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Limosilactobacillus fermentum JL-3 isolated from "Jiangshui" ameliorates hyperuricemia by degrading uric acid.

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.

SUBMITTER: Wu Y

PROVIDER: S-EPMC8007157 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundUric 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.MethodsTo 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.ResultsPurine-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.

Project description:MUC5B is the predominant glycoprotein in saliva and is instrumental in the establishment and maintenance of multi-species eubiotic biofilms in the oral cavity. Investigations of the aciduric Lactobacillaceae family, and its role in biofilms emphasizes the diversity across different genera of the proteolytic systems involved in the nutritional utilization of mucins. We have characterized a cysteine protease from Limosilactobacillus fermentum, MdpL (Mucin degrading protease from Limosilactobacillus) with a high protein backbone similarity with commensals that exploit mucins for attachment and nutrition. MdpL was shown to be associated with the bacterial cell surface, in close proximity to MUC5B, which was sequentially degraded into low molecular weight fragments. Mapping the substrate preference revealed multiple hydrolytic sites of proteins with a high O-glycan occurrence, although hydrolysis was not dependent on the presence of O-glycans. However, since proteolysis of immunoglobulins was absent, and general protease activity was low, a preference for glycoproteins similar to MUC5B in terms of glycosylation and structure is suggested. MdpL preferentially hydrolyzed C-terminally located hydrophobic residues in peptides larger than 20 amino acids, which hinted at a limited sequence preference. To secure proper enzyme folding and optimal conditions for activity, L. fermentum incorporates a complex system that establishes a reducing environment. The importance of overall reducing conditions was confirmed by the activity boosting effect of the added reducing agents L-cysteine and DTT. High activity was retained in low to neutral pH 5.5-7.0, but the enzyme was completely inhibited in the presence of Zn2+. Here we have characterized a highly conserved mucin degrading protease from L. fermentum. MdpL, that together with the recently discovered O-glycanase and O-glycoprotease enzyme groups, increases our understanding of mucin degradation and complex biofilm dynamics.

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Limosilactobacillus fermentum JL-3 isolated from "Jiangshui" ameliorates hyperuricemia by degrading uric acid.

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