At The Species Level

It has been recognized that disturbances of the normal gut microbiome participate in the pathogenesis and progression of diverse chronic diseases, such as obesity (16), diabetes (17), hypertension (18), and liver cirrhosis (19), and the effect of gut microbiota in HUA has been explored gradually in recent years. For example, the current known interactions between the gut microbiota and HUA include that certain microbiota can regulate the synthesis and catabolism of purine and uric acid (such as Escherichia coli and Lactobacillus), produce some SCFAs or change the number and distribution of uric acid transporter. All of those studies have shown a strong correlation between the gut microbiota and HUA. However, most of them are animal experiments and the microbiota sequencing method is 16S rRNA, specific alterations of the gut microbiota composition and function between HUA (especially in males with HUA and high levels of liver enzymes) in asymptomatic people for physical examination have been rarely reported.



In view of the fact that most patients with HUA are asymptomatic and the intestinal microecology can change correspondingly in other disease states, our study is the first to select asymptomatic people for physical examination as the research subjects to explore the gut microbiome disturbances in males with HUA and high levels of liver enzymes and choose whole-genome shotgun sequencing technology, which are the two highlights and advantages of this research. Our results elucidated that there may do exist some targeted biomarkers of the gut microbiota and have the potential to be used as non-invasive, safe, and easy diagnostic tools for HUA. The new targeted biomarkers could be applied as a supplement to the traditional HUA diagnostic method to some extent. In this study, we found that the level of SUA accompanied by WC, BMI, AST, ALT, GGT, Scr, and TG in the HUA group were significantly higher than that of the control group, while HDL was lower than the control group.



Besides, the levels of FPG, Glyco Care blood sugar formula pressure, TC, LDL, and inflammation indicators (WBC, PLT, NEUT, and NLR) were slightly, but not significantly, higher in the HUA group than in the healthy controls, TBIL and IBIL were of the opposite trend. Previous studies have confirmed that HUA is closely related to the occurrence of gout, metabolic syndrome, type 2 diabetes, hypertension, cardiovascular disease, chronic kidney disease, and so on, and it is an independent risk factor for the disease (20), which is consistent with our results. Numerous studies have shown that HUA is closely related to metabolic syndrome (obesity, hypertension, hyperlipidemia, insulin resistance), and the two factors are mutually causal and form a vicious circle (21-24). This comorbidity of chronic diseases suggests that there is a certain correlation between chronic diseases. Our results also suggest that HUA is associated with obesity and metabolism-related indicators, such as high levels of liver enzymes (5, 25), worse homeostasis in lipid and bilirubin Glyco Care Formulaglucose metabolism, and poorer kidney function.



Although the mean hepatic function was within the "current consensus normal reference range," it had been already at a high level. Study has verified that when ALT exceeds 26 U/L, the occurrence of liver fibrosis increased, and it is suitable to adjust the reference range of liver function (26). In short, HUA is a metabolic disease related to habits, customs, age, gender, and inherited factors, and HUA is also correlated with obesity, hypertension, diabetes, renal failure, dyslipidemia, and liver diseases (27-29). Of course, the specific mechanism needs further study. As for the gut microbiotas, we found that the gut bacterial diversity in HUA group was reduced significantly compared with that of healthy controls and the community of the microbiota was also of significant difference between the two groups. Just as Requena et al. 30) had mentioned the diversity of microbiota was closely associated with our health, the result of our study indicated that the gut microbiota may have altered significantly from a normal healthy status to the development of HUA.



Firmicutes and Actinobacteria increased significantly. At the species level, totally 51 species were of significant difference after removing the low occurrence rate and low abundance species. Among them, 37 species were enriched in the healthy controls and 14 species were enriched in the HUA group. This suggests that maybe it is these significantly different populations in abundance that cause the significant changes in the composition of gut microbiota HUA. 43FAA); Actinobacteria (Collinsella aerofaciens) increased. Interestingly, most of the gut microbiomes enriched in HUA group not only had significant positive correlations with the clinical characteristics, but also most of them are responsible for the production of SCFAs, while those microbiomes enriched in the healthy controls had highly negatively correlated with these clinical indexes. CENTFERM-PWY and PWY-6590) were enriched in the healthy controls. Importantly, both of the two pathways had significantly positive correlations with the above bacterials. 0.903 and 0.902 relatively) and had frequent correlations with clinical parameters, Roseburia hominis was the bacteria that most negatively correlated with clinical parameters and can produce large amounts of SCFAs, which play key protective roles against inflammation (39-41). As is known to all, Odoribacter splanchnicus is expressed in human intestine and its complete genome had been sequenced (42), and now it is recognized as a common butyric-acid producing bacterium, which has been reclassified from Bacteroides splanchnicus (34). In a recent study, Odoribacter splanchnicus together with Akkermansia muciniphila, has been associated with a healthy fasting serum lipid profile (43). The administration of prebiotics and the use of polyphenols have been stated as effective dietary strategies to modulate gut microbiota composition, which could induce the abundance of friendly bacteria, namely Akkermansia muciniphila, associated to health benefits in metabolic syndrome (44-46). Our study evidenced that HUA state may reduce or Glyco Care Formulaglucose metabolism inhibit the growth of those "beneficial" bacterial members.