Effect of regulating gut microbiota using probiotics on functional changes in the brain: protocol for a systematic review

INTRODUCTION: There is a growing number of randomised controlled trials (RCTs) that focus on functional changes in the brain detected by functional MRI (fMRI) and gut microbiota composition changes after using probiotics. However, the effect of probiotics on functional changes in the brain through gut microbiota remains controversial in existing RCTs. Furthermore, to our knowledge, there is no systematic review to evaluate the effect of probiotics on functional changes in the brain through gut microbiota. Therefore, we aim to summarise literatures evaluating the potential association between probiotics, gut microbiota and functional changes in the brain to elucidate whether probiotics influence gut microbiota and affect functional changes in the brain through gut microbiota. METHODS AND ANALYSIS: China National Knowledge Infrastructure, Wanfang Data, VIP Databases (the Chongqing VIP Chinese Science and Technology Periodical Database), SinoMed, PubMed, Web of Science, MEDLINE (The National Library of Medicine), EMBASE (Excerpt Medica Database), Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov will be searched until July 2019. The Grey Literature in Europe (OpenSIGLE) database and Google search engine will also be used. The reference lists of each included study will be reviewed to determine whether there are any further relevant studies. RCTs using probiotics compared with a placebo/control will be included. We will use risk of bias assessment and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of evidence. The results of the systematic review will be synthesised narratively in the domains of the three primary outcome measures: (1) Increased/decreased activity in brain regions or altered functional connectivity (FC) of brain detected by fMRI and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (2) Changes in composition and diversity of the gut microbiota and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (3) Increased/decreased activity in brain regions or altered FC of brain detected by fMRI and the changes in composition or diversity of the gut microbiota after administration of probiotics. ETHICS AND DISSEMINATION: The results will be disseminated through a peer-reviewed publication. As no private and confidential patient data will be included in the reporting, there are no ethical considerations associated with this protocol. PROSPERO REGISTRATION NUMBER: CRD42019145114.