Gut microbiome-related effects of berberine and

ARTICLEGutmicrobiome-relatedeffectsofberberineandprobioticsontype2diabetes(thePREMOTEstudy)YifeiZhang1,19,YanyunGu1,19,HuahuiRen2,19,ShujieWang1,19,HuanziZhong2,19,XinjieZhao3,JingMa4,XuejiangGu5,YaomingXue6,ShanHuang7,JialinYang8,LiChen9,GangChen10,ShenQu11,JunLiang12,LiQin13,QinHuang14,YongdePeng15,QiLi3,XiaolinWang3,PingKong2,GuixueHou2,MengyuGao2,ZhunShi2,XuelinLi1,YixuanQiu1,YuanqiangZou2,HuanmingYang2,16,JianWang2,16,GuowangXu3,ShenghanLai17,JunhuaLi2,18✉,GuangNing1&WeiqingWang1✉Humangutmicrobiomeisapromisingtargetformanagingtype2diabetes(T2D).Measuresalteringgutmicrobiotalikeoralintakeofprobioticsorberberine(BBR),abacteriostaticagent,meritmetabolichomoeostasis.Wehenceconductedarandomized,double-blind,placebo-controlledtrialwithnewlydiagnosedT2Dpatientsfrom20centresinChina.Four-hundred-nineeligibleparticipantswereenroled,randomlyassigned(1:1:1:1)andcompleteda12-weektreatmentofeitherBBR-alone,probiotics+BBR,probiotics-alone,orplacebo,afteraone-weekrun-inofgentamycinpretreatment.Thechangesinglycatedhaemoglobin,astheprimaryoutcome,intheprobiotics+BBR(least-squaresmean[95%CI],−1.04[−1.19,−0.89]%)andBBR-alonegroup(−0.99[−1.16,−0.83]%)weresignificantlygreaterthanthatintheplaceboandprobiotics-alonegroups(−0.59[−0.75,−0.44]%,−0.53[−0.68,−0.37]%,P<0.001).BBRtreatmentinducedmoregastrointestinalsideeffects.FurthermetagenomicsandmetabolomicstudiesfoundthatthehypoglycaemiceffectofBBRismediatedbytheinhibitionofDCAbiotransformationbyRuminococcusbromii.Therefore,ourstudyreportsa