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Song Y, Liu S, Zhang L, Zhao W, Qin Y, Liu M. The effect of gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review and network meta-analysis. Front Nutr 2025; 11:1470185. [PMID: 39834471 PMCID: PMC11743284 DOI: 10.3389/fnut.2024.1470185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 12/11/2024] [Indexed: 01/22/2025] Open
Abstract
Background The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease. Method A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval. Results A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33]. Conclusion The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored. Systematic review registration https://www.crd.york.ac.uk/prospero/, CRD42023450093.
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Affiliation(s)
- Yijia Song
- Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- The First Clinical Medical School of Henan University of Chinese Medicine, Zhengzhou, China
- The Nursing School of Henan University of Chinese Medicine, Zhengzhou, China
| | - Sutong Liu
- Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Lihui Zhang
- Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- The First Clinical Medical School of Henan University of Chinese Medicine, Zhengzhou, China
| | - Wenxia Zhao
- Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Yuanmei Qin
- Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- The Nursing School of Henan University of Chinese Medicine, Zhengzhou, China
| | - Minghao Liu
- Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
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Zhou L, Gong L, Liu Z, Xiang J, Ren C, Xu Y. Probiotic interventions with highly acid-tolerant Levilactobacillus brevis strains improve lipid metabolism and gut microbial balance in obese mice. Food Funct 2025; 16:112-132. [PMID: 39621366 DOI: 10.1039/d4fo03417a] [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: 12/11/2024]
Abstract
Many studies have shown that specific lactic acid bacteria (LAB) strains can delay obesity, offering a viable alternative to medications and surgeries. However, the mining and development of highly effective LAB strains for obesity control is still limited. In this study, the naturally highly acid-tolerant and gamma-aminobutyric acid-producing Levilactobacillus brevis D17 and its glnR deletion strain were used to investigate their anti-obesity effects. In an 8-week mouse experiment, L. brevis D17 and its glnR-deletion strain D17ΔglnR significantly reduced weight gain by 28.4% and 29.1%, respectively, improving abnormal serum indicators and glucose metabolism caused by a high-fat diet. Furthermore, L. brevis D17 and its glnR-deletion strain D17ΔglnR successfully colonized in the gut. Both D17 and D17ΔglnR interventions significantly restored the relative abundance of Muribaculaceae, Ileibacterium valens, Lactobacillus, Faecalibaculum, Bifidobacterium globosum, Akkermansia muciniphila, and Romboutsia ilealis, whereas they significantly reduced potentially harmful bacteria like Leptogranulimonas, Flintibacter, and Alistipes. Additionally, L. brevis intervention effectively decreased the levels of primary bile acids and increased secondary bile acids in the gut, thus balancing bile acid metabolism. The transcriptional analysis suggested that D17 and D17ΔglnR interventions may activate the AMPK signaling pathway in the liver to inhibit lipogenesis, activate the cAMP pathway to promote lipolysis, and inhibit pro-inflammatory macrophage infiltration to block inflammatory responses. These results indicate that L. brevis D17 and its glnR-deletion mutant strain D17ΔglnR show great potential in combating obesity. Moreover, these results also provide insights into the underlying mechanism behind their anti-obesity properties.
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Affiliation(s)
- Liping Zhou
- Lab of Brewing Microbiology and Applied Enzymology, Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, China.
| | - Luchan Gong
- Lab of Brewing Microbiology and Applied Enzymology, Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, China.
| | - Zhihao Liu
- Lab of Brewing Microbiology and Applied Enzymology, Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, China.
| | - Jinfeng Xiang
- Lab of Brewing Microbiology and Applied Enzymology, Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, China.
| | - Cong Ren
- Lab of Brewing Microbiology and Applied Enzymology, Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, China.
- China Key Laboratory of Microbiomics and Eco-brewing Technology for Light Industry, Wuxi 214122, Jiangsu, China
| | - Yan Xu
- Lab of Brewing Microbiology and Applied Enzymology, Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, China.
- China Key Laboratory of Microbiomics and Eco-brewing Technology for Light Industry, Wuxi 214122, Jiangsu, China
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Yaghmaei H, Bahanesteh A, Soltanipur M, Takaloo S, Rezaei M, Siadat SD. The Role of Gut Microbiota Modification in Nonalcoholic Fatty Liver Disease Treatment Strategies. Int J Hepatol 2024; 2024:4183880. [PMID: 39444759 PMCID: PMC11498984 DOI: 10.1155/2024/4183880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 08/25/2024] [Accepted: 10/05/2024] [Indexed: 10/25/2024] Open
Abstract
One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.
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Affiliation(s)
- Hessam Yaghmaei
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
| | | | - Masood Soltanipur
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sobhan Takaloo
- Biomedical Engineering Department, Hamedan University of Technology, Hamedan, Iran
| | - Mahdi Rezaei
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
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Zhang L, Wang F, Wang R, Sun B, Liu PJ. Effects of probiotics, prebiotics, and synbiotics on cardiometabolic risk factors in children and adolescents with overweight or obesity: a systematic review and Bayesian network meta-analysis. Crit Rev Food Sci Nutr 2024:1-15. [PMID: 39340527 DOI: 10.1080/10408398.2024.2409956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2024]
Abstract
The efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) -2.13 kg/m2, 95% credible interval (CrI) [-2.7, -1.57]), waist circumference (MD -1.34 cm, 95% CrI [-2.33, -0.35]), total cholesterol (MD -6.55 mg/dL, 95% CrI [-10.61, -2.45]), triglycerides (MD -3.71 mg/dL, 95% CrI [-5.76, -1.67]), leptin (MD -3.99 ng/mL, 95% CrI [-4.68, -3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD -1.21 mg/L, 95% CrI [-1.45, -0.97]). Synbiotics were effective in reducing BMI-z score (MD -0.07, 95% CrI [-0.10, -0.04]) and LDL-C (MD -1.54 mg/dL, 95% CrI [-1.98, -1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings.
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Affiliation(s)
- Liang Zhang
- Department of Rehabilitation Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Fang Wang
- Department of Clinical Nutrition, Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China
| | - Rui Wang
- Department of Clinical Nutrition, Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China
| | - Bowen Sun
- Department of Linguistics, University of Manitoba, Winnipeg, Canada
| | - Peng Ju Liu
- Department of Clinical Nutrition, Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China
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Wang T, Zhang X, Fan L, Zhao Y, Zhang Z, Cao Z, Xu Y, Lee S, Lim C, Zhang S. Complete genome sequence and anti-obesity potential of Lactiplantibacillus plantarum HOM2217 in 3T3-L1 cells and high-fat diet-fed rats. Front Microbiol 2024; 15:1436378. [PMID: 39323881 PMCID: PMC11422070 DOI: 10.3389/fmicb.2024.1436378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/27/2024] [Indexed: 09/27/2024] Open
Abstract
The global prevalence of obesity is rising year by year, which has become a public health problem worldwide. Many animal and clinical studies have shown that Lactiplantibacillus plantarum is considered an ideal probiotic and potential supplement for the treatment of obesity. In this study, we aimed to complete the genome sequence of L. plantarum HOM2217, which was isolated from human milk, and study its physiological characteristics and anti-obesity effects in 3T3-L1 cells and rats fed a high-fat diet (HFD) to determine its potential as a starter for functional food products. Whole-genome analysis demonstrated that HOM2217 contained a single circular chromosome of 3,267,529 bp with a GC content of 44.5% and one plasmid (62,350 bp) with a GC content of 38.5%. Compared to the reference strains, HOM2217 demonstrated superior tolerance to gastrointestinal conditions, higher adhesion to intestinal epithelial cell lines, potent antimicrobial activity against Enterobacter cloacae ATCC 13047, and effective cholesterol removal ability in vitro. Treatment with heat-killed HOM2217 significantly reduced lipid accumulation and intracellular triglyceride production in 3T3-L1 adipocytes. Daily treatment of HFD-fed rats with HOM2217 for 7 weeks decreased body weight, body weight gain, and body fat without changes in food intake. HOM2217 also significantly increased the serum high-density lipoprotein cholesterol (HDL-C) level, decreased the serum tumor necrosis factor (TNF-α) and increased short-chain fatty acid (SCFA) (formic acid, acetic acid, and butyric acid) levels in the cecum. Thus, HOM2217 could potentially prevent obesity in rats by inhibiting inflammatory responses and regulating lipid metabolism and SCFAs expression. Therefore, HOM2217 has potential as an alternative treatment for obesity.
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Affiliation(s)
- Tingting Wang
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Xiao Zhang
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Linlin Fan
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Ying Zhao
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Zhengwen Zhang
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Zhonghua Cao
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Ying Xu
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
| | - Suwon Lee
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
| | - Chongyoon Lim
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
| | - Shiqi Zhang
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
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Serbis A, Polyzos SA, Paschou SA, Siomou E, Kiortsis DN. Diet, exercise, and supplements: what is their role in the management of the metabolic dysfunction-associated steatotic liver disease in children? Endocrine 2024; 85:988-1006. [PMID: 38519764 DOI: 10.1007/s12020-024-03783-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 03/13/2024] [Indexed: 03/25/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the main cause of chronic liver disease in children and adolescents. Indeed, epidemiological studies have shown that MASLD affects up to 40% of children with obesity. Despite the recent approval of medications that target weight loss in adolescents that could have benefits on pediatric MASLD, lifestyle interventions, such as diet and exercise, remain the mainstay of our therapeutic approach. More specifically, studies on diet alone have focused on the possible role of carbohydrate or fat restriction, albeit without a definite answer on the best approach. Weight loss after dietary intervention in children with obesity and MASLD has a beneficial effect, regardless of the diet used. In relation to the role of exercise in MASLD reversal, indirect evidence comes from studies showing that a sedentary lifestyle leading to poor fitness, and low muscle mass is associated with MASLD. However, research on the direct effect of exercise on MASLD in children is scarce. A combination of diet and exercise seems to be beneficial with several studies showing improvement in surrogate markers of MASLD, such as serum alanine aminotransferase and hepatic fat fraction, the latter evaluated with imaging studies. Several dietary supplements, such as vitamin E, probiotics, and omega-3 fatty acid supplements have also been studied in children and adolescents with MASLD, but with equivocal results. This review aims to critically present available data on the effects of lifestyle interventions, including diet, exercise, and dietary supplements, on pediatric MASLD, thus suggesting a frame for future research that could enhance our knowledge on pediatric MASLD management and optimize clinicians' approach to this vexing medical condition.
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Affiliation(s)
- Anastasios Serbis
- Department of Pediatrics, School of Medicine, University of Ioannina, Ioannina, Greece.
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stavroula A Paschou
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ekaterini Siomou
- Department of Pediatrics, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios N Kiortsis
- Laboratory of Physiology, Medical School, University of Ioannina, Ioannina, Greece
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Niu Y, Li J, Qian H, Liang C, Shi X, Bu S. Evaluation of efficacy and safety of Lacticaseibacillus rhamnosus LRa05 in the eradication of Helicobacter pylori: a randomized, double-blind, placebo-controlled trial. Front Immunol 2024; 15:1450414. [PMID: 39234246 PMCID: PMC11371625 DOI: 10.3389/fimmu.2024.1450414] [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: 06/17/2024] [Accepted: 07/30/2024] [Indexed: 09/06/2024] Open
Abstract
Aim This study aims to evaluate the efficacy of Lacticaseibacillus rhamnosus LRa05 supplementation in enhancing Helicobacter pylori (H. pylori) eradication rate and alleviating the gastrointestinal side effects associated with bismuth quadruple therapy. Methods H. pylori-positive patients were randomized to receive levofloxacin-based bismuth quadruple therapy combined either probiotic LRa05 or a placebo for two weeks, followed by LRa05 (1 × 1010 CFU) or maltodextrin for the next two weeks. H. pylori infection was detected by 13C breath test pre- and post-treatment. Blood and stool samples were collected at week 0 and week 4 for routine and biochemical analysis, and serum inflammatory markers. Gastrointestinal symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS). Intestinal microbiota was analyzed using 16S rRNA sequencing. The research was listed under the Chinese Clinical Trial Registry (ChiCTR2300072220), and written informed consent was obtained from all participants. Results The LRa05 group exhibited a trend toward higher H. pylori eradication rates (86.11%) compared to the placebo group (82.86%), though the difference was not statistically significant. Significant reductions in neutrophil count, alanine aminotransferase, aspartate aminotransferase, pepsinogen I, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) (p < 0.05) suggest that LRa05 supplementation may mitigate inflammation, enhance liver function, and potential aid in early cancer prevention. GSRS symptom scores showed that LRa05 alleviated abdominal pain, acid reflux, bloating, and diarrhea, enhancing patient compliance. Furthermore, 16S rRNA sequencing showed that LRa05 countered the antibiotic-induced disruption of gut microbiota diversity, primarily by increasing beneficial bacteria. Conclusion Although LRa05 did not significantly improve the success rate of H. pylori eradication therapy, it has the potential to improve liver function and reduced levels of inflammatory markers such as IL-6 and TNF-α in the body, regulating the inflammatory response. In addition, it played a positive role in alleviating the adverse symptoms and gut microbiota disturbances caused by eradication therapy, providing a possible way to improve the overall health of patients and demonstrating promising clinical potential. Clinical Trial Registration http://www.chictr.org.cn, identifier ChiCTR2300072220.
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Affiliation(s)
- Yue Niu
- Department of Gastroenterology, Jinshan Hospital, Fudan University, Shanghai, China
| | - Jing Li
- Department of Gastroenterology, Jinshan Hospital, Fudan University, Shanghai, China
| | - Hongwei Qian
- Department of General Practice, Shihua Community Health Service Center in Jinshan District, Shanghai, China
| | - Chunli Liang
- Department of Gastroenterology, Jinshan Hospital, Fudan University, Shanghai, China
| | - Xinyi Shi
- Department of General Practice, Shihua Community Health Service Center in Jinshan District, Shanghai, China
| | - Shurui Bu
- Department of Gastroenterology, Jinshan Hospital, Fudan University, Shanghai, China
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Służały P, Paśko P, Galanty A. Natural Products as Hepatoprotective Agents-A Comprehensive Review of Clinical Trials. PLANTS (BASEL, SWITZERLAND) 2024; 13:1985. [PMID: 39065511 PMCID: PMC11280762 DOI: 10.3390/plants13141985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/18/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024]
Abstract
The hepatoprotective effects of natural products have been a significant focus in recent decades due to the growing demand for the help in the treatment of hepatic impairments. This review specifically delves into the findings of clinical trials involving 13 selected natural products, namely plants and their derived compounds (e.g., artichoke, berberine, and turmeric), algae (e.g., spirulina), probiotics, and other products like phospholipids and vitamin D. A literature search was performed in the Scopus database, PubMed, and Google Scholar, covering all articles found up to June 2024. Artichoke, berberine, chlorella, chicory, green tea, probiotics, phospholipids, schisandra, silymarin, spirulina, and vitamin D caused a decrease in liver enzymes, while for cinnamon and turmeric such an effect was either not observed or not convincing. The presented results indicate that some natural products might satisfactorily improve hepatic outcomes in NAFLD, NASH, and other liver disorders; however, further studies and metanalyses are needed to clearly demonstrate their effectiveness.
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Affiliation(s)
- Piotr Służały
- Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland;
| | - Paweł Paśko
- Department of Food Chemistry and Nutrition, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland;
| | - Agnieszka Galanty
- Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland;
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Vinothkanna A, Shi‐Liang X, Karthick Rajan D, Prathiviraj R, Sekar S, Zhang S, Wang B, Liu Z, Jia A. Feasible mechanisms and therapeutic potential of food probiotics to mitigate diabetes‐associated cancers: A comprehensive review and in silico validation. FOOD FRONTIERS 2024; 5:1476-1511. [DOI: 10.1002/fft2.406] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
AbstractPeople with diabetes mellitus (DM) and hyperglycemia are linked with cancer risk. Diabetes and cancer have been corroborated by high morbidity and mortality rates. Studies revealed that elevated levels of insulin secretions trigger insulin‐like growth factor 1 (IGF‐1) production. Moreover, IGF‐1 is a key regulator involved in promoting cancer cell progression and is linked with DM. Cancer drug resistance and ototoxic effects can adversely affect the health and lifespan of an individual. However, naturally derived bioactive compounds are gaining attention for their nontoxic properties and specific behavior. Likewise, probiotics have also been regarded as safe and successful alternatives to treat DM‐linked cancers. The present review aims to highlight the therapeutic potential and feasible functions of probiotics to mitigate or inhibit DM‐associated cancers. Meanwhile, the intracellular signaling cascades involved in promoting DM‐linked cancer are enumerated for future prospective research. However, metabolomics interactions and protein–protein interactions are to be discussed for deeper insights into affirmative principles in diabetic‐linked cancers. Drug discovery and innovative preclinical evaluation need further adjuvant and immune‐enhancement therapies. Furthermore, the results of the in silico assessment could provide scientific excellence of IGF‐1 in diabetes and cancer. Overall, this review summarizes the mechanistic insights and therapeutic targets for diabetes‐associated cancer.
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Affiliation(s)
- Annadurai Vinothkanna
- Hainan Affiliated Hospital of Hainan Medical University Hainan General Hospital Haikou China
- School of Life and Health Sciences Hainan University Haikou China
| | - Xiang Shi‐Liang
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences Hainan University Haikou China
| | - Durairaj Karthick Rajan
- Department of Cell Biology, School of Life Sciences Central South University Changsha Hunan China
| | | | - Soundarapandian Sekar
- Department of Biotechnology Bharathidasan University Tiruchirappalli Tamil Nadu India
| | - Shubing Zhang
- Department of Cell Biology, School of Life Sciences Central South University Changsha Hunan China
| | - Bo Wang
- Hainan Affiliated Hospital of Hainan Medical University Hainan General Hospital Haikou China
| | - Zhu Liu
- School of Life and Health Sciences Hainan University Haikou China
| | - Ai‐Qun Jia
- Hainan Affiliated Hospital of Hainan Medical University Hainan General Hospital Haikou China
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Yang Y, Yang L, Wu J, Hu J, Wan M, Bie J, Li J, Pan D, Sun G, Yang C. Optimal probiotic combinations for treating nonalcoholic fatty liver disease: A systematic review and network meta-analysis. Clin Nutr 2024; 43:1224-1239. [PMID: 38643738 DOI: 10.1016/j.clnu.2024.04.004] [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: 08/22/2023] [Revised: 03/20/2024] [Accepted: 04/01/2024] [Indexed: 04/23/2024]
Abstract
BACKGROUND Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients. METHODS The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. RESULTS A total of 35 RCTs involving 2212 NAFLD patients were included in the analysis. For primary outcomes, Lactobacillus + Bifidobacterium + Streptococcus exhibited the highest probability of being the finest probiotic combination in terms of enhancing acceptability as well as reducing AST (SMD: -1.95 95% CI: -2.90, -0.99), ALT (SMD = -1.67, 95% CI: -2.48, -0.85), and GGT levels (SMD = -2.17, 95% CI: -3.27, -1.06). In terms of the secondary outcomes, Lactobacillus + Bifidobacterium + Streptococcus was also the best probiotic combination for reducing BMI (SMD = -0.45, 95% CI: -0.86, -0.04), LDL levels (SMD = -0.45, 95% CI: -0.87, -0.02), TC levels (SMD = -1.09, 95% CI: -1.89, -0.29), and TNF-α levels (SMD = -1.73, 95% CI: -2.72, -0.74). CONCLUSION This network meta-analysis revealed that Lactobacillus + Bifidobacterium + Streptococcus may be the most effective probiotic combination for the treatment of liver enzymes, lipid profiles, and inflammation factors. These findings can be used to guide the development of a probiotics-based treatment guideline for NAFLD since there are few direct comparisons between different therapies.
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Affiliation(s)
- Yafang Yang
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Ligang Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
| | - Jiale Wu
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Jing Hu
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Min Wan
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Jindi Bie
- Department of Clinical Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Jiaxin Li
- Department of Clinical Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Da Pan
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
| | - Guiju Sun
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
| | - Chao Yang
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China.
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11
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Mei EH, Yao C, Chen YN, Nan SX, Qi SC. Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease. World J Hepatol 2024; 16:688-702. [PMID: 38818294 PMCID: PMC11135273 DOI: 10.4254/wjh.v16.i5.688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/26/2024] [Accepted: 04/07/2024] [Indexed: 05/22/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.
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Affiliation(s)
- En-Hua Mei
- Shanghai Medical College, Fudan University, Shanghai 200000, China
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Chao Yao
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Yi-Nan Chen
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Shun-Xue Nan
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Sheng-Cai Qi
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China.
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12
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Amini-Salehi E, Hassanipour S, Keivanlou MH, Shahdkar M, Orang Goorabzarmakhi M, Vakilpour A, Joukar F, Hashemi M, Sattari N, Javid M, Mansour-Ghanaei F. The impact of gut microbiome-targeted therapy on liver enzymes in patients with nonalcoholic fatty liver disease: an umbrella meta-analysis. Nutr Rev 2024; 82:815-830. [PMID: 37550264 DOI: 10.1093/nutrit/nuad086] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/09/2023] Open
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome-targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear. OBJECTIVES This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population. DATA SOURCE A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD. DATA EXTRACTION Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies. DATA ANALYSIS A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], -10.21; 95% confidence interval [CI], -13.29, -7.14; P < 0.001), aspartate aminotransferase (AST; ES, -8.86; 95%CI, -11.39, -6.32; P < 0.001), and γ-glutamyltransferase (ES, -5.56; 95%CI, -7.92, -3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, -8.69; 95%CI, -11.01, -6.37; P < 0.001) and ALT (ES, -9.82; 95%CI, -11.59, -8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, -11.40; 95%CI, -13.91, -8.88; P < 0.001) and ALT (ES, -11.87; 95%CI, -13.80, -9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, -2.96; 95%CI, -8.12, 2.18, P = 0.259; and ES, -4.69; 95%CI, -13.53, 4.15, P = 0.299, respectively). CONCLUSION Gut microbiome-targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome-targeted therapies in the treatment of the NAFLD population. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42022346998.
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Affiliation(s)
- Ehsan Amini-Salehi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Milad Shahdkar
- School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Azin Vakilpour
- School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Hashemi
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Nazila Sattari
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
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13
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Silva-Sperb AS, Moraes HA, Barcelos STA, de Moura BC, Longo L, Michalczuk MT, Cerski CTS, Uribe-Cruz C, da Silveira TR, Álvares-da-Silva MR, Dall’Alba V. Probiotic supplementation for 24 weeks in patients with non-alcoholic steatohepatitis: the PROBILIVER randomized clinical trial. Front Nutr 2024; 11:1362694. [PMID: 38600992 PMCID: PMC11004384 DOI: 10.3389/fnut.2024.1362694] [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: 12/28/2023] [Accepted: 03/08/2024] [Indexed: 04/12/2024] Open
Abstract
Background and aim Considering the increasing prevalence of non-alcoholic steatohepatitis (NASH) and treatment gaps, this study aimed to evaluate the effect of probiotic supplementation on liver function markers, nutritional status, and clinical parameters. Methods This double-blind, randomized clinical trial (ClinicalTrials.gov ID: NCT0346782) included adult outpatients with biopsy-proven NASH. The intervention consisted of 24 weeks of supplementation with the probiotic mix Lactobacillus acidophilus (1 × 109 CFU) + Lactobacillus rhamnosus (1 × 109 CFU) + Lactobacillus paracasei (1 × 109 CFU) + Bifidobacterium lactis (1 × 109 CFU), or placebo, twice a day. The following parameters were evaluated: demographic and clinical data, transient elastography (FibroScan), liver enzymes, NAFLD fibrosis score, fatty liver index, laboratory assessment, serum concentration of toll-like receptor-4 (sTLR-4) and cytokeratin 18 (CK-18), anthropometric data, dietary intake, and physical activity. Regarding data analysis, the comparison between the groups was based on the delta of the difference of each variable analyzed (value at the end of treatment minus the baseline value) using the t-test for independent samples or the Mann-Whitney U-test. Results Forty-four patients with NASH completed the trial (51.4 ± 11.6 years). At baseline, 87% of participants had a mild liver fibrosis degree on biopsy, normal values of liver enzymes, transient elastography values consistent with grade 1 fibrosis in both groups, increased waist circumference (WC), a BMI of 30.97 kg/m2, and 76% presented with metabolic syndrome (MetS). After the intervention, no differences were observed between the probiotic and placebo groups in terms of MetS, WC, BMI scores, or liver enzyme levels (p > 0.05 for all). The elastography values remained consistent with grade 1 fibrosis in both groups. Although CK-18 was reduced in both groups, a larger effect size was noted in the probiotic group (D = 1.336). sTLR-4 was also reduced in both groups, with no difference between groups (p = 0.885). Conclusion Intervention with probiotics in the early stages of NASH demonstrated no significant change in hepatic and clinical parameters. Clinical trial registration ClinicalTrials.gov, identifier NCT0346782.
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Affiliation(s)
- Amanda Souza Silva-Sperb
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Helena Abadie Moraes
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | | | - Bruna Concheski de Moura
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Larisse Longo
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Matheus Truccolo Michalczuk
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Carlos Thadeu Schmidt Cerski
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Unit of Surgical Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Carolina Uribe-Cruz
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Themis Reverbel da Silveira
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Mário Reis Álvares-da-Silva
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Valesca Dall’Alba
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Nutrition Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
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14
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Rasaei N, Heidari M, Esmaeili F, Khosravi S, Baeeri M, Tabatabaei-Malazy O, Emamgholipour S. The effects of prebiotic, probiotic or synbiotic supplementation on overweight/obesity indicators: an umbrella review of the trials' meta-analyses. Front Endocrinol (Lausanne) 2024; 15:1277921. [PMID: 38572479 PMCID: PMC10987746 DOI: 10.3389/fendo.2024.1277921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 02/27/2024] [Indexed: 04/05/2024] Open
Abstract
Background There is controversial data on the effects of prebiotic, probiotic, or synbiotic supplementations on overweight/obesity indicators. Thus, we aimed to clarify this role of biotics through an umbrella review of the trials' meta-analyses. Methods All meta-analyses of the clinical trials conducted on the impact of biotics on overweight/obesity indicators in general populations, pregnant women, and infants published until June 2023 in PubMed, Web of Sciences, Scopus, Embase, and Cochrane Library web databases included. The meta-analysis of observational and systematic review studies without meta-analysis were excluded. We reported the results by implementing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart. The Assessment of Multiple Systematic Reviews-2 (AMSTAR2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological quality and quality of evidence. Results Overall, 97 meta-analysis studies were included. Most studies were conducted on the effect of probiotics in both genders. Consumption of prebiotic: 8-66 g/day, probiotic: 104 -1.35×1015 colony-forming unit (CFU)/day, and synbiotic: 106-1.5×1011 CFU/day and 0.5-300 g/day for 2 to 104 weeks showed a favorable effect on the overweight/obesity indicators. Moreover, an inverse association was observed between biotics consumption and overweight/obesity risk in adults in most of the studies. Biotics did not show any beneficial effect on weight and body mass index (BMI) in pregnant women by 6.6×105-1010 CFU/day of probiotics during 1-25 weeks and 1×109-112.5×109 CFU/capsule of synbiotics during 4-8 weeks. The effect of biotics on weight and BMI in infants is predominantly non-significant. Prebiotics and probiotics used in infancy were from 0.15 to 0.8 g/dL and 2×106-6×109 CFU/day for 2-24 weeks, respectively. Conclusion It seems biotics consumption can result in favorable impacts on some anthropometric indices of overweight/obesity (body weight, BMI, waist circumference) in the general population, without any significant effects on birth weight or weight gain during pregnancy and infancy. So, it is recommended to intake the biotics as complementary medications for reducing anthropometric indices of overweight/obese adults. However, more well-designed trials are needed to elucidate the anti-obesity effects of specific strains of probiotics.
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Affiliation(s)
- Niloufar Rasaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
- Network of Interdisciplinarity in Neonates and Infants (NINI), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mohammadreza Heidari
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fataneh Esmaeili
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepehr Khosravi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Baeeri
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Ozra Tabatabaei-Malazy
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Solaleh Emamgholipour
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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15
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Kwon JE, Hong W, Jeon H, Kim CS, Kim H, Kang SC. Suppression of P2X4 and P2X7 by Lactobacillus rhamnosus vitaP1: effects on hangover symptoms. AMB Express 2024; 14:30. [PMID: 38491208 PMCID: PMC10942966 DOI: 10.1186/s13568-024-01685-5] [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: 12/06/2023] [Accepted: 03/01/2024] [Indexed: 03/18/2024] Open
Abstract
This study aimed to identify substances including Lactobacillus rhamnosus vitaP1 (KACC 92054P) that alleviate hangover-induced emotional anxiety and liver damage. The association between emotional anxiety caused by hangover and the genes P2X4, P2X7, SLC6A4 was investigated. In vitro and in vivo analyses were conducted to assess the influence of free-panica on alcohol-induced upregulated gene expression. Additionally, the concentration of AST, ALT, alcohol, and acetaldehyde in blood was measured. Free-panica, consisting of five natural products (Phyllanthus amarus, Phoenix dactylifera, Vitis vinifera, Zingiber officinale, and Lactobacillus rhamnosus), were evaluated for their regulatory effects on genes involved in alcohol-induced emotional anxiety and liver damage. The combination of these natural products in free-panica successfully restored emotional anxiety, and the concentration of AST, ALT, alcohol, and acetaldehyde in blood to those of the normal control group. These findings support the potential development of free-panica as a health functional food or medicinal intervention for relieving hangover symptoms and protecting liver from alcohol consumption.
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Affiliation(s)
- Jeong Eun Kwon
- Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin, Gyeonggi, 17104, Republic of Korea
| | - Woojae Hong
- Department of Biomechatronic Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Hyelin Jeon
- Mbiometherapeutics Co., Ltd., Seongnam, Gyeonggi, 13488, Republic of Korea
| | - Cha Soon Kim
- Genencell Co., Ltd. Yongin, Gyeonggi, 16950, Republic of Korea
| | - Hyunggun Kim
- Department of Biomechatronic Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea.
| | - Se Chan Kang
- Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin, Gyeonggi, 17104, Republic of Korea.
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Virk MS, Virk MA, He Y, Tufail T, Gul M, Qayum A, Rehman A, Rashid A, Ekumah JN, Han X, Wang J, Ren X. The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs. Nutrients 2024; 16:546. [PMID: 38398870 PMCID: PMC10893534 DOI: 10.3390/nu16040546] [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: 01/27/2024] [Revised: 02/10/2024] [Accepted: 02/14/2024] [Indexed: 02/25/2024] Open
Abstract
Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.
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Affiliation(s)
- Muhammad Safiullah Virk
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | | | - Yufeng He
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Tabussam Tufail
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
- University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore 54000, Pakistan
| | - Mehak Gul
- Department of Internal Medicine, Sheikh Zayed Hospital, Lahore 54000, Pakistan
| | - Abdul Qayum
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Abdur Rehman
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Arif Rashid
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - John-Nelson Ekumah
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Xu Han
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Junxia Wang
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
| | - Xiaofeng Ren
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; (M.S.V.)
- Institute of Food Physical Processing, Jiangsu University, Zhenjiang 212013, China
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Nicastro E, D'Antiga L. Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease : Pediatric Fatty Liver and Probiotics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1449:113-133. [PMID: 39060734 DOI: 10.1007/978-3-031-58572-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described.
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Affiliation(s)
- Emanuele Nicastro
- Pediatric Hepatology, Gastroenterology, and Transplantation Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy.
| | - Lorenzo D'Antiga
- Pediatric Hepatology, Gastroenterology, and Transplantation Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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18
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Velayati A, Kareem I, Sedaghat M, Sohrab G, Nikpayam O, Hedayati M, Abhari K, Hejazi E. Does symbiotic supplementation which contains Bacillus Coagulans Lactobacillus rhamnosus, Lactobacillus acidophilus and fructooligosaccharide has favourite effects in patients with type-2 diabetes? A randomised, double-blind, placebo-controlled trial. Arch Physiol Biochem 2023; 129:1211-1218. [PMID: 34077686 DOI: 10.1080/13813455.2021.1928225] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 05/04/2021] [Indexed: 12/15/2022]
Abstract
This study aimed to determine the effect of Bacillus Coagulans symbiotic supplementation on metabolic factors and inflammation in patients with type-2 diabetes. In this clinical trial, 50 patients with type-2 diabetes were randomly assigned to the symbiotic (containing Bacillus Coagulans + Lactobacillus rhamnosus + Lactobacillus acidophilus and fructooligosaccharide) or placebo groups to receive one sachet daily for 12 weeks. Glycaemic Index, lipid profile, and hs-CRP were measured at the beginning and end of the study. Analysis of covariance demonstrated that fasting blood glucose (FBG), insulin, homeostatic Model Assessment for Insulin Resistance (HOMA-IR), β-cell function (HOMA-β) (p <.05) and hs-CRP (p <.05) significantly declined in the treatment group compared with the placebo group. So, the current study indicated that Bacillus Coagulans symbiotic supplementation could improve metabolic factors and inflammation in patients with type-2 diabetes.
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Affiliation(s)
- Aynaz Velayati
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
| | - Iman Kareem
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
| | - Meghdad Sedaghat
- Depatment of Internal Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Golbon Sohrab
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
| | - Omid Nikpayam
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Khadijeh Abhari
- Food Sciences and Technology Department, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Hejazi
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
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19
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Farías C, Cisternas C, Gana JC, Alberti G, Echeverría F, Videla LA, Mercado L, Muñoz Y, Valenzuela R. Dietary and Nutritional Interventions in Nonalcoholic Fatty Liver Disease in Pediatrics. Nutrients 2023; 15:4829. [PMID: 38004223 PMCID: PMC10674812 DOI: 10.3390/nu15224829] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/06/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is pediatrics' most common chronic liver disease. The incidence is high in children and adolescents with obesity, which is associated with an increased risk of disease progression. Currently, there is no effective drug therapy in pediatrics; therefore, lifestyle interventions remain the first line of treatment. This review aims to present an updated compilation of the scientific evidence for treating this pathology, including lifestyle modifications, such as exercise and dietary changes, highlighting specific nutritional strategies. The bibliographic review was carried out in different databases, including studies within the pediatric population where dietary and/or nutritional interventions were used to treat NAFLD. Main interventions include diets low in carbohydrates, free sugars, fructose, and lipids, in addition to healthy eating patterns and possible nutritional interventions with n-3 polyunsaturated fatty acids (EPA and DHA), amino acids (cysteine, L-carnitine), cysteamine, vitamins, and probiotics (one strain or multi-strain). Lifestyle changes remain the main recommendation for children with NAFLD. Nevertheless, more studies are required to elucidate the effectiveness of specific nutrients and bioactive compounds in this population.
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Affiliation(s)
- Camila Farías
- Department of Nutrition, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Camila Cisternas
- Department of Nutrition, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Juan Cristobal Gana
- Department of Pediatric Gastroenterology and Nutrition, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330023, Chile
| | - Gigliola Alberti
- Department of Pediatric Gastroenterology and Nutrition, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330023, Chile
| | - Francisca Echeverría
- Nutrition and Dietetic School, Department of Health Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
| | - Luis A Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380000, Chile
| | - Lorena Mercado
- Department of Nutrition, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Yasna Muñoz
- Department of Nutrition, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
- Escuela de Nutrición y Dietética, Facultad de Farmacia, Universidad de Valparaíso, Valparaíso 2360134, Chile
| | - Rodrigo Valenzuela
- Department of Pediatric Gastroenterology and Nutrition, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330023, Chile
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20
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Rupasinghe K, Hind J, Hegarty R. Updates in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Children. J Pediatr Gastroenterol Nutr 2023; 77:583-591. [PMID: 37592398 DOI: 10.1097/mpg.0000000000003919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/19/2023]
Abstract
The obesity epidemic is one of the major health concerns of the 21st century. Nonalcoholic fatty liver disease (NAFLD) is linked with the increased adiposity associated with obesity. NAFLD has become the most frequent cause of chronic liver disease in adults and children worldwide. Metabolic dysfunction-associated fatty liver disease (MAFLD) also known in children as pediatric fatty liver disease (PeFLD) type 2 has begun to supersede NAFLD as the preferred nomenclature in the pediatric population. Evidence suggests the etiology of MAFLD is multifactorial, related to the complex interplay of hormonal, nutritional, genetic, and environmental factors. Current limitations in accurate diagnostic biomarkers have rendered it a diagnosis of exclusion and it is important to exclude alternative or coexisting causes of PeFLD. Lifestyle changes and modifications remains the primary treatment modality in MAFLD in children. Weight loss of 7%-10% is described as reversing MAFLD in most patients. The Mediterranean diet also shows promise in reversing MAFLD. Pharmacological intervention is debatable in children, and though pediatric trials have not shown promise, other agents undergoing adult clinical trials show promise. This review outlines the latest evidence in pediatric MAFLD and its management.
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Affiliation(s)
- Kushila Rupasinghe
- From the Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK
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21
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Borka Balas R, Meliț LE, Lupu A, Lupu VV, Mărginean CO. Prebiotics, Probiotics, and Synbiotics-A Research Hotspot for Pediatric Obesity. Microorganisms 2023; 11:2651. [PMID: 38004665 PMCID: PMC10672778 DOI: 10.3390/microorganisms11112651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/24/2023] [Accepted: 10/27/2023] [Indexed: 11/26/2023] Open
Abstract
Childhood obesity is a major public health problem worldwide with an increasing prevalence, associated not only with metabolic syndrome, insulin resistance, hypertension, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD), but also with psychosocial problems. Gut microbiota is a new factor in childhood obesity, which can modulate the blood lipopolysaccharide levels, the satiety, and fat distribution, and can ensure additional calories to the host. The aim of this review was to assess the differences and the impact of the gut microbial composition on several obesity-related complications such as metabolic syndrome, NAFLD, or insulin resistance. Early dysbiosis was proven to be associated with an increased predisposition to obesity. Depending on the predominant species, the gut microbiota might have either a positive or negative impact on the development of obesity. Prebiotics, probiotics, and synbiotics were suggested to have a positive effect on improving the gut microbiota and reducing cardio-metabolic risk factors. The results of clinical trials regarding probiotic, prebiotic, and synbiotic administration in children with metabolic syndrome, NAFLD, and insulin resistance are controversial. Some of them (Lactobacillus rhamnosus bv-77, Lactobacillus salivarius, and Bifidobacterium animalis) were proven to reduce the body mass index in obese children, and also improve the blood lipid content; others (Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Enterococcus faecium, and fructo-oligosaccharides) failed in proving any effect on lipid parameters and glucose metabolism. Further studies are necessary for understanding the mechanism of the gut microbiota in childhood obesity and for developing low-cost effective strategies for its management.
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Affiliation(s)
- Reka Borka Balas
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology, Gheorghe Marinescu Street, No. 38, 540136 Târgu Mureș, Romania; (R.B.B.); (C.O.M.)
| | - Lorena Elena Meliț
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology, Gheorghe Marinescu Street, No. 38, 540136 Târgu Mureș, Romania; (R.B.B.); (C.O.M.)
| | - Ancuța Lupu
- Department of Pediatrics, University of Medicine and Pharmacy Gr. T. Popa Iași, Universității Street No 16, 700115 Iași, Romania; (A.L.); (V.V.L.)
| | - Vasile Valeriu Lupu
- Department of Pediatrics, University of Medicine and Pharmacy Gr. T. Popa Iași, Universității Street No 16, 700115 Iași, Romania; (A.L.); (V.V.L.)
| | - Cristina Oana Mărginean
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology, Gheorghe Marinescu Street, No. 38, 540136 Târgu Mureș, Romania; (R.B.B.); (C.O.M.)
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22
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Rong L, Ch'ng D, Jia P, Tsoi KKF, Wong SH, Sung JJY. Use of probiotics, prebiotics, and synbiotics in non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2023; 38:1682-1694. [PMID: 37409560 DOI: 10.1111/jgh.16256] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 05/18/2023] [Accepted: 05/29/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND AND AIM Patients with non-alcoholic fatty liver disease (NAFLD) exhibit compositional changes in their gut microbiome, which represents a potential therapeutic target. Probiotics, prebiotics, and synbiotics are microbiome-targeted therapies that have been proposed as treatment for NAFLD. We aim to systematically review the effects of these therapies in liver-related outcomes of NAFLD patients. METHODS We conducted a systematic search in Embase (Ovid), Medline (Ovid), Scopus, Cochrane, and EBSCOhost from inception to August 19, 2022. We included randomized controlled trials (RCTs) that treated NAFLD patients with prebiotics and/or probiotics. We meta-analyzed the outcomes using standardized mean difference (SMD) and assessed study heterogeneity using Cochran's Q test and I2 statistics. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool. RESULTS A total of 41 (18 probiotics, 17 synbiotics, and 6 prebiotics) RCTs were included. Pooled data demonstrated that the intervention had significantly improved liver steatosis (measured by ultrasound grading) (SMD: 4.87; 95% confidence interval [CI]: 3.27, 7.25), fibrosis (SMD: -0.61 kPa; 95% CI: -1.12, -0.09 kPa), and liver enzymes including alanine transaminase (SMD: -0.86 U/L; 95% CI: -1.16, -0.56 U/L), aspartate transaminase (SMD: -0.87 U/L; 95% CI: -1.22, -0.52 U/L), and gamma-glutamyl transferase (SMD: -0.77 U/L; 95% CI: -1.26, -0.29 U/L). CONCLUSIONS Microbiome-targeted therapies were associated with significant improvements in liver-related outcomes in NAFLD patients. Nevertheless, limitations in existing literature like heterogeneity in probiotic strains, dosage, and formulation undermine our findings. This study was registered with PROSPERO (CRD42022354562) and supported by the Nanyang Technological University Start-up Grant and Wang Lee Wah Memorial Fund.
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Affiliation(s)
- Lim Rong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Daniel Ch'ng
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Pingping Jia
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
| | - Kelvin K F Tsoi
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
- Stanley Ho Big Data Analytics Research Centre, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
| | - Sunny H Wong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Joseph J Y Sung
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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23
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Li Z, Yuan H, Chu H, Yang L. The Crosstalk between Gut Microbiota and Bile Acids Promotes the Development of Non-Alcoholic Fatty Liver Disease. Microorganisms 2023; 11:2059. [PMID: 37630619 PMCID: PMC10459427 DOI: 10.3390/microorganisms11082059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/27/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023] Open
Abstract
Recently the roles of gut microbiota are highly regarded in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The intestinal bacteria regulate the metabolism of bile acids depending on bile salt hydrolase (BSH), 7-dehydroxylation, hydroxysteroid dehydrogenase (HSDH), or amide conjugation reaction, thus exerting effects on NAFLD development through bile acid receptors such as farnesoid X receptor (FXR), Takeda G-protein-coupled bile acid protein 5 (TGR5), and vitamin D receptor (VDR), which modulate nutrient metabolism and insulin sensitivity via interacting with downstream molecules. Reversely, the composition of gut microbiota is also affected by the level of bile acids in turn. We summarize the mutual regulation between the specific bacteria and bile acids in NAFLD and the latest clinical research based on microbiota and bile acids, which facilitate the development of novel treatment modalities in NAFLD.
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Affiliation(s)
| | | | | | - Ling Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China; (Z.L.); (H.Y.); (H.C.)
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24
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Avelar-Rodríguez D, Peña-Vélez R, Popov J, Hill L, Ryan PM. Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:418-427. [PMID: 36412490 DOI: 10.17235/reed.2022.8796/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
BACKGROUND non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD. METHODS PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. RESULTS five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %). CONCLUSIONS there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children.
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Affiliation(s)
| | - Rubén Peña-Vélez
- Gastroenterología y Nutrición, Hospital General de Puebla "Dr. Eduardo Vázquez N", México
| | - Jelena Popov
- College of Medicine and Health. University College Cork
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Sandel P, Ma L, Wang H, Pasman EA. You Are What You Eat: A Review on Dietary Interventions for Treating Pediatric Nonalcoholic Fatty Liver Disease. Nutrients 2023; 15:3350. [PMID: 37571287 PMCID: PMC10421125 DOI: 10.3390/nu15153350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/20/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
As the obesity pandemic worsens, cases of pediatric nonalcoholic fatty liver disease (NAFLD) and complications of this disease, such as progressive liver failure, in young adults will continue to rise. Lifestyle changes in the form of dietary modifications and exercise are currently first-line treatments. Large pediatric-specific randomized controlled trials to support specific interventions are currently lacking. A variety of dietary modifications in children with NAFLD have been suggested and studied with mixed results, including low-sugar and high-protein diets, the Mediterranean diet, and the Dietary Approach to Stop Hypertension (DASH). The roles of dietary supplements such as Vitamin E, polyunsaturated fatty acids (PUFAs), ginger, and probiotics have also been investigated. A further understanding of specific dietary interventions and supplements is needed to provide both generalizable and sustainable dietary recommendations to reverse the progression of NAFLD in the pediatric population.
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Affiliation(s)
- Piper Sandel
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Lawrence Ma
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Helen Wang
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Eric A. Pasman
- Division of Pediatric Gastroenterology, Department of Pediatrics, Naval Medical Center San Diego, San Diego, CA 92134, USA;
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
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26
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Escouto GS, Port GZ, Tovo CV, Fernandes SA, Peres A, Dorneles GP, Houde VP, Varin TV, Pilon G, Marette A, Buss C. Probiotic Supplementation, Hepatic Fibrosis, and the Microbiota Profile in Patients with Nonalcoholic Steatohepatitis: A Randomized Controlled Trial. J Nutr 2023; 153:1984-1993. [PMID: 37225124 DOI: 10.1016/j.tjnut.2023.05.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 04/28/2023] [Accepted: 05/19/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Promising results in improvement of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) have been identified following probiotic (PRO) treatment. OBJECTIVES To evaluate PRO supplementation on hepatic fibrosis, inflammatory and metabolic markers, and gut microbiota in NASH patients. METHODS In a double-blind, placebo-controlled clinical trial, 48 patients with NASH with a median age of 58 y and median BMI of 32.7 kg/m2 were randomly assigned to receive PROs (Lactobacillus acidophilus 1 × 109 colony forming units and Bifidobacterium lactis 1 × 109 colony forming units) or a placebo daily for 6 mo. Serum aminotransferases, total cholesterol and fractions, C-reactive protein, ferritin, interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and leptin were assessed. To evaluate liver fibrosis, Fibromax was used. In addition, 16S rRNA gene-based analysis was performed to evaluate gut microbiota composition. All assessments were performed at baseline and after 6 mo. For the assessment of outcomes after treatment, mixed generalized linear models were used to evaluate the main effects of the group-moment interaction. For multiple comparisons, Bonferroni correction was applied (α = 0.05/4 = 0.0125). Results for the outcomes are presented as mean and SE. RESULTS The AST to Platelet Ratio Index (APRI) score was the primary outcome that decreased over time in the PRO group. Aspartate aminotransferase presented a statistically significant result in the group-moment interaction analyses, but no statistical significance was found after the Bonferroni correction. Liver fibrosis, steatosis, and inflammatory activity presented no statistically significant differences between the groups. No major shifts in gut microbiota composition were identified between groups after PRO treatment. CONCLUSIONS Patients with NASH who received PRO supplementation for 6 mo presented improvement in the APRI score after treatment. These results draw attention to clinical practice and suggest that supplementation with PROs alone is not sufficient to improve enzymatic liver markers, inflammatory parameters, and gut microbiota in patients with NASH. This trial was registered at clinicaltrials.gov as NCT02764047.
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Affiliation(s)
- Giselle S Escouto
- Graduate Study Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gabriela Z Port
- Graduate Study Program (GSP) in Medicine: Hepatology (GSP-Hepatology), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Cristiane V Tovo
- Graduate Study Program (GSP) in Medicine: Hepatology (GSP-Hepatology), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Sabrina A Fernandes
- Graduate Study Program (GSP) in Medicine: Hepatology (GSP-Hepatology), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Alessandra Peres
- Basic Health Sciences Department, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gilson P Dorneles
- Graduate Study Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Vanessa P Houde
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - Thibault V Varin
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - Geneviève Pilon
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - André Marette
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - Caroline Buss
- Graduate Study Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Nutrition Department, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
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27
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Mosca A, Maggiore G. Malattia grassa del fegato: tra fattori ambientali e predisposizione genetica. MEDICO E BAMBINO 2023; 42:355-362. [DOI: 10.53126/meb42355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is now recognized as the hepatic manifestation of the metabolic syndrome and is the most common cause of chronic liver disease in both adults and children. It is assumed that a genetic predisposition associated with epigenetic factors participates in the evolution of this condition. Visceral obesity and insulin-resistence (IR) have always been considered as key factors linking Metabolic Syndrome (MetS) and NAFLD, but a multifactorial pathogenesis characterized by the interaction between genetic background and environmental factors is increasingly recognized as a key point in the development of metabolic disorders associated with NAFLD. In fact, in patients with NAFLD, insulin resistance, arterial hypertension, abdominal obesity, dyslipidemia and reduced intestinal permeability have often been found, as well as a higher prevalence of comorbidities such as coronary artery disease, obstructive sleep apnea, polycystic ovary syndrome and osteopenia, which define a MetS framework. Early diagnosis is needed to prevent disease progression through primarily lifestyle interventions. Unfortunately, to date, there is no recommended pharmacological intervention in a pediatric setting. However, a variety of new pharmacological agents are under clinical study. To achieve this, studies on the pathways that link the genetic background to the environment before and after birth to the development of NAFLD and MetS and on the molecular mechanisms that define NASH should be increased. Therefore, it is desirable that future studies may be useful in terms of population screening to identify individuals at risk for NAFLD and Mets.
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Affiliation(s)
- Antonella Mosca
- Epatogastroenterologia, Nutrizione, Endoscopia Digestiva e Clinica del Trapianto di Fegato, Ospedal
| | - Giuseppe Maggiore
- Epatogastroenterologia, Nutrizione, Endoscopia Digestiva e Clinica del Trapianto di Fegato, Ospedal
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28
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Atazadegan MA, Heidari-Beni M, Entezari MH, Sharifianjazi F, Kelishadi R. Effects of synbiotic supplementation on anthropometric indices and body composition in overweight or obese children and adolescents: a randomized, double-blind, placebo-controlled clinical trial. World J Pediatr 2023; 19:356-365. [PMID: 36484872 PMCID: PMC9734986 DOI: 10.1007/s12519-022-00664-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 11/17/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Recently, beneficial effects of probiotics and/or prebiotics on cardio-metabolic risk factors in adults have been shown. However, existing evidence has not been fully established for pediatric age groups. This study aimed to assess the effect of synbiotic on anthropometric indices and body composition in overweight or obese children and adolescents. METHODS This randomized double-blind, placebo-controlled trial was conducted among 60 participants aged 8-18 years with a body mass index (BMI) equal to or higher than the 85th percentile. Participants were randomly divided into two groups that received either a synbiotic capsule containing 6 × 109 colony forming units (CFU) Lactobacillus coagulans SC-208, 6 × 109 CFU Lactobacillus indicus HU36 and fructooligosaccharide as a prebiotic (n = 30) or a placebo (n = 30) twice a day for eight weeks. Anthropometric indices and body composition were measured at baseline and after the intervention. RESULTS The mean (standard deviation, SD) age was 11.07 (2.00) years and 11.23 (2.37) years for the placebo and synbiotic groups, respectively (P = 0.770). The waist-height ratio (WHtR) decreased significantly at the end of the intervention in comparison with baseline in the synbiotic group (0.54 ± 0.05 vs. 0.55 ± 0.05, P = 0.05). No significant changes were demonstrated in other anthropometric indices or body composition between groups. CONCLUSIONS Synbiotic supplementation might be associated with a reduction in WHtR. There were no significant changes in other anthropometric indices or body composition.
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Affiliation(s)
- Mohammad Amin Atazadegan
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Motahar Heidari-Beni
- Department of Nutrition, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Mohammad Hassan Entezari
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Roya Kelishadi
- Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
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Loy MH, Usseglio J, Lasalandra D, Gold MA. Probiotic Use in Children and Adolescents with Overweight or Obesity: A Scoping Review. Child Obes 2023; 19:145-159. [PMID: 35723657 DOI: 10.1089/chi.2022.0059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Context: Probiotics have been proposed as a prevention or treatment for pediatric overweight and obesity. Objective: Conduct a scoping review on probiotic use in children and adolescents with overweight or obesity and those with weight-related conditions and to identify knowledge gaps and research priorities. Data Sources: Seven databases using keywords and medical subject heading terms for articles reporting probiotic use in children or adolescents with overweight or obesity published from database conception until initiation of the study. Study Selection: Articles reporting primary data on probiotics use in children or adolescents with overweight or obesity. Data Extraction: We utilized the Arksey and O'Malley framework, PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, followed a predetermined study protocol for level-one abstract and level-two full-text screenings, synthesized information into subject-area domains, and identified research gaps. Limitations: Heterogeneity of probiotic interventions, host factors, and genomics. Results: Database search yielded 1356 unique articles with 19 randomized placebo-controlled studies, 945 participants, duration of interventions from 8 weeks to 9 months. Disease indications included Nonalcoholic Fatty Liver Disease, insulin resistance, hypercholesterolemia, Prader-Willi Syndrome, metabolic syndrome, and obesity. Limited and heterogeneous evidence for probiotic use in children and adolescents with weight-related conditions noted. Heterogeneity among published articles in probiotic strains, doses, design, biomarkers, confirmation, and outcomes observed. Conclusions: Despite complex existing and limited data, studies to date of children and adolescents with overweight and obesity demonstrate potential beneficial treatment effects of probiotics on BMI, adiposity, metabolic parameters, inflammatory markers, fatty liver, transaminase levels, and glucose metabolism. Clinical trials to address heterogeneous results are needed.
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Affiliation(s)
- Michelle H Loy
- Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
- Department of Medicine, Weill Cornell Medicine, New York, NY, USA
- Integrative Health and Well-Being, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY, USA
| | - John Usseglio
- Health Sciences Library, Columbia University Irving Medical Center, New York, NY, USA
| | | | - Melanie A Gold
- Heilbrunn Department of Population and Family Health, Columbia University Mailman School of Public Health, New York, NY, USA
- Section of Adolescent Medicine, Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA
- Center for Community Health and Education, School-Based Health Centers, NewYork Presbyterian, New York, NY, USA
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Rizzo M, Colletti A, Penson PE, Katsiki N, Mikhailidis DP, Toth PP, Gouni-Berthold I, Mancini J, Marais D, Moriarty P, Ruscica M, Sahebkar A, Vinereanu D, Cicero AFG, Banach M, Al-Khnifsawi M, Alnouri F, Amar F, Atanasov AG, Bajraktari G, Banach M, Gouni-Berthold I, Bhaskar S, Bielecka-Dąbrowa A, Bjelakovic B, Bruckert E, Bytyçi I, Cafferata A, Ceska R, Cicero AF, Chlebus K, Collet X, Daccord M, Descamps O, Djuric D, Durst R, Ezhov MV, Fras Z, Gaita D, Gouni-Berthold I, Hernandez AV, Jones SR, Jozwiak J, Kakauridze N, Kallel A, Katsiki N, Khera A, Kostner K, Kubilius R, Latkovskis G, John Mancini G, David Marais A, Martin SS, Martinez JA, Mazidi M, Mikhailidis DP, Mirrakhimov E, Miserez AR, Mitchenko O, Mitkovskaya NP, Moriarty PM, Mohammad Nabavi S, Nair D, Panagiotakos DB, Paragh G, Pella D, Penson PE, Petrulioniene Z, Pirro M, Postadzhiyan A, Puri R, Reda A, Reiner Ž, Radenkovic D, Rakowski M, Riadh J, Richter D, Rizzo M, Ruscica M, Sahebkar A, Serban MC, Shehab AM, Shek AB, Sirtori CR, Stefanutti C, Tomasik T, Toth PP, Viigimaa M, Valdivielso P, Vinereanu D, Vohnout B, von Haehling S, Vrablik M, Wong ND, Yeh HI, Zhisheng J, Zirlik A. Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP). Pharmacol Res 2023; 189:106679. [PMID: 36764041 DOI: 10.1016/j.phrs.2023.106679] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/11/2023]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
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Affiliation(s)
- Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
| | - Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, Turin, Italy
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, Medical School, University College London (UCL), London, UK
| | - Peter P Toth
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA
| | - Ioanna Gouni-Berthold
- Department of Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany
| | - John Mancini
- Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - David Marais
- Chemical Pathology Division of the Department of Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
| | - Patrick Moriarty
- Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Dragos Vinereanu
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Arrigo Francesco Giuseppe Cicero
- Hypertension and Cardiovascular disease risk research center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; IRCCS Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
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Metabolic-Associated Fatty Liver Disease and the Gut Microbiota. Endocrinol Metab Clin North Am 2023. [PMID: 37495339 DOI: 10.1016/j.ecl.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
As an important sequela of the burgeoning global obesity problem, metabolic-associated fatty liver disease (MAFLD) has gained increasing prominence recently. The gut-liver axis (GLA) provides a direct conduit to the liver for the gut microbiota and their metabolic by-products (including secondary bile acids, ethanol, and trimethylamine). These GLA-related factors, including the host inflammatory response and integrity of the gut mucosal wall, likely contribute to the pathogenesis of MAFLD. Accordingly, these GLA-related factors are targets for possible preventive and treatment strategies for MAFLD, and include probiotics, prebiotics, bile acids, short-chain fatty acids, fecal microbiota transplantation, carbon nanoparticles, and bacteriophages.
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Zagmignan A, Mendes YC, Mesquita GP, dos Santos GDC, Silva LDS, de Souza Sales AC, Castelo Branco SJDS, Junior ARC, Bazán JMN, Alves ER, de Almeida BL, Santos AKM, Firmo WDCA, Silva MRC, Cantanhede Filho AJ, de Miranda RDCM, da Silva LCN. Short-Term Intake of Theobroma grandiflorum Juice Fermented with Lacticaseibacillus rhamnosus ATCC 9595 Amended the Outcome of Endotoxemia Induced by Lipopolysaccharide. Nutrients 2023; 15:nu15041059. [PMID: 36839417 PMCID: PMC9962425 DOI: 10.3390/nu15041059] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 02/08/2023] [Accepted: 02/14/2023] [Indexed: 02/23/2023] Open
Abstract
Endotoxemia is a condition caused by increasing levels of lipopolysaccharide (LPS) characterized by an impaired systemic response that causes multiple organ dysfunction. Lacticaseibacillus rhamnosus ATCC 9595 is a strain with probiotic potential which shows immunomodulatory properties. The incorporation of this bacterium in food rich in bioactive compounds, such as cupuaçu juice (Theobroma grandiflorum), could result in a product with interesting health properties. This work evaluated the effects of the oral administration of cupuaçu juice fermented with L. rhamnosus on the outcome of LPS-induced endotoxemia in mice. C57BL/6 mice (12/group) received oral doses (100 µL) of saline solution and unfermented or fermented cupuaçu juice (108 CFU/mL). After 5 days, the endotoxemia was induced by an intraperitoneal injection of LPS (10 mg/kg). The endotoxemia severity was evaluated daily using a score based on grooming behavior, mobility, presence of piloerection, and weeping eyes. After 6 h and 120 h, the mice (6/group) were euthanized for analysis of cell counts (in peritoneal lavage and serum) and organ weight. L. rhamnosus grew in cupuaçu juice and produced organic acids without the need for supplementation. The bacteria counts were stable in the juice during storage at 4 °C for 28 days. The fermentation with L. rhamnosus ATCC 9595 changed the metabolites profile of cupuaçu juice due to the biotransformation and enhancement of some compounds. In general, the administration of L. rhamnosus-fermented juice allowed a significant improvement in several characteristics of endotoxemic status (weight loss, hypothermia, severity index, cell migration). In addition, treatment with fermented juice significantly reduced the weight of the spleen, liver, intestine, and kidneys compared to the saline-treated endotoxemic group. Taken together, our data show that short-term intake therapy of cupuaçu juice fermented with L. rhamnosus ATCC 9595 can reduce systemic inflammation in an experimental model of LPS-induced endotoxemia in mice.
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Affiliation(s)
- Adrielle Zagmignan
- Laboratório de Patogenicidade Microbiana, Universidade CEUMA, São Luís 65075-120, Brazil
- Programa de Pós-Graduação em Gestão de Serviços e Programas de Saúde, Universidade CEUMA, São Luís 65075-120, Brazil
- Laboratório de Microbiologia Ambiental, Universidade CEUMA, São Luís 65075-120, Brazil
- Correspondence:
| | - Yasmim Costa Mendes
- Laboratório de Patogenicidade Microbiana, Universidade CEUMA, São Luís 65075-120, Brazil
| | | | | | - Lucas dos Santos Silva
- Laboratório de Patogenicidade Microbiana, Universidade CEUMA, São Luís 65075-120, Brazil
| | | | | | | | | | - Edinalva Rodrigues Alves
- Programa de Pós-Graduação em Gestão de Serviços e Programas de Saúde, Universidade CEUMA, São Luís 65075-120, Brazil
| | | | - Anne Karoline Maiorana Santos
- Laboratório de Extração e Cromatografia, Instituto Federal de Educação, Ciência e Tecnologia do Maranhão, Campus Monte Castelo, São Luís 65030-005, MA, Brazil
| | - Wellyson da Cunha Araújo Firmo
- Programa de Pós-Graduação em Gestão de Serviços e Programas de Saúde, Universidade CEUMA, São Luís 65075-120, Brazil
- Centro de Ciências da Saúde, Campus Imperatriz, Universidade Estadual da Região Tocantina do Maranhão, Imperatriz 65900-000, MA, Brazil
| | | | - Antônio José Cantanhede Filho
- Laboratório de Extração e Cromatografia, Instituto Federal de Educação, Ciência e Tecnologia do Maranhão, Campus Monte Castelo, São Luís 65030-005, MA, Brazil
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Zhou X, Wang J, Zhou S, Liao J, Ye Z, Mao L. Efficacy of probiotics on nonalcoholic fatty liver disease: A meta-analysis. Medicine (Baltimore) 2023; 102:e32734. [PMID: 36705359 PMCID: PMC9875992 DOI: 10.1097/md.0000000000032734] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 01/04/2023] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVES The intestinal flora is closely related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study intends to systematically evaluate the efficacy and safety of probiotics in the treatment of NAFLD through a meta-analysis of published randomized controlled trials. METHODS This study was conducted through a search of published randomized controlled trials using probiotic-related drugs for the treatment of nonalcoholic fatty liver disease (up to April 6, 2022). The JADAD evaluation table was used to evaluate the quality of the literatures included in the search, and the risk of bias was evaluated according to the Cochrane evaluation manual. Finally, RevMan5.4 software was used for meta-analysis. RESULTS A total of 21 randomized clinical trials involving 1037 patients with NAFLD were included in this study. Meta-analysis results showed that after probiotic intervention, liver function, blood lipid level, blood glucose levels and insulin levels were significantly reduced, which had a good effect on improving hepatic steatosis. However, it did not significantly improve BMI, inflammatory factors, or homeostasis model assessment of insulin resistance. Through the subgroup analysis of the course of treatment, it was found that ALT, GGT, TG, and blood sugar improved better in the probiotic treatment course of greater than or equal to 12 weeks. CONCLUSION This study shows that the use of probiotics therapy has a good regulating effect on liver function, steatosis, blood glucose level, insulin level and blood lipid level in NAFLD patients.
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Affiliation(s)
- Xiangyu Zhou
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jincheng Wang
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Sufang Zhou
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jiajia Liao
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Zuoyu Ye
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Leiming Mao
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
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Hegarty R, Kyrana E, Fitzpatrick E, Dhawan A. Fatty liver disease in children (MAFLD/PeFLD Type 2): unique classification considerations and challenges. Ther Adv Endocrinol Metab 2023; 14:20420188231160388. [PMID: 36968656 PMCID: PMC10034351 DOI: 10.1177/20420188231160388] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 02/11/2023] [Indexed: 03/24/2023] Open
Abstract
In children, fatty liver disease is a group of disorders that often overlaps with inherited metabolic disorders (IMDs), which requires prompt diagnosis and specific management. Metabolic dysfunction-associated fatty liver disease (MAFLD) or, formerly, non-alcoholic fatty liver disease (NAFLD) is the hepatic component of a multisystemic disease that requires a positive criteria in metabolic dysfunction for diagnosis. However, in children, the diagnosis of MAFLD is one of the exclusions of an IMD [paediatric fatty liver disease (PeFLD) type 1] including the possibility that an IMD can be identified in the future following investigations that may be negative at the time. Therefore, while children with fatty liver with metabolic dysfunction could be classified as MAFLD (PeFLD type 2) and managed that way, those who do not fulfil the criteria for metabolic dysfunction should be considered separately bearing in mind the possibility of identifying a yet undiagnosed IMD (PeFLD type 3). This concept is ever more important in a world where MAFLD is the most common cause of liver disease in children and adolescents in whom about 7% are affected. The disease is only partially understood, and awareness is still lacking outside hepatology and gastroenterology. Despite its increasing pervasiveness, the management is far from a one-size-fits-all. Increasing complexities around the genetic, epigenetic, non-invasive modalities of assessment, psychosocial impacts, therapeutics, and natural history of the disease have meant that an individualised approach is required. This is where the challenge lies so that children with fatty liver are considered on their own merits. The purpose of this review is to give a clinical perspective of fatty liver disease in children with relevance to metabolic dysfunction.
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Affiliation(s)
- Robert Hegarty
- Paediatric Liver, GI and Nutrition Centre, and
MowatLabs, King’s College Hospital, London, UK
| | - Eirini Kyrana
- Paediatric Liver, GI and Nutrition Centre, and
MowatLabs, King’s College Hospital, London, UK
| | - Emer Fitzpatrick
- Department of Gastroenterology, Hepatology and
Nutrition, Our Lady’s Hospital Crumlin, Dublin, Ireland
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Porchia LM, Vazquez-Marroquin G, Ochoa-Précoma R, Pérez-Fuentes R, Gonzalez-Mejia ME. Probiotics' effect on visceral and subcutaneous adipose tissue: a systematic review of randomized controlled trials. Eur J Clin Nutr 2022; 76:1646-1656. [PMID: 35418606 DOI: 10.1038/s41430-022-01135-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 03/22/2022] [Accepted: 03/25/2022] [Indexed: 11/08/2022]
Abstract
Probiotics are shown to alter the microbiota, leading to a favorable environment, in which weight loss and metabolic parameters are improve. However, the results on probiotics' effect on specific types of central adipose tissues, mainly visceral (VAT) and subcutaneous adipose tissue (SAT), are conflicting. Therefore, we conducted a systematic review, aimed to evaluate the effects of probiotics on VAT and SAT. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of probiotics on VAT and SAT. Fixed effects were used to calculate the pooled difference in means (DM) and 95% confidence intervals (95%CI). Fourteen publications met the inclusion criteria, which consisted of 1523 participants. For VAT, overall, there was a significant decrease (DM = -3.63 cm2, 95% CI: -5.08 to -2.17, p < 0.001). When stratified by type of probiotic, single Bifidobacterium (DM = -4.49 cm2, 95% CI:-7.37 to -1.61, p = 0.002) and single Lactobacillus probiotics (DM = -3.84 cm2, 95% CI:-5.74 to -1.93, p < 0.001) resulted in significant reductions. Mixed probiotics had no effect. For SAT, overall, there was a significant decrease (DM = -2.91 cm2, 95% CI:-4.82 to -1.01, p = 0.003), and when stratified by type of probiotic, single Lactobacillus (DM = -3.39 cm2, 95% CI:-5.90 to -0.88, p = 0.008) and mixed probiotics (DM = -5.97 cm2, 95% CI:-10.32 to -1.62, p = 0.007) resulted in a significant decrease. Single Bifidobacterium probiotics had no effect. Using meta-regression, no association was observed between the total daily probiotic dose and VAT or SAT reduction. This study shows that probiotics have a beneficial effect on central adiposity. Single Lactobacillus-based probiotics reduced VAT and SAT, whereas Bifidobacterium-based probiotics reduce VAT.
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Affiliation(s)
- Leonardo M Porchia
- Laboratorio de Fisiopatología en Enfermedades Crónicas, Centro de investigación Biomédica de Oriente, IMSS. Delegación Puebla, Carretera Federal Atlixco Metepec Km. 4.5, Colonia Centro, C.P, 74360, Atlixco, Puebla, México
| | - Gabriela Vazquez-Marroquin
- Posgrado en Ciencias Biológicas, Universidad Autónoma de Tlaxcala, Carretera Federal Tlaxcala, Puebla. S/N; Km. 1.5, Tlaxcala, Tlaxcala, 90062, Mexico
| | - Renata Ochoa-Précoma
- Facultad de Medicina, Benemérita Universidad Autónoma de Puebla. Calle 13 Sur 2901, Colonia Volcanes, C.P. 72420, Puebla, Puebla, México
| | - Ricardo Pérez-Fuentes
- Laboratorio de Fisiopatología en Enfermedades Crónicas, Centro de investigación Biomédica de Oriente, IMSS. Delegación Puebla, Carretera Federal Atlixco Metepec Km. 4.5, Colonia Centro, C.P, 74360, Atlixco, Puebla, México
- Facultad de Medicina, Benemérita Universidad Autónoma de Puebla. Calle 13 Sur 2901, Colonia Volcanes, C.P. 72420, Puebla, Puebla, México
| | - M Elba Gonzalez-Mejia
- Facultad de Medicina, Benemérita Universidad Autónoma de Puebla. Calle 13 Sur 2901, Colonia Volcanes, C.P. 72420, Puebla, Puebla, México.
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Theodoridis X, Kalopitas G, Vadarlis A, Bakaloudi DR, Gkiourtzis Ν, Dionysopoulos G, Karanika E, Tsekitsidi E, Chourdakis M. Comparative efficacy of different treatment modalities in the management of pediatric non-alcoholic fatty liver disease: A systematic review and network meta-analysis. Pharmacol Ther 2022; 240:108294. [PMID: 36183848 DOI: 10.1016/j.pharmthera.2022.108294] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 09/09/2022] [Accepted: 09/26/2022] [Indexed: 12/15/2022]
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) in children is constantly rising. Lifestyle modification is the cornerstone of the management of pediatric NAFLD. Even though several clinical trials have been conducted, there are barely any approved medications or supplements that can be used in the management of pediatric NAFLD. The aim of our study was to systematically review the current literature and perform a network meta-analysis to compare the different treatment interventions in pediatric NAFLD. Pubmed/Medline, Embase and Scopus were searched from inception to 2 December 2021. The primary outcomes were changes in alanine transaminase (`concentrations. Secondary outcomes were changes in aspartate aminotransferase (AST), lipidemic and other biochemical parameters concentrations and body mass index (BMI) values. The evaluation of transitivity was performed by comparing the distribution of potential effect modifiers across the difference comparisons. Our study included 1241 participants from 18 studies. Different interventions such as omega 3 fatty acids and probiotics seem to exert possible beneficial effects in the management of pediatric NAFLD. Vitamin D and vitamin E supplementation alone or in combination with other interventions also seem to be beneficial in specific patient groups. Several interventions such as omega-3 fatty acids, probiotics and vitamin D and E can be combined with lifestyle modification to manage pediatric NAFLD. Decisions should be individualized based on the patient's profile. Future studies with optimal methodology are needed to draw safe and applicable conclusions.
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Affiliation(s)
- Xenophon Theodoridis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Georgios Kalopitas
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; Division of Gastroenterology and Hepatology, 1(st) Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Andreas Vadarlis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; Department of Gastroenterology and Hepatology, General Hospital of Thessaloniki "G. Papanikolaou", Thessaloniki, Greece.
| | - Dimitra Rafailia Bakaloudi
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Νikolaos Gkiourtzis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; 4(th) Department of Pediatrics, Papageorgiou University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Georgios Dionysopoulos
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Evangelia Karanika
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Eirini Tsekitsidi
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
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Fiore G, Magenes VC, DI Profio E, Milanta C, Calcaterra V, Diamanti A, Campoy C, Zuccotti G, Verduci E. Gut microbiota in obesity and related comorbidities in children and adolescents: the role of biotics in treatment. Minerva Pediatr (Torino) 2022; 74:632-649. [PMID: 35708037 DOI: 10.23736/s2724-5276.22.06964-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Obesity is a complex pathology, globally spread, with a multifactorial pathogenesis, strictly linked with lifestyle, hormones, genetic and epigenetic factors. Evidence supports that obesity, and its comorbidities, are related to changes in gut microbiota, partially responsible of the modulation of energy metabolism. EVIDENCE ACQUISITION Pediatric obesity has been associated with lower bacterial diversity and differences in composition of the gut microbiota, also varying according to the metabolic status of obese subjects. Indeed, differences in distributions and activity of microorganisms in the gut of metabolically healthy and unhealthy obese children have been highlighted. EVIDENCE SYNTHESIS Based on human studies, this review aims to discuss gut microbiota alterations in obese children and adolescents and its role in obese-related complications. Moreover, the role of biotics (probiotics, prebiotics, synbiotics and -marginally- postbiotics) has been analyzed as modulator of obesity-related dysbiosis. CONCLUSIONS As a conclusion, a deeper knowledge about biotic mechanisms of action would be of great interest to implement the clinical care of children and adolescents with obesity and related comorbidities.
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Affiliation(s)
- Giulia Fiore
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Vittoria C Magenes
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Elisabetta DI Profio
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Chiara Milanta
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Valeria Calcaterra
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.,Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, Pavia, Italy
| | - Antonella Diamanti
- Unit of Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital, Rome, Italy
| | - Cristina Campoy
- Centre of Excellence for Pediatric Research EURISTIKOS, Department of Pediatrics, University of Granada, Granada, Spain
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.,L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.,Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, Milan, Italy
| | - Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy - .,Department of Health Sciences, University of Milan, Milan, Italy
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Wang JS, Liu JC. Intestinal microbiota in the treatment of metabolically associated fatty liver disease. World J Clin Cases 2022; 10:11240-11251. [PMID: 36387806 PMCID: PMC9649557 DOI: 10.12998/wjcc.v10.i31.11240] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/07/2022] [Accepted: 09/27/2022] [Indexed: 02/05/2023] Open
Abstract
Metabolically associated fatty liver disease (MAFLD) is a common cause of chronic liver disease, the hepatic manifestation of metabolic syndrome. Despite the increasing incidence of MAFLD, no effective treatment is available. Recent research indicates a link between the intestinal microbiota and liver diseases such as MAFLD. The composition and characteristics of the intestinal microbiota and therapeutic perspectives of MAFLD are reviewed in the current study. An imbalance in the intestinal microbiota increases intestinal permeability and exposure of the liver to adipokines. Furthermore, we focused on reviewing the latest "gut-liver axis" targeted therapy.
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Affiliation(s)
- Ji-Shuai Wang
- Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Jin-Chun Liu
- Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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Lin YC, Lin HF, Wu CC, Chen CL, Ni YH. Pathogenic effects of Desulfovibrio in the gut on fatty liver in diet-induced obese mice and children with obesity. J Gastroenterol 2022; 57:913-925. [PMID: 35976494 DOI: 10.1007/s00535-022-01909-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 07/24/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD. METHODS C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L. reuteri) or Lactobacillus rhamnosus GG plus Bifidobacterium animalis subsp. lactis BB12 (LGG plus BB12). Their fecal microbiomes identified by 16S rRNA sequencing were correlated with the severity of fatty liver. We then used a human cohort to confirm the role of the microbe(s). The HFD-fed mice were administrated with the identified bacterium, Desulfovibrio. The histopathological changes in the liver and ileum were analyzed. RESULTS Lactobacillus and Bifidobacterium improved hepatic steatosis and fibrosis in HFD-fed mice, which was related to the decreased abundance of Desulfovibrio in feces. Further human study confirmed the amount of D. piger in the fecal microbiota of obese children with NAFLD was increased. We then administered D. piger and found aggravated hepatic steatosis and fibrosis in HFD-fed mice. Hepatic expression of CD36 was significantly increased in HFD-fed mice gavaged with D. piger. In HepG2 cells, overexpression of CD36 increased lipid droplets, whereas knockdown of CD36 decreased lipid droplets. HFD-fed mice gavaged with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 density in the ileum tissue. CONCLUSIONS Our findings provide novel insights into the role of Desulfovibrio dysregulation in NAFLD. Modulation of Desulfovibrio may be a potential target for the treatment of NAFLD.
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Affiliation(s)
- Yu-Cheng Lin
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Asia Eastern University of Science and Technology, New Taipei City, Taiwan
| | - Hsueh-Fang Lin
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Chi-Chien Wu
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Chun-Liang Chen
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Yen-Hsuan Ni
- Departments of Pediatrics, College of Medicine, National Taiwan University, No.8, Chung Shan S. Rd., Taipei City, 10002, Taiwan.
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Abenavoli L, Maurizi V, Rinninella E, Tack J, Di Berardino A, Santori P, Rasetti C, Procopio AC, Boccuto L, Scarpellini E. Fecal Microbiota Transplantation in NAFLD Treatment. Medicina (B Aires) 2022; 58:medicina58111559. [PMID: 36363516 PMCID: PMC9695159 DOI: 10.3390/medicina58111559] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/26/2022] [Accepted: 10/27/2022] [Indexed: 11/06/2022] Open
Abstract
Introduction: Gut microbiota is not only a taxonomic biologic ecosystem but is also involved in human intestinal and extra-intestinal functions such as immune system modulation, nutrient absorption and digestion, as well as metabolism regulation. The latter is strictly linked to non-alcoholic fatty liver disease (NAFLD) pathophysiology. Materials and methods: We reviewed the literature on the definition of gut microbiota, the concepts of “dysbiosis” and “eubiosis”, their role in NAFLD pathogenesis, and the data on fecal microbiota transplantation (FMT) in these patients. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, eubiosis, dysbiosis, bile acids, NAFLD, and FMT. Results: Gut microbiota qualitative and quantitative composition is different in healthy subjects vs. NALFD patients. This dysbiosis is associated with and involved in NAFLD pathogenesis and evolution to non-acoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). In detail, microbial-driven metabolism of bile acids (BAs) and interaction with hepatic and intestinal farnesoid nuclear X receptor (FXR) have shown a determinant role in liver fat deposition and the development of fibrosis. Over the use of pre- or probiotics, FMT has shown preclinical and initial clinical promising results in NAFLD treatment through re-modulation of microbial dysbiosis. Conclusions: Promising clinical data support a larger investigation of gut microbiota dysbiosis reversion through FMT in NAFLD using randomized clinical trials to design precision-medicine treatments for these patients at different disease stages.
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Affiliation(s)
- Ludovico Abenavoli
- Department of Health Sciences, University “Magna Græcia”, 88100 Catanzaro, Italy
| | - Valentina Maurizi
- Internal Medicine Residency Program, Università Politecnica delle Marche, 60121 Ancona, Italy
| | - Emanuele Rinninella
- Clinical Nutrition Unit, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Jan Tack
- T.A.R.G.I.D., Gasthuisberg University Hospital, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
| | - Arianna Di Berardino
- Clinical Nutrition and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy
| | - Pierangelo Santori
- Hepatology and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy
| | - Carlo Rasetti
- Clinical Nutrition and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy
- Hepatology and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy
| | | | - Luigi Boccuto
- Healthcare Genetics and Genomics Doctoral Program, School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, 105 Sikes Hall, Clemson, SC 29631, USA
| | - Emidio Scarpellini
- T.A.R.G.I.D., Gasthuisberg University Hospital, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
- Clinical Nutrition and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy
- Correspondence: ; Tel.: +3907-3579-3301; Fax: +3907-3579-3306
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Kobayashi T, Iwaki M, Nakajima A, Nogami A, Yoneda M. Current Research on the Pathogenesis of NAFLD/NASH and the Gut-Liver Axis: Gut Microbiota, Dysbiosis, and Leaky-Gut Syndrome. Int J Mol Sci 2022; 23:ijms231911689. [PMID: 36232990 PMCID: PMC9570241 DOI: 10.3390/ijms231911689] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/27/2022] [Accepted: 09/28/2022] [Indexed: 11/05/2022] Open
Abstract
Global lifestyle changes have led to an increased incidence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), requiring further in-depth research to understand the mechanisms and develop new therapeutic strategies. In particular, high-fat and high-fructose diets have been shown to increase intestinal permeability, which can expose the liver to endotoxins. Indeed, accumulating evidence points to a link between these liver diseases and the intestinal axis, including dysbiosis of the gut microbiome and leaky-gut syndrome. Here, we review the mechanisms contributing to these links between the liver and small intestine in the pathogenesis of NAFLD/NASH, focusing on the roles of intestinal microbiota and their metabolites to influence enzymes essential for proper liver metabolism and function. Advances in next-generation sequencing technology have facilitated analyses of the metagenome, providing new insights into the roles of the intestinal microbiota and their functions in physiological and pathological mechanisms. This review summarizes recent research linking the gut microbiome to liver diseases, offering new research directions to elucidate the detailed mechanisms and novel targets for treatment and prevention.
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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The Benefit of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: A Meta-analysis of Randomized Control Trials. J Pediatr Gastroenterol Nutr 2022; 75:e31-e37. [PMID: 35758473 DOI: 10.1097/mpg.0000000000003537] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES We conducted a systematic review and meta-analysis to provide a summary of the current literature about the efficacy of probiotics in pediatric nonalcoholic fatty liver disease (NAFLD). METHODS A systematic literature search through major electronic databases was carried out for RCTs till September 9, 2021, investigating the efficacy of probiotics in the treatment of pediatric patients with NAFLD. Weighted mean differences (WMD) and Standard Deviations (SD) were used to calculate continuous outcomes and a Risk Ratio with 95% CI was used for dichotomous outcomes. RESULTS In total, 4 RCTs with 238 pediatric patients with NAFLD were included in the study. Probiotic supplementation revealed a statistically significant difference in transaminases' levels (ALT: WMD = -7.51 IU/L, 95% CI, -11.28 to -3.73, I 2 = 0%, P < 0.0001; AST: WMD = -6.46 IU/L, 95% CI, -9.31 to -3.61, I 2 = 0%, P < 0.00001), anthropometric characteristics, total cholesterol, triglycerides and ultrasonographic steatosis improvement. CONCLUSIONS According to the data of this meta-analysis, probiotic supplementation, and especially supplementation of Lactobacillus acidophilus in combination with other strains of Bifidobacterium or Lactobacillus may be beneficial in the improvement of transaminases', lipid parameters' levels, ultrasonographic, and anthropometric characteristics in children with NAFLD. Current evidence does not allow specifying the exact beneficial strain of probiotics mentioned above. The possible effect of probiotics on liver histology improvement in pediatric NAFLD should be examined in future studies.
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The Biotics Family: Current Knowledge and Future Perspectives in Metabolic Diseases. Life (Basel) 2022; 12:life12081263. [PMID: 36013442 PMCID: PMC9410396 DOI: 10.3390/life12081263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 07/30/2022] [Accepted: 08/14/2022] [Indexed: 11/16/2022] Open
Abstract
Globally, metabolic diseases such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease pose a major public health threat. Many studies have confirmed the causal relationship between risk factors and the etiopathogenesis of these diseases. Despite this, traditional therapeutic management methods such as physical education and diet have proven insufficient. Recently, researchers have focused on other potential pathways for explaining the pathophysiological variability of metabolic diseases, such as the involvement of the intestinal microbiota. An understanding of the relationship between the microbiome and metabolic diseases is a first step towards developing future therapeutic strategies. Currently, much attention is given to the use of biotics family members such as prebiotics (lactolose, soy oligosaccharides, galactooligosaccharides, xylooligosaccharides or inulin) and probiotics (genera Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus or Enterococcus). They can be used both separately and together as synbiotics. Due to their direct influence on the composition of the intestinal microbiota, they have shown favorable results in the evolution of metabolic diseases. The expansion of the research area in the biotics family has led to the discovery of new members, like postbiotics. In the age of personalized medicine, their use as therapeutic options is of great interest to our study.
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Metabolic dysfunction-associated fatty liver disease in obese youth with insulin resistance and type 2 diabetes. Curr Opin Pediatr 2022; 34:414-422. [PMID: 35836399 DOI: 10.1097/mop.0000000000001138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW The aim of this review is to present the new definition of the disease, defining the epidemiology, risk factors with a particular attention to the role of insulin resistance (IR) and to define the main treatments explored. RECENT FINDINGS Nonalcoholic fatty liver disease (NAFLD) was previously considered a primary liver disease, but it would be more correct to consider it a component of the metabolic syndrome (MetS) in which IR might play a key role. Based on these findings, it has been recently proposed to modify the classic term of NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) that better reflects the pathophysiology of this complex disease. SUMMARY Currently, no treatments approved in childhood are available, thus the only recommended approach is the prevention and correction of the known risk factors, and particularly of IR. However, further studies are needed to better clarify the pathogenetic mechanisms of NAFLD in order to establish more tailored therapies.
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Huang Y, Wang X, Zhang L, Zheng K, Xiong J, Li J, Cong C, Gong Z, Mao J. Effect of Probiotics Therapy on Nonalcoholic Fatty Liver Disease. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:7888076. [PMID: 35677177 PMCID: PMC9170412 DOI: 10.1155/2022/7888076] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 04/30/2022] [Accepted: 05/13/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world. The pathogenesis of NAFLD is complex and multifactorial. Clinical studies have shown that alterations in the gut microbiota play a key role in NAFLD. The purpose of this study was to analyze the effect of probiotic supplementation on the treatment of NAFLD patients based on various indicators. METHODS We conducted a meta-analysis investigating the relationship between NAFLD and probiotic supplementation. Embase, PubMed, and Web of Science databases were searched by computer, and then, eligible studies were identified. Finally, a total of high-quality randomized controlled trials were selected involving 1403 participants. Meta-analysis was performed using the RevMan 5.3 software which was systematically searched for works published through Dec. 1, 2021, in the present study. RESULTS The meta-analysis results showed that the probiotics supplementation improved hepatocyte injury and significantly reduced the level of ALT (P = 0.00001), AST (P = 0.0009), GGT (P = 0.04), TG (P = 0.01), LDL-C (P = 0.0005), HDL-C (P = 0.0002), insulin (P = 0.003), IR (P = 0.03), BMI (P = 0.03), TNF-α (P = 0.03), and CRP (P = 0.02), respectively, in NAFLD patients. CONCLUSION The present study suggests that probiotics therapy may improve liver enzyme levels, regulated lipid metabolism, reduced insulin resistance, and improved inflammation in NAFLD patients. It supports the potential role of probiotics supplementation in the treatment of NAFLD.
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Affiliation(s)
- Yuanshe Huang
- Anshun University, Guizhou, Anshun 561000, China
- College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Xiaodong Wang
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
| | - Lai Zhang
- Anshun University, Guizhou, Anshun 561000, China
| | - Ke Zheng
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016, China
| | - Jie Xiong
- Department of Pharmacy, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders/Chongqing Key Laboratory of Pediatrics/Children's Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Jing Li
- Anshun University, Guizhou, Anshun 561000, China
| | - Chunlei Cong
- Anshun University, Guizhou, Anshun 561000, China
| | - Zhaomiao Gong
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
| | - Jingxin Mao
- College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
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Kanchanasurakit S, Kositamongkol C, Lanoi K, Nunta M, Saetuan T, Chaiyakunapruk N, Saokaew S, Phisalprapa P. Effects of Synbiotics, Probiotics, and Prebiotics on Liver Enzymes of Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis. Front Nutr 2022; 9:880014. [PMID: 35669067 PMCID: PMC9167056 DOI: 10.3389/fnut.2022.880014] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 04/13/2022] [Indexed: 12/24/2022] Open
Abstract
Background A systematic review and network meta-analysis was primarily conducted to compare the effects of synbiotics, probiotics, and prebiotics on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Moreover, their effects on body mass index (BMI), waist circumference (WC), lipid profile, fasting blood sugar (FBS), and homeostatic model assessment-insulin resistance (HOMA-IR) of patients with non-alcoholic fatty liver disease (NAFLD) were investigated and analyzed as secondary outcomes. Methods The randomized controlled trials (RCTs), limited to the English language, were searched through PubMed, the Web of Science, Embase, CLINAHL Plus, and the Cochrane Library from inception to February 2, 2022. The eligible studies were reviewed and their risk-of-bias and heterogeneity were assessed. Both direct and indirect evidence were assembled using a random-effects model. The effects of the intervention were presented as weighted mean differences (WMD) with 95% confidence interval (95% CI). Results Of 3,864 identified records, a total of 1,389 patients with NAFLD from 26 RCTs were included in the analyses. Among these, 241 were diagnosed with non-alcoholic steatohepatitis. The quality assessment reported a moderate risk of bias from most studies. Among adult patients with NAFLD, when compared with placebo, synbiotics provided the largest effect on reductions of AST (-12.71 IU/L; 95% CI: -16.95, -8.47), WC (-2.26 cm; 95% CI: -2.98, -1.54), total cholesterol (-22.23 mg/dl; 95% CI: -29.55, -14.90), low-density lipoproteins (-17.72 mg/dl; 95% CI: -25.23, -10.22), and FBS (-6.75 mg/dl; 95% CI: -10.67, -2.84). Probiotics lowered ALT (-14.46 IU/L; 95% CI: -21.33, -7.59) and triglycerides (-20.97 mg/dl; 95% CI: -40.42, -1.53) the most. None had significant impact on BMI, high-density lipoproteins, and HOMA-IR changes. Conclusion Synbiotics and probiotics are likely to be the most potential effective treatments for AST and ALT reduction in adult patients with NAFLD, respectively. Although liver enzymes cannot exactly define the severity of NAFLD, unlike the results from biopsy or imaging tests, they are important indicators that can monitor the status of the disease and provide benefits for clinical management. Systematic Review Registration [https://www.crd.york.ac.uk/prospero/display_reco rd.php?ID], identifier [CRD42020200301].
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Affiliation(s)
- Sukrit Kanchanasurakit
- Unit of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
- Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
- Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
- Division of Clinical Pharmacy, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
- Division of Pharmaceutical Care, Department of Pharmacy, Phrae Hospital, Phrae, Thailand
| | - Chayanis Kositamongkol
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Kamonnat Lanoi
- Division of Clinical Pharmacy, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
| | - Monnaree Nunta
- Division of Clinical Pharmacy, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
| | - Thaksaporn Saetuan
- Division of Clinical Pharmacy, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
| | - Nathorn Chaiyakunapruk
- Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, United States
- IDEAS Center, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, United States
| | - Surasak Saokaew
- Unit of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
- Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
- Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
- Division of Social and Administrative Pharmacy, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
| | - Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Lee SHF, Ahmad SR, Lim YC, Zulkipli IN. The Use of Probiotic Therapy in Metabolic and Neurological Diseases. Front Nutr 2022; 9:887019. [PMID: 35592636 PMCID: PMC9110960 DOI: 10.3389/fnut.2022.887019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 03/29/2022] [Indexed: 12/20/2022] Open
Abstract
The human gut is home to trillions of microbes that interact with host cells to influence and contribute to body functions. The number of scientific studies focusing on the gut microbiome has exponentially increased in recent years. Studies investigating factors that may potentially affect the gut microbiome and may be used for therapeutic purposes in diseases where dysbioses in the gut microbiome have been shown are of particular interest. This review compiles current evidence available in the scientific literature on the use of probiotics to treat metabolic diseases and autism spectrum disorders (ASDs) to analyze the efficacy of probiotics in these diseases. To do this, we must first define the healthy gut microbiome before looking at the interplay between the gut microbiome and diseases, and how probiotics affect this interaction. In metabolic diseases, such as obesity and diabetes, probiotic supplementation positively impacts pathological parameters. Conversely, the gut–brain axis significantly impacts neurodevelopmental disorders such as ASDs. However, manipulating the gut microbiome and disease symptoms using probiotics has less pronounced effects on neurodevelopmental diseases. This may be due to a more complex interplay between genetics and the environment in these diseases. In conclusion, the use of microbe-based probiotic therapy may potentially have beneficial effects in ameliorating the pathology of various diseases. Validation of available data for the development of personalized treatment regimens for affected patients is still required.
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Prikhodko VA, Bezborodkina NN, Okovityi SV. Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. Biomedicines 2022; 10:274. [PMID: 35203484 PMCID: PMC8869100 DOI: 10.3390/biomedicines10020274] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/22/2022] [Accepted: 01/24/2022] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), or metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by high global incidence and prevalence, a tight association with common metabolic comorbidities, and a substantial risk of progression and associated mortality. Despite the increasingly high medical and socioeconomic burden of NAFLD, the lack of approved pharmacotherapy regimens remains an unsolved issue. In this paper, we aimed to provide an update on the rapidly changing therapeutic landscape and highlight the major novel approaches to the treatment of this disease. In addition to describing the biomolecules and pathways identified as upcoming pharmacological targets for NAFLD, we reviewed the current status of drug discovery and development pipeline with a special focus on recent evidence from clinical trials.
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Affiliation(s)
- Veronika A. Prikhodko
- Department of Pharmacology and Clinical Pharmacology, Saint Petersburg State Chemical and Pharmaceutical University, 14A Prof. Popov Str., 197022 St. Petersburg, Russia;
| | - Natalia N. Bezborodkina
- Zoological Institute, Russian Academy of Sciences, 1 Universitetskaya emb., 199034 St. Petersburg, Russia;
| | - Sergey V. Okovityi
- Department of Pharmacology and Clinical Pharmacology, Saint Petersburg State Chemical and Pharmaceutical University, 14A Prof. Popov Str., 197022 St. Petersburg, Russia;
- Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, Saint Petersburg State University, 7/9 Universitetskaya emb., 199034 St. Petersburg, Russia
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