|
1
|
Fu H, Yang T, Ni H, Li J, Liu F, Liu J, Yin Y. A low-protein soybean-free diet improves carcass traits and meat quality and modulates the colonic microbiota in Daweizi pigs. Front Vet Sci 2025; 11:1516198. [PMID: 39981135 PMCID: PMC11841500 DOI: 10.3389/fvets.2024.1516198] [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: 10/24/2024] [Accepted: 12/30/2024] [Indexed: 02/22/2025] Open
Abstract
Introduction Soybean meal is an excellent protein source and is widely used in pig feed. However, the Americas account for more than 80% of global soybean production, so European and Asia swine production largely depends on soybean imports. The use of safe and functional unconventional feed sources can effectively alleviate worldwide protein shortage problems. Methods Here, we formulated a low-protein soybean-free diet (LPNS) for growing and fattening pigs using rice, potatoes, tea, and other unconventional feed sources. Thirty-six healthy Daweizi pigs (average body weight 23.60 ± 1.34 kg) were raised under the same conditions and randomly assigned to two dietary treatments: (1) Con group, corn-soybean base meal; (2) LPNS group. When the average weight of pigs in the group reached 85 kg, two pigs per pen were randomly selected and euthanized for collection of the colonic digesta and carcass traits and for meat quality determination. Results Compared with the corn-soybean based diet, the LPNS diet decreased the average daily gain (ADG) and feed conversion ratio (FCR) of Daweizi pigs but had a lower cost per kilogram of gain. In addition, the LPNS diet significantly increased leanness and decreased the fat-skin rate and bone rate of Daweizi pigs. The cooking loss of meat decreased, and unsaturated fatty acids such as C22:6 and n-3 PUFA significantly increased in the LPNS group. Moreover, the purine content in the meat substantially decreased with the LPNS diet. The 16S rDNA analysis revealed that the LPNS diet greatly modified the composition of the colonic microbiota community, with a decrease in the Firmicutes/Bacteroidetes ratio and an increase in the abundance of Lactobacillus spp. Discussion The use of functional herbs along with a low-protein diet helped to regulate fat and purine metabolism in fatty-type pigs. The LPNS diet formulated with unconventional-feed sources not only helps reduce the feed cost in swine production but also improves the carcass traits and meat quality of pigs, which is more suitable for small-scale pig farming.
Collapse
Affiliation(s)
- Haohua Fu
- Department of Animal Science, Hunan Agriculture University, Changsha, China
| | - Taoming Yang
- Department of Animal Science, Hunan Agriculture University, Changsha, China
| | - Hengjia Ni
- Department of Animal Science, Hunan Agriculture University, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Hunan Research Center of Livestock and Poultry Sciences, South Central Experimental Station of Animal Nutrition and Feed Science in the Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Jing Li
- Department of Animal Science, Hunan Agriculture University, Changsha, China
| | - Fenfen Liu
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Hunan Research Center of Livestock and Poultry Sciences, South Central Experimental Station of Animal Nutrition and Feed Science in the Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Jingbo Liu
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, China
| | - Yulong Yin
- Department of Animal Science, Hunan Agriculture University, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Hunan Research Center of Livestock and Poultry Sciences, South Central Experimental Station of Animal Nutrition and Feed Science in the Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| |
Collapse
|
|
2
|
Wang Q, Liang J, Zou Q, Wang W, Yan G, Guo R, Yuan T, Wang Y, Liu X, Liu Z. Tryptophan Metabolism-Regulating Probiotics Alleviate Hyperuricemia by Protecting the Gut Barrier Integrity and Enhancing Colonic Uric Acid Excretion. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024. [PMID: 39564988 DOI: 10.1021/acs.jafc.4c07716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Abstract
The balance of gut microbiota affects uric acid synthesis and excretion, influencing the development of hyperuricemia. This study aimed to investigate the effects and mechanisms of probiotics on hyperuricemia and adenine- and potassium oxonate-induced colonic damage. After two months of gavage at 109 CFU/day, the probiotic strains Lactobacillus rhamnosus UA260 and Lactobacillus plantarum YU28, identified through in vitro screening, significantly reduced serum uric acid levels in hyperuricemia mice from 109.71 ± 56.33 to 38.76 ± 15.06 and 33.22 ± 6.91 μmol/L, respectively. These strains attenuated inflammatory, repaired gut barrier damage, and enhanced colonic uric acid transporter function, thereby promoting uric acid excretion. Furthermore, the probiotics significantly reshaped gut microbiota by increasing the abundance of beneficial bacteria, including Lactobacillus and Coprococcus, while modulating tryptophan, purine, and riboflavin metabolism. Changes in tryptophan metabolites, specifically indole-3-propionic acid and indole-3-acetic acid, were correlated with xanthine oxidase activity, colonic injury, and the expression of the uric acid transporter protein ABCG2 during treatment. Probiotics intervention activated aryl hydrocarbon receptor pathways. These findings suggest that probiotics alleviate hyperuricemia and colonic inflammatory by regulating gut microbiota composition and tryptophan microbial metabolite pathways. Probiotics that modulate tryptophan microbial metabolism may provide a potential strategy for treating or preventing hyperuricemia.
Collapse
Affiliation(s)
- Qianxu Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Northwest A&F University Shenzhen Research Institute, Shenzhen 518000, China
| | - Jiarui Liang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Northwest A&F University Shenzhen Research Institute, Shenzhen 518000, China
| | - Qianhui Zou
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Northwest A&F University Shenzhen Research Institute, Shenzhen 518000, China
| | - Wenxiu Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Guiming Yan
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Rui Guo
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Northwest A&F University Shenzhen Research Institute, Shenzhen 518000, China
| | - Tian Yuan
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China
- Northwest A&F University Shenzhen Research Institute, Shenzhen 518000, China
| | - Yutang Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Xuebo Liu
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
| | - Zhigang Liu
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
- Northwest A&F University Shenzhen Research Institute, Shenzhen 518000, China
- Shaanxi Precision Nutrition and Health Research Institute, Xi'an 710300, China
| |
Collapse
|
|
3
|
Hu C. Regulating uric acid. eLife 2024; 13:e104493. [PMID: 39526888 PMCID: PMC11554302 DOI: 10.7554/elife.104493] [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] [Indexed: 11/16/2024] Open
Abstract
Certain strains of a bacterium found in the gut of some animals, Lactobacillus plantarum, are able to counter hyperuricemia, a condition caused by high levels of uric acid in the blood.
Collapse
Affiliation(s)
- Caihong Hu
- College of Animal Sciences, Zhejiang UniversityHangzhouChina
| |
Collapse
|
|
4
|
Fu Y, Luo XD, Li JZ, Mo QY, Wang X, Zhao Y, Zhang YM, Luo HT, Xia DY, Ma WQ, Chen JY, Wang LH, Deng QY, Ben L, Kashif Saleemi M, Jiang XZ, Chen J, Miao K, Lin ZP, Zhang P, Ye H, Cao QY, Zhu YW, Yang L, Tu Q, Wang W. Host-derived Lactobacillus plantarum alleviates hyperuricemia by improving gut microbial community and hydrolase-mediated degradation of purine nucleosides. eLife 2024; 13:e100068. [PMID: 39508089 PMCID: PMC11542919 DOI: 10.7554/elife.100068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus, can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout.
Collapse
Affiliation(s)
- Yang Fu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Xiao-Dan Luo
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Jin-Ze Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Qian-Yuan Mo
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Xue Wang
- State Key Laboratory of Microbial Technology, Shandong UniversityShandongChina
| | - Yue Zhao
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - You-Ming Zhang
- State Key Laboratory of Microbial Technology, Shandong UniversityShandongChina
| | - Hao-Tong Luo
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Dai-Yang Xia
- School of Marine Sciences, Sun Yat-sen University, and Southern Marine Science and Engineering Guangdong LaboratoryZhuhaiChina
| | - Wei-Qing Ma
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Jian-Ying Chen
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Li-Hau Wang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Qiu-Yi Deng
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Lukuyu Ben
- International Livestock Research InstituteNairobiKenya
| | | | - Xian-Zhi Jiang
- Microbiome Research Center, Moon (Guangzhou) Biotech Co. LtdGuangdongChina
| | - Juan Chen
- Microbiome Research Center, Moon (Guangzhou) Biotech Co. LtdGuangdongChina
| | - Kai Miao
- CancerCenter, Faculty of Health Sciences, University of MacauMacauChina
| | - Zhen-Ping Lin
- Shantou Baisha Research Institute of Origin Species of Poultry and StockShantouChina
| | - Peng Zhang
- Chimelong Safari Park, Chimelong Group CoGuangzhouChina
| | - Hui Ye
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Qing-Yun Cao
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Yong-Wen Zhu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Lin Yang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| | - Qiang Tu
- Helmholtz International Lab for Anti-Infectives, Shandong University–Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong UniversityQingdaoChina
- Shenzhen Key Laboratory of Genome Manipulation and Biosynthesis, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesShenzhenChina
| | - Wence Wang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural UniversityGuangzhouChina
| |
Collapse
|
|
5
|
Singh AK, Durairajan SSK, Iyaswamy A, Williams LL. Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies. World J Gastroenterol 2024; 30:4404-4410. [PMID: 39494101 PMCID: PMC11525862 DOI: 10.3748/wjg.v30.i40.4404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 09/14/2024] [Accepted: 09/26/2024] [Indexed: 10/16/2024] Open
Abstract
Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.
Collapse
Affiliation(s)
- Abhay Kumar Singh
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, TN 610005, India
| | - Siva Sundara Kumar Durairajan
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, TN 610005, India
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
| | - Ashok Iyaswamy
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China
- Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641021, India
| | - Leonard L Williams
- Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, United States
| |
Collapse
|
|
6
|
Dudala SS, T.C. V, A VN, D JB. Modeling and optimization of uricase production from a novel Pseudomonas mosselii using response surface methodology and artificial neural network. BIOMASS CONVERSION AND BIOREFINERY 2024; 14:21865-21880. [DOI: 10.1007/s13399-023-04468-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 05/28/2023] [Accepted: 06/04/2023] [Indexed: 09/27/2023]
|
|
7
|
Ye Z, Ji B, Peng Y, Song J, Zhao T, Wang Z. Screening and Characterization of Probiotics Isolated from Traditional Fermented Products of Ethnic-Minorities in Northwest China and Evaluation Replacing Antibiotics Breeding Effect in Broiler. Pol J Microbiol 2024; 73:275-295. [PMID: 39213263 PMCID: PMC11398283 DOI: 10.33073/pjm-2024-025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 05/25/2024] [Indexed: 09/04/2024] Open
Abstract
In this study, Lactobacillus fermentum DM7-6 (DM7-6), Lactobacillus plantarum DM9-7 (DM9-7), and Bacillus subtilis YF9-4 (YF9-4) were isolated from traditional fermented products. The survival rate of DM7-6, DM9-7, and YF9-4 in simulated intestinal gastric fluid reached 61.29%, 44.82%, and 55.26%, respectively. These strains had inhibition ability against common pathogens, and the inhibition zone diameters were more than 7 mm. Antioxidant tests showed these strains had good scavenging capacity for superoxide anion, hydroxyl radical and DPPH, and the total reduction capacity reached 65%. Then DM7-6, DM9-7 and YF9-4 were fed to broilers to study the effects on antioxidant capacity, immune response, biochemical indices, tissue morphology, and gut microbiota. 180 healthy broilers were allocated randomly into six experimental groups. SOD, GSH-Px, and T-AOC in broilers serum were detected, and the results showed probiotics significantly improve antioxidant capacity compared to CK group, while antibiotics showed the opposite result. Besides, IgA, IgM, IgG, TNF-α, and IL-2 indicated it could significantly improve immunity by adding probiotics in broilers diets. However, antibiotics reduced immunoglobulin levels and enhanced inflammation index. Biochemical indicators and tissue morphology showed probiotics had a protective effect on metabolic organs. Gut microbiota analysis proved antibiotics could significantly decrease microbial community diversity and increase the proportion of opportunistic pathogens, while probiotics could improve the diversity of gut microbiota and promote the colonization of beneficial microorganisms. In summary, probiotics DM7-6, DM9-7, and YF9-4 can improve the broiler's health by improving antioxidant capacity and immune function, regulating gut microbiota, and can be used as alternative probiotics for antibiotics-free breeding of broilers.
Collapse
Affiliation(s)
- Ze Ye
- Key Laboratory of Microbial Resources Exploitation and Application of Gansu Province, Institute of Biology, Gansu Academy of Sciences, Lanzhou, China
| | - Bin Ji
- Key Laboratory of Microbial Resources Exploitation and Application of Gansu Province, Institute of Biology, Gansu Academy of Sciences, Lanzhou, China
| | - Yinan Peng
- Key Laboratory of Microbial Resources Exploitation and Application of Gansu Province, Institute of Biology, Gansu Academy of Sciences, Lanzhou, China
| | - Jie Song
- Key Laboratory of Microbial Resources Exploitation and Application of Gansu Province, Institute of Biology, Gansu Academy of Sciences, Lanzhou, China
| | - Tingwei Zhao
- Key Laboratory of Microbial Resources Exploitation and Application of Gansu Province, Institute of Biology, Gansu Academy of Sciences, Lanzhou, China
| | - Zhiye Wang
- Key Laboratory of Microbial Resources Exploitation and Application of Gansu Province, Institute of Biology, Gansu Academy of Sciences, Lanzhou, China
- School of Life Science, Lanzhou University of Technology, Lanzhou, China
| |
Collapse
|
|
8
|
Zhu W, Bi S, Fang Z, Iddrisu L, Deng Q, Sun L, Gooneratne R. Priestia megaterium ASC-1 Isolated from Pickled Cabbage Ameliorates Hyperuricemia by Degrading Uric Acid in Rats. Microorganisms 2024; 12:832. [PMID: 38674776 PMCID: PMC11052324 DOI: 10.3390/microorganisms12040832] [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: 03/24/2024] [Revised: 04/10/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Pickled cabbage, a traditional fermented food rich in functional microorganisms, can effectively control hyperuricemia and gout. In this study, a Priestia megaterium ASC-1 strain with strong uric acid (UA) degradation ability was isolated from pickled cabbage. After oral administration for 15 days, ASC-1 was stably colonized in the rats in this study. ASC-1 significantly reduced UA levels (67.24%) in hyperuricemic rats. Additionally, ASC-1 alleviated hyperuricemia-related inflammatory response, oxidative stress, and blood urea nitrogen. Intestinal microbial diversity results showed that ASC-1 restored intestinal injury and gut flora dysbiosis caused by hyperuricemia. These findings suggest that P. megaterium ASC-1 may be used as a therapeutic adjuvant for the treatment of hyperuricemia.
Collapse
Affiliation(s)
- Wenjuan Zhu
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology, Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (W.Z.); (S.B.); (L.I.); (Q.D.); (L.S.)
| | - Siyuan Bi
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology, Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (W.Z.); (S.B.); (L.I.); (Q.D.); (L.S.)
| | - Zhijia Fang
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology, Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (W.Z.); (S.B.); (L.I.); (Q.D.); (L.S.)
| | - Lukman Iddrisu
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology, Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (W.Z.); (S.B.); (L.I.); (Q.D.); (L.S.)
| | - Qi Deng
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology, Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (W.Z.); (S.B.); (L.I.); (Q.D.); (L.S.)
| | - Lijun Sun
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology, Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (W.Z.); (S.B.); (L.I.); (Q.D.); (L.S.)
| | - Ravi Gooneratne
- Department of Wine, Food and Molecular Biosciences, Lincoln University, Lincoln 7647, Canterbury, New Zealand;
| |
Collapse
|
|
9
|
Feng ZP, Wang XY, Xin HY, Huang SL, Huang HY, Xin Q, Zhang XH, Xin HW. Gut microbiota plays a significant role in gout. J Med Microbiol 2024; 73. [PMID: 38629677 DOI: 10.1099/jmm.0.001824] [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] [Indexed: 04/19/2024] Open
Abstract
With the development of social economy, the incidence of gout is increasing, which is closely related to people's increasingly rich diet. Eating a diet high in purine, fat, sugar and low-fibre for a long time further aggravates gout by affecting uric acid metabolism. The renal metabolism mechanism of uric acid has been thoroughly studied. To find a new treatment method for gout, increasing studies have recently been conducted on the mechanism of intestinal excretion, metabolism and absorption of uric acid. The most important research is the relationship between intestinal microbiota and the risk of gout. Gut microbiota represent bacteria that reside in a host's gastrointestinal tract. The composition of the gut microbiota is associated with protection against pathogen colonization and disease occurrence. This review focuses on how gut microbiota affects gout through uric acid and discusses the types of bacteria that may be involved in the occurrence and progression of gout. We also describe potential therapy for gout by restoring gut microbiota homeostasis and reducing uric acid levels. We hold the perspective that changing intestinal microbiota may become a vital method for effectively preventing or treating gout.
Collapse
Affiliation(s)
- Zhi-Peng Feng
- Key Laboratory of Research on Human Genetic Diseases Research at Universities of Inner Mongolia Autonomous Region, School of Basic Medicine, Chifeng University, Chifeng, Inner Mongolian Autonomous Region 024000, PR China
- Department of Gastroenterology, Yueyang Hospital Affiliated to Hunan Normal University, Yueyang, Hunan 414000, PR China
- Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, PR China
| | - Xiao-Yan Wang
- The Doctoral Scientific Research Center, People's Hospital of Lianjiang, Guangdong 524400, PR China
- The Doctoral Scientific Research Center, People's Hospital of Lianjiang, Guangdong Medical University, Guangdong 524400, PR China
| | - Hong-Yi Xin
- The Doctoral Scientific Research Center, People's Hospital of Lianjiang, Guangdong 524400, PR China
- The Doctoral Scientific Research Center, People's Hospital of Lianjiang, Guangdong Medical University, Guangdong 524400, PR China
| | - Shao-Li Huang
- Clinical Laboratory, People's Hospital of Lianjiang, Guangdong 524400, PR China
| | - Hong-Yu Huang
- Department of Surgery, People's Hospital of Lianjiang, Guangdong 524400, PR China
| | - Qiang Xin
- Graduate School, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, PR China
- Department of Internal Medicine, Ulanqab General Hospital of Traditional Chinese Medicine and Mongolian Medicine, Hugeji Street South, Industry and Agriculture Street West, Jining New District, Ulanqab, Inner Mongolia 012000, PR China
| | - Xi-He Zhang
- The Doctoral Scientific Research Center, People's Hospital of Lianjiang, Guangdong 524400, PR China
- The Doctoral Scientific Research Center, People's Hospital of Lianjiang, Guangdong Medical University, Guangdong 524400, PR China
| | - Hong-Wu Xin
- Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, PR China
| |
Collapse
|
|
10
|
Zou Y, Ro KS, Jiang C, Yin D, Zhao L, Zhang D, Du L, Xie J. The anti-hyperuricemic and gut microbiota regulatory effects of a novel purine assimilatory strain, Lactiplantibacillus plantarum X7022. Eur J Nutr 2024; 63:697-711. [PMID: 38147149 DOI: 10.1007/s00394-023-03291-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/28/2023] [Indexed: 12/27/2023]
Abstract
PURPOSE Probiotics have been reported to effectively alleviate hyperuricemia and regulate the gut microbiota. The aim of this work was to study the in vivo anti-hyperuricemic properties and the mechanism of a novel strain, Lactiplantibacillus plantarum X7022. METHODS Purine content and mRNA expression of purine assimilation related enzymes were determined by HPLC and qPCR, respectively. Hyperuricemic mice were induced by potassium oxonate and hypoxanthine. Uric acid (UA), blood urea nitrogen, creatinine and renal inflammation were examined by kits. The expression of renal UA transporters was subjected to western blotting. Kidney tissues were sectioned for histological analysis. The fecal short-chain fatty acids (SCFAs) were determined by HPLC, and gut microbiota was investigated using the 16S rDNA metagenomic sequencing. RESULTS L. plantarum X7022 possesses a complete purine assimilation pathway and can exhaust xanthine, guanine, and adenine by 82.1%, 33.1%, and 12.6%, respectively. The strain exhibited gastrointestinal viability as 44% at the dose of 109 CFU/mL in mice. After four-week administration of the strain, a significant decrease of 35.5% in the serum UA level in hyperuricemic mice was achieved. The diminished contents of fecal propionate and butyrate were dramatically boosted. The treatment also alleviated renal inflammation and restored renal damage. The above physiological changes may due to the inhibited xanthine oxidase (XO) activity, as well as the expressional regulation of UA transporters (GLUT9, URAT1 and OAT1) to the normal level. Notably, gut microbiota dysbiosis in hyperuricemic mice was improved with the inflammation and hyperuricemia related flora depressed, and SCFAs production related flora promoted. CONCLUSION The strain is a promising probiotic strain for ameliorating hyperuricemia.
Collapse
Affiliation(s)
- Yuan Zou
- State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, School of Biotechnology, East China University of Science and Technology, P. O. Box 283130 # Meilong Rd, Shanghai, 200237, People's Republic of China
| | - Kum-Song Ro
- State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, School of Biotechnology, East China University of Science and Technology, P. O. Box 283130 # Meilong Rd, Shanghai, 200237, People's Republic of China
- Department of Biotechnology, Faculty of Life Science, Kim Hyong Jik University of Education, Pyongyang, Democratic People's Republic of Korea
| | - Chentian Jiang
- State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, School of Biotechnology, East China University of Science and Technology, P. O. Box 283130 # Meilong Rd, Shanghai, 200237, People's Republic of China
| | - Deyi Yin
- State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, School of Biotechnology, East China University of Science and Technology, P. O. Box 283130 # Meilong Rd, Shanghai, 200237, People's Republic of China
| | - Li Zhao
- State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, School of Biotechnology, East China University of Science and Technology, P. O. Box 283130 # Meilong Rd, Shanghai, 200237, People's Republic of China
| | - Daihui Zhang
- Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing, 210042, Jiangsu, People's Republic of China
| | - Lei Du
- State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, School of Biotechnology, East China University of Science and Technology, P. O. Box 283130 # Meilong Rd, Shanghai, 200237, People's Republic of China.
| | - Jingli Xie
- State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, School of Biotechnology, East China University of Science and Technology, P. O. Box 283130 # Meilong Rd, Shanghai, 200237, People's Republic of China
- Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), Shanghai, 200237, People's Republic of China
| |
Collapse
|
|
11
|
Fu Y, Chen YS, Xia DY, Luo XD, Luo HT, Pan J, Ma WQ, Li JZ, Mo QY, Tu Q, Li MM, Zhao Y, Li Y, Huang YT, Chen ZX, Li ZJ, Bernard L, Dione M, Zhang YM, Miao K, Chen JY, Zhu SS, Ren J, Zhou LJ, Jiang XZ, Chen J, Lin ZP, Chen JP, Ye H, Cao QY, Zhu YW, Yang L, Wang X, Wang WC. Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model. NPJ Biofilms Microbiomes 2024; 10:25. [PMID: 38509085 PMCID: PMC10954633 DOI: 10.1038/s41522-024-00486-9] [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: 09/21/2023] [Accepted: 02/06/2024] [Indexed: 03/22/2024] Open
Abstract
Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.
Collapse
Affiliation(s)
- Yang Fu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Yong-Song Chen
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Dai-Yang Xia
- School of Marine Sciences, Sun Yat-sen University, and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519082, China
| | - Xiao-Dan Luo
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Hao-Tong Luo
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Jie Pan
- Hunan Shihua Biotech Co. Ltd., Changsha, 410000, China
| | - Wei-Qing Ma
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Jin-Ze Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Qian-Yuan Mo
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Qiang Tu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, Shandong, China
| | - Meng-Meng Li
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng, 252000, China
| | - Yue Zhao
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Yu Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Yi-Teng Huang
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Zhi-Xian Chen
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Zhen-Jun Li
- Key Laboratory of Carcinogenesis and Translational Research, Departments of Lymphoma, Radiology and Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, 100080, China
| | - Lukuyu Bernard
- International Livestock Research Institute, Nairobi, 00100, Kenya
| | - Michel Dione
- International Livestock Research Institute, Nairobi, 00100, Kenya
| | - You-Ming Zhang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, Shandong, China
| | - Kai Miao
- Cancer Center, Faculty of Health Sciences, University of Macau, Macau, SAR, China
| | - Jian-Ying Chen
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Shan-Shan Zhu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Jie Ren
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Ling-Juan Zhou
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Xian-Zhi Jiang
- Microbiome Research Center, Moon (Guangzhou) Biotech Co. Ltd., Guangzhou, 510535, China
| | - Juan Chen
- Microbiome Research Center, Moon (Guangzhou) Biotech Co. Ltd., Guangzhou, 510535, China
| | - Zhen-Ping Lin
- Shantou Baisha Research Institute of Origin Species of Poultry and Stock, Shantou, 515041, China
| | - Jun-Peng Chen
- Shantou Baisha Research Institute of Origin Species of Poultry and Stock, Shantou, 515041, China
| | - Hui Ye
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Qing-Yun Cao
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Yong-Wen Zhu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Lin Yang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
| | - Xue Wang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, Shandong, China.
| | - Wen-Ce Wang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
| |
Collapse
|
|
12
|
Kim D, Moon JS, Kim JE, Jang YJ, Choi HS, Oh I. Evaluation of purine-nucleoside degrading ability and in vivo uric acid lowering of Streptococcus thermophilus IDCC 2201, a novel antiuricemia strain. PLoS One 2024; 19:e0293378. [PMID: 38386624 PMCID: PMC10883578 DOI: 10.1371/journal.pone.0293378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 01/19/2024] [Indexed: 02/24/2024] Open
Abstract
This study evaluated 15 lactic acid bacteria with a focus on their ability to degrade inosine and hypo-xanthine-which are the intermediates in purine metabolism-for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, Lactiplantibacillus plantarum CR1 and Lactiplantibacillus pentosus GZ1 were found to have the highest nucleoside degrading rates, and they were therefore selected for further characterization. S. thermophilus IDCC 2201, which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected for further characterization. These three selected strains were examined in terms of their probiotic effect on lowering serum uric acid in a Sprague-Dawley (SD) rat model of potassium oxonate (PO)-induced hyperuricemia. Among these three strains, the level of serum uric acid was most reduced by S. thermophilus IDCC 2201 (p < 0.05). Further, analysis of the microbiome showed that administration of S. thermophlilus IDCC 2201 led to a significant difference in gut microbiota composition compared to that in the group administered with PO-induced hyperuricemia. Moreover, intestinal short-chain fatty acids (SCFAs) were found to be significantly increased. Altogether, the results of this work indicate that S. thermophilus IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and also restores intestinal flora and SCFAs, ultimately suggesting that S. thermophilus IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.
Collapse
Affiliation(s)
- Dayoung Kim
- Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong, Korea
| | - Jin Seok Moon
- Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong, Korea
| | - Ji Eun Kim
- Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong, Korea
| | - Ye-Ji Jang
- Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong, Korea
| | - Han Sol Choi
- Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong, Korea
| | - Ikhoon Oh
- Research Laboratories, ILDONG Pharmaceutical Co., Ltd., Hwaseong, Korea
| |
Collapse
|
|
13
|
Yang R, Ahmad S, Liu H, Xu Q, Yin C, Liu Y, Zhang H, Yan H. Biodegradation of Cholesterol by Enterococcus faecium YY01. Microorganisms 2023; 11:2979. [PMID: 38138122 PMCID: PMC10745435 DOI: 10.3390/microorganisms11122979] [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: 10/27/2023] [Revised: 12/08/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
Cholesterol (CHOL) is one of the risk factors causing the blockage of the arterial wall, atherosclerosis, coronary heart disease, and other serious cardiovascular diseases. Here, a promising bacterial strain for biodegrading CHOL was successfully isolated from the gut of healthy individuals and identified as Enterococcus faecium YY01 with an analysis of the 16S rDNA sequence. An initial CHOL of 1.0 g/L was reduced to 0.5 g/L in 5 days, and glucose and beef extract were found to be optimal carbon and nitrogen sources for the rapid growth of YY01, respectively. To gain further insight into the mechanisms underlying CHOL biodegradation, the draft genome of YY01 was sequenced using Illumina HiSeq. Choloylglycine hydrolase, acyltransferase, and alkyl sulfatase was encoded by gene0586, gene1890, and gene2442, which play crucial roles in converting 3α, 7α, 12α-trihydroxy-5β-choranic acid to choline-CoA and then choline-CoA to bile acid. Notably, choloylglycine hydrolase was closely related to the biosynthesis of both primary and secondary bile acid. The findings of this study provide valuable insights into the metabolism pathway of CHOL biodegradation by YY01 and offer a potential avenue for the development of bacterioactive drugs against hypercholesterolemia.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Hai Yan
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; (R.Y.); (S.A.); (H.L.); (Q.X.); (C.Y.); (Y.L.); (H.Z.)
| |
Collapse
|
|
14
|
Wang X, Yang S, Lu J, Xie G, Wu D. Screening and application of purine degrading Limosilactobacillus fermentum LF-1 from Huangjiu fermentation broth. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:7921-7931. [PMID: 37490358 DOI: 10.1002/jsfa.12881] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/02/2023] [Accepted: 07/25/2023] [Indexed: 07/27/2023]
Abstract
BACKGROUND As the important building blocks of nucleic acids, purines are alkaloids and responsible for hyperuricemia and gout. The purine content in Huangjiu is higher, and mainly exists in the form of free bases, which is easier to be absorbed by human body. However, the currently available reports on purine in Huangjiu mainly focus on detection methods and content survey. No studies on the regulation of the purine content in Huangjiu have been reported. RESULTS Eighty-four strains, with the degradation capacity of purine, were screened from the fermentation broth of Huangjiu. In detail, the isolated lactic acid bacteria (LAB) strain 75 # showed the strongest degradation ability of guanosine, inosine and four purines, which reduce their levels by 83.4% (guanosine), 97.4% (inosine), 95.1% (adenine), 95.0% (guanine), 94.9% (hypoxanthine) and 65.9% (xanthine), respectively. Subsequently, the LAB strain 75# was identified to be Limosilactobacillus fermentum by 16S rRNA gene sequencing, which was named as Limosilactobacillus fermentum LF-1 and applied to the fermentation of Huangjiu in the laboratory. Compared with the fermentation broth of Huangjiu without adding L. fermentum LF-1, the content of purine compounds in the fermentation broth inoculated with L. fermentum LF-1 was reduced by 64.7%. In addition, the fermented Huangjiu had richer flavor compounds, and the physicochemical indices were in accordance with the national standard of Chinese Huangjiu. CONCLUSION The screened strain L. fermentum LF-1 may be a promising probiotic for the development of a novel that can efficiently degrade purine in Huangjiu. © 2023 Society of Chemical Industry.
Collapse
Affiliation(s)
- Xianglin Wang
- The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
- National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, China
- School of Biotechnology, Jiangnan University, Wuxi, China
| | - Shaojie Yang
- The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
- National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, China
- School of Biotechnology, Jiangnan University, Wuxi, China
| | - Jian Lu
- The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
- National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, China
- School of Biotechnology, Jiangnan University, Wuxi, China
| | - Guangfa Xie
- Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, College of Biology and Environmental Engineering, Zhejiang Shuren University, Hangzhou, China
| | - Dianhui Wu
- The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
- National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, China
- School of Biotechnology, Jiangnan University, Wuxi, China
- Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, College of Biology and Environmental Engineering, Zhejiang Shuren University, Hangzhou, China
| |
Collapse
|
|
15
|
You Y, Zhao Y, Chen M, Pan Y, Luo Z. Effects of empagliflozin on serum uric acid level of patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr 2023; 15:202. [PMID: 37840144 PMCID: PMC10577917 DOI: 10.1186/s13098-023-01182-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 10/05/2023] [Indexed: 10/17/2023] Open
Abstract
BACKGROUND Serum uric acid levels are higher in patients with type 2 diabetes and prediabetes compared to healthy individuals, and hyperuricemia causes a significant rate of complications and mortality through heart and kidney diseases. Accordingly, the present systematic review and meta-analysis aimed to investigate the effect of empagliflozin on serum uric acid levels. MATERIALS AND METHODS Electronic databases, including PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were used to search papers until May 22, 2023. Data analysis was conducted by STATA Version 14, and P-value < 0.05 were considered statistically significant. RESULTS The results obtained from the combination of 12 studies with 7801 samples of diabetic patients indicated that in the empagliflozin group, the serum uric acid levels of the patients decreased ([standardized mean difference (SMD): - 1.97 (95%CI - 3.39, - 0.55)], Systolic blood pressure (SBP) [SMD: - 2.62 (95%CI - 3.87, - 1.37)] and diastolic blood pressure (DBP) [SMD: - 0.49 (95%CI - 0.68, - 0.29)]). On the other side, empagliflozin treatment did not affect the patients' HbA1c levels ([SMD: - 2.85 (95%CI - 6.14, 0.45)], eGFR [SMD: 0.78 (95%CI - 0.63, 2.18)], creatinine [SMD:0.11 (95%CI - 0.10, 0.31)], LDL [SMD: 0.14 (95%CI - 0.43, 0.71)], and HDL [SMD:1.38 (95%CI - 0.22, 2.99)]). Compared with the placebo, empagliflozin was more effective in reducing the uric acid levels ([SMD: - 1.34 (95%CI - 2.05, - 0.63)], SBP [SMD: - 2.11 (95%CI - 3.89, - 0.33)], and HbA1c [SMD: - 1.04 (95%CI - 1.95, - 0.13)]). Moreover, compared with sitagliptin also, empagliflozin was more effective in reducing uric acid levels ([SMD: - 1 (95%CI - 1.78, - 0.22)], and creatinine [SMD: - 1.60 (95%CI - 2.28, - 0.92)]) and increasing eGFR levels [SMD: 0.99 (95%CI: 0.37, 1.62)] of the patients. Compared with dapagliflozin also, empagliflozin caused a reduction in eGFR level [SMD: - 0.45 (95%CI - 0.82, - 0.08)]. CONCLUSION Empagliflozin treatment was effective in controlling diabetic patients' hyperuricemia and hypertension.
Collapse
Affiliation(s)
- Yinyuan You
- Department of Pharmacy, Baoan Central Hospital of Shenzhen, No.3, Xiyuan Street, Bao' an District, Shenzhen, Shenzhen, 518102, China
| | - Yu Zhao
- Department of Pharmacy, Baoan Central Hospital of Shenzhen, No.3, Xiyuan Street, Bao' an District, Shenzhen, Shenzhen, 518102, China
| | - Mujuan Chen
- Department of Pharmacy, Baoan Central Hospital of Shenzhen, No.3, Xiyuan Street, Bao' an District, Shenzhen, Shenzhen, 518102, China
| | - Ying Pan
- Department of Pharmacy, Baoan Central Hospital of Shenzhen, No.3, Xiyuan Street, Bao' an District, Shenzhen, Shenzhen, 518102, China
| | - Zhenhui Luo
- Department of Pharmacy, Baoan Central Hospital of Shenzhen, No.3, Xiyuan Street, Bao' an District, Shenzhen, Shenzhen, 518102, China.
| |
Collapse
|
|
16
|
Du X, Jiang Y, Sun Y, Cao X, Zhang Y, Xu Q, Yan H. Biodegradation of Inosine and Guanosine by Bacillus paranthracis YD01. Int J Mol Sci 2023; 24:14462. [PMID: 37833910 PMCID: PMC10573016 DOI: 10.3390/ijms241914462] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 09/01/2023] [Accepted: 09/06/2023] [Indexed: 10/15/2023] Open
Abstract
Both inosine and guanosine are precursors of uric acid that may cause the diseases of hyperuricemia and gout in humans. Here, a promising bacterial strain for efficiently biodegrading both inosine and guanosine was successfully isolated from a healthy human intestine and identified as Bacillus paranthracis YD01 with 16S rRNA analysis. An initial amount of 49.6 mg·L-1 of inosine or 49.9 mg·L-1 of guanosine was completely removed by YD01 within 12 h, which showed that YD01 had a strong ability to biodegrade inosine and guanosine. Furthermore, the initial amount of 49.2 mg·L-1 of inosine or 49.5 mg·L-1 of guanosine was totally catalyzed by the intracellular crude enzymes of YD01 within 6 h, and the initial inosine amount of 49.6 mg·L-1 or guanosine of 49.7 mg·L-1 was biodegraded by the extracellular crude enzymes of YD01 within 9 h. Illumina Hiseq sequencing and database gene annotation were used to elucidate the genomic characteristics of B. paranthracis YD01. Purine nucleoside phosphorylase, encoded by gene 1785, gene 3933, and gene 4403, was found in the KEEG database, which played a crucial role in the biodegradation of inosine and guanosine. The results of this study provide valuable insights into the mechanisms for biodegrading inosine and guanosine using B. paranthracis YD01.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Hai Yan
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; (X.D.)
| |
Collapse
|
|
17
|
Luo D, Yang BY, Qin K, Shi CY, Wei NS, Li H, Qin YX, Liu G, Qin XL, Chen SY, Guo XJ, Gan L, Xu RL, Dong BQ, Li J. Untargeted Metabolomics of Feces Reveals Diagnostic and Prognostic Biomarkers for Active Tuberculosis and Latent Tuberculosis Infection: Potential Application for Precise and Non-Invasive Identification. Infect Drug Resist 2023; 16:6121-6138. [PMID: 37719654 PMCID: PMC10505020 DOI: 10.2147/idr.s422363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 08/31/2023] [Indexed: 09/19/2023] Open
Abstract
Purpose Distinguishing latent tuberculosis infection (LTBI) from active tuberculosis (ATB) is important to control the prevalence of tuberculosis; however, there is currently no effective method. The aim of this study was to discover specific metabolites through fecal untargeted metabolomics to discriminate ATB, individuals with LTBI, and healthy controls (HC) and to probe the metabolic perturbation associated with the progression of tuberculosis. Patients and Methods Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to comprehensively detect compounds in fecal samples from HC, LTBI, and ATB patients. Differential metabolites between the two groups were screened, and their underlying biological functions were explored. Candidate metabolites were selected and enrolled in LASSO regression analysis to construct diagnostic signatures for discriminating between HC, LTBI, and ATB. A receiver operating characteristic (ROC) curve was applied to evaluate diagnostic value. A nomogram was constructed to predict the risk of progression of LTBI. Results A total of 35 metabolites were found to exist differentially in HC, LTBI, and ATB, and eight biomarkers were selected. Three diagnostic signatures based on the eight biomarkers were constructed to distinguish between HC, LTBI, and ATB, demonstrating excellent discrimination performance in ROC analysis. A nomogram was successfully constructed to evaluate the risk of progression of LTBI to ATB. Moreover, 3,4-dimethylbenzoic acid has been shown to distinguish ATB patients with different responses to etiological tests. Conclusion This study constructed diagnostic signatures based on fecal metabolic biomarkers that effectively discriminated HC, LTBI, and ATB, and established a predictive model to evaluate the risk of progression of LTBI to ATB. The results provide scientific evidence for establishing an accurate, sensitive, and noninvasive differential diagnosis scheme for tuberculosis.
Collapse
Affiliation(s)
- Dan Luo
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
- Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Bo-Yi Yang
- The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Kai Qin
- The Second Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Chong-Yu Shi
- The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Nian-Sa Wei
- The Second Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Hai Li
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Yi-Xiang Qin
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Gang Liu
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Xiao-Ling Qin
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Shi-Yi Chen
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Xiao-Jing Guo
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Li Gan
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Ruo-Lan Xu
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Bai-Qing Dong
- Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
| | - Jing Li
- Deparment of Physiology, School of Basic Medical Sciences of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| |
Collapse
|
|
18
|
Cao X, Cai J, Zhang Y, Liu C, Song M, Xu Q, Liu Y, Yan H. Biodegradation of Uric Acid by Bacillus paramycoides-YC02. Microorganisms 2023; 11:1989. [PMID: 37630550 PMCID: PMC10460076 DOI: 10.3390/microorganisms11081989] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 08/27/2023] Open
Abstract
High serum uric acid levels, known as hyperuricemia (HUA), are associated with an increased risk of developing gout, chronic kidney disease, cardiovascular disease, diabetes, and other metabolic syndromes. In this study, a promising bacterial strain capable of biodegrading uric acid (UA) was successfully isolated from Baijiu cellar mud using UA as the sole carbon and energy source. The bacterial strain was identified as Bacillus paramycoides-YC02 through 16S rDNA sequence analysis. Under optimal culture conditions at an initial pH of 7.0 and 38 °C, YC02 completely biodegraded an initial UA concentration of 500 mg/L within 48 h. Furthermore, cell-free extracts of YC02 were found to catalyze and remove UA. These results demonstrate the strong biodegradation ability of YC02 toward UA. To gain further insight into the mechanisms underlying UA biodegradation by YC02, the draft genome of YC02 was sequenced using Illumina HiSeq. Subsequent analysis revealed the presence of gene1779 and gene2008, which encode for riboflavin kinase, flavin mononucleotide adenylyl transferase, and flavin adenine dinucleotide (FAD)-dependent urate hydroxylase. This annotation was based on GO or the KEEG database. These enzymes play a crucial role in the metabolism pathway, converting vitamin B2 to FAD and subsequently converting UA to 5-hydroxyisourate (HIU) with the assistance of FAD. Notably, HIU undergoes a slow non-enzymatic breakdown into 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) and (S)-allantoin. The findings of this study provide valuable insights into the metabolism pathway of UA biodegradation by B. paramycoides-YC02 and offer a potential avenue for the development of bacterioactive drugs against HUA and gout.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Hai Yan
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; (X.C.); (J.C.)
| |
Collapse
|
|
19
|
Rodríguez JM, Garranzo M, Segura J, Orgaz B, Arroyo R, Alba C, Beltrán D, Fernández L. A randomized pilot trial assessing the reduction of gout episodes in hyperuricemic patients by oral administration of Ligilactobacillus salivarius CECT 30632, a strain with the ability to degrade purines. Front Microbiol 2023; 14:1111652. [PMID: 36865781 PMCID: PMC9971985 DOI: 10.3389/fmicb.2023.1111652] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/17/2023] [Indexed: 02/16/2023] Open
Abstract
Introduction Hyperuricemia and gout are receiving an increasing scientific and medical attention because of their relatively high prevalence and their association with relevant co-morbidities. Recently, it has been suggested that gout patients have an altered gut microbiota. The first objective of this study was to investigate the potential of some Ligilactobacillus salivarius strains to metabolize purine-related metabolites. The second objective was to evaluate the effect of administering a selected potential probiotic strain in individuals with a history of hyperuricemia. Methods Inosine, guanosine, hypoxanthine, guanine, xanthine, and uric acid were identified and quantified by high-performance liquid chromatography analysis. The uptake and biotransformation of these compounds by a selection of L. salivarius strains were assessed using bacterial whole cells and cell-free extracts, respectively. The efficacy of L. salivarius CECT 30632 to prevent gout was assessed in a pilot randomized controlled clinical trial involving 30 patients with hyperuricemia and a history of recurrent gout episodes. Half of the patients consumed L. salivarius CECT 30632 (9 log10 CFU/day; probiotic group; n = 15) for 6 months while the remaining patients consumed allopurinol (100-300 mg/daily; control group; n = 15) for the same period. The clinical evolution and medical treatment received by the participants were followed, as well as the changes in several blood biochemical parameters. Results L. salivarius CECT 30632 was the most efficient strain for inosine (100%), guanosine (100%) and uric acid (50%) conversion and, therefore, it was selected for the pilot clinical trial. In comparison with the control group, administration of L. salivarius CECT 30632 resulted in a significant reduction in the number of gout episodes and in the use of gout-related drugs as well as an improvement in some blood parameters related to oxidative stress, liver damage or metabolic syndrome. Conclusion Regular administration of L. salivarius CECT 30632 reduced serum urate levels, the number of gout episodes and the pharmacological therapy required to control both hyperuricemia and gout episodes in individuals with a history of hyperuricemia and suffering from repeated episodes of gout.
Collapse
Affiliation(s)
- Juan M. Rodríguez
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain,Juan M. Rodríguez, ✉
| | - Marco Garranzo
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain
| | - José Segura
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain
| | - Belén Orgaz
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain
| | - Rebeca Arroyo
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - Claudio Alba
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - David Beltrán
- Centro de Diagnóstico Médico, Ayuntamiento de Madrid, Madrid, Spain
| | - Leónides Fernández
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain,*Correspondence: Leónides Fernández, ✉
| |
Collapse
|
|
20
|
Eliseev MS, Kharlamova EN, Zhelyabina OV, Lila AM. Microbiota as a new pathogenetic factor in the development of chronic hyperuricemia and gout. Part 2: gout therapy and the gut microbiota. MODERN RHEUMATOLOGY JOURNAL 2022. [DOI: 10.14412/1996-7012-2022-6-7-11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The article presents current data on the effect of drugs for the treatment of gout on the composition and function of the intestinal microbiota. The potential possibilities of pre- and probiotics use for the prevention and complex therapy of gout are discussed, therapeutic effect may be associated with their impact on the uric acid synthesis and intestinal excretion, as well as with anti-inflammatory properties. The need for further research in this area is emphasized.
Collapse
Affiliation(s)
| | | | | | - A. M. Lila
- V.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
| |
Collapse
|
|
21
|
Tong S, Zhang P, Cheng Q, Chen M, Chen X, Wang Z, Lu X, Wu H. The role of gut microbiota in gout: Is gut microbiota a potential target for gout treatment. Front Cell Infect Microbiol 2022; 12:1051682. [PMID: 36506033 PMCID: PMC9730829 DOI: 10.3389/fcimb.2022.1051682] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 11/11/2022] [Indexed: 11/25/2022] Open
Abstract
Numerous studies have demonstrated that gut microbiota is essential for the host's health because it regulates the host's metabolism, endocrine, and immune systems. In recent years, increasing evidence has shown that gut microbiota plays a role in the onset and progression of gout. Changes in the composition and metabolism of the gut microbiota, result in abnormalities of uric acid degradation, increasing uric acid generation, releasing pro-inflammatory mediators, and intestinal barrier damage in developing gout. As a result, gout therapy that targets gut microbiota has drawn significant interest. This review summarized how the gut microbiota contributes to the pathophysiology of gout and how gout affects the gut microbiota. Additionally, this study explained how gut microbiota might serve as a unique index for the diagnosis of gout and how conventional gout treatment medicines interact with it. Finally, prospective therapeutic approaches focusing on gut microbiota for the prevention and treatment of gout were highlighted, which may represent a future avenue in gout treatment.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Xiaoyong Lu
- *Correspondence: Xiaoyong Lu, ; Huaxiang Wu,
| | - Huaxiang Wu
- *Correspondence: Xiaoyong Lu, ; Huaxiang Wu,
| |
Collapse
|
|
22
|
Zhu J, Li Y, Chen Z, Gao K, Lin G, Chen S, Li L, Ge H. Screening of lactic acid bacteria strains with urate-lowering effect from fermented dairy products. J Food Sci 2022; 87:5118-5127. [PMID: 36250495 DOI: 10.1111/1750-3841.16351] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/01/2022] [Accepted: 09/21/2022] [Indexed: 11/26/2022]
Abstract
Hyperuricemia is a well-known cause of gout and also a risk factor for various comorbidities. Current agents like xanthine oxidase inhibitors prevent hyperuricemia, but usually induce severe side effects. Alternative strategies, such as novel dietary supplementations, are necessary for the management of hyperuricemia. Lactic acid bacteria (LAB) have been used in human diet for a long time with a good safety record. In this study, 345 LAB strains isolated from traditional fermented dairy products were tested for assimilating abilities of guanosine. Two LAB strains, Lacticaseibacillus rhamnosus 1155 (LR1155) and Limosilactobacillus fermentum 2644 (LF2644), showing great capacities of guanosine transformation and degradation were selected. Compared to LR1155, LF2644 showed a better effect with 100.00% transforming rate and 55.10% degrading rate. In an in vivo test, a hyperuricemic rat model was established and the results showed that administration of LR1155 (p < 0.01) or LF2644 (p < 0.01) prevented the rise of serum uric acid with more than 20% decrease when compared with the hyperuricemia rats. In addition, an increased fecal uric acid level was observed in LF2644 or LR1155 treated rats (LR1155-M p < 0.05, others p < 0.01). This study proved that LR1155 and LF2644 can be promising candidates of dietary supplements for prevention or improvement of hyperuricemia. PRACTICAL APPLICATION: The LAB strains tested in this study could be considered as good potential probiotic candidates for dietary supplements because of their urate-lowering effects, which provide a novel antihyperuricemic strategy with advantages of safety and sustainability.
Collapse
Affiliation(s)
- Jun Zhu
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China
| | - Yanjun Li
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China.,College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, P.R. China
| | - Zuoguo Chen
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China
| | - Kan Gao
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China
| | - Guodong Lin
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China
| | - Su Chen
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China
| | - Li Li
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China
| | - Hongjuan Ge
- Research and Development Department, Hangzhou Wahaha Group Co., Ltd., Hangzhou, P.R. China.,Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, P.R. China
| |
Collapse
|
|
23
|
Li Y, Zhu J, Lin G, Gao K, Yu Y, Chen S, Chen L, Chen Z, Li L. Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats. Front Nutr 2022; 9:993951. [PMID: 36245501 PMCID: PMC9562091 DOI: 10.3389/fnut.2022.993951] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/06/2022] [Indexed: 11/26/2022] Open
Abstract
Hyperuricemia is the main cause of gout and involved in the occurrence of multiple diseases, such as hypertension, metabolic disorders and chronic kidney disease. Emerging evidence suggests that lactic acid bacteria (LAB) have shown the beneficial effects on the prevention or treatment of hyperuricemia. In this study, the urate-lowering effect of two LAB strains, Lacticaseibacillus rhamnosus 1155 (LR1155) and Limosilactobacillus fermentum 2644 (LF2644) on hyperuricemic rats were investigated. A hyperuricemic rat model was induced by the intragastric treatment of potassium oxonate, combined with a high purine diet. The oral administration of LR1155, LF2644, or a combination of LR1155 and LF2644 for 4 weeks significantly prevented the rise of the serum uric acid (UA) induced by hyperuricemia. LR1155 and LF2644 significantly elevated the fecal UA levels, increased the UA content and up-regulated gene expression of UA transporter, ATP-binding cassette subfamily G-2 (ABCG2), in colon and jejunum tissues, suggesting the accelerated UA excretion from the intestine. Besides, LR1155 significantly inhibited the activity of xanthine oxidase (XOD) in liver and serum, benefited the reduce of UA production. In addition, LF2644 strengthened the gut barrier functions through an up-regulation of the gene expressions for occluding and mucin2, accompanied with the reduced inflammatory indicators of lipopolysaccharide (LPS) and interleukin-1β (IL-1β) in hyperuricemic rat. Moreover, using 16s rDNA high-throughput sequencing of feces, LR1155 was shown to improve the hyperuricemia induced gut microbial dysbiosis. The genera Roseburia, Butyricicoccus, Prevotella, Oscillibacter, and Bifidobacterium may associate with the effect of LR1155 on microbiota in hyperuricemic rats. Collectively, the results indicated that LR1155 and LF2644 exhibit urate-lowering effects and could be used alone or in combination as a new adjuvant treatment for hyperuricemia.
Collapse
Affiliation(s)
- Yanjun Li
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| | - Jun Zhu
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
- *Correspondence: Jun Zhu,
| | - Guodong Lin
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| | - Kan Gao
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| | - Yunxia Yu
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| | - Su Chen
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| | - Lie Chen
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| | - Zuoguo Chen
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| | - Li Li
- Department of Research and Development, Hangzhou Wahaha Group Co., Ltd., Hangzhou, China
- Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou, China
| |
Collapse
|
|
24
|
Li J, Li J, Fan L. Recent Advances in Alleviating Hyperuricemia Through Dietary Sources: Bioactive Ingredients and Structure–activity Relationships. FOOD REVIEWS INTERNATIONAL 2022. [DOI: 10.1080/87559129.2022.2124414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Jun Li
- State Key laboratory of Food Science & Technology, Jiangnan University, Wuxi, Jiangsu, China
- Institute of Food Processing Technology, Guizhou Academy of Agricultural Sciences, Guiyang, China
| | - Jinwei Li
- State Key laboratory of Food Science & Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Liuping Fan
- State Key laboratory of Food Science & Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- Collaborat Innovat Ctr Food Safety & Qual Control, Jiangnan University, Wuxi, Jiangsu, China
| |
Collapse
|
|
25
|
Sun L, Ni C, Zhao J, Wang G, Chen W. Probiotics, bioactive compounds and dietary patterns for the effective management of hyperuricemia: a review. Crit Rev Food Sci Nutr 2022; 64:2016-2031. [PMID: 36073759 DOI: 10.1080/10408398.2022.2119934] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Hyperuricemia is closely linked with an increased risk of developing hypertension, diabetes, renal failure and other metabolic syndromes. Probiotics, bioactive compounds and dietary patterns are safe cost-efficient ways to control hyperuricemia, whereas comprehensive reviews of their anti-hyperuricemic mechanisms are limited. This review summarizes the roles of probiotics, bioactive compounds and dietary patterns in treating hyperuricemia and critically reviews the possible mechanisms by which these interventions exert their activities. The dietary patterns are closely related to the occurrence of hyperuricemia through the indirect action of gut microbiota or the direct effects of host purine metabolism. The Mediterranean and Dietary Approaches to Stop Hypertension diets help reduce serum uric acid concentrations and thus prevent hyperuricemia. Meanwhile, probiotics alleviate hyperuricemia by ways of absorbing purine, restoring gut microbiota dysbiosis and inhibiting xanthine oxidase (XO) activity. Bioactive compounds such as polyphenols, peptides and alkaloids exert various anti-hyperuricemic effects, by regulating urate transporters, blocking the active sites of XO and inhibiting the toll-like receptor 4/nuclear factor kappa B signaling pathway and NOD-, LRR- and pyrin domain-containing protein 3 signaling pathway. This review will assist people with hyperuricemia to adopt a healthy diet and contribute to the application of natural products with anti-hyperuricemic activity.
Collapse
Affiliation(s)
- Lei Sun
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Caixin Ni
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, Jiangsu, China
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, Jiangsu, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, China
| |
Collapse
|
|
26
|
Wang Z, Li Y, Liao W, Huang J, Liu Y, Li Z, Tang J. Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout. Front Cell Infect Microbiol 2022; 12:935723. [PMID: 36034697 PMCID: PMC9399429 DOI: 10.3389/fcimb.2022.935723] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
The incidence of hyperuricemia (HUA) and gout continuously increases and has become a major public health problem. The gut microbiota, which colonizes the human intestine, has a mutually beneficial and symbiotic relationship with the host and plays a vital role in the host's metabolism and immune regulation. Structural changes or imbalance in the gut microbiota could cause metabolic disorders and participate in the synthesis of purine-metabolizing enzymes and the release of inflammatory cytokines, which is closely related to the occurrence and development of the metabolic immune disease HUA and gout. The gut microbiota as an entry point to explore the pathogenesis of HUA and gout has become a new research hotspot. This review summarizes the characteristics of the gut microbiota in patients with HUA and gout. Meanwhile, the influence of different dietary structures on the gut microbiota, the effect of the gut microbiota on purine and uric acid metabolism, and the internal relationship between the gut microbiota and metabolic endotoxemia/inflammatory factors are explored. Moreover, the intervention effects of probiotics, prebiotics, and fecal microbial transplantation on HUA and gout are also systematically reviewed to provide a gut flora solution for the prevention and treatment of related diseases.
Collapse
Affiliation(s)
- Zhilei Wang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuchen Li
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wenhao Liao
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ju Huang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanping Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhiyong Li
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Jianyuan Tang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
27
|
Cao J, Liu Q, Hao H, Bu Y, Tian X, Wang T, Yi H. Lactobacillus paracasei X11 Ameliorates Hyperuricemia and Modulates Gut Microbiota in Mice. Front Immunol 2022; 13:940228. [PMID: 35874662 PMCID: PMC9296831 DOI: 10.3389/fimmu.2022.940228] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 06/08/2022] [Indexed: 11/17/2022] Open
Abstract
Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the potential effect of alleviating HUA. The purpose of this study was to screen probiotics with UA-lowering activity and explore the underlying mechanism. The UA-lowering activity of 20 lactic acid bacteria strains was investigated in vitro, and the effect of candidate probiotics on UA metabolism was evaluated using the HUA Balb/c mouse model. The results showed that Lactobacillus paracasei X11 had excellent UA-lowering activity in vitro, which could degrade nucleotides and nucleosides completely within 30 min, and the degradation rates of purine and trioxypurine could reach 83.25% and 80.42%, respectively. In addition, oral administration of L. paracasei X11 could reduce serum UA by 52.45% and inhibit renal proinflammatory cytokine IL-1β by 50.69%, regulating adenosine deaminase (ADA), xanthine oxidase (XOD), and transporter expression (GLUT9, NPT1, and URAT1) to a normal level. Moreover, it could restore the ratio of Bacteroidetes to Firmicutes (Bac/Firm ratio) and showed a positive effect on the recovery of the intestinal microbiota. These findings provided fundamental information about the UA-lowering properties of probiotics, which suggested that L. paracasei X11 had the potential to be developed as a novel probiotic strain to ameliorate HUA.
Collapse
Affiliation(s)
- Jiayuan Cao
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Qiqi Liu
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Haining Hao
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Yushan Bu
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Xiaoying Tian
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Ting Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Huaxi Yi
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| |
Collapse
|
|
28
|
Fang XY, Qi LW, Chen HF, Gao P, Zhang Q, Leng RX, Fan YG, Li BZ, Pan HF, Ye DQ. The Interaction Between Dietary Fructose and Gut Microbiota in Hyperuricemia and Gout. Front Nutr 2022; 9:890730. [PMID: 35811965 PMCID: PMC9257186 DOI: 10.3389/fnut.2022.890730] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 04/14/2022] [Indexed: 12/12/2022] Open
Abstract
With the worldwide epidemics of hyperuricemia and associated gout, the diseases with purine metabolic disorders have become a serious threat to human public health. Accumulating evidence has shown that they have been linked to increased consumption of fructose in humans, we hereby made a timely review on the roles of fructose intake and the gut microbiota in regulating purine metabolism, together with the potential mechanisms by which excessive fructose intake contributes to hyperuricemia and gout. To this end, we focus on the understanding of the interaction between a fructose-rich diet and the gut microbiota in hyperuricemia and gout to seek for safe, cheap, and side-effect-free clinical interventions. Furthermore, fructose intake recommendations for hyperuricemia and gout patients, as well as the variety of probiotics and prebiotics with uric acid-lowering effects targeting the intestinal tract are also summarized to provide reference and guidance for the further research.
Collapse
Affiliation(s)
- Xin-yu Fang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Liang-wei Qi
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Hai-feng Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Peng Gao
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Qin Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Rui-xue Leng
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Yin-guang Fan
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Bao-zhu Li
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Hai-feng Pan
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
| | - Dong-qing Ye
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui, Hefei, China
- *Correspondence: Dong-qing Ye
| |
Collapse
|
|
29
|
Yin H, Liu N, Chen J. The Role of the Intestine in the Development of Hyperuricemia. Front Immunol 2022; 13:845684. [PMID: 35281005 PMCID: PMC8907525 DOI: 10.3389/fimmu.2022.845684] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 01/31/2022] [Indexed: 12/30/2022] Open
Abstract
Gout is a common inflammatory arthritis caused by the deposition of sodium urate crystals in the joints. Hyperuricemia is the fundamental factor of gout. The onset of hyperuricemia is related to purine metabolism disorders or uric acid excretion disorders. Current studies have shown that the intestine is an important potential organ for the excretion of uric acid outside the kidneys. The excretion of uric acid of gut is mainly achieved through the action of uric acid transporters and the catabolism of intestinal flora, which plays an important role in the body’s uric acid balance. Here we reviewed the effects of intestinal uric acid transporters and intestinal flora on uric acid excretion, and provide new ideas for the treatment of hyperuricemia and gout.
Collapse
Affiliation(s)
- Hui Yin
- Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital, The First Hospital of Nanchang Medical College, Nanchang, China.,Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China
| | - Na Liu
- Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital, The First Hospital of Nanchang Medical College, Nanchang, China.,Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China
| | - Jie Chen
- Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital, The First Hospital of Nanchang Medical College, Nanchang, China.,Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China
| |
Collapse
|
|
30
|
Potential Probiotic Lacticaseibacillus paracasei MJM60396 Prevents Hyperuricemia in a Multiple Way by Absorbing Purine, Suppressing Xanthine Oxidase and Regulating Urate Excretion in Mice. Microorganisms 2022; 10:microorganisms10050851. [PMID: 35630296 PMCID: PMC9146106 DOI: 10.3390/microorganisms10050851] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/13/2022] [Accepted: 04/19/2022] [Indexed: 02/04/2023] Open
Abstract
Hyperuricemia is a metabolic disorder caused by increased uric acid (UA) synthesis or decreased UA excretion. Changes in eating habits have led to an increase in the consumption of purine-rich foods, which is closely related to hyperuricemia. Therefore, decreased purine absorption, increased UA excretion, and decreased UA synthesis are the main strategies to ameliorate hyperuricemia. This study aimed to screen the lactic acid bacteria (LAB) with purine degrading ability and examine the serum UA-lowering effect in a hyperuricemia mouse model. As a result, Lacticaseibacillus paracasei MJM60396 was selected from 22 LAB isolated from fermented foods for 100% assimilation of inosine and guanosine. MJM60396 showed probiotic characteristics and safety properties. In the animal study, the serum uric acid was significantly reduced to a normal level after oral administration of MJM60396 for 3 weeks. The amount of xanthine oxidase, which catalyzes the formation of uric acid, decreased by 81%, and the transporters for excretion of urate were upregulated. Histopathological analysis showed that the damaged glomerulus, Bowman’s capsule, and tubules of the kidney caused by hyperuricemia was relieved. In addition, the impaired intestinal barrier was recovered and the expression of tight junction proteins, ZO-1 and occludin, was increased. Analysis of the microbiome showed that the relative abundance of Muribaculaceae and Lachnospiraceae bacteria, which were related to the intestinal barrier integrity, was increased in the MJM60396 group. Therefore, these results demonstrated that L. paracasei MJM60396 can prevent hyperuricemia in multiple ways by absorbing purines, decreasing UA synthesis by suppressing xanthine oxidase, and increasing UA excretion by regulating urate transporters.
Collapse
|
|
31
|
Lee Y, Kim N, Werlinger P, Suh DA, Lee H, Cho JH, Cheng J. Probiotic Characterization of Lactobacillus brevis MJM60390 and In Vivo Assessment of Its Antihyperuricemic Activity. J Med Food 2022; 25:367-380. [PMID: 35438552 DOI: 10.1089/jmf.2021.k.0171] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Uric acid is the final product of purine metabolism in human. The increase of serum uric acid is tightly related to the incidence of hyperuricemia and gout. Also, it has been reported that the intake of purine-rich foods like meat and seafood is associated with an increased risk of gout. Therefore, the reduction of purine absorption is one of therapeutic approaches to prevent hyperuricemia and gout. Currently, probiotics are being studied for the management of hyperuricemia and gout. In this study, we aimed to investigate the effect of Lactobacillus brevis MJM60390 on hyperuricemia induced by a high-purine diet and potassium oxonate in a mouse model. L. brevis MJM60390 among 24 lactic acid bacteria isolated from fermented foods showed the highest ability to assimilate inosine and guanosine in vitro and typical probiotic characteristics, like the absence of bioamine production, D-lactate production, hemolytic activity, as well as tolerance to simulated orogastrointestinal conditions and adherence to Caco-2 cells. In an in vivo animal study, the uric acid level in serum was significantly reduced to a normal level after oral administration of L. brevis MJM60390 for 2 weeks. The activity of xanthine oxidase catalyzing the formation of uric acid was also inhibited by 30%. Interestingly, damage to the glomerulus, Bowman's capsule, and tubules in the hyperuricemia model were reversed by supplementation with this strain. Fecal microbiome analysis revealed that L. brevis MJM60390 supplementation enhanced the relative abundance of the Rikenellaceae family, which produces the short-chain fatty acid butyrate and helps to maintain good gut condition. Therefore, these results demonstrated that L. brevis MJM60390 can be a probiotic candidate to prevent hyperuricemia.
Collapse
Affiliation(s)
- Youjin Lee
- Graduate School of Interdisciplinary Program of Biomodulation, and Myongji University, Yongin-si, Gyeonggi-Do, Korea
| | - Neagawooridwimeu Kim
- Graduate School of Interdisciplinary Program of Biomodulation, and Myongji University, Yongin-si, Gyeonggi-Do, Korea
| | - Pia Werlinger
- Graduate School of Interdisciplinary Program of Biomodulation, and Myongji University, Yongin-si, Gyeonggi-Do, Korea
| | - Dong-A Suh
- Graduate School of Interdisciplinary Program of Biomodulation, and Myongji University, Yongin-si, Gyeonggi-Do, Korea
| | - Hanki Lee
- Graduate School of Interdisciplinary Program of Biomodulation, and Myongji University, Yongin-si, Gyeonggi-Do, Korea
| | - Joo-Hyung Cho
- Graduate School of Interdisciplinary Program of Biomodulation, and Myongji University, Yongin-si, Gyeonggi-Do, Korea
| | - Jinhua Cheng
- Graduate School of Interdisciplinary Program of Biomodulation, and Myongji University, Yongin-si, Gyeonggi-Do, Korea.,Myongji Bioefficacy Research Center, Myongji University, Yongin-si, Gyeonggi-Do, Korea
| |
Collapse
|
|
32
|
Zhao H, Lu Z, Lu Y. The potential of probiotics in the amelioration of hyperuricemia. Food Funct 2022; 13:2394-2414. [PMID: 35156670 DOI: 10.1039/d1fo03206b] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hyperuricemia is a common disease caused by metabolic disorders or the excessive intake of high-purine foods. Persistent hyperuricemia in extreme cases induces gout, and asymptomatic hyperuricemia is probably linked to other metabolic diseases, such as hypertension. The typical damage caused by asymptomatic hyperuricemia includes inflammation, oxidative stress and gut dysbiosis. Probiotics have broad potential applications as food additives, not as drug therapies, in the amelioration of hyperuricemia. In this review, we describe novel methods for potential hyperuricemia amelioration with probiotics. The pathways through which probiotics may ameliorate hyperuricemia are discussed, including the decrease in uric acid production through purine assimilation and XOD (xanthine oxidase) inhibition as well as enhanced excretion of uric acid production by promoting ABCG2 (ATP binding cassette subfamily G member 2) activity, respectively. Three possible probiotic-related therapeutic pathways for alleviating the syndrome of hyperuricemia are also summarized. The first mechanism is to alleviate the oxidation and inflammation induced by hyperuricemia through the inhibition of NLRP3 inflammasome, the second is to restore damaged intestinal epithelium barriers and prevent gut microbiota dysbiosis, and the third is to enhance the innate immune system by increasing the secretion of immunoglobulin A (sIgA) to resist the stimulus by hyperuricemia. We propose that future research should focus on superior strain resource isolation and insight into the cause-effect mechanisms of probiotics for hyperuricemia amelioration. The safety and effects of the application of probiotics in clinical use also need verification.
Collapse
Affiliation(s)
- Hongyuan Zhao
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China.
| | - Zhaoxin Lu
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China.
| | - Yingjian Lu
- College of Food Science & Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China.
| |
Collapse
|
|
33
|
Wu Y, Ye Z, Feng P, Li R, Chen X, Tian X, Han R, Kakade A, Liu P, Li X. Limosilactobacillus fermentum JL-3 isolated from "Jiangshui" ameliorates hyperuricemia by degrading uric acid. Gut Microbes 2022; 13:1-18. [PMID: 33764849 PMCID: PMC8007157 DOI: 10.1080/19490976.2021.1897211] [Citation(s) in RCA: 101] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Recent studies into the beneficial effects of fermented foods have shown that this class of foods are effective in managing hyperuricemia and gout. In this study, the uric acid (UA) degradation ability of Limosilactobacillus fermentum JL-3 strain, isolated from "Jiangshui" (a fermented Chinese food), was investigated. In vitro results showed that JL-3 strain exhibited high degradation capacity and selectivity toward UA. After oral administration to mice for 15 days, JL-3 colonization was continuously detected in the feces of mice. The UA level in urine of mice fed with JL-3 was similar with the control group mice. And the serum UA level of the former was significantly lower (31.3%) than in the control, further confirmed the UA-lowering effect of JL-3 strain. Limosilactobacillus fermentum JL-3 strain also restored some of the inflammatory markers and oxidative stress indicators (IL-1β, MDA, CRE, blood urea nitrogen) related to hyperuricemia, while the gut microbial diversity results showed that JL-3 could regulate gut microbiota dysbiosis caused by hyperuricemia. Therefore, the probiotic Limosilactobacillus fermentum JL-3 strain is effective in lowering UA levels in mice and could be used as a therapeutic adjunct agent in treating hyperuricemia.
Collapse
Affiliation(s)
- Ying Wu
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, China,Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Ze Ye
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, China
| | - Pengya Feng
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Rong Li
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, China,Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Xiao Chen
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Xiaozhu Tian
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, China,Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Rong Han
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Apurva Kakade
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Pu Liu
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China,CONTACT Xiangkai Li Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| | - Xiangkai Li
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, China,Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China
| |
Collapse
|
|
34
|
Liang M, Liu J, Chen W, He Y, Kahaer M, Li R, Tian T, Liu Y, Bai B, Cui Y, Yang S, Xiong W, Ma Y, Zhang B, Sun Y. Diagnostic model for predicting hyperuricemia based on alterations of the gut microbiome in individuals with different serum uric acid levels. Front Endocrinol (Lausanne) 2022; 13:925119. [PMID: 36237183 PMCID: PMC9553226 DOI: 10.3389/fendo.2022.925119] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 09/05/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND We aimed to assess the differences in the gut microbiome among participants with different uric acid levels (hyperuricemia [HUA] patients, low serum uric acid [LSU] patients, and controls with normal levels) and to develop a model to predict HUA based on microbial biomarkers. METHODS We sequenced the V3-V4 variable region of the 16S rDNA gene in 168 fecal samples from HUA patients (n=50), LSU patients (n=61), and controls (n=57). We then analyzed the differences in the gut microbiome between these groups. To identify gut microbial biomarkers, the 107 HUA patients and controls were randomly divided (2:1) into development and validation groups and 10-fold cross-validation of a random forest model was performed. We then established three diagnostic models: a clinical model, microbial biomarker model, and combined model. RESULTS The gut microbial α diversity, in terms of the Shannon and Simpson indices, was decreased in LSU and HUA patients compared to controls, but only the decreases in the HUA group were significant (P=0.0029 and P=0.013, respectively). The phylum Proteobacteria (P<0.001) and genus Bacteroides (P=0.02) were significantly increased in HUA patients compared to controls, while the genus Ruminococcaceae_Ruminococcus was decreased (P=0.02). Twelve microbial biomarkers were identified. The area under the curve (AUC) for these biomarkers in the development group was 84.9% (P<0.001). Notably, an AUC of 89.1% (P<0.001) was achieved by combining the microbial biomarkers and clinical factors. CONCLUSIONS The combined model is a reliable tool for predicting HUA and could be used to assist in the clinical evaluation of patients and prevention of HUA.
Collapse
Affiliation(s)
- Meiting Liang
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
- Department of Pathology, School of Basic Medical Sciences, XinJiang Second Medical College, Karamay, China
| | - Jingkun Liu
- Department of Oncology, The First Affiliated Hospital of XinJiang Medical University, Urumqi, China
| | - Wujin Chen
- Department of Morphological Center, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Yi He
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
- Department of Pathology, School of Basic Medical Sciences, XinJiang Second Medical College, Karamay, China
| | - Mayina Kahaer
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Rui Li
- Department of Human Parasitology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Tingting Tian
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Yezhou Liu
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Bing Bai
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Yuena Cui
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Shanshan Yang
- Department of Clinical Laboratory, Xinjiang Medical University Affiliated Fifth People’s Hospital, Urumqi, China
| | - Wenjuan Xiong
- Department of Clinical Laboratory, Xinjiang Medical University Affiliated Fifth People’s Hospital, Urumqi, China
| | - Yan Ma
- Department of Clinical Laboratory, Xinjiang Medical University Affiliated Second People’s Hospital, Urumqi, China
| | - Bei Zhang
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Yuping Sun
- Departent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
- Key Laboratory of Xinjiang Uygur Autonomous Region, Laboratory of Molecular Biology of Endemic Diseases, Urumqi, China
- *Correspondence: Yuping Sun,
| |
Collapse
|
|
35
|
Han J, Wang Z, Lu C, Zhou J, Li Y, Ming T, Zhang Z, Wang ZJ, Su X. The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation. Food Funct 2021; 12:9030-9042. [PMID: 34382991 DOI: 10.1039/d1fo01884a] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hyperuricaemia is a disease associated with elevated serum uric acid content, which has emerged rapidly in recent decades. The drugs used to treat clinical hyperuricaemia have side effects, and their safety is poor. However, anserine is a natural carnosine derivative that shows an anti-hyperuricaemic effect. A previous study demonstrated that anserine inhibits uric acid synthesis and promotes uric acid excretion, but there is no evidence regarding the effect of anserine from the perspective of the gut microbiota. In this study, the anti-hyperuricaemic and anti-inflammatory effects of anserine were explored in a diet-induced hyperuricaemic mouse model. Anserine alleviated hyperuricaemia and renal inflammation phenotypes, inhibited uric acid biosynthesis, promoted uric acid excretion, and inhibited NLRP3 inflammasome and TLR4/MyD88/NF-κB signalling pathway activation. The results showed that the anti-hyperuricaemic effect of anserine was dependent on the gut microbiota in the germ-free mice experiment. Furthermore, anserine treatment reversed gut microbiota dysbiosis, repaired the intestinal epithelial barrier and increased short-chain fatty acid production. Moreover, the anti-hyperuricaemic effect of anserine was transmissible by transplanting the faecal microbiota from anserine-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, we identified a new and safe prebiotic material to alleviate hyperuricaemia and provided ideas for the development of oligopeptides.
Collapse
Affiliation(s)
- Jiaojiao Han
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| | - Ziyan Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| | - Chenyang Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| | - Jun Zhou
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| | - Ye Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| | - Tinghong Ming
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| | - Zhen Zhang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| | - Zaijie Jim Wang
- Department of Biopharmaceutical Sciences, University of Illinois, Chicago, USA
| | - Xiurong Su
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. and School of Marine Science, Ningbo University, Ningbo, China
| |
Collapse
|
|
36
|
Ni C, Li X, Wang L, Li X, Zhao J, Zhang H, Wang G, Chen W. Lactic acid bacteria strains relieve hyperuricaemia by suppressing xanthine oxidase activity via a short-chain fatty acid-dependent mechanism. Food Funct 2021; 12:7054-7067. [PMID: 34152353 DOI: 10.1039/d1fo00198a] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Globally, the incidence of hyperuricaemia is steadily increasing. The evidence increasingly suggests an association between hyperuricaemia and the gut microbiota, which may enable the development of a novel therapeutic approach. We studied the effects of treatment with lactic acid bacteria (LAB) on hyperuricaemia and their potential underlying mechanisms. A mouse model of hyperuricaemia was generated by oral gavage with hypoxanthine and intraperitoneal injections of potassium oxonate for 2 weeks. The anti-hyperuricaemic activities of 10 LAB strains relative to allopurinol as a positive drug control were investigated in the mouse model. Lactobacillus rhamnosus R31, L. rhamnosus R28-1 and L. reuteri L20M3 effectively reduced the uric acid (UA) concentrations in serum and urine and the xanthine oxidase (XOD) activity levels in serum and hepatic tissue in mice with hyperuricaemia. These strains also reversed the elevated lipopolysaccharide (LPS) concentration, hepatic inflammation and slight renal injury associated with hyperuricaemia. A correlation analysis revealed that UA-reducing LAB strains promoted short-chain fatty acid (SCFA) production to suppress serum and hepatic XOD activity by increasing the abundances of SCFA production-related gut bacterial taxa. However, the UA-reducing effects of LAB strains might not be mediated by purine degradation. In summary, L. rhamnosus R31, L. rhamnosus R28-1 and L. reuteri L20M3 relieved hyperuricaemia in our mouse model by promoting SCFA production in a purine degradation-independent manner. Our findings suggest a novel therapeutic approach involving LAB strains for hyperuricaemia.
Collapse
Affiliation(s)
- Caixin Ni
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
| | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Screening and Evaluation of Purine-Nucleoside-Degrading Lactic Acid Bacteria Isolated from Winemaking Byproducts In Vitro and Their Uric Acid-Lowering Effects In Vivo. FERMENTATION-BASEL 2021. [DOI: 10.3390/fermentation7020074] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
In Taiwan, adult hyperuricemia affects as many as 1 in 4 males and 1 in 6 females, who are predominantly young adults aged 19–45. In this study, lactic acid bacteria (LAB) with acid tolerance, bile salt tolerance and high affinity to intestinal cells were extracted from the side products of alcohol fermentation (distillers’ grains). These bacteria were evaluated for their ability to lower uric acid levels. Qualitative identification and quantitative analysis were performed using high-performance liquid chromatography (HPLC) on the purine-degrading enzymes to select purine-decomposing LAB for animal testing. When the final concentration of purine compounds reached 0.1% and 1%, seven strains of LAB showed potential in degrading purine compounds. HPLC was used to analyze their purine-degrading abilities, and the three best performing LAB strains, (107) 8–16, (107) tau 1–3, and (107) 6–10 were screened for further animal testing with Wistar rats. By the third week, the results showed that strain (107) 6–10 could prevent formation and reduce the levels of blood urea nitrogen (BUN) in yeast extract/potassium oxonate-induced hyperuricemia. The multi-strain lactic acid bacteria (MLAB) performed best for uric acid reduction in the serum and down regulated BUN. Yeast extract/potassium oxonate-induced hyperuricemia had no impact on serum creatinine, while LAB did not affect the creatinine concentration. In summary, MLAB not only protects kidney function but is also effective in regulating uric acid concentration in the body. Hence, MLAB can be used as a functional food supplement that prevents or aids the treatment of hyperuricemia in a rodent model.
Collapse
|
|
38
|
Kuo YW, Hsieh SH, Chen JF, Liu CR, Chen CW, Huang YF, Ho HH. Lactobacillus reuteri TSR332 and Lactobacillus fermentum TSF331 stabilize serum uric acid levels and prevent hyperuricemia in rats. PeerJ 2021; 9:e11209. [PMID: 33986988 PMCID: PMC8101448 DOI: 10.7717/peerj.11209] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 03/13/2021] [Indexed: 01/13/2023] Open
Abstract
Background Uric acid (UA) is the end product of purine metabolism in the liver and is excreted by the kidneys. When purine metabolism is impaired, the serum UA level will be elevated (hyperuricemia) and eventually lead to gout. During evolution, humans and some primates have lost the gene encoding uricase, which is vital in UA metabolism. With the advances of human society, the prevalence of hyperuricemia has dramatically increased because of the refined food culture. Hyperuricemia can be controlled by drugs, such as allopurinol and probenecid. However, these drugs have no preventive effect and are associated with unpleasant side effects. An increasing number of probiotic strains, which are able to regulate host metabolism and prevent chronic diseases without harmful side effects, have been characterized. The identification of probiotic strains, which are able to exert beneficial effects on UA metabolism, will provide an alternative healthcare strategy for patients with hyperuricemia, especially for those who are allergic to anti-hyperuricemia drugs. Methods To elicit hyperuricemia, rats in the symptom control group (HP) were injected with potassium oxonate and fed a high-purine diet. Rats in the probiotic groups received the high-purine diet, oxonate injection, and supplements of probiotic strains TSR332, TSF331, or La322. Rats in the blank control group (C) received a standard diet (AIN-93G) and oxonate injection. Results Purine-utilizing strains of probiotics were screened using high-pressure liquid chromatography (HPLC) in vitro, and the lowering effect on serum UA levels was analyzed in hyperuricemia rats in vivo. We found that Lactobacillus reuteri strain TSR332 and Lactobacillus fermentum strain TSF331 displayed significantly strong assimilation of inosine (90%; p = 0.00003 and 59%; p = 0.00545, respectively) and guanosine (78%; p = 0.00012 and 51%; p = 0.00062, respectively) within 30 min in vitro. Further animal studies revealed that serum UA levels were significantly reduced by 60% (p = 0.00169) and 30% (p = 0.00912), respectively, in hyperuricemic rats treated with TSR332 and TSF331 for 8 days. Remarkably, TSR332 ameliorated the occurrence of hyperuricemia, and no evident side effects were observed. Overall, our study indicates that TSR332 and TSF331 are potential functional probiotic strains for controlling the development of hyperuricemia.
Collapse
Affiliation(s)
- Yi-Wei Kuo
- Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan
| | - Shih-Hung Hsieh
- Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan
| | - Jui-Fen Chen
- Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan
| | - Cheng-Ruei Liu
- Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan
| | - Ching-Wei Chen
- Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan
| | - Yu-Fen Huang
- Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan
| | - Hsieh-Hsun Ho
- Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan
| |
Collapse
|
|
39
|
James A, Ke H, Yao T, Wang Y. The Role of Probiotics in Purine Metabolism, Hyperuricemia and Gout: Mechanisms and Interventions. FOOD REVIEWS INTERNATIONAL 2021. [DOI: 10.1080/87559129.2021.1904412] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Armachius James
- Beijing Advanced Innovation Centre for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, China
- Rizhao HUAWEI Institute of Comprehensive Health Industries, Rizhao, China
| | - Hengming Ke
- Department of Biochemistry and Biophysics and Lineberger Comprehensive Centre, The University of North Carolina, Chapel Hill, USA
| | - Ting Yao
- Beijing Advanced Innovation Centre for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, China
- Rizhao HUAWEI Institute of Comprehensive Health Industries, Rizhao, China
| | - Yousheng Wang
- Beijing Advanced Innovation Centre for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, China
- Rizhao HUAWEI Institute of Comprehensive Health Industries, Rizhao, China
| |
Collapse
|
|
40
|
Wang J, Chen Y, Zhong H, Chen F, Regenstein J, Hu X, Cai L, Feng F. The gut microbiota as a target to control hyperuricemia pathogenesis: Potential mechanisms and therapeutic strategies. Crit Rev Food Sci Nutr 2021; 62:3979-3989. [PMID: 33480266 DOI: 10.1080/10408398.2021.1874287] [Citation(s) in RCA: 146] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Hyperuricemia (HUA) is a metabolic disorder caused by abnormal uric acid (UA) metabolism, which is a complex physiological process involving multiple organs (liver, kidney, and intestine). Although UA metabolism in the liver and kidneys has been elucidated, only a few studies have focused on the process in the intestine. With our growing knowledge of the effects of gut microorganisms on health, the gut microbiota has been identified as a new target for HUA treatment. In this review, the relationship between HUA and the gut microbiota is elucidated, and anti-hyperuricemia mechanisms targeting the intestine are discussed, such as the promotion of purine and UA catabolism by the gut microbiota, increases in UA excretion by the gut microbiota and its metabolites, regulation of UA absorption or secretion in the intestinal tract by certain transporters, and the intestinal inflammatory response to the gut microbiota. Additionally, probiotics (Bifidobacteria and Lactobacilli) and prebiotics (polyphenols, peptides, and phytochemicals) with UA-lowering effects targeting the intestinal tract are summarized, providing reference and guidance for further research.
Collapse
Affiliation(s)
- Jing Wang
- Ningbo Research Institute, Zhejiang University, Ningbo, China.,College of Biosystems Engineering and Food Science, Zhejiang University, Beijing, China
| | - Yong Chen
- College of Biosystems Engineering and Food Science, Zhejiang University, Beijing, China.,College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Hao Zhong
- Ningbo Research Institute, Zhejiang University, Ningbo, China.,College of Biosystems Engineering and Food Science, Zhejiang University, Beijing, China
| | - Fang Chen
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Joe Regenstein
- Department of Food Science, Cornell University, Ithaca, NY, USA
| | - Xiaosong Hu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Luyun Cai
- Ningbo Research Institute, Zhejiang University, Ningbo, China.,College of Biosystems Engineering and Food Science, Zhejiang University, Beijing, China
| | - Fengqin Feng
- Ningbo Research Institute, Zhejiang University, Ningbo, China.,College of Biosystems Engineering and Food Science, Zhejiang University, Beijing, China
| |
Collapse
|
|
41
|
Kondratiuk VE, Tarasenko OM, Karmazina OM, Taranchuk VV. Impact of the Synbiotics and Urate-Lowering Therapy on Gut Microbiota and Cytokine Profile in Patients with Chronic Gouty Arthritis. J Med Life 2021; 13:490-498. [PMID: 33456597 PMCID: PMC7803318 DOI: 10.25122/jml-2020-0065] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The main goal of our study is the impact evaluation of complex urate-lowering therapy with the synbiotic addition on fecal microbiota and cytokine profile in patients with primary gout. During our study, 130 men (mean age 55.5 ± 9.4 years) with gout (duration 7.7 ± 7.1 years) were examined. All patients were divided into two treatment groups. The main group (n = 68) was taking allopurinol at 300 mg per day dose and additionally a synbiotic. The comparison group (n = 62) received allopurinol monotherapy without synbiotic intake. The therapy duration was 3 months. Evaluation of therapy efficiency was marked by blood uric acid changes, cytokine levels, CRP and fecal microbiota condition. After treatment, stabilization of the gut microbiota parameters was observed, which was leading to normalization uricemia levels (40.3% vs. 21%, p <0.01) in the main group patients. Addition of synbiotic to allopurinol leads to a blood uric acid lowering (18.7% vs. 13.3%, p <0.01), CRP reduction (75% vs. 26.3%, p <0.01) as well as decrease of cytokines level: IL-1β, IL-6, IL-8, IL-10 and TNFα (all p <0.001). After a 3-month gout treatment, a group of patients who received complex therapy with synbiotic inclusion showed signs of disease remission characterized by inflammation activity reducing, fecal microbiota condition normalization and a more pronounced decrease in laboratory markers comparing to control group.
Collapse
|
|
42
|
Chadha J. In vitro effects of sub-inhibitory concentrations of amoxicillin on physiological responses and virulence determinants in a commensal strain of Escherichia coli. J Appl Microbiol 2021; 131:682-694. [PMID: 33387370 DOI: 10.1111/jam.14987] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 12/14/2020] [Accepted: 12/26/2020] [Indexed: 02/06/2023]
Abstract
AIMS The goal was to study the effects of sub-minimum inhibitory concentrations (sub-MICs) of amoxicillin (AMX) on various physiological responses and virulence determinants in a commensal strain of Escherichia coli. MATERIALS AND RESULTS The commensal strain was passaged under various sub-MICs of AMX and its effect on bacterial growth, motility, biofilm formation, expression of outer membrane proteins (OMPs) and cell adhesion was analysed. Bacterial growth was diminished at 1/2 and 1/4 MICs of AMX with significant reduction in growth rate. Using crystal violet (CV) assays and quantification of surface polysaccharides we observed strong biofilm formation, together with reduced swimming motility in E. coli at 1/2 MIC of AMX. Differential OMP expression upon AMX sub-MIC exposure coincided with enhanced cell adhesion to HT-29 cells in vitro. The results demonstrated that sub-MICs of AMX can stimulate unpredictable changes in commensal bacterial strains which can be a potent source for the propagation of antibiotic resistance. CONCLUSIONS The study reports that AMX at 1/2 MIC significantly compromised bacterial growth and swimming motility, alongside inducing biofilm formation. This was also accompanied by upregulation of a single OMP which subsequently increased cell adhesion capabilities in E. coli at 1/2 MIC, thereby enhancing its colonization and survival abilities within the gut microsphere. SIGNIFICANCE AND IMPACT OF THE STUDY For the first time, the effects of AMX sub-MICs on a commensal E. coli strain were described. The results corroborate on how antibiotics can act as stimulatory molecules and determine the pathogenicity of commensal bacteria in vivo that can disseminate resistance to other intestinal pathogens or microbes.
Collapse
Affiliation(s)
- J Chadha
- Department of Microbiology, University of Delhi South Campus, New Delhi, India
| |
Collapse
|
|
43
|
Fermented Feed Supplement Relieves Caecal Microbiota Dysbiosis and Kidney Injury Caused by High-Protein Diet in the Development of Gosling Gout. Animals (Basel) 2020; 10:ani10112139. [PMID: 33213092 PMCID: PMC7698594 DOI: 10.3390/ani10112139] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/02/2020] [Accepted: 11/04/2020] [Indexed: 12/13/2022] Open
Abstract
Firstly, forty-eight 1-day-old goslings were randomly allocated to four groups and were fed diets containing crude protein (CP) at different concentrations: 160, 180, 200, and 220 g/kg in Experiment One. We found a dose-dependent relationship between the dietary protein levels and morbidity of gosling gout. The concentration of serum uric acid (UA), creatinine (Cr), and urea nitrogen (UN), and the activity of xanthine oxidase in the 220CP groups were significantly higher than those in the low-protein diet groups. Beneficial microbes, including Akkermansia, Lactococcus, and Butyricicoccus were enriched in the ceca of healthy goslings, while the microbes Enterococcus, Enterobacteriaceae, and Bacteroides were enriched in those with gout. Then, we explored the effects of fermented feed on gosling gout caused by high-protein diets in Experiment Two. A total of 720 1-day-old goslings were randomly allotted to four experimental groups: CN (162.9 g/kg CP), CNF (167.5 g/kg CP, replacing 50 g/kg of the basal diet with fermented feed), HP (229.7 g/kg CP, a high-protein diet), and HPF (230.7 g/kg CP, replacing 50 g/kg of the high-protein diet with fermented feed). We found that the cumulative incidence of gout increased in the HP group compared with that in the control, but decreased in the HPF group compared to that in the HP group. Similarly, the concentration of serum UA in the HP group was higher than that in the CN group, but decreased in the HPF group. Meanwhile, compared with the HP group, using fermented feed in diets decreased the abundance of Enterococcus in the ceca of goslings, while increasing the abundance of Lactobacillus. These results suggest that appropriate dietary protein levels and the fermented feed supplement might relieve the kidney injury and gut microbiota dysbiosis caused by high-protein diets in the development of gosling gout.
Collapse
|
|
44
|
Comparison of northeast sauerkraut fermentation between single lactic acid bacteria strains and traditional fermentation. Food Res Int 2020; 137:109553. [DOI: 10.1016/j.foodres.2020.109553] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 07/10/2020] [Accepted: 07/11/2020] [Indexed: 12/18/2022]
|
|
45
|
Yamauchi T, Oi A, Kosakamoto H, Akuzawa-Tokita Y, Murakami T, Mori H, Miura M, Obata F. Gut Bacterial Species Distinctively Impact Host Purine Metabolites during Aging in Drosophila. iScience 2020; 23:101477. [PMID: 32916085 PMCID: PMC7520893 DOI: 10.1016/j.isci.2020.101477] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 07/16/2020] [Accepted: 08/17/2020] [Indexed: 12/13/2022] Open
Abstract
Gut microbiota impacts the host metabolome and affects its health span. How bacterial species in the gut influence age-dependent metabolic alteration has not been elucidated. Here we show in Drosophila melanogaster that allantoin, an end product of purine metabolism, is increased during aging in a microbiota-dependent manner. Allantoin levels are low in young flies but are commonly elevated upon lifespan-shortening dietary manipulations such as high-purine, high-sugar, or high-yeast feeding. Removing Acetobacter persici in the Drosophila microbiome attenuated age-dependent allantoin increase. Mono-association with A. persici, but not with Lactobacillus plantarum, increased allantoin in aged flies. A. persici increased allantoin via activation of innate immune signaling IMD pathway in the renal tubules. On the other hand, analysis of bacteria-conditioned diets revealed that L. plantarum can decrease allantoin by reducing purines in the diet. These data together demonstrate species-specific regulations of host purine levels by the gut microbiome.
Collapse
Affiliation(s)
- Toshitaka Yamauchi
- Department of Genetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Ayano Oi
- Department of Genetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Hina Kosakamoto
- Department of Genetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Yoriko Akuzawa-Tokita
- Department of Genetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Takumi Murakami
- Department of Informatics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
| | - Hiroshi Mori
- Department of Informatics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
| | - Masayuki Miura
- Department of Genetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Fumiaki Obata
- Department of Genetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| |
Collapse
|
|
46
|
Wu J, Wei Z, Cheng P, Qian C, Xu F, Yang Y, Wang A, Chen W, Sun Z, Lu Y. Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis. Am J Cancer Res 2020; 10:10665-10679. [PMID: 32929373 PMCID: PMC7482825 DOI: 10.7150/thno.43528] [Citation(s) in RCA: 250] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 08/14/2020] [Indexed: 12/21/2022] Open
Abstract
Background: Gut microbiota, which plays a crucial role in inflammatory bowel diseases (IBD), might have therapeutic benefits for ulcerative colitis or Crohn's disease. Targeting gut microbiota represents a new treatment strategy for IBD patients. Rhein is one of the main components of rhubarb and exhibits poor oral bioavailability but still exerts anti-inflammatory effects in some diseases. Therefore, we investigated the effect of rhein on colitis and studied its possible mechanisms. Methods: The chronic mouse colitis model was induced by four rounds of 2% dextran sulfate sodium (DSS) treatment. The mice were treated with 50 mg/kg and 100 mg/kg rhein daily, body weight, colon length, histological score, inflammatory cytokines in serum or intestine, and fecal lipocalin 2 concentration were determined. Th17 cell, Th1 cell and Th2 cell infiltration in the mesenteric lymph node were analyzed by flow cytometry. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 4.0. We also assessed intestinal barrier permeability and performed 16s rDNA sequencing. Lactobacillus sp. was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate the contribution of gut microbiota. Results: Rhein could significantly alleviate DSS-induced chronic colitis. Uric acid was identified as a crucial modulator of colitis and rhein treatment led to decreased uric acid levels. We determined that rhein changed purine metabolism indirectly, while the probiotic Lactobacillus was involved in the regulation of host metabolism. Uric acid resulted in a worsened intestinal barrier, which could be rescued by rhein. We further confirmed that rhein-treated gut microbiota was sufficient to relieve DSS-induced colitis by FMT. Conclusion: We showed that rhein could modulate gut microbiota, which indirectly changed purine metabolism in the intestine and subsequently alleviated colitis. Our study has identified a new approach to the clinical treatment of colitis.
Collapse
|
|
47
|
Xiao Y, Zhang C, Zeng X, Yuan Z. Microecological treatment of hyperuricemia using Lactobacillus from pickles. BMC Microbiol 2020; 20:195. [PMID: 32631233 PMCID: PMC7336419 DOI: 10.1186/s12866-020-01874-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 06/24/2020] [Indexed: 12/26/2022] Open
Abstract
Background Hyperuricemia is one of the important risk factors for gout, arteriosclerosis, cardiovascular and cerebrovascular disease. Lactobacillus has attracted much attention due to its role in the regulation of intestinal function and tumor resistance, but its ability to reduce uric acid is unclear. Pickles are a traditional fermented food rich in lactic acid bacteria (LAB). Results LAB strains were isolated from 18 pickles and their tolerance to acid bile salts, trypsin, pepsin were evaluated after screening by nucleoside degradation. 16S rDNA sequence analysis was used to identify LAB strains. Furthermore, we established rat model of hyperuricemia and demonstrated that Lactobacillus could alleviate hyperuricemia and reduce kidney injury. Conclusion This study suggests that microecological treatment with Lactobacillus represents a feasible option for patients with chronic hyperuricemia.
Collapse
Affiliation(s)
- Yuanxun Xiao
- Department of LiWan Hospital, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China
| | - Congxin Zhang
- Department of LiWan Hospital, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
| | - Xianli Zeng
- Department of LiWan Hospital, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China
| | - Zhichao Yuan
- Department of LiWan Hospital, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China
| |
Collapse
|
|
48
|
Morais AHA, Passos TS, Maciel BLL, da Silva-Maia JK. Can Probiotics and Diet Promote Beneficial Immune Modulation and Purine Control in Coronavirus Infection? Nutrients 2020; 12:E1737. [PMID: 32532069 PMCID: PMC7352643 DOI: 10.3390/nu12061737] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 05/30/2020] [Accepted: 06/05/2020] [Indexed: 02/07/2023] Open
Abstract
Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for this virus, it is emergingly urgent to find effective and validated methods to prevent and treat COVID-19 infection. In this context, alternatives related to nutritional therapy might help to control the infection. This narrative review proposes the importance and role of probiotics and diet as adjunct alternatives among the therapies available for the treatment of this new coronavirus. This review discusses the relationship between intestinal purine metabolism and the use of Lactobacillus gasseri and low-purine diets, particularly in individuals with hyperuricemia, as adjuvant nutritional therapies to improve the immune system and weaken viral replication, assisting in the treatment of COVID-19. These might be promising alternatives, in addition to many others that involve adequate intake of vitamins, minerals and bioactive compounds from food.
Collapse
Affiliation(s)
- Ana H. A. Morais
- Nutrition Postgraduate Program, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil; (B.L.L.M.); (J.K.d.S.-M.)
- Biochemistry Postgraduate Program, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil
- Department of Nutrition, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil;
| | - Thais S. Passos
- Department of Nutrition, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil;
| | - Bruna L. L. Maciel
- Nutrition Postgraduate Program, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil; (B.L.L.M.); (J.K.d.S.-M.)
- Department of Nutrition, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil;
| | - Juliana K. da Silva-Maia
- Nutrition Postgraduate Program, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil; (B.L.L.M.); (J.K.d.S.-M.)
- Department of Nutrition, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil;
| |
Collapse
|
|
49
|
Yang L, Chang B, Guo Y, Wu X, Liu L. The role of oxidative stress-mediated apoptosis in the pathogenesis of uric acid nephropathy. Ren Fail 2020; 41:616-622. [PMID: 31269852 PMCID: PMC6610514 DOI: 10.1080/0886022x.2019.1633350] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Objective: By copying the uric acid nephropathy rat model, the oxidative stress injury of mitochondria was caused in renal tubular epithelial cells and the relationship between the injury and the induction of cell apoptosis was identified. Methods: All rats were randomly divided into NC (normal control, NC) group, HUA (high uric acid, HUA) group and GSH (reductive glutathione, GSH) group. The values were quantitatively tested in the kidney tissues, including 24-h urinary protein quantity, serum creatinine, blood uric acid, the MDA (malondialdehyde, MDA) and SOD (superoxide dismutase, SOD) oxidative stress indicators. The expression of p53, Bax and caspase-9/-3 were detected by immunoblotting. TUNEL assays were used to detect the apoptosis of renal tubular epithelial cells. Result: In HUA and GSH groups, the 24-h urinary protein(24UTP), serum creatinine, and blood uric acid increased gradually with the increase of the replication cycle and the increase was significant compared to the NC group (p < .05). Compared to the NC group, MDA increased whereas SOD decreased. The expression of apoptotic proteins, such as p53, Bax, and caspase-9/-3 in the mitochondria was significantly different (p < .05). TUNEL assay revealed that the renal tubular epithelial cells in HUA group were largely apoptotic, whereas the GSH group improved significantly. Conclusion: Mitochondria incurred the substantial damage due to being in a state of oxidative stress, which was the primary cause of apoptosis in the renal tubule epithelial cells. GSH exhibited the effective resistance to the influence of oxidative stress and can restore the damage in the renal tubular epithelial cells.
Collapse
Affiliation(s)
- Lijuan Yang
- a Department of Physiology , Bengbu Medical College , Bengbu , People's Republic of China
| | - Baochao Chang
- b Department of Nephrology , The First Affiliated Hospital of Bengbu Medical College , Bengbu , People's Republic of China
| | - Yaling Guo
- b Department of Nephrology , The First Affiliated Hospital of Bengbu Medical College , Bengbu , People's Republic of China
| | - Xueping Wu
- b Department of Nephrology , The First Affiliated Hospital of Bengbu Medical College , Bengbu , People's Republic of China
| | - Lei Liu
- b Department of Nephrology , The First Affiliated Hospital of Bengbu Medical College , Bengbu , People's Republic of China
| |
Collapse
|
|
50
|
Effects of Alismatis Rhizoma and Rhizoma Smilacis Glabrae Decoction on Hyperuricemia in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:4541609. [PMID: 31511779 PMCID: PMC6714326 DOI: 10.1155/2019/4541609] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 07/28/2019] [Accepted: 08/01/2019] [Indexed: 11/18/2022]
Abstract
The combination of Alismatis Rhizoma (AR) and Rhizoma Smilacis Glabrae (RSG), as Chinese herb medicine, has been used for their uric acid-lowering effect. However, the effects and mechanism of the combination of the two medicines have not been fully reported. Therefore, to explore the effects of AR-RSG combination decoction on the treatment of chronic hyperuricemia (HUA) in rats as well as the underlying mechanisms, in this study, at the first stage, a long-term HUA rats model was established by gavage of oteracil potassium plus adenine; allopurinol was used as the positive control, and the uric acid-lowering effects of AR or RSG decoction alone with low and high dose were evaluated, respectively. Serum uric acid (UA) and xanthine oxidase (XOD) were determined mainly, and pathological analysis of the kidney and liver was carried out after sacrifice of the animals. And then, at the second stage, four dose groups of AR-RSG combination treatment were investigated in HUA rats. In addition to the indicators measured at the first stage, the expression of urate anion exchanger 1 (URAT1) in rat kidney was determined by immunohistochemistry. We discovered that the UA levels of the model group in both stages were significantly and steadily higher than those of control groups. AR and RSG alone or in combination possess ability to decrease serum UA level of HUA rats, with effects more marked in the combination groups. The uric acid-lowering mechanism of AR-RSG combination may be related to its inhibiting activity of XOD, improving kidney damage and downregulating the expression of URAT1 in kidney.
Collapse
|