Clinical Effect Of Moxibustion On Irritable Bowel Syndrome With Diarrhea And Its Effect Of Gut-Brain Axis

Objective1.To observe the clinical effect and safety of moxibustion in patients with irritable bowel syndrome with diarrhea(IBS-D);2.To observe the regulation effect of moxibustion on microbe and brain function of IBS-D patients,in order to provide a scientific basis for clinical moxibustion treatment of IBS,and also lay a foundation for further promotion and application of moxibustion prevention and treatment of IBS in the future.MethodPart I: Observation of clinical effects of moxibustion on IBS-D patients Seventy-four patients with IBS-D were randomized into a mild moxibustion group and a pseudo-mild moxibustion group.The mild moxibustion group applied a moxibustion on the 2.8cm diameter refined moxibustion moxibustion rack and 3-5cm away from the acupoint surface.The pseudo-mild moxibustion group used the same moxibustion frame to ignite and 8-10 cm away from the acupoint surface.The acupoints were Tianshu(double)and Zusanli(double)in both groups.Each acupoint is moxibustion for 30 minutes,once every other day,3 times a week,a total of 6 weeks of moxibustion.At the end of the course,follow-up was performed at 12 weeks,18 weeks,and 24 weeks.The clinical effects of the two groups were observed by using the apparent response(AR),IBS severity score(SSS),fecal trait score(BSS),IBS patient-specific quality of life(IBS-QOL)and hospital anxiety and depression scale(HADS).TCM symptom score observation was evaluated.Part II: Study on the regulation of moxibustion on the microbe of IBS-D patients1.Using 16 S r DNA sequencing technology to observe IBS-D patients and post-infectious Irritable bowel syndrome with diarrhea(PI-IBS-D)patients and Healthy Controls(HC)Structural characteristics of the gut microbe.2.To observe the effects of mild moxibustion and pseudo-mild moxibustion on thestructure and diversity of intestinal flora in patients with IBS-D.Part III: Study on the regulation of moxibustion on brain function in IBS-D patients1.Resting state functional magnetic resonance imaging(rs-f MRI)was used to observe the brain morphological structure(grey volume,cortical thickness)and resting state of IBS-D patients,PI-IBS-D patients and HC subjects.Brain functional activity[low frequency amplitude(ALFF)and difference in whole brain functional connectivity with the third subregion of the right insula(dorsal non-granular insula)as seed points];and further observation of significantly different brains in IBS-D patients Correlation between brain function connectivity values and intestinal flora structural parameters.2.To observe the effect of mild moxibustion and pseudo-mild moxibustion on the whole brain functional connectivity of IBS-D patients with the third subregion of the right insula(dorsal non-granular insula)as seed points.ResultPart I: Observation of clinical effects of moxibustion on IBS-D patients1.AR significant relief response: FAS and PPS ser showed that the total effective rate of the mild moxibustion group during the treatment and follow-up period was significantly higher than that of the pseudo-temperature and moxibustion group(P<0.05).2.SSS scores and its dimensions: Both FAS and PPS set showed a significant reduction in SSS total scores at the end of treatment and during follow-up between the mild moxibustion group and the pseudo-mild moxibustion group compared with baseline.(all P<0.001);The total score of SSS in the mild moxibustion group was significantly improved(P<0.05)compared with pseudo-mild moxibustion groups.Compared with baseline,the severity of abdominal pain,severity of abdominal distension,satisfaction with defecation habits,and daily life scores in the mild moxibustion group were significantly lower at the end of treatment and follow-up(both P<0.001).There was no significant difference in the FAS collection of the pseudo-mild moxibustion group.Sexual differences and PPS set scores were significantly lower(all P<0.05);comparison between groups,mild moxibustion group abdominal pain severity,abdominal pain days,abdominal distension severity,defecation habit satisfaction and daily life scores improved more significantly(both P<0.05).3.BSS Score: FAS and PPS set showed that compared with baseline,the BSSscores of the mild moxibustion group and the pseudo-mild moxibustion group were significantly lower(P< 0.001),the difference between the groups was not statistically significant;The 12-week BSS score of the mild moxibustion group was significantly lower than that after treatment(P<0.05),and the scores of the pseudo-mild moxibustion group were not significantly lower than those of the treatment group.The BSS scores of the mild moxibustion group were significantly improved(P<0.001).4.IBS-QOL Score and its dimensions: FAS set and PPS set showed that compared with baseline,the total IBS-QOL score,anxiety,behavioral disorder,and health anxiety scores in the mild moxibustion group decreased significantly(P<0.05),false Only the anxiety anxiety score was significantly decreased in the mild moxibustion group(P<0.05),and the difference between the groups was not statistically significant.5.HADS score: FAS and PPS set showed that compared with baseline,the HADS-a and HADS-d scores were significantly lower in the mild moxibustion group(P<0.05,P<0.001),and the treatment of the pseudo-mild moxibustion group ended.The difference was not statistically significant,and the difference between the groups was not statistically significant.6.TCM Symptom Scores: FAS and PPS showed that compared with baseline,the mild moxibustion group ended the treatment of abdominal pain,bloating,diarrhea frequency,post-expiratory pain reduction,bowel stagnation,poor food intake,poor waist and knees,The cold and total scores of the cold limbs were significantly decreased(P<0.05).The treatment of abdominal pain,frequency of diarrhea,pain reduction after diarrhea,fatigue,cold limbs and total scores were significantly decreased in the pseudo-mild moxibustion group(P<0.05),the abdominal pain in the mild moxibustion group was significantly lower(P<0.05),and there was no significant difference.Part II: Study on the regulation of moxibustion on the microbe of IBS-D patients1.Structural characteristics of microbe in IBS-D patients(1)Differences in the number of otu between the three groups: the number of intestinal microbes in the IBS-D patients and PI-IBS-D patients were lower than those in the HC subjects,and the number of intestinal microbes in the PI-IBS-D patients decreased the most..(2)Differences in species and abundance of the three groups of subjects: At the gate level,there were significant differences between Bacteroidetes,Firmicutes andFusobacteria(all P<0.05).There are significant differences in the levels of Clostridia,Gammaproteobacteria,Bacteroidia,Fusobacteriia,and Betaproteobacteria.P<0.05);significant in the order of Clostridiales,Enterobacteriales,Bacteroidales,Burkholderiales and Fusobacteriales Sexual differences(both P<0.05);in the family level,Veillonellaceae,Prevotellaceae,Lachnospiraceae,Enterobacteriaceae,and Clostridiaceae There are significant differences(both P<0.05);in the genus Blautia,Prevotella,Escherichia,Faecalibacterium,Veillonella,Lachnospira and There were significant differences in the genus Ruminococcus(both P<0.05);at the species level,Ruminococcus gnavus,Escherichia coli,Prevotella copri,and Bacillus phlei(There were significant differences between Faecalibacterium prausnitzii and Bacteroides ovatus(both P<0.05).(3)LEf Se analysis: Firmicutes and Bacteroidetes are the major species that distinguish the microbe between HC subjects and IBS-D patients and PI-IBS-D patients.2.The regulation of moxibustion on the microbe of IBS-D patients(1)Number of OTU: The number of OTU was basically unchanged before and after treatment in the mild moxibustion group,while the number of OTU in the pseudo-mild moxibustion group was significantly reduced.The comparison between the groups showed that the number of OTU in the mild moxibustion group increased,and the number of unique OTU in the pseudo-warm moxibustion group decreased.(2)Species and abundance analysis: The mild moxibustion group and the pseudo-mild moxibustion group have certain adjustment effects on the classification levels of the doors,classes,orders,families,genera and species.(3)LEf Se analysis: In mild moxibustion treatment and mild moxibustion group Streptococcaceae,Streptococcus,Fusobacteria,Fusobacteriia Fusobacteriales,Fusobacteria(Fusobacteriaceae),Clostridium and Bilophila are more enriched;the pseudo-mild moxibustion group is more enriched with Firmicutes,Clostridia and Clostridiales..Part III: Study on the regulation of moxibustion on brain function in IBS-D patients1.Differences in brain morphological structure(grey volume,cortical thickness)between IBS-D patients,PI-IBS-D patients and HC subjects(1)Differences in gray matter volume between the three groups: The main effect analysis showed that there were significant differences in the volume of bilateral inferior frontal gyrus,right occipital ventral midline and bilateral hippocampus in thethree groups(P<0.05).Post hoc effect analysis showed that IBS-D patients were characterized by bilateral frontal gyrus and increased volume of the right occipital region.(2)Differences in cortical thickness between the three groups: The primary effect analysis showed significant differences in the thickness of the bilateral inferior frontal gyrus,left isthmus,and bilateral occipital sinus in the three groups(P<0.05).Post hoc effect analysis showed that IBS-D patients were characterized by bilateral inferior frontal gyrus and increased thickness of the bilateral occipital ventral middle,characterized by a decrease in left vestibular thickness.2.Results of brain function activities(low frequency amplitude at rest)in IBS-D patients(1)Characteristics of resting brain function and correlation with disease status in three groups of subjects: gender and age were analyzed as covariates.The main effect analysis showed that the three groups of subjects had right basal ganglia,bilateral fusiform gyrus,right Lateral forearm,right island,lateral occipital lobes,left frontal gyrus,right temporal iliac crest,bilateral occipital ventral middle,right central anterior gyrus,left frontal gyrus,and bilateral thalamus The difference in alff values was statistically significant(both P<0.05).Post hoc effects analysis showed that IBS-D patients were characterized by a significant increase in the right basal ganglia,right frontal gyrus,right isthmus,and bilateral thalamic alff values,with bilateral occipital lateral and left frontal median,The alveolar value in the middle of the bilateral occipital lobes,the bilateral fusiform gyrus,the lateral occipital lobes,and the right iliac crest were significantly reduced.Correlation analysis showed that the alff value of the right insula was significantly negatively correlated with SSS score and HADS-a in IBS-D patients(P<0.05),and was significantly positively correlated with IBS-QOL score(P<0.05).(2)Differences in functional connectivity between whole brain and insula seed points: gender and age were analyzed as covariates.The main effect analysis showed that the three groups had bilateral upper frontal,right frontal gyrus,left temporal gyrus,Bilateral iliac crest,bilateral iliac crest,bilateral iliac crest,left fusiform gyrus,left hippocampus,bilateral apical lobes,bilateral anterior wedge,left central posterior,right island There were significant differences in functional connectivity between the gyrus,bilateral cingulate gyrus,the left occipital region,the left hippocampus,the left thalamus and the right basal ganglia(all P<0.05).The post hoc effect analysis showedthat the left iliac crest,the left inferior parietal lobe,the bilateral anterior wedge,the bilateral anterior wedge,the left central posterior gyrus,and the left thalamic functional connectivity were significantly reduced in IBS-D patients(P<0.05).(3)Correlation between characteristic brain regions and characteristic flora of IBS-D patients: There were significant correlations between species and abundance of 7genus levels of microbe and FC difference brain regions,respectively,Brouse(Blautia),Prevotella,Veillonella,Faecalibacterium,Fusobacterium,Lachnospira,and Escherichia Significant differences(all P<0.05).3.Effect of moxibustion on brain function connectivity in IBS-D patients(1)After the mild moxibustion treatment,the left side of the island,the right side of the island,the left temporal gyrus,the right temporal gyrus,the left lower lobule,the left hippocampus and the left anterior wedge anterior leaf functional connectivity value increased significantly(all P<0.05),the left central anterior gyrus,right frontal middle gyrus,bilateral central lobular lobe and left basal ganglia functional connectivity were significantly lower(both P<0.05);false mild moxibustion after treatment The functional connectivity of the superior sulcus and the left anterior wedge was significantly increased(both P<0.05),and the right thalamic functional connectivity was significantly decreased(P<0.05).(2)After mild moxibustion treatment,IBS-D patients with left cerebral dorsal non-granular area and right frontal gyrus,right frontal gyrus,right lower inferior gyrus,left central anterior gyrus,right inferior temporal gyrus,right sling The functional connectivity of the anterior gyrus,the superior lobule on the right side,the lateral occipital lobe and the bilateral basal ganglia were significantly decreased(P<0.05).The non-granular area of the dorsal left cerebral island of IBS-D patients after pseudo-mild moxibustion treatment The function value of the right inferior temporal gyrus was significantly lower(P<0.05).Conclusion1.Mild moxibustion therapy can significantly improve the disease severity,fecal trait score,anxiety and depression in IBS-D patients,and improve the quality of life of patients.It is a safe and effective treatment.2.IBS-D patients compared with PI-IBS-D patients and HC subjects microbe levels(phylum,class,orders,family,genus,species)composition and abundance are significant differences And the number of microbe OTU decreased significantly;mildmoxibustion has a certain adjustment effect on the structure and diversity of microbe in IBS-D patients.Mild moxibustion may achieve the clinical effect of treatment of IBS-D by optimizing the structure of the flora.3.IBS-D patients compared with PI-IBS-D patients and HC subjects have significant differences in brain area values;mild moxibustion may affect the brain island-sensory motor network and brain islands of IBS-D patients-default The model network resting state function is connected to achieve the clinical effect of treating IBS-D.