| Objective:Fibromyalgia（FM）is a complex disease characterized by chronic and extensive skeletal muscle pain.Its incidence is high and there is still no effective treatment in clinical practice,many patients’quality of life is seriously affected.And the pathogenesis of FM is still very unclear.The aim of this study was to explore whether ozonated water enema could improving the disorder gut microbiome of FM patients and relieve symptoms of patients with FM.Design:We performed a randomized,double-blind study of individuals with FM（n=72）,6 patients were excluded,the remaining 66 patients were randomly divided into O3group and control group,a total of 8 patients in the O3group were lost to follow-up,and3 patients in the control group were lost to follow-up.Finally,A total of 25 patients in the O3group and 30 patients in the control group were included.After enrollment,all previous fibromyalgia medications were discontinued and duloxetine 60mg/day was administered orally for 1 week for drug washout.All patients underwent painless colonoscopy was performed under Intravenous anesthesia after enrollment to exclude Intestinal diseases such as colonic tumors,multiple polyps,ulcers,tuberculosis,and inflammatory bowel disease.The O3group received first treatment was performed under colonoscopy,a total of 750ml of ozonated water was infused into the ileocecal region after enrollment.On the second day,the patients were given rectal perfusion of500ml of ozonated water,and once every other day,a total of 7 times of treatment,while the control group received deionized water enema with the same dose and frequency.All patients were instructed to continue taking duloxetine capsules orally,and the dose was adjusted according to symptoms.Before the treatment,gender,age,body mass index（BMI）,numerical rating scale（NRS）,widespread pain index（WPI）,Hamilton anxiety scale（HAMA）,Pittsburgh sleep quality（PSQI）scores and dose of duloxetine,were compared with those of the control group.After the treatment,patients’NRS,WPI,HAMA scores and dose of duloxetine were assessed at 1 week,1 month,3months and 6 months to evaluate the treatment effect,PSQI scores were only assessed at 1 month,3 months and 6 months after the treatment.The feces of O3group before and after treatment were compared with those of 25 healthy people from the physical examination center of Shanghai East Hospital for 16S r RNA analysis.All the patients were collected before enema therapy.Results:Before treatment,there were no significant differences in gender,age,BMI,NRS score,WPI score,HAMA score,PSQI score,duloxetine dosage between the control group and the O3group（p>0.05）.,which were comparable.After the ozonated enema,compared with the control group,the pain of the O3group was significantly relieved,except WPI score,the NRS,HAMA and PSQI score decreased to varying degrees at each follow-up time point（p<0.001）,WPI scores were also significantly reduced after 1 week and 1 month of treatment（p<0.05）,but there was no significant difference between the two groups at 3 months after treatment（p>0.05）and the dose of duloxetine was lower than that of the control group.The gut microbiome of FM was characterized with lower alpha-diversity and distinct overall microbial composition compared with healthy control（p<0.05）,and the dominant microbiome was also significantly different from that of the healthy control group（p<0.001）.However,after received ozone treatment,the gut microbiome of FM patients was significantly improved,and the difference in the composition of gut microbiome between FM patients and healthy controls was significantly reduced.The metabolic function of gut microbiome to pain-related neurotransmitters is significantly different in FM patients compare with the healthy control.In addition,these related microbiotas like Bacteroides,Bifidobacterium,Lactobacillus,etc.also showed significant changes.Conclusion:This study confirmed that the symptoms of pain,anxiety,sleep disorders,were effectively relieved after the treatment of FM patients with ozonated water enema,and the dose of duloxetine was significantly reduced.and gut microbiome disorder was also improved,and suggests the potential for improving gut microbiome disorder as therapeutic target to intervene FM. |
