Abstract
Anxiety disorder is one of the most prevalent psychiatric disorders. The high prevalence of comorbid gastrointestinal disorders and anxiety, as well as various limitations in current therapy, have necessitated the search for alternative techniques. The Gut-Brain Axis is the connecting link between the gut and the brain. One of the reasons for the Gut-Brain Axis malfunction resulting in HPA axis stimulation and anxiety is intestinal barrier dysfunction. Gut microorganisms, lipopolysaccharides, and other factors can stimulate the disruption of this intestinal barrier. Tight junction proteins, the epithelial barrier, the mucosal membrane, the Toll-like receptor/Myeloid differentiation factor 88 pathway, the activated immune system, and the HPA axis could all be potential targets for anxiety caused by intestinal barrier disruption. Quercetin and Rebamipide, Berberine and Agomelatine, Angiotensin II receptor type 1 blockers, and Lubiprostone can act on these targets to provide an anxiolytic effect.
Keywords: Anxiety, intestinal barrier dysfunction, gut brain axis, tight junction proteins, immune system, HPA axis, cortisol.
Graphical Abstract
[http://dx.doi.org/10.2217/fnl.11.34] [PMID: 21901080]
[http://dx.doi.org/10.2174/18715273113129990102] [PMID: 24040796]
[http://dx.doi.org/10.31887/DCNS.2015.17.3/bbandelow] [PMID: 26487813]
[http://dx.doi.org/10.1038/sj.mp.4001551] [PMID: 15278097]
[http://dx.doi.org/10.1007/s00406-014-0502-z] [PMID: 24705634]
[PMID: 28539843]
[http://dx.doi.org/10.1371/journal.pone.0133283] [PMID: 26222511]
[http://dx.doi.org/10.1111/nmo.13619] [PMID: 31056802]
[PMID: 24974805]
[http://dx.doi.org/10.1155/2012/486067] [PMID: 22956940]
[http://dx.doi.org/10.1016/j.jpsychores.2016.06.001] [PMID: 27411754]
[http://dx.doi.org/10.4103/IJPSYM.IJPSYM_46_17] [PMID: 29284804]
[http://dx.doi.org/10.1007/s13410-018-0684-4]
[PMID: 25830558]
[http://dx.doi.org/10.1016/B978-0-12-405941-2.00021-3]
[http://dx.doi.org/10.3389/fncel.2015.00392] [PMID: 26528128]
[http://dx.doi.org/10.1046/j.1440-1746.2003.03032.x] [PMID: 12702039]
[http://dx.doi.org/10.1016/j.pain.2009.06.017] [PMID: 19595511]
[http://dx.doi.org/10.1016/j.diabet.2016.09.004] [PMID: 27745826]
[http://dx.doi.org/10.1210/jendso/bvz039] [PMID: 32099951]
[http://dx.doi.org/10.1007/s00018-012-1070-x] [PMID: 22782113]
[http://dx.doi.org/10.1083/jcb.142.1.117] [PMID: 9660867]
[http://dx.doi.org/10.1083/jcb.200510043] [PMID: 16365161]
[http://dx.doi.org/10.1038/nri2653] [PMID: 19855405]
[http://dx.doi.org/10.1016/j.jinf.2017.12.013] [PMID: 29291933]
[http://dx.doi.org/10.1186/1741-7015-9-24] [PMID: 21401922]
[http://dx.doi.org/10.3748/wjg.v20.i39.14126] [PMID: 25339801]
[http://dx.doi.org/10.1186/s12876-014-0189-7] [PMID: 25407511]
[http://dx.doi.org/10.1016/j.ajpath.2018.12.016] [PMID: 30711488]
[http://dx.doi.org/10.1152/physrev.00018.2018] [PMID: 31460832]
[http://dx.doi.org/10.2527/jas.2008-1339] [PMID: 18791134]
[http://dx.doi.org/10.1007/s12325-020-01338-6] [PMID: 32291647]
[http://dx.doi.org/10.1053/j.gastro.2009.01.072] [PMID: 19462507]
[http://dx.doi.org/10.1177/09680519030090050901] [PMID: 14577850]
[http://dx.doi.org/10.1016/j.ajpath.2012.10.014] [PMID: 23201091]
[http://dx.doi.org/10.4049/jimmunol.1402598]
[http://dx.doi.org/10.1038/nri1391] [PMID: 15229469]
[http://dx.doi.org/10.1111/apt.12950] [PMID: 25262969]
[http://dx.doi.org/10.1038/mp.2012.77] [PMID: 22688187]
[http://dx.doi.org/10.1016/j.jcmgh.2021.02.007] [PMID: 33610769]
[http://dx.doi.org/10.1016/j.molmed.2016.04.003] [PMID: 27178527]
[http://dx.doi.org/10.1371/journal.pone.0218384] [PMID: 31211803]
[http://dx.doi.org/10.5320/wjr.v7.i1.17]
[http://dx.doi.org/10.1038/s41598-019-51067-2] [PMID: 31601922]
[http://dx.doi.org/10.1021/acsinfecdis.7b00139] [PMID: 29094594]
[http://dx.doi.org/10.1152/ajpgi.00245.2020] [PMID: 32902315]
[http://dx.doi.org/10.1152/ajpgi.2001.281.4.G907] [PMID: 11557510]
[http://dx.doi.org/10.1016/j.autneu.2004.11.012] [PMID: 15919243]
[http://dx.doi.org/10.1016/S0016-5085(00)70373-8] [PMID: 10833495]
[http://dx.doi.org/10.1053/j.gastro.2004.10.043] [PMID: 15633135]
[http://dx.doi.org/10.1007/s40473-014-0010-5] [PMID: 24834378]
[http://dx.doi.org/10.1007/7854_2014_299] [PMID: 24659553]
[http://dx.doi.org/10.1016/j.ejphar.2008.03.008] [PMID: 18417116]
[http://dx.doi.org/10.1155/2020/4892415] [PMID: 32419805]
[http://dx.doi.org/10.1016/j.jnutbio.2009.01.008] [PMID: 19423323]
[http://dx.doi.org/10.3390/molecules16021471] [PMID: 21311414]
[http://dx.doi.org/10.1016/j.pnpbp.2010.04.025] [PMID: 20447436]
[http://dx.doi.org/10.33549/physiolres.933776] [PMID: 30044120]
[http://dx.doi.org/10.1002/fft2.50]
[http://dx.doi.org/10.3945/jn.108.100867] [PMID: 19297429]
[http://dx.doi.org/10.1039/c3fo30241e] [PMID: 23644882]
[http://dx.doi.org/10.1016/j.intimp.2015.06.036] [PMID: 26218279]
[http://dx.doi.org/10.1016/0014-2999(92)90065-C] [PMID: 1313372]
[http://dx.doi.org/10.1016/j.intimp.2020.107136] [PMID: 33218942]
[http://dx.doi.org/10.1007/s10753-015-0271-5] [PMID: 26454448]
[http://dx.doi.org/10.1016/j.ejphar.2013.02.010] [PMID: 23428631]
[http://dx.doi.org/10.1254/jphs.FP0071422] [PMID: 18360096]
[http://dx.doi.org/10.1016/S0891-5849(00)00471-8] [PMID: 11165875]
[http://dx.doi.org/10.1007/s00535-010-0332-3] [PMID: 20924615]
[http://dx.doi.org/10.1017/S1461145711000356] [PMID: 21473810]
[http://dx.doi.org/10.1016/j.pnpbp.2012.07.003] [PMID: 22789661]
[PMID: 19300571]
[http://dx.doi.org/10.1038/nrd3140] [PMID: 20577266]
[http://dx.doi.org/10.1016/j.euroneuro.2018.05.006] [PMID: 30135032]
[http://dx.doi.org/10.1007/s40495-019-00207-3]
[http://dx.doi.org/10.1002/ptr.2399] [PMID: 18618524]
[http://dx.doi.org/10.1016/j.ejphar.2008.05.043] [PMID: 18585703]
[http://dx.doi.org/10.3389/fphar.2018.00557] [PMID: 30186157]
[http://dx.doi.org/10.1016/j.lfs.2004.04.032] [PMID: 15350820]
[http://dx.doi.org/10.4196/kjpp.2012.16.6.379] [PMID: 23269899]
[http://dx.doi.org/10.1016/j.physbeh.2019.03.024] [PMID: 30922821]
[http://dx.doi.org/10.1055/s-2001-10874] [PMID: 11270727]
[http://dx.doi.org/10.3389/fphar.2017.00042] [PMID: 28217099]
[http://dx.doi.org/10.1016/j.biopha.2019.109206] [PMID: 31306972]
[http://dx.doi.org/10.1016/j.fitote.2009.02.005] [PMID: 19243699]
[http://dx.doi.org/10.1124/jpet.118.248831] [PMID: 29752427]
[http://dx.doi.org/10.1042/CS20180236] [PMID: 29712882]
[http://dx.doi.org/10.3389/fphar.2019.00318] [PMID: 31001119]
[http://dx.doi.org/10.1016/j.regpep.2004.12.015] [PMID: 15837532]
[http://dx.doi.org/10.1210/endo.142.9.8366] [PMID: 11517166]
[http://dx.doi.org/10.1016/S1734-1140(12)70730-2] [PMID: 22580520]
[http://dx.doi.org/10.1016/j.bpsc.2018.05.007] [PMID: 29980493]
[http://dx.doi.org/10.1111/bph.14965] [PMID: 31883108]
[http://dx.doi.org/10.1007/s10620-011-1801-0] [PMID: 21769655]
[http://dx.doi.org/10.1016/j.mayocp.2016.01.015] [PMID: 27046523]
[http://dx.doi.org/10.1159/000503054] [PMID: 31536982]
[http://dx.doi.org/10.1111/nmo.13477] [PMID: 30284340]
[http://dx.doi.org/10.1371/journal.pone.0175626] [PMID: 28410406]
[http://dx.doi.org/10.1016/j.brainres.2007.01.037] [PMID: 17306778]