The Association Between Small Intestinal Bacterial Overgrowth And Diarrhea-predominant Irritable Bowel Syndrome By Gut Microbiota And Its Treatment

Diarrhea-predominant irritable bowel syndrome(IBS-D),the major subtype of IBS,is one of the most common functional gastrointestinal diseases.The Clinical features of IBS-D include abdominal pain,diarrhea,abdominal distension or bloating.IBS-D is often accompanied by anxiety,depression,fibromyalgia,migraine and interstitial cystitis,which causes great psychological burden to patients,affects seriously patients' quality of life and wasts medical resources.The exact etiology and pathogenesis are still unclear,which may include changes in intestinal motility,visceral sensitivity,immunity,dysfunction of brain-gut axis,epithelial barrier and intestinal microbiota were also found to be related with IBS-D.Recently,with the in-depth research on human intestinal microbiota,numerous studies have found that intestinal microbiota may be an important cause of IBS-D,and the disruption of intestinal microbiota is closely related to initiation and development of IBS-D.Small intestinal bacterial overgrowth(SIBO)is a pathological phenomenon with intestinal microbiota imbalance,characterized by abnormal types and high abundance of intestinal microbiota in the small intestine,resulting in abdominal discomfort,diarrhea,bloating and weight loss and other symptoms.Thus,there were similarities between SIBO and IBS-D in pathogenesis and manifestations.In addition,the prevalence of SIBO in IBS-D patients was significantly higher than that in healthy population,suggesting that SIBO may be related to IBS-D.Therefore,this study focused on the correlation,the role of intestinal microbiota between SIBO and IBS-D and the efficacy of fecal bacterial transplantation in IBS-D with SIBO patients.Firstly,a Meta-analysis was set to investigate the correlation between three subtypes of IBS and SIBO.Next,we recruited IBS-D patients to compare the prevalence of SIBO between IBS-D patients and healthy population.Meanwhile,we further analyzed the difference of symptoms and intestinal microbiota between SIBO positive and SIBO negative IBS-D patients.Finally,IBS-D patients with SIBO was treated by our patented “Enterobacteria capsules”(Invention patent number: ZL.2015 1 0304041.4)to investigate the efficacy and safety of “Enterobacteria capsules”.Therefore,it will provide new clinical evidence and help to develop novel treatment for IBS-D patients with SIBO.Material and Methods:1.Meta-analysis of the correlation between irritable bowel syndrome and small intestinal bacterial overgrowthIn this section,10 case-control studies were included,in which IBS patients as subjects and healthy people as controls.We investigated the prevalence of SIBO in IBS patients and healthy people by Meta-analysis,and found the positive correlation between IBS-D and SIBO.2.Whether small intestinal bacterial overgrowth is associated with diarrhea-predominant irritable bowel syndromeIn this part,60 pairs of IBS-D patients and healthy controls were recruited in Daping hospital,Army Military Medical University.All subjects underwent a lactose breath test(LBT)to diagnose the SIBO.IBS-D patients were divided into the positive SIBO group and negative SIBO group.Symptoms were evaluated through clinical questionnaires.Furthermore,the differences of fecal microbiota between two subgroups were detected using 16 S rRNA sequencing.3.The evaluation of efficacy and safety of fecal bacteria transplantation(FMT)in treating IBS-D patients with SIBO.In this study,50 IBS-D with SIBO patients were selected and randomly divided into two groups.A randomized double-blind placebo control trial was used to observe the relief of symptom,SIBO cure rate and changes of intestinal microbiota for 12 weeks.Results:1.Meta-analysis of the correlation between irritable bowel syndrome and small intestinal bacterial overgrowth1.1 There were 10 case-control studies in this Meta-analysis,which included 1033 IBS patients and 656 healthy people.The study participants were from China,India,Iran,South Korea,Italy and the United States.1.2 The Meta-analysis results showed that the prevalence of SIBO in IBS population was significantly higher than that in healthy population(38.8% VS 21.5%,P < 0.05),which was not affected by the diagnostic criteria of IBS,IBS subtypes,SIBO detection method and geographical location.1.3 The prevalence of SIBO was 36.5% in IBS-D patients and 26.9% in other IBS subtypes patients.The prevalence of SIBO in IBS-D patients was higher than that in other IBS subtypes patients(P < 0.05),suggesting that IBS-D may be a risk factor for SIBO.2.Small intestinal bacterial overgrowth is associated with diarrhea-predominant irritable bowel syndrome by increasing mainly Prevotella abundance2.1 SIBO prevalence was significantly higher in IBS-D patients than in healthy people;2.2 IBS-D with SIBO patients had more severe symptoms than IBS-D without SIBO patients;2.3 There were significantly different intestinal microbiota between IBS-D with SIBO and IBS-D without SIBO patients,mainly in the composition of intestinal microbiota and the abundance of Prevotella,which may play an important role between IBS-D and SIBO.3.Efficacy and safety of “enterobacteria capsules” in treating IBS-D with SIBO patients.3.1 Compared with the placebo group,“Enterobacteria capsule” significantly alleviated the symptoms,improved their quality of life,reduced anxiety and depression,and improved cure rate of SIBO in IBS-D with SIBO patients.3.2 After the treatment in the “Enterobacteria capsules” group,the Shannon index and Simpson index of the patients' intestinal microbiota gradually approached to the donor,and the Prevotella abundance of the patients were significantly reduced and approached to the donor.By further comparing the changes of intestinal microbiota of "effective" and "ineffective",it can be seen that "effective" has obvious changes of intestinal microbiota,which is similar to diversity and microbiota abundance of the donor,while "ineffective" has no obvious changes of intestinal microbiota.3.3“Enterobacteria capsules” is a safe and effective treatment of IBS-D patients with SIBO,accompanied with fewer adverse reactions.Conclusion:1.The prevalence of SIBO in IBS patients(three subtypes)was higher than that in healthy control groups,and IBS-D might be a risk factor for SIBO,suggesting that IBS-D was associated with SIBO.2.Our case-control study also showed that IBS-D was associated with SIBO,which might be associated with the composition of intestinal microbiota and the abundance of Prevotella.3.The results of our randomized controlled trial showed that “Enterobacteria capsules” could restore diversity,composition of intestinal microbiota and abundance of Prevotella to reconstruct the homeostasis of intestinal microbiota and improve the symptoms,such as abdominal pain,diarrhea and abdominal distention.In summary,our Meta-analysis showed the prevalence of SIBO in IBS-D patients was higher than healthy people.Secondly,we compared the symptoms and intestinal microbiota between SIBO positive and SIBO negative in IBS-D patients,the results indicated that intestinal microbiota played an important role between SIBO and IBS-D.Finally,IBS-D with SIBO patients was treated by FMT to restore homeostasis of intestinal microbiota through randomized controlled trials.This study provided a direction for further study on the mechanism of the correlation between IBS-D and SIBO and a new method for clinical treatment of IBS-D with SIBO patients.There were still some limitations in this study.Firstly,the sample size of case-control study and randomized controlled study is small,which may not represent the broad population of patients.Secondly,although our study found that intestinal microbiota played an important role between IBS-D and SIBO,the definite mechanism needs to be further studied.Finally,clinical effect of "enterobacteria capsule" FMT(84% effective,16% ineffective)may be related to the individual characteristics of patients,but the precise reasons and mechanisms need to be further studied.