Effects Of Compound Probiotics On Adjuvant Treatment Of Gout And Its Potential Mechanism

Gout is a metabolic disease caused by disorders of uric acid(UA)metabolism.Modern lifestyles and dietary habits have increased the incidence of gout.In the clinical treatment of gout,UA-lowering is considered as the primary goal.UA is in dynamic balance in the body,with close to 1/3 of UA excreted by intestine,and gut microbiota plays an important role.However,defects urease in human makes the incidence of human gout much higher than that of the model animals such as rats,so it is necessary to investigate the UA-lowering effect of probiotics based on clinical trials.In this study,160 patients with gout and 20 healthy controls(HCs)were recruited,feces of 20 patients and HCs were sequenced to characterize the gut microbiota of gout,then 160 gout patients were randomly divided into probiotic group(n = 120)and placebo(n = 40)to investigate the effect of probiotic co-administrated with febuxostat in the treatment of gout during 2-month intervention.At 0M and 2M,serum and feces were collected,serum samples were tested for UA and other indicators,feces were tested for metagenome and metabolism,disease-related questionnaires were also collected.Main results were as follow:(1)Based on fecal metagenomic data from NCBI,optimal integration of bins was established to obtain more high-quality MAGs,which provides a better method for mechanistic resolution of UA reduction by probiotics.(2)Compared with HCs,gut microbiota of gout showed severely dysbiosis,microbial diversity significant decrease,characterized by decreased SCFAs-producing bacteria such as Faecalibacterium prausnitzii,Eubacterium rectale and Lachnospira eligens,and Prevotella copri clade＿A and Collinsella aerofaciens were significantly increased.Purine metabolism,amino acid metabolism and glycolytic pathways were significantly altered,and several species in Bifidobacterium,and Lactobacillus were involved in the processes.(3)Compared with placebo group,the Probio-X significantly reduced UA level and incidence of acute gout in patients,increased achievement rate of treatment(P < 0.05).Patients in the probiotic group were divided into Pro A group(<360 μmol/L at 2M)and Pro B group(>360 μmol/L at 2M).Improvements in the level of UA,Cr and TG and GIS scores have been found in Pro A group,but not in Pro B group,suggesting that coadministration of probiotic complexes provide additional benefits,but the effects vary individually.(4)Probiotic significantly modulated gut microbial structure of gout,including increased the abundance of beneficial bacteria such as Bifidobacterium animalis,Lacticasribacillus paracasei and F.prausnitzii,inhibited disease-related bacteria and regulated the correlation network of bacteria,reduced genic abundance related to UA production and metabolic pathways of amino acid and mucin degradation,which suggested Probio-X decreased UA level by adjusting gut microbiota and their pathways.(5)The metabolites in the placebo and Pro B group were similar,but were disparate from Pro A group.Overall,hypoxanthine,xanthine,and vitamins were significant higher in Pro A group,while bile acids were significantly lower,which were associated with UA,inflammation,and oxidative stress.Meanwhile,serum hypoxanthine was significantly increased and IL-1β and XOD were significantly decreased in Pro A group,indicating that Probio-X reduced UA level and suppress inflammation by inhibiting the activity of XOD and regulating the levels of key metabolites such as gut bile acids.(6)Based on random forest model,12 SGBs were found to be significantly different in the gut of patients in Pro A and Pro B groups at baseline,which differentiated the response to probiotics accurately.There were more SCFA-producing bacteria in Pro A group and more potentially pathogenic bacteria in Pro B group,suggesting the composition of the gut microbiota in baseline influenced the effect of probiotics on health.In conclusion,this study developed a metagenome binning method to reveal the characteristics of the gut microbiota in gout as for gut microbial diversity and function.As well as combined with the gut metabolome to analyze the potential mechanism of Probio-X adjust treatment on gout.It not only provides new ideas for the clinical treatment of gout,but also provides new probiotic strains and new directions for the development of precise probiotics for gout microecological therapy.