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The incidence of hyperuricemia (HUA) and gout is increasing year by year, and it is showing a trend of younger age, which has become a major public health problem. intestinal flora colonizes the human intestine and has a mutually beneficial symbiotic relationship with the host, playing an important role in host immune regulation. Intestinal flora is involved in the synthesis of purine metabolic enzymes and the release of inflammatory cytokine . Its structural changes or imbalances can cause metabolic disorders, which are closely related to the occurrence and development of metabolic immune diseases. The study found that HUA and gout patients have an imbalance in intestinal microbial flora. Therefore, in-depth study of the relationship between intestinal microbiota and HUA and gout is expected to make it a target for the prevention and treatment of related diseases .Recently, Traditional Chinese Medicine Regulation of Metabolic Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Traditional Medicine, Sichuan Key Laboratory, , published its results in the journal Front CellIn affect Microbiol. (influence factor 6.073), reviewing the characteristics of intestinal flora in HUA and gout patients, and discussing the effects of intestinal flora on purine and uric acid metabolism, as well as the intervention effects of probiotics, prebiotic and fecal bacteria transplantation on HUA and gout, in order to provide new solutions for disease prevention and treatment. Intestinal microbiota characteristics of
HUA and gout patients
HUA patients in intestinal microbiota richness and diversity decreased, and the composition changed . Compared with the control group, probiotics such as Faebacterium, Bacillus and Bacteroidetein were significantly increased in asymptomatic HUA patients. The increase in these probiotics is considered a compensatory phenomenon.
There are also abnormalities in the richness and diversity of intestinal flora in patients with gout. The relative abundance of of the genus Presian, Clostridium and Bacteroidetein increased, while the relative abundance of Enterobacteriaceae and butyrate-producing bacteria decreased. At the same time, studies have shown that the pathogenic bacteria of conditional Bacteroidetes , ryrococcal, Clostridium erysipelas, anaerobic bacteria and other increase in gout patients. In addition, most clinical studies have ruled out the effects of underlying diseases and antibiotic treatment, and other factors, such as diet, smoking and alcohol consumption, are important factors in regulating intestinal flora. Intestinal flora
HUA and gout pathogenesis
The type changes, quantity imbalance, or localization metastasis of intestinal flora are all related to various diseases. The metabolites produced by it, such as short-chain fatty acid and amino acid metabolites, also further participate in various physiological activities of the host through various channels. The human body excretes UA mainly through the kidney and intestines. About 70% of UA is excreted through the kidneys, and most of the rest is excreted with feces or further catabolizes 2 through intestinal flora. Recent studies have shown that intestinal flora can affect the activity of purine metabolism , xanthine oxidase (XOD), xanthine dehydrogenase (XHD) and urease , and then change the production and excretion of UA (Figure 1).
Figure 1 Mechanism of action of intestinal flora on uric acid and purine metabolism
amino acid metabolism also plays an important role in the occurrence and development of HUA and gout. Studies have shown that Enterobacteriaceae is related to amino acid metabolism and environmental perception, which together leads to an increase in serum UA and C reactive protein levels in gout patients. lipopolysaccharide is a component of the cytoplasm of Gram-negative bacteria in the intestinal bacterial flora. Changes in the intestinal flora can increase intestinal permeability, leading to changes in lipopolysaccharides entering the circulatory system, thereby controlling metabolic endotoxinemia, inflammation and other related diseases.
The above discussion reveals the impact of intestinal flora on body metabolism. In addition, intestinal flora can also affect inflammatory response. Intestinal flora and its short-chain fatty acids produced play a key role in regulating the body's inflammatory response to monosodium urate (MSU) crystals.
Intestinal flora As a potential therapeutic target for HUA and gout
In the treatment of HUA and gout, the two most commonly used types of uric acid-lowering drugs in clinical practice are drugs that inhibit uric acid synthesis ( allopurinol and febulistat, etc.) and drugs that increase uric acid excretion ( benzylbromalon and probenecid , etc.), but these drugs may have adverse reactions such as gastrointestinal discomfort, diarrhea, and rash 2.HUA and gout are currently found to have a close connection with intestinal flora, which may bring new hope for the treatment of such patients. At present, through microecological treatment methods such as probiotics, prebiotics, and fecal bacteria transplantation, regulating the intestinal microecological balance, and thus preventing HUA and gout has become a hot topic in clinical research.
related studies have shown that yogurt taken Lactobacillus PA-3 can improve their UA levels in healthy people, HUA and gout patients. The study also found that the Lactobacillus campylobacter in probiotics has the ability to efficiently degrade purine nucleosides. chicory water extract is an excellent prebiotic. Research has found that chicory can improve intestinal microecology, and can reduce the lipopolysaccharide levels in the cecum contents and peripheral blood, while reducing UA levels. In addition, there is increasing evidence that transplantation of through fecal bacteria can cause significant changes in fecal microbial composition. Currently, in the treatment of chronic intestinal diseases, cirrhosis , fatty liver, obesity and other diseases, many studies have shown that fecal bacteria transplantation has good efficacy 2.
However, at the same time, many problems are still to be solved. On the one hand, other microorganisms are prone to breeding during microbial culture. Therefore, it is very important to ensure the safety of microorganisms and prevent the contamination of bacteria . Another problem is that the patient's condition needs to be considered, and accurate diagnosis and proper examination are very necessary.
Generally speaking, the application of intestinal microbiota in HUA and gout treatment is still in its infancy, and its effectiveness and safety of in vitro, in vivo and clinical trials need to be gradually verified before it can be widely used. Problems such as the complexity of intestinal flora, the lack of evidence-based medicine for new treatments, and the lack of clinical data need to be further analyzed and explored in future research.
Summary
Intestinal dysbiosis in gout patients is mainly manifested as a conditional increase in pathogenic bacteria and a decrease in bacteria that promotes the production of anti-inflammatory cytokines. Intestinal flora is involved in purine and uric acid metabolism. Imbalance in the intestinal flora can increase UA concentration, and long-term deposition of UA in the joint can cause gout. Intestinal dysbiosis may also lead to the development of gout by inducing the body to produce endotoxin , causing chronic inflammation or changing the metabolism of short-chain fatty acids. At present, some progress has been made in the relationship between intestinal microbiota and HUA and gout, which not only helps to elucidate the pathogenesis, but may also provide new directions for the diagnosis and treatment of such patients and provide new targets for the treatment of gout.
References:
.Wang Z, Li Y, Liao W, et al. Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout[J]. Front Cell Infect Microbiol. 2022 Aug 10;12:935723. doi: 10.3389/fcimb.2022.935723. PMID: 36034697; PMCID: PMC9399429.. Chen Rourou, Liu Yu. Research progress on the correlation between hyperuricemia and gout and intestinal flora[J]. Journal of Nanjing Medical University (Natural Science Edition), 2020, 40(10):1560-1564. DOI:10.7655/NYDXBNS20201031.
