that showed altered abundance in CRC patients and the mechanisms by which some of them aid in the development of chemoresistance. RESULTS Types of gut microbiota present and methods of analyzing them were discussed. We observed that numerous microbiota showed altered abundance in CRC patients and could act as a biomarker for CRC diagnosis and treatment. Further, it was demonstrated that microbes also have a role in the development of chemoresistance by mechanisms like immune system activation, drug modification, and autophagy modulation. Finally, the key issue of the growing global problem of antimicrobial resistance and its relationship with CRC was highlighted. CONCLUSION This review discussed the role of gut microbiota dysbiosis on colorectal cancer progression and the development of chemoresistance.
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Affiliation(s)
- Navami Koyande
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy- 502284, India
| | - Madhusree Gangopadhyay
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy- 502284, India
| | - Shashidhar Thatikonda
- Department of Civil Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy- 502284, India
| | - Aravind Kumar Rengan
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy- 502284, India.
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17
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Characterization of the fecal microbiota in gastrointestinal cancer patients and healthy people. Clin Transl Oncol 2022; 24:1134-1147. [PMID: 35167015 DOI: 10.1007/s12094-021-02754-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 12/08/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND The incidence and mortality of gastrointestinal (GI) tumors are high in China. Some studies suggest that the gut microbiota is related to the occurrence and development of tumors. At present, there are no prospective studies based on the correlation between gastrointestinal tumors and gut microbiota in the Chinese population. The objective of this report is to characterize the fecal microbiota in healthy control participants and patients with esophageal cancer, gastric cancer, and colorectal cancer. METHODS Patients with locally advanced or metastatic esophageal, gastric, and colorectal cancer were enrolled, and healthy people were included as controls. 16S rRNA sequencing was used to analyze the characteristics of fecal microbiota. PICRUSt software was used for functional prediction. RESULTS Significant differences in the composition and abundance of fecal microbiota were identified between gastrointestinal cancer patients (n = 130) and healthy controls (n = 147). The abundance of Faecalibacterium prausnitzii, Clostridium clostridioforme and Bifidobacterium adolescent in tumor groups were all significantly lower than in the control group (P < 0.05). The levels of Blautia producta and R. faecis in the gastric (n = 46) and colorectal cancer (n = 44) groups were significantly lower than those in the control group (P < 0.05). The level of Butyricicoccus pullicaecorum in the esophageal cancer (n = 40) and gastric cancer groups was significantly lower than that in the control group (P < 0.05). B. fragilis, Akkermansia muciniphila, Clostridium hathewayi and Alistipes finegoldii were overabundant in the different tumor groups compared with the control (P < 0.05). We observed significant differences in functional metabolism and cell biological function between the tumor and control groups (P < 0.05). Optimal microbial markers were identified on a random forest model and achieved an area under the curve of 85.59% between 130 GI cancer samples and 147 control samples. The respective AUC values were 86.89%, 97.11%, and 79.1% in detecting esophageal cancer, gastric cancer, and colorectal cancer. CONCLUSIONS Patients with esophageal or gastric cancers had similar features of fecal bacteria as those with colorectal cancer. The metabolic function of fecal bacteria in the gastrointestinal cancer patients and the healthy controls were different. The microbial signatures may potentially be applied to distinguish GI cancer patients from healthy people as a non-invasive diagnostic biomarker.
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18
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The role of microbiota in colorectal cancer. Folia Microbiol (Praha) 2022; 67:683-691. [PMID: 35534716 DOI: 10.1007/s12223-022-00978-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 05/02/2022] [Indexed: 11/04/2022]
Abstract
Cancer is one of the most important causes of death throughout the world, and the mortality rate is increasing significantly due to the aging of the population. One of the most common types of cancer is colorectal cancer (CRC). Human microbial ecosystems use metabolism to make important impacts on the body physiology. An intensive literature review was made to investigate the correlations between human gut microbiota and the incidence of CRC. The results of these studies show that there are differences in the composition of microbiota between CRC patients and normal people and the microorganisms in CRC patients are very different from healthy individuals. Therefore, changes in the microbiome can be used as a biomarker for the early detection of CRC. On the other hand, the intestinal flora is may be act as a powerful weapon against CRC in the future.
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19
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Jiang QL, Lu Y, Zhang MJ, Cui ZY, Pei ZM, Li WH, Lu LG, Wang JJ, Lu YY. Mucosal bacterial dysbiosis in patients with nodular lymphoid hyperplasia in the terminal ileum. World J Gastroenterol 2022; 28:811-824. [PMID: 35317097 PMCID: PMC8900573 DOI: 10.3748/wjg.v28.i8.811] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/19/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nodular lymphoid hyperplasia (NLH) in the small intestine is a rare benign lesion characterized by multiple small nodules on the intestinal surface. Patients with terminal ileal NLH may experience long-term abdominal pain, diarrhea, and abdominal distension, among other symptoms. Supplementation with probiotics could mitigate these symptoms. NLH is linked to the immune system, and it may result from accumulation of plasma-cell precursors due to a maturational defect during the development of B lymphocytes. The intestinal microbiome plays an essential role in the immune system. Thus, we speculate that the gut flora plays a key role in terminal ileal NLH.
AIM To explore the correlation between intestinal flora and terminal ileal NLH.
METHODS We collected mucosal biopsy samples that were obtained via colonoscopy from 15 patients with terminal ileal NLH (the test group) and 15 normal subjects (the control group). We subsequently performed 16S-rRNA gene amplicon sequencing of these samples, and the results were evaluated using alpha diversity, beta diversity and microbial composition analyses. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used to predict the metabolic pathways and orthologous groups according to the Kyoto Encyclopedia of Genes and Genomes database.
RESULTS Compared with the control group, the terminal ileal NLH group showed an increased alpha diversity (P < 0.05). The overall intestinal microbiota in the NLH group was significantly different from that of the control group (P < 0.05), implying that there was the dysbiosis in the terminal ileal NLH patients. The relative abundance of phylum Bacteroidetes was significantly lower in the NLH group, while that of Patescibacteria and Campilobacterota was significantly higher. The genus Bacteroides was the dominant gut microbiota in both groups, but its abundance was significantly lower in the test group than it was in the control group. Conversely, the relative abundances of Haemophilus, Streptococcus, Pseudomonas, Actinomyces, TM7X, Fusobacterium nucleatum, Parvimonas, Granulicatella, Helicobacter, and the [Eubacterium] nodatum group were significantly higher in the test group than they were in the control group. In addition, several altered metabolic pathways, orthologous groups, and modules were found. For example, the Peptidoglycan biosynthesis and Aminoacyl tRNA biosynthesis were both increased in the test group.
CONCLUSION Maintaining the microbial balance and supplementing targeted protective bacteria could improve symptoms and potentially reduce the risk of lymphoma transformation in patients with terminal ileal NLH.
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Affiliation(s)
- Qiao-Li Jiang
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
| | - You Lu
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
| | - Meng-Jie Zhang
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
| | - Zhen-Yu Cui
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
| | - Zhong-Mei Pei
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
| | - Wen-Hua Li
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
| | - Lun-Gen Lu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Jing-Jing Wang
- Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Ying-Ying Lu
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
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20
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Davoodvandi A, Fallahi F, Tamtaji OR, Tajiknia V, Banikazemi Z, Fathizadeh H, Abbasi-Kolli M, Aschner M, Ghandali M, Sahebkar A, Taghizadeh M, Mirzaei H. An Update on the Effects of Probiotics on Gastrointestinal Cancers. Front Pharmacol 2021; 12:680400. [PMID: 34992527 PMCID: PMC8724544 DOI: 10.3389/fphar.2021.680400] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 11/26/2021] [Indexed: 12/28/2022] Open
Abstract
Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.
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Affiliation(s)
- Amirhossein Davoodvandi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Farzaneh Fallahi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Omid Reza Tamtaji
- Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Vida Tajiknia
- Department of Surgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zarrin Banikazemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hadis Fathizadeh
- Department of Laboratory Sciences, Sirjan Faculty of Medicine Sciences, Sirjan, Iran
| | - Mohammad Abbasi-Kolli
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Maryam Ghandali
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Taghizadeh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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The Anti-Tumor Effect of Lactococcus lactis Bacteria-Secreting Human Soluble TRAIL Can Be Enhanced by Metformin Both In Vitro and In Vivo in a Mouse Model of Human Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13123004. [PMID: 34203951 PMCID: PMC8232584 DOI: 10.3390/cancers13123004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/25/2021] [Accepted: 06/11/2021] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Colorectal cancer (CRC) is a major cause of morbidity and mortality in Europe, and accounts for over 10% of all cancer-related deaths worldwide. These indicate an urgent need for novel therapeutic options in CRC. Here, we analysed if genetically modified non-pathogenic Lactococcus lactis bacteria can be used for local delivery of human recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and induction of tumor cells death in vitro and in vivo in CRC mouse model. We showed that modified L. lactis bacteria were able to secrete biologically active human soluble TRAIL (L. lactis(hsTRAIL+)), which selectively eliminated human CRC cells in vitro, and was further strengthened by metformin (MetF). Our results from in vitro studies were confirmed in vivo using subcutaneous NOD-SCID mouse model of human CRC. The data showed a significant reduction of the tumor growth by intratumor injection of L. lactis(hsTRAIL+) bacteria producing hsTRAIL. This effect could be further enhanced by oral administration of MetF. Abstract Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis of many cancer cells, including CRC cells, being non-harmful for normal ones. However, recombinant form of human TRAIL failed in clinical trial when administered intravenously. To assess the importance of TRAIL in CRC patients, new form of TRAIL delivery would be required. Here we used genetically modified, non-pathogenic Lactococcus lactis bacteria as a vehicle for local delivery of human soluble TRAIL (hsTRAIL) in CRC. Operating under the Nisin Controlled Gene Expression System (NICE), the modified bacteria (L. lactis(hsTRAIL+)) were able to induce cell death of HCT116 and SW480 human cancer cells and reduce the growth of HCT116-tumor spheres in vitro. This effect was cancer cell specific as the cells of normal colon epithelium (FHC cells) were not affected by hsTRAIL-producing bacteria. Metformin (MetF), 5-fluorouracil (5-FU) and irinotecan (CPT-11) enhanced the anti-tumor actions of hsTRAIL in vitro. In the NOD-SCID mouse model, treatment of subcutaneous HCT116-tumors with L. lactis(hsTRAIL+) bacteria given intratumorally, significantly reduced the tumor growth. This anti-tumor activity of hsTRAIL in vivo was further enhanced by oral administration of MetF. These findings indicate that L. lactis bacteria could be suitable for local delivery of biologically active human proteins. At the same time, we documented that anti-tumor activity of hsTRAIL in experimental therapy of CRC can be further enhanced by MetF given orally, opening a venue for alternative CRC-treatment strategies.
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Dikeocha IJ, Al-Kabsi AM, Eid EEM, Hussin S, Alshawsh MA. Probiotics supplementation in patients with colorectal cancer: a systematic review of randomized controlled trials. Nutr Rev 2021; 80:22-49. [PMID: 34027974 DOI: 10.1093/nutrit/nuab006] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
CONTEXT Colorectal cancer (CRC) is a leading cause of cancer deaths. Recently, much attention has been given to the microbiome and probiotics as preventive and therapeutic approaches to CRC and the mechanisms involved. OBJECTIVES To interpret the findings of randomized controlled trials (RCTs) of probiotics relative to patients with CRC and to outline challenges of and future directions for using probiotics in the management and prevention of CRC. DATA SOURCES Web of Science, PubMed, ProQuest, Wile, y and Scopus databases were searched systematically from January 17-20, 2020, in accordance with PRISMA guidelines. STUDY SELECTION Primacy RCTs that reported the effects of administration to patients with CRC of a probiotic vs a placebo were eligible to be included. DATA EXTRACTION The studies were screened and selected independently by 2 authors on the basis of prespecified inclusion and exclusion criteria. The data extraction and risk-of-bias assessment were also performed independently by 2 authors. RESULTS A total of 23 RCTs were eligible for inclusion. Probiotics supplementation in patients with CRC improved their quality of life, enhanced gut microbiota diversity, reduced postoperative infection complications, and inhibited pro-inflammatory cytokine production. The use of certain probiotics in patients with CRC also reduced the side effects of chemotherapy, improved the outcomes of surgery, shortened hospital stays, and decreased the risk of death. Bifidobacteria and Lactobacillus were the common probiotics used across all studies. CONCLUSION Probiotics have beneficial effects in patients with CRC regardless of the stage of cancer. There is an opportunity for probiotics to be used in mainstream health care as a therapy in the fight against CRC, especially in early stages; however, larger clinical trialsof selected or a cocktail of probiotics are needed to confirm the efficacy, dosage, and interactions with chemotherapeutics agents. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42020166865.
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Affiliation(s)
- Ifeoma Julieth Dikeocha
- I.J. Dikeocha, A.M. Al-Kabsi, and S. Hussin are with the Faculty of Medicine, University of Cyberjaya, Cyberjaya, Selangor, Malaysia. E.E.M. Eid is with the Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah, Saudi Arabia. M.A. Alshawsh is with the Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Abdelkodose Mohammed Al-Kabsi
- I.J. Dikeocha, A.M. Al-Kabsi, and S. Hussin are with the Faculty of Medicine, University of Cyberjaya, Cyberjaya, Selangor, Malaysia. E.E.M. Eid is with the Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah, Saudi Arabia. M.A. Alshawsh is with the Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Eltayeb E M Eid
- I.J. Dikeocha, A.M. Al-Kabsi, and S. Hussin are with the Faculty of Medicine, University of Cyberjaya, Cyberjaya, Selangor, Malaysia. E.E.M. Eid is with the Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah, Saudi Arabia. M.A. Alshawsh is with the Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Salasawati Hussin
- I.J. Dikeocha, A.M. Al-Kabsi, and S. Hussin are with the Faculty of Medicine, University of Cyberjaya, Cyberjaya, Selangor, Malaysia. E.E.M. Eid is with the Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah, Saudi Arabia. M.A. Alshawsh is with the Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Mohammed Abdullah Alshawsh
- I.J. Dikeocha, A.M. Al-Kabsi, and S. Hussin are with the Faculty of Medicine, University of Cyberjaya, Cyberjaya, Selangor, Malaysia. E.E.M. Eid is with the Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah, Saudi Arabia. M.A. Alshawsh is with the Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Gonçalves AR, Ambrogini O, Forones NM. NONINVASIVE BREATH TESTS FOR DIAGNOSIS OF SIBO AND LACTOSE INTOLERANCE IN PATIENTS ON CHEMOTHERAPY TREATMENT FOR COLORECTAL AND GASTRIC CÂNCER. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:26-31. [PMID: 33909793 DOI: 10.1590/s0004-2803.202100000-06] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/15/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Worldwide, colorectal cancer (CRC) and gastric cancer (GC) are the third and the fifth most prevalent, respectively. Diarrhea is a common symptom in patients on chemotherapy or radiotherapy treatment and can reduce treatment tolerance. Surgical resections and chemotherapy change the intestinal microbiota that can lead to lactose intolerance, small intestinal bacterial overgrowth (SIBO). OBJECTIVE The aim of the study was to evaluate the frequency of diarrhea in patients with CRC and GC on chemotherapy with SIBO or intolerance of lactose. METHODS This is a descriptive and observational study with patients of both sexes, over 18 years old, in treatment in the Gastro-Oncology outpatient clinic of the Federal University of São Paulo. Patients with a confirmed diagnosis of CRC or GC during chemotherapy treatment were included. To detect bacterial overgrowth and lactose intolerance, breath hydrogen test with lactulose and lactose was done. Number and aspects of the evacuations and toxicity degree were collected. For the nutritional assessment, weight and height were performed to calculate the BMI. and the Patient Generated Subjective Global Assessment (PG-SGA). RESULTS A total of 33 patients were included, 29 with CRC and 3 with GC. Most of them were male (57.57%), mean age of 60.03±10.01 years and in chemotherapy with fluoropyrimidine and oxaliplatin (54.5%). Diarrhea was present in 57.6% and 30.3% had toxicity grade 2. According to the BMI, 78.9% were eutrophics, obese or overweight, but according to PG-SGA, 84.9% had moderate or severe nutritional risk grade. Between patients, 45% had lactose intolerance and 9% SIBO. Diarrhea grade 2-3 was observed in 66.6% of patients with SIBO and 66.7% of that with lactose intolerance. No statistical difference was observed between patients with SIBO or lactose intolerance and grade of diarrhea. CONCLUSION Diarrhea was a frequent symptom in chemotherapy patients with gastric or colorectal cancer independent of the presence of SIBO or lactose intolerance. Surgery and chemotherapy treatment impacted in the intestinal habit of patients. Diagnosis of other causes of diarrhea may contribute to a better tolerance to treatment and quality of life.
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Affiliation(s)
- Aline Rufino Gonçalves
- Universidade Federal de São Paulo, Disciplina de Gastroenterologia, São Paulo, SP, Brasil
| | - Orlando Ambrogini
- Universidade Federal de São Paulo, Disciplina de Gastroenterologia, São Paulo, SP, Brasil
| | - Nora Manoukian Forones
- Universidade Federal de São Paulo, Disciplina de Gastroenterologia, São Paulo, SP, Brasil
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Ma G, Du H, Hu Q, Yang W, Pei F, Xiao H. Health benefits of edible mushroom polysaccharides and associated gut microbiota regulation. Crit Rev Food Sci Nutr 2021; 62:6646-6663. [PMID: 33792430 DOI: 10.1080/10408398.2021.1903385] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Edible mushrooms have been an important part of the human diet for thousands of years, and over 100 varieties have been cultivated for their potential human health benefits. In recent years, edible mushroom polysaccharides (EMPs) have been studied for their activities against obesity, inflammatory bowel disease (IBD), and cancer. Particularly, accumulating evidence on the exact causality between these health risks and specific gut microbiota species has been revealed and characterized, and most of the beneficial health effects of EMPs have been associated with its reversal impacts on gut microbiota dysbiosis. This demonstrates the key role of EMPs in decreasing health risks through gut microbiota modulation effects. This review article compiles and summarizes the latest studies that focus on the health benefits and underlying functional mechanisms of gut microbiota regulation via EMPs. We conclude that EMPs can be considered a dietary source for the improvement and prevention of several health risks, and this review provides the theoretical basis and technical guidance for the development of novel functional foods with the utilization of edible mushrooms.
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Affiliation(s)
- Gaoxing Ma
- College of Food Science and Engineering, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing, People's Republic of China.,Department of Food Science, University of Massachusetts, Amherst, Massachusetts, USA
| | - Hengjun Du
- Department of Food Science, University of Massachusetts, Amherst, Massachusetts, USA
| | - Qiuhui Hu
- College of Food Science and Engineering, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing, People's Republic of China
| | - Wenjian Yang
- College of Food Science and Engineering, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing, People's Republic of China
| | - Fei Pei
- College of Food Science and Engineering, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing, People's Republic of China
| | - Hang Xiao
- Department of Food Science, University of Massachusetts, Amherst, Massachusetts, USA
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25
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Xu F, Li N, Wang C, Xing H, Chen D, Wei Y. Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study. BMC Gastroenterol 2021; 21:54. [PMID: 33549047 PMCID: PMC7866462 DOI: 10.1186/s12876-021-01630-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 01/26/2021] [Indexed: 12/16/2022] Open
Abstract
Background Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated. Methods In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy. Results Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none. Conclusions This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO. Trial registry This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).
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Affiliation(s)
- Fenghua Xu
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Ning Li
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Chun Wang
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Hanyang Xing
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Dongfeng Chen
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Yanling Wei
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China.
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26
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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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27
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Dharmarajan TS, Pitchumoni CS. Small Intestinal Bacterial Overgrowth Syndrome. GERIATRIC GASTROENTEROLOGY 2021:1617-1643. [DOI: 10.1007/978-3-030-30192-7_62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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28
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Nickles MA, Hasan A, Shakhbazova A, Wright S, Chambers CJ, Sivamani RK. Alternative Treatment Approaches to Small Intestinal Bacterial Overgrowth: A Systematic Review. J Altern Complement Med 2020; 27:108-119. [PMID: 33074705 DOI: 10.1089/acm.2020.0275] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background: Broad-spectrum antibiotics are the first-line treatment for small intestinal bacterial overgrowth (SIBO). However, many antibiotics have a considerable side-effect profile and SIBO commonly reoccurs after successful eradication with antibiotics. Alternative therapies such as probiotics, therapeutic diets, and herbal medicines have been used to individualize SIBO management, particularly in recalcitrant cases. Objectives: The objective of this review is to evaluate the role of alternative therapies in SIBO treatment. Data Sources: EMBASE, MEDLINE, and the Cochrane Central Register were systematically searched for clinical studies evaluating alternative therapies in the management of SIBO. Study Eligibility Criteria: Human studies in which an alternative intervention was used to treat SIBO were included. Alternative interventions were defined as an intervention that included a probiotic supplement, herbal preparation, or a dietary change. Randomized controlled trials (RCTs), nonrandomized clinical trials with or without a control, and crossover studies were included. Study Appraisal: The following information was extracted from the selected studies: study type, study participants, SIBO subtype, intervention, comparison, outcome measures, relevant results, relevant side effects, and Jadad score. Results: Eight studies met inclusion criteria. The studies evaluated probiotics (n = 5), therapeutic diet (n = 1), and herbal medicines (n = 2). Among these studies, there were four RCTs, two open-label single-arm studies, one randomized, double-blind crossover study, and one two-arm open-label study with crossover. Main results are summarized. Limitations: There may be studies not captured by the defined search criteria. Additionally, studies used different methodologies in both breath testing and measurement of clinical symptoms, making it difficult to draw conclusions on SIBO eradication and symptom improvement across studies. Conclusions and Implications: Our findings suggest preliminary evidence for a role of alternative therapies in the treatment of SIBO. However, robust clinical trials are generally lacking. Existing studies tend to be small and lack standardized formulations of treatment. Breath testing protocols and clinical symptom measurement greatly varied between studies. Large-scale, randomized, placebo-controlled trials are needed to further evaluate the best way to utilize alternative therapies in the treatment of SIBO.
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Affiliation(s)
- Melissa A Nickles
- College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Aliza Hasan
- Department of Dermatology, University of California-Davis, Sacramento, CA, USA
| | | | | | - Cynthia J Chambers
- College of Medicine, California Northstate University, Elk Grove, CA, USA.,Pacific Skin Institute, Sacramento, CA, USA.,Zen Dermatology, Sacramento, CA, USA
| | - Raja K Sivamani
- Department of Dermatology, University of California-Davis, Sacramento, CA, USA.,College of Medicine, California Northstate University, Elk Grove, CA, USA.,Pacific Skin Institute, Sacramento, CA, USA.,Zen Dermatology, Sacramento, CA, USA.,Department of Biological Sciences, California State University, Sacramento, CA, USA
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The effects of probiotics on reducing the colorectal cancer surgery complications: A periodic review during 2007–2017. Clin Nutr 2020; 39:2358-2367. [PMID: 31831184 DOI: 10.1016/j.clnu.2019.11.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 10/09/2019] [Accepted: 11/04/2019] [Indexed: 02/01/2023]
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Castro-Herrera VM, Rasmussen C, Wellejus A, Miles EA, Calder PC. In Vitro Effects of Live and Heat-Inactivated Bifidobacterium animalis Subsp. Lactis, BB-12 and Lactobacillus rhamnosus GG on Caco-2 Cells. Nutrients 2020; 12:nu12061719. [PMID: 32521765 PMCID: PMC7352502 DOI: 10.3390/nu12061719] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 05/26/2020] [Accepted: 06/05/2020] [Indexed: 12/17/2022] Open
Abstract
Probiotic–host interaction can be cell-to-cell or through metabolite production. Dead (inactive) organisms could interact with the host, leading to local effects and possible health benefits. This research examined the effects of live and heat-inactivated Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) and Lactobacillus rhamnosus GG (LGG) on cultured Caco-2 cells focusing on epithelial integrity and production of inflammatory mediators. Live organisms increased transepithelial electrical resistance (TEER), a barrier-integrity marker, with LGG having a greater effect than BB-12. When mildly heat-treated, both organisms had a more modest effect on TEER than when alive. When they were heat-inactivated, both organisms had only a limited effect on TEER. Neither live nor heat-inactivated organisms affected production of six inflammatory mediators produced by Caco-2 cells compared to control conditions. Pre-treatment with heat-inactivated LGG or BB-12 did not alter the decline in TEER caused by exposure to an inflammatory cocktail of cytokines. However, pre-treatment of Caco-2 cells with heat-inactivated organisms alone or their combination decreased the production of interleukin (IL)-6, IL-18, and vascular endothelial growth factor. To conclude, while the live organisms improve the epithelial barrier using this model, neither live nor heat-inactivated organisms directly elicit an inflammatory response by the epithelium. Pre-treatment with heat-inactivated BB-12 or LGG can reduce some components of the response induced by an inflammatory stimulus.
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Affiliation(s)
- Vivian M. Castro-Herrera
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (E.A.M.); (P.C.C.)
- Correspondence: ; Tel.:+44-(0)7548126403
| | | | - Anja Wellejus
- Chr. Hansen A/S, 2970 Hoersholm, Denmark; (C.R.); (A.W.)
| | - Elizabeth A. Miles
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (E.A.M.); (P.C.C.)
| | - Philip C. Calder
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (E.A.M.); (P.C.C.)
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, UK
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31
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The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response. Cancers (Basel) 2020; 12:cancers12061406. [PMID: 32486066 PMCID: PMC7352899 DOI: 10.3390/cancers12061406] [Citation(s) in RCA: 203] [Impact Index Per Article: 40.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/24/2020] [Accepted: 05/28/2020] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.
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32
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Watson KM, Gaulke CA, Tsikitis VL. Understanding the microbiome: a primer on the role of the microbiome in colorectal neoplasia. Ann Gastroenterol 2020; 33:223-236. [PMID: 32382225 PMCID: PMC7196612 DOI: 10.20524/aog.2020.0467] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 01/24/2020] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer is a leading cause of cancer-related death internationally, with mounting evidence pointing to the role of the microbiome in adenoma and cancer development. This article aims to provide clinicians with a foundation for understanding the field of research into the microbiome. We also illustrate the various ways in which the microbiota have been linked to colorectal cancer, with a specific focus on microbiota with identified virulence factors, and also on the ways that byproducts of microbiota metabolism may result in oncogenesis. We also review strategies for manipulating the microbiome for therapeutic effects.
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Affiliation(s)
- Katherine M. Watson
- Department of Surgery, Oregon Health & Science University, Portland, OR (Katherine M. Watson, Vassiliki Liana Tsikitis)
| | | | - Vassiliki Liana Tsikitis
- Department of Surgery, Oregon Health & Science University, Portland, OR (Katherine M. Watson, Vassiliki Liana Tsikitis)
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33
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Evaluation of the antitumor immune responses of probiotic Bifidobacterium bifidum in human papillomavirus-induced tumor model. Microb Pathog 2020; 145:104207. [PMID: 32325236 DOI: 10.1016/j.micpath.2020.104207] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 03/17/2020] [Accepted: 04/15/2020] [Indexed: 01/18/2023]
Abstract
As of present, a number of studies have shown anti-cancer effects of different strains of probiotics, but the precise host immunological mechanisms of these antitumor effects remain unclear. Thus, the aim of current study was to investigate the preventive-therapeutic effects of oral versus intravenous administration of probiotic Bifidobacterium bifidum on immune response and tumor growth of C57BL/6 mice bearing transplanted TC-1 cell of human papillomavirus (HPV)-related tumor, expressing HPV-16 E6/E7 oncogenes. Our major findings are that the intravenous or oral administration of Bifidobacterium bifidum effectively induces antitumor immune responses and inhibits tumor growth in mice. Compared to oral route only, intravenous administration of probiotic Bifidobacterium bifidum into tumor-bearing mice leads to the activation of tumor-specific IL-12 and IFN-γ, lymphocyte proliferation, CD8+ cytolytic responses that control and eradicate tumor growth. These observations meant intravenous administration of probiotics is an effective anticancer approach through modulation of the immune system. The potential of probiotic Bifidobacterium bifidum as an immunomodulator in the treatment of cervical cancer could be further explored.
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Bahmani S, Azarpira N, Moazamian E. Anti-colon cancer activity of Bifidobacterium metabolites on colon cancer cell line SW742. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:835-842. [PMID: 31530527 DOI: 10.5152/tjg.2019.18451] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND/AIMS Bacteria species, which are used as probiotics, are lactic acid bacteria. The majority of them are under the genera Bifidobacterium and Lactobacillus. The aim of the present study was to isolate and identify Bifidobacterium and to evaluate the effects of their 24 h and 120 h cell-free supernatants (CFS) from both cultures on colon cancer cell line. MATERIALS AND METHODS In the present study, 84 samples of dairy products, infant feces, and probiotic capsule were collected, and Bifidobacterium was isolated. Gram stain, biochemical tests, and molecular identification were done for the isolation and identification of Bifidobacterium. Cytotoxicity effects of CFS derived from both cultures of isolated Bifidobacterium were assessed on colon cancer cell lines. RESULTS In the present study, 17 isolates of Bifidobacterium were identified. The results show that Bifidobacterium was most frequently associated with infant feces and dairy products, whereas the lowest rate was associated with local milk. After the effects of CFS on colon cancer cell line, two isolates were identified from infant feces and probiotic capsule; they had the highest ability in inhibiting the growth of cancer cells. Bifidobacterium bifidum was effective in combating cancer cells and was associated with a substantial improvement in gastrointestinal cancer. CONCLUSION The study has shown that the regular ingested probiotics could prevent the development of colorectal cancer. During the present study, the produced CFS could inhibit the growth of colon cancer cells. In conclusion, probiotics have good potential to be introduced as a new approach to colon cancer treatment.
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Affiliation(s)
- Sepideh Bahmani
- Department of Microbiology, Islamic Azad University School of Science, Fars, Iran; Young Researchers and Elite Club, Islamic Azad University, Shiraz, Iran
| | - Negar Azarpira
- Organ Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Elham Moazamian
- Young Researchers and Elite Club, Islamic Azad University, Shiraz, Iran
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Abstract
PURPOSE OF REVIEW This paper seeks to highlight GI motility disorders that are frequently present in patients with a malignancy. GI dysmotility can occur due to the cancer itself or as a consequence of medical and surgical treatments. Often, symptoms are nonspecific and the diagnosis requires a high index of suspicion. The goal of the paper is to review the common motility problems seen in patients with cancer, their clinical manifestations, and options for management. RECENT FINDINGS Studies show that newer endoscopy techniques such as endoscopic mucosal dissection can cause esophageal dysmotility. Opioid-induced constipation is frequently encountered in patients with cancer. Motility disorders in cancer patient can lead to clinical morbidity, poor quality of life, and malnutrition. Newer diagnostic tests and medical and surgical treatments may be helpful in improving the diagnosis and management of these disorders.
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Affiliation(s)
- Mehnaz A Shafi
- University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1466, Houston, TX, 77030, USA.
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36
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Alomari M, Nusairat L, Al Momani L, Chadalavada P, Covut F, Olayan M, Young M, Romero-Marrero C. Effects of Probiotics on Intestinal Failure-Associated Liver Disease in Adult Patients Receiving Prolonged Parenteral Support: A Tertiary Care Center Experience. Nutr Clin Pract 2019; 35:454-463. [PMID: 31721285 DOI: 10.1002/ncp.10437] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND It has been hypothesized that dysbiosis plays a significant role in the pathogenesis of intestinal failure-associated liver disease (IFALD). Therefore, we aimed to investigate the effect of probiotics on IFALD in patients receiving parenteral support, namely home parenteral nutrition (HPN) and home intravenous fluids (HIVFs). METHODS We retrospectively reviewed charts of patients with intestinal failure who received HPN or HIVF for >2 weeks at our tertiary center between January 2005 and August 2016. We excluded patients <18 years of age, patients with other causes of liver disease, patients who used probiotics for <30 days, patients with <6 months' follow-up, and those who had long-term antibiotic use (>30 days). Bivariable and multivariable logistic regression analyses were used in this study. RESULTS A total of 282 patients who received parenteral support were included. Eighty-five percent of our sample received PN. A total of 78 (27.7%) patients used probiotics. The prevalence of IFALD in patients who used probiotics was 35.9% vs 54.4% in patients who did not use probiotics, P = .005. In multivariable analysis, only small-bowel length of 10-90 cm and HPN use showed a significant impact on IFALD, odds ratio (OR) = 4.394 (95% confidence interval [CI], 1.635-11.814; P = .003) and OR = 4.502 (95% CI 1.412-14.351; P = .011), respectively. CONCLUSION Our study revealed that the prevalence of IFALD was comparable among the probiotic users and nonusers. Only small bowel length of 1090 cm and HPN use showed a significant impact on IFALD.
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Affiliation(s)
- Mohammad Alomari
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Leen Nusairat
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Laith Al Momani
- Department of Internal Medicine, East Tennessee State University, Johnson City, Tennessee, USA
| | | | - Fahrettin Covut
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - May Olayan
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Mark Young
- Department of Gastroenterology and Hepatology, East Tennessee State University, Johnson City, Tennessee, USA
| | - Carlos Romero-Marrero
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Qian L, Gao R, Huang J, Qin H. Supplementation of triple viable probiotics combined with dietary intervention is associated with gut microbial improvement in humans on a high-fat diet. Exp Ther Med 2019; 18:2262-2270. [PMID: 31452713 DOI: 10.3892/etm.2019.7801] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 06/20/2019] [Indexed: 12/13/2022] Open
Abstract
Numerous animal studies have demonstrated that oral probiotics may have a beneficial role in preventing obesity, inflammatory bowel disease and even colorectal cancer, which are all associated with a high-fat diet (HFD). However, the underlying beneficial effects of combined probiotic and dietary intervention on the gut microbiota of 'non-patient' individuals previously on an HFD have yet to be fully elucidated. In the present study, fecal samples were obtained from 36 volunteers on a high-fat diet and after dietary intervention for 4 months, and 16S rDNA sequencing was applied to identify how probiotics and dietary intervention had altered the composition of the microbiota. The results demonstrated that probiotics treatment and dietary intervention in combination raised the diversity of lumen microbes compared with their individual applications. A markedly separated distribution (β-diversity) was observed, confirming the difference in gut microbiota composition among the treatment groups. Bacterial taxonomic analysis demonstrated that the relative abundance of 30 species was altered among the groups following dietary intervention and/or probiotic supplementation. The majority of the species that exhibited a population increase belonged to two butyrate-producing families, Ruminococcaceae and Lachnospiraceae, whereas the species with reduced populations mainly belonged to the Bacteroidaceae family. Collectively, these results suggest that combined probiotic and dietary intervention is able to improve the gut microbiota composition of human subjects on an HFD.
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Affiliation(s)
- Leimin Qian
- Department of Gastrointestinal Surgery, Jiangyin People's Hospital, Jiangyin, Jiangsu 214400, P.R. China
| | - Renyuan Gao
- Department of General Surgery, The Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China
| | - Jianming Huang
- Department of Gastrointestinal Surgery, Jiangyin People's Hospital, Jiangyin, Jiangsu 214400, P.R. China
| | - Huanlong Qin
- Department of General Surgery, The Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China
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Bruno G, Zaccari P, Rocco G, Scalese G, Panetta C, Porowska B, Pontone S, Severi C. Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified. World J Gastroenterol 2019; 25:2706-2719. [PMID: 31235994 PMCID: PMC6580352 DOI: 10.3748/wjg.v25.i22.2706] [Citation(s) in RCA: 151] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 04/02/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.
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Affiliation(s)
- Giovanni Bruno
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Piera Zaccari
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Giulia Rocco
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Giulia Scalese
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Cristina Panetta
- Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
| | - Barbara Porowska
- Department of Cardio-Thoracic, Vascular Surgery and Transplants, Sapienza University of Rome, Rome 00161, Italy
| | - Stefano Pontone
- Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
| | - Carola Severi
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
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Abstract
In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut.
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Saus E, Iraola-Guzmán S, Willis JR, Brunet-Vega A, Gabaldón T. Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential. Mol Aspects Med 2019; 69:93-106. [PMID: 31082399 PMCID: PMC6856719 DOI: 10.1016/j.mam.2019.05.001] [Citation(s) in RCA: 222] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 05/08/2019] [Indexed: 02/08/2023]
Abstract
The gastrointestinal tract harbors most of the microbiota associated with humans. In recent years, there has been a surge of interest in assessing the relationships between the gut microbiota and several gut alterations, including colorectal cancer. Changes in the gut microbiota in patients suffering colorectal cancer suggest a possible role of host-microbe interactions in the origin and development of this malignancy and, at the same time, open the door for novel ways of preventing, diagnosing, or treating this disease. In this review we survey current knowledge on the healthy microbiome of the gut and how it is altered in colorectal cancer and other related disease conditions. In describing past studies we will critically assess technical limitations of different approaches and point to existing challenges in microbiome research. We will have a special focus on host-microbiome interaction mechanisms that may be important to explain how dysbiosis can lead to chronic inflammation and drive processes that influence carcinogenesis and tumor progression in colon cancer. Finally, we will discuss the potential of recent developments of novel microbiota-based therapeutics and diagnostic tools for colorectal cancer.
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Affiliation(s)
- Ester Saus
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Susana Iraola-Guzmán
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Jesse R Willis
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Anna Brunet-Vega
- Oncology Service, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
| | - Toni Gabaldón
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain.
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Pichon M, Burucoa C. Impact of the Gastro-Intestinal Bacterial Microbiome on Helicobacter-Associated Diseases. Healthcare (Basel) 2019; 7:E34. [PMID: 30813360 PMCID: PMC6473412 DOI: 10.3390/healthcare7010034] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 02/18/2019] [Accepted: 02/20/2019] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori is a bacterium that selectively infects the gastric epithelium of half of the world population. The microbiome, community of microorganisms gained major interest over the last years, due to its modification associated to health and disease states. Even if most of these descriptions have focused on chronic disorders, this review describes the impact of the intestinal bacterial microbiome on host response to Helicobacter associated diseases. Microbiome has a direct impact on host cells, major barrier of the gastro-intestinal tract, but also an indirect impact on immune system stimulation, by enhancing or decreasing non-specific or adaptive response. In microbial infections, especially in precancerous lesions induced by Helicobacter pylori infection, these modifications could lead to different outcome. Associated to data focusing on the microbiome, transcriptomic analyses of the eukaryote response would lead to a complete understanding of these complex interactions and will allow to characterize innovative biomarkers and personalized therapies.
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Affiliation(s)
- Maxime Pichon
- Bacteriology and Infection Control Laboratory, Infectious Agents Department, University Hospital of Poitiers, 86021 Poitiers, France.
- Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, EA 4331, Faculté de Médecine et de Pharmacie, University of Poitiers, 86022 Poitiers, France.
| | - Christophe Burucoa
- Bacteriology and Infection Control Laboratory, Infectious Agents Department, University Hospital of Poitiers, 86021 Poitiers, France.
- Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, EA 4331, Faculté de Médecine et de Pharmacie, University of Poitiers, 86022 Poitiers, France.
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Chen D, Wu J, Jin D, Wang B, Cao H. Fecal microbiota transplantation in cancer management: Current status and perspectives. Int J Cancer 2018; 145:2021-2031. [PMID: 30458058 PMCID: PMC6767494 DOI: 10.1002/ijc.32003] [Citation(s) in RCA: 182] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 10/22/2018] [Accepted: 11/13/2018] [Indexed: 02/06/2023]
Abstract
The human gut is home to a large and diverse microbial community, comprising about 1,000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent preclinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer‐treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota.
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Affiliation(s)
- Danfeng Chen
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Jingyi Wu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Duochen Jin
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
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Ding C, Tang W, Fan X, Wu G. Intestinal microbiota: a novel perspective in colorectal cancer biotherapeutics. Onco Targets Ther 2018; 11:4797-4810. [PMID: 30147331 PMCID: PMC6097518 DOI: 10.2147/ott.s170626] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
It is believed that genetic factors, immune system dysfunction, chronic inflammation, and intestinal microbiota (IM) dysbiosis contribute to the pathogenesis of colorectal cancer (CRC). The beneficial role played by the direct regulation of IM in inflammatory bowel disease treatment is identified by the decreased growth of harmful bacteria and the increased production of anti-inflammatory factors. Interestingly, gut microbiota has been proven to inhibit tumor formation and progression in inflammation/carcinogen-induced CRC mouse models. Recently, evidence has indicated that IM is involved in the negative regulation of tumor immune response in tumor microenvironment, which then abolishes or accelerates anticancer immunotherapy in several tumor animals. In clinical trials, a benefit of IM-based CRC therapies in improving the intestinal immunity balance, epithelial barrier function, and quality of life has been reported. Meanwhile, specific microbiota signature can modulate host's sensitivity to chemo-/radiotherapy and the prognosis of CRC patients. In this review, we aim to 1) summarize the potential methods of IM-based therapeutics according to the recent results; 2) explore its roles and underlying mechanisms in combination with other therapies, especially in biotherapeutics; 3) discuss its safety, deficiency, and future perspectives.
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Affiliation(s)
- Chenbo Ding
- Medical School of Southeast University, Nanjing, Jiangsu Province, People's Republic of China,
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, People's Republic of China,
| | - Wendong Tang
- Medical School of Southeast University, Nanjing, Jiangsu Province, People's Republic of China,
| | - Xiaobo Fan
- Medical School of Southeast University, Nanjing, Jiangsu Province, People's Republic of China,
| | - Guoqiu Wu
- Medical School of Southeast University, Nanjing, Jiangsu Province, People's Republic of China,
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, People's Republic of China,
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Jin XF, Spampatti MP, Spitzweg C, Auernhammer CJ. Supportive therapy in gastroenteropancreatic neuroendocrine tumors: Often forgotten but important. Rev Endocr Metab Disord 2018; 19:145-158. [PMID: 29464446 DOI: 10.1007/s11154-018-9443-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Neuroendocrine tumors (NETs) are a group of rare and heterogeneous malignancies that can develop in various organs. A significant number of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is functionally active and presents with symptoms related to the secretion of biologically active substances, leading to the development of distinct clinical syndromes. There are various therapeutic approaches for GEP-NETs, including curative surgery, palliative surgery, local-ablative and loco-regional therapies as well as systemic therapeutic options including peptide receptor radionuclide therapy, cytotoxic therapy, and molecularly targeted therapies. Specific supportive therapy of patients with NETs includes management or prevention of hormone-related clinical syndromes and paraneoplastic states. Supportive therapy plays a key role in NET treatment. Supportive therapy includes debulking surgery and interventional radiologic techniques to reduce tumour bulk or load, as well as systemic medical treatment options to manage or prevent hypersecretion syndromes and treatment-related side effects. Supportive therapies are a type of of comprehensive treatment addressing the patient as a whole person throughout the process of NET treatment. Therefore, supportive therapy also encompasses psychosocial support, expert nursing, nutritional support and management of cancer related pain.
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Affiliation(s)
- Xi-Feng Jin
- Department of Internal Medicine IV, University-Hospital Campus Grosshadern, Ludwig-Maximilian University of Munich, Munich, Germany
| | - Matilde P Spampatti
- Department of Internal Medicine II, University-Hospital Campus Grosshadern, Ludwig-Maximilian University of Munich, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universitaet Muenchen, Ludwig-Maximilians-University of Munich, Campus Grosshadern, Marchioninistr, 15, 81377, Munich, Germany
| | - Christine Spitzweg
- Department of Internal Medicine IV, University-Hospital Campus Grosshadern, Ludwig-Maximilian University of Munich, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universitaet Muenchen, Ludwig-Maximilians-University of Munich, Campus Grosshadern, Marchioninistr, 15, 81377, Munich, Germany
| | - Christoph J Auernhammer
- Department of Internal Medicine IV, University-Hospital Campus Grosshadern, Ludwig-Maximilian University of Munich, Munich, Germany.
- Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universitaet Muenchen, Ludwig-Maximilians-University of Munich, Campus Grosshadern, Marchioninistr, 15, 81377, Munich, Germany.
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Belei O, Olariu L, Dobrescu A, Marcovici T, Marginean O. Is It Useful to Administer Probiotics Together With Proton Pump Inhibitors in Children With Gastroesophageal Reflux? J Neurogastroenterol Motil 2018; 24:51-57. [PMID: 29291607 PMCID: PMC5753903 DOI: 10.5056/jnm17059] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 08/12/2017] [Accepted: 10/13/2017] [Indexed: 02/06/2023] Open
Abstract
Background/Aims Gastroesophageal reflux disease (GERD) is a frequent condition diagnosed in children and treated with proton pump inhibitors (PPI). Long-term PPI administration can alter intestinal bacterial population by suppressing the gastric acid barrier and may cause diarrhea. The aim of this study is to evaluate the prevalence of small intestinal bacterial overgrowth assessed by glucose hydrogen breath test among children that received 12 weeks of PPI with or without probiotics (Lactobacillus reuteri DSM 17938) associated, compared to controls. Methods Glucose hydrogen breath test was performed before PPI treatment and after 12 weeks of PPI treatment to 128 consecutive children with GERD (1–18 years old) and a control group (120 healthy children). The children with GERD were randomized into 2 groups: placebo group (64 who received PPI and placebo for 12 weeks) and probiotics group (64 who received PPI and probiotics for 12 weeks). Results After 12 weeks of treatment, dysbiosis was detected among 56.2% of children from placebo group (36/64), compared to 6.2% of children from the probiotics group (4/64, P < 0.001). Bacterial overgrowth was detected in 5% of controls (6/120). Probiotics group had a lower prevalence of dysbiosis, similar to controls (P = 0.740). Conclusion Probiotics administration decreased the rate of dysbiosis among children treated with PPI.
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Affiliation(s)
- Oana Belei
- First Pediatric Clinic, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania
| | - Laura Olariu
- First Pediatric Clinic, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania
| | - Andreea Dobrescu
- Genetics Department, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania
| | - Tamara Marcovici
- First Pediatric Clinic, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania
| | - Otilia Marginean
- First Pediatric Clinic, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania
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Su T, Lai S, Lee A, He X, Chen S. Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth. J Gastroenterol 2018; 53:27-36. [PMID: 28770351 DOI: 10.1007/s00535-017-1371-9] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 07/15/2017] [Indexed: 02/06/2023]
Abstract
The use of proton pump inhibitors (PPIs) may potentially predispose to the development of small intestinal bacterial overgrowth (SIBO), but this association is controversial due to conflicting results from studies conducted to date. The aim of this meta-analysis was to evaluate the association between the use of PPIs and the risk of SIBO. We systematically searched the online PubMed, Embase, and Cochrane Library databases and Web of Science for relevant articles published up to November 2016. Two researchers identified and extracted data independent of each other. The pooled analysis was performed using the generic inverse-variance random-effects model. Subgroup and sensitivity analysis were conducted to assess the stability and heterogeneity of the pooled results. The risk of publication bias was evaluated by assessing for funnel plot asymmetry and by Egger's test and Begg's test. A total of 19 articles met the eligibility criteria for the meta-analysis, reporting on 7055 subjects. The pooled odds ratio (OR) showed a statistically significant association between increased risk of SIBO and PPI use (OR 1.71, 95% confidence interval 1.20-2.43). Subgroup analyses demonstrated an association between SIBO and PPI use in studies that employed small bowel aspirates culture and glucose hydrogen breath tests (GHBT) as diagnostic tests for SIBO. Our meta-analysis suggests that the use of PPI moderately increases the risk of SIBO, thereby highlighting the need for appropriate prescribing of PPIs.
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Affiliation(s)
- Tingting Su
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China.,Institute of Gastroenterology, Zhejiang University, Hangzhou, 310016, Zhejiang, China
| | - Sanchuan Lai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China.,Institute of Gastroenterology, Zhejiang University, Hangzhou, 310016, Zhejiang, China
| | - Allen Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Michigan Hospital, Ann Arbor, MI, USA.
| | - Xingkang He
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China.,Institute of Gastroenterology, Zhejiang University, Hangzhou, 310016, Zhejiang, China
| | - Shujie Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China. .,Institute of Gastroenterology, Zhejiang University, Hangzhou, 310016, Zhejiang, China.
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Abstract
PURPOSE OF REVIEW Probiotics can be used as an adjuvant for cancer prevention or/and treatment through their abilities to modulate intestinal microbiota and host immune response. Although most of the recent reviews have focused on the potential role of probiotics against colon cancer, only few of them include the probiotic effect on extraintestinal cancers. The present review covers the most important findings from the literature published during the past 20 months (from January 2015 to August 2016) regarding the probiotics-mediated suppression of both gastrointestinal and extraintestinal cancers and the underlying mechanisms. RECENT FINDINGS A comprehensive literature search in Pubmed, Science direct and Google scholar databases was conducted to locate all relevant articles that investigated the effect of probiotics on prevention/treatment of both gastrointestinal and extraintestinal cancers. Different mechanisms for the beneficial effects of probiotics against cancer were also discussed, mainly via modulation of gut microbiota which thereby influences host metabolism and immunity. SUMMARY Despite laboratory-based studies having demonstrated encouraging outcomes that probiotics possess antitumor effects, the benefits should not be exaggerated before we get more results from human clinical trials. These are very important before the medical community can accept the use of probiotics as an alternative therapy for cancer control.
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48
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Probiotics for Preventing and Treating Small Intestinal Bacterial Overgrowth: A Meta-Analysis and Systematic Review of Current Evidence. J Clin Gastroenterol 2017; 51:300-311. [PMID: 28267052 DOI: 10.1097/mcg.0000000000000814] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The present study conducted a meta-analysis and systematic review of current evidence to assess the efficacy of probiotics in preventing or treating small intestinal bacterial overgrowth (SIBO). Relevant studies from PubMed, Embase, and the Cochrane Central Register of Controlled Trials, until May 2016, were assimilated. The prevention efficacy was assessed by the incidence of SIBO in the probiotic group, and the treatment efficacy by the SIBO decontamination rate, reduction in H2 concentration, and symptom improvement. The relative risk (RR) and weighted mean difference (WMD) were used as effect measures and the random-effects model used for meta-analysis. A total of 14 full-text articles and 8 abstracts were included for the systematic review, and 18 studies were eligible for data synthesis. Patients on probiotic usage showed an insignificant trend toward low SIBO incidence [RR=0.54; 95% confidence intervals (CI), 0.19-1.52; P=0.24]. The pooled SIBO decontamination rate was 62.8% (51.5% to 72.8%). The probiotics group showed a significantly higher SIBO decontamination rate than the nonprobiotic group (RR=1.61; 95% CI, 1.19-2.17; P<0.05). Also, the H2 concentration was significantly reduced among probiotic users (WMD=-36.35 ppm; 95% CI, -44.23 to -28.47 ppm; P<0.05). Although probiotics produced a marked decrease in the abdominal pain scores (WMD=-1.17; 95% CI, -2.30 to -0.04; P<0.05), it did not significantly reduce the daily stool frequency (WMD=-0.09; 95% CI, -0.47 to 0.29). Therefore, the present findings indicated that probiotics supplementation could effectively decontaminate SIBO, decrease H2 concentration, and relieve abdominal pain, but were ineffective in preventing SIBO.
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