Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders

Sigrid Breit, Aleksandra Kupferberg, Gerhard Rogler, Gregor Hasler, Sigrid Breit, Aleksandra Kupferberg, Gerhard Rogler, Gregor Hasler

Abstract

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.

Keywords: PTSD; depression; inflammatory bowel disease; meditation; nutrition; probiotics; vagus nerve stimulation; yoga.

Figures

Figure 1
Figure 1
Overview over the basic anatomy and functions of the vagus nerve.

References

    1. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol (2015) 28:203–9.
    1. Hagemann D, Meier JJ, Gallwitz B, Schmidt WE. [Appetite regulation by ghrelin – a novel neuro-endocrine gastric peptide hormone in the gut-brain-axis]. Z Gastroenterol (2003) 41:929–36.10.1055/s-2003-41853
    1. Bonaz B, Sinniger V, Pellissier S. Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel disease. J Intern Med (2017) 282:46–63.10.1111/joim.12611
    1. Evrensel A, Ceylan ME. The gut-brain axis: the missing link in depression. Clin Psychopharmacol Neurosci (2015) 13:239–44.10.9758/cpn.2015.13.3.239
    1. Leclercq S, Forsythe P, Bienenstock J. Posttraumatic stress disorder: does the gut microbiome hold the key? Can J Psychiatry (2016) 61:204–13.10.1177/0706743716635535
    1. Goverse G, Stakenborg M, Matteoli G. The intestinal cholinergic anti-inflammatory pathway. J Physiol (2016) 594:5771–80.10.1113/JP271537
    1. Berry D. Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing. Proc Natl Acad Sci U S A (2013) 110:4720–5.10.1073/pnas.1219247110
    1. George MS, Ward HE, Ninan PT, Pollack M, Nahas Z, Anderson B, et al. A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. Brain Stimulat (2008) 1:112–21.10.1016/j.brs.2008.02.001
    1. Rod K. Observing the effects of mindfulness-based meditation on anxiety and depression in chronic pain patients. Psychiatr Danub (2015) 27(Suppl 1):S209–11.
    1. Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A (2016) 113:8284–9.10.1073/pnas.1605635113
    1. Moser G. The role of hypnotherapy for the treatment of inflammatory bowel diseases. Expert Rev Gastroenterol Hepatol (2014) 8:601–6.10.1586/17474124.2014.917955
    1. Peters SL, Muir JG, Gibson PR. Review article: gut-directed hypnotherapy in the management of irritable bowel syndrome and inflammatory bowel disease. Aliment Pharmacol Ther (2015) 41:1104–15.10.1111/apt.13202
    1. Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science (2011) 334:98–101.10.1126/science.1209985
    1. Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci (2000) 85:1–17.10.1016/S1566-0702(00)00215-0
    1. Mukudai S, Sugiyama Y, Hisa Y. Dorsal motor nucleus of the vagus. Neuroanatomy and Neurophysiology of the Larynx. Tokyo: Springer; (2016). p. 97–102.
    1. Wang F-B, Powley TL. Vagal innervation of intestines: afferent pathways mapped with new en bloc horseradish peroxidase adaptation. Cell Tissue Res (2007) 329:221–30.10.1007/s00441-007-0413-7
    1. Babic T, Browning KN. The role of vagal neurocircuits in the regulation of nausea and vomiting. Eur J Pharmacol (2014) 722:38–47.10.1016/j.ejphar.2013.08.047
    1. Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation. J Physiol (2016) 594:5781–90.10.1113/JP271539
    1. Peters JH, Gallaher ZR, Ryu V, Czaja K. Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy. J Comp Neurol (2013) 521:3584–99.10.1002/cne.23374
    1. Phillips RJ, Baronowsky EA, Powley TL. Regenerating vagal afferents reinnervate gastrointestinal tract smooth muscle of the rat. J Comp Neurol (2000) 421:325–46.10.1002/(SICI)1096-9861(20000605)421:3<325::AID-CNE3>;2-9
    1. Phillips RJ, Baronowsky EA, Powley TL. Long-term regeneration of abdominal vagus: efferents fail while afferents succeed. J Comp Neurol (2003) 455:222–37.10.1002/cne.10470
    1. Browning KN, Travagli RA. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol (2014) 4:1339–68.10.1002/cphy.c130055
    1. Furness JB, Callaghan BP, Rivera LR, Cho H-J. The enteric nervous system and gastrointestinal innervation: integrated local and central control. Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease Advances in Experimental Medicine and Biology. New York, NY: Springer; (2014). p. 39–71.
    1. Schemann M. Control of gastrointestinal motility by the “gut brain” – the enteric nervous system. J Pediatr Gastroenterol Nutr (2005) 41(Suppl 1):S4–6.10.1097/01.scs.0000180285.51365.55
    1. Schemann M, Neunlist M. The human enteric nervous system. Neurogastroenterol Motil (2004) 16(Suppl 1):55–9.10.1111/j.1743-3150.2004.00476.x
    1. Goldstein A, Hofstra R, Burns A. Building a brain in the gut: development of the enteric nervous system. Clin Genet (2013) 83:307–16.10.1111/cge.12054
    1. Furness JB. Integrated neural and endocrine control of gastrointestinal function. The Enteric Nervous System Advances in Experimental Medicine and Biology. Cham: Springer; (2016). p. 159–73.
    1. Tubbs RS, Rizk E, Shoja MM, Loukas M, Barbaro N, Spinner RJ. Nerves and Nerve Injuries: Vol 1: History, Embryology, Anatomy, Imaging, and Diagnostics. Cambridge, Massachusetts: Academic Press; (2015).
    1. Howland RH. Vagus nerve stimulation. Curr Behav Neurosci Rep (2014) 1:64–73.10.1007/s40473-014-0010-5
    1. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res (2002) 53:865–71.10.1016/S0022-3999(02)00429-4
    1. Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci (2008) 31:464–8.10.1016/j.tins.2008.06.006
    1. Mayer EA, Savidge T, Shulman RJ. Brain gut microbiome interactions and functional bowel disorders. Gastroenterology (2014) 146:1500–12.10.1053/j.gastro.2014.02.037
    1. Gacias M, Gaspari S, Santos P-MG, Tamburini S, Andrade M, Zhang F, et al. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. Elife (2016) 5:e13442.10.7554/eLife.13442
    1. Foster JA, McVey Neufeld K-A. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci (2013) 36:305–12.10.1016/j.tins.2013.01.005
    1. Neufeld K-AM, Kang N, Bienenstock J, Foster JA. Effects of intestinal microbiota on anxiety-like behavior. Commun Integr Biol (2011) 4:492–4.10.4161/cib.4.4.15702
    1. Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu X-N, et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J Physiol (2004) 558:263–75.10.1113/jphysiol.2004.063388
    1. Berthoud H-R. Vagal and hormonal gut-brain communication: from satiation to satisfaction. Neurogastroenterol Motil (2008) 20(Suppl 1):64–72.10.1111/j.1365-2982.2008.01104.x
    1. Bewick GA. Bowels control brain: gut hormones and obesity. Biochem Med (Zagreb) (2012) 22:283–97.10.11613/BM.2012.032
    1. Berthoud H-R. The vagus nerve, food intake and obesity. Regul Pept (2008) 149:15–25.10.1016/j.regpep.2007.08.024
    1. Owyang C, Heldsinger A. Vagal control of satiety and hormonal regulation of appetite. J Neurogastroenterol Motil (2011) 17:338–48.10.5056/jnm.2011.17.4.338
    1. Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science (2005) 307:1909–14.10.1126/science.1109951
    1. Rehfeld JF, Bungaard JR, Friis-Hansen L, Goetze JP. On the tissue-specific processing of procholecystokinin in the brain and gut – a short review. J Physiol Pharmacol (2003) 54(Suppl 4):73–9.
    1. Sayegh AI, Ritter RC. Vagus nerve participates in CCK-induced Fos expression in hindbrain but not myenteric plexus. Brain Res (2000) 878:155–62.10.1016/S0006-8993(00)02731-1
    1. Tanaka T, Katsuma S, Adachi T, Koshimizu T, Hirasawa A, Tsujimoto G. Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn Schmiedebergs Arch Pharmacol (2008) 377:523–7.10.1007/s00210-007-0200-8
    1. Little TJ, Horowitz M, Feinle-Bisset C. Role of cholecystokinin in appetite control and body weight regulation. Obes Rev (2005) 6:297–306.10.1111/j.1467-789X.2005.00212.x
    1. Lal S, Kirkup AJ, Brunsden AM, Thompson DG, Grundy D. Vagal afferent responses to fatty acids of different chain length in the rat. Am J Physiol Gastrointest Liver Physiol (2001) 281:G907–15.10.1152/ajpgi.2001.281.4.G907
    1. MacIntosh CG, Morley JE, Wishart J, Morris H, Jansen JB, Horowitz M, et al. Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging. J Clin Endocrinol Metab (2001) 86:5830–7.10.1210/jcem.86.12.8107
    1. Rogers RC, Hermann GE. Mechanisms of action of CCK to activate central vagal afferent terminals. Peptides (2008) 29:1716–25.10.1016/j.peptides.2008.06.023
    1. Skibicka KP, Dickson SL. Enteroendocrine hormones – central effects on behavior. Curr Opin Pharmacol (2013) 13:977–82.10.1016/j.coph.2013.09.004
    1. Harro J. CCK and NPY as anti-anxiety treatment targets: promises, pitfalls, and strategies. Amino Acids (2006) 31:215–30.10.1007/s00726-006-0334-x
    1. Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev (2007) 8:21–34.10.1111/j.1467-789X.2006.00270.x
    1. Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature (2006) 444:854–9.10.1038/nature05484
    1. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature (2000) 407:908–13.10.1038/35038090
    1. Date Y. The vagus nerve and ghrelin function. Central Functions of the Ghrelin Receptor: The Receptors. New York, NY: Springer; (2014). p. 53–61.
    1. Date Y. Ghrelin and the vagus nerve. Methods Enzymol (2012) 514:261–9.10.1016/B978-0-12-381272-8.00016-7
    1. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab (2001) 86:5992.10.1210/jcem.86.12.8111
    1. Alamri BN, Shin K, Chappe V, Anini Y. The role of ghrelin in the regulation of glucose homeostasis. Horm Mol Biol Clin Investig (2016) 26:3–11.10.1515/hmbci-2016-0018
    1. Kentish S, Li H, Philp LK, O’Donnell TA, Isaacs NJ, Young RL, et al. Diet-induced adaptation of vagal afferent function. J Physiol (2012) 590:209–21.10.1113/jphysiol.2011.222158
    1. Kentish SJ, O’Donnell TA, Isaacs NJ, Young RL, Li H, Harrington AM, et al. Gastric vagal afferent modulation by leptin is influenced by food intake status. J Physiol (2013) 591:1921–34.10.1113/jphysiol.2012.247577
    1. Depoortere I. Taste receptors of the gut: emerging roles in health and disease. Gut (2014) 63:179–90.10.1136/gutjnl-2013-305112
    1. Jeon T-I, Seo Y-K, Osborne TF. Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK. Biochem J (2011) 438:33–7.10.1042/BJ20110009
    1. Janssen S, Laermans J, Verhulst P-J, Thijs T, Tack J, Depoortere I. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A (2011) 108:2094–9.10.1073/pnas.1011508108
    1. Becker C, Neurath MF, Wirtz S. The intestinal microbiota in inflammatory bowel disease. ILAR J (2015) 56:192–204.10.1093/ilar/ilv030
    1. Sundman E, Olofsson PS. Neural control of the immune system. Adv Physiol Educ (2014) 38:135–9.10.1152/advan.00094.2013
    1. Tracey KJ. The inflammatory reflex. Nature (2002) 420:nature01321.10.1038/nature01321
    1. Bradley JR. TNF-mediated inflammatory disease. J Pathol (2008) 214:149–60.10.1002/path.2287
    1. Rogler G. Resolution of inflammation in inflammatory bowel disease. Lancet Gastroenterol Hepatol (2017) 2:521–30.10.1016/S2468-1253(17)30031-6
    1. Goehler LE, Gaykema RP, Hansen MK, Anderson K, Maier SF, Watkins LR. Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci (2000) 85:49–59.10.1016/S1566-0702(00)00219-8
    1. Tracey KJ. Reflex control of immunity. Nat Rev Immunol (2009) 9:418–28.10.1038/nri2566
    1. Browning KN, Verheijden S, Boeckxstaens GE. The vagus nerve in appetite regulation, mood, and intestinal inflammation. Gastroenterology (2017) 152:730–44.10.1053/j.gastro.2016.10.046
    1. Pavlov VA, Tracey KJ. The vagus nerve and the inflammatory reflex – linking immunity and metabolism. Nat Rev Endocrinol (2012) 8:743–54.10.1038/nrendo.2012.189
    1. Bernik TR, Friedman SG, Ochani M, DiRaimo R, Ulloa L, Yang H, et al. Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med (2002) 195:781–8.10.1084/jem.20011714
    1. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature (2000) 405:458–62.10.1038/35013070
    1. Bajbouj M, Merkl A, Schlaepfer TE, Frick C, Zobel A, Maier W, et al. Two-year outcome of vagus nerve stimulation in treatment-resistant depression. J Clin Psychopharmacol (2010) 30:273–81.10.1097/JCP.0b013e3181db8831
    1. Fornai F, Ruffoli R, Giorgi FS, Paparelli A. The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation. Eur J Neurosci (2011) 33:2169–78.10.1111/j.1460-9568.2011.07707.x
    1. Sackeim HA, Brannan SK, Rush AJ, George MS, Marangell LB, Allen J. Durability of antidepressant response to vagus nerve stimulation (VNS). Int J Neuropsychopharmacol (2007) 10:817–26.10.1017/S1461145706007425
    1. Rong P, Liu J, Wang L, Liu R, Fang J-L, Zhao J, et al. Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study. J Affect Disord (2016) 195:172–9.10.1016/j.jad.2016.02.031
    1. Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, et al. Vagus nerve stimulation (VNS™) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology (2001) 25:713.10.1016/S0893-133X(01)00271-8
    1. Daban C, Martinez-Aran A, Cruz N, Vieta E. Safety and efficacy of vagus nerve stimulation in treatment-resistant depression. A systematic review. J Affect Disord (2008) 110:1–15.10.1016/j.jad.2008.02.012
    1. Carreno FR, Frazer A. Vagal nerve stimulation for treatment-resistant depression. Neurotherapeutics (2017) 14:716–27.10.1007/s13311-017-0537-8
    1. Chae J-H, Nahas Z, Lomarev M, Denslow S, Lorberbaum JP, Bohning DE, et al. A review of functional neuroimaging studies of vagus nerve stimulation (VNS). J Psychiatr Res (2003) 37:443–55.10.1016/S0022-3956(03)00074-8
    1. Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, et al. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology (2006) 31:1345–55.10.1038/sj.npp.1301082
    1. Pardo JV, Sheikh SA, Schwindt GC, Lee JT, Kuskowski MA, Surerus C, et al. Chronic vagus nerve stimulation for treatment-resistant depression decreases resting ventromedial prefrontal glucose metabolism. Neuroimage (2008) 42:879–89.10.1016/j.neuroimage.2008.04.267
    1. George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, et al. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry (2005) 58:364–73.10.1016/j.biopsych.2005.07.028
    1. Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry (2005) 58:347–54.10.1016/j.biopsych.2005.05.025
    1. Homan P, Neumeister A, Nugent AC, Charney DS, Drevets WC, Hasler G. Serotonin versus catecholamine deficiency: behavioral and neural effects of experimental depletion in remitted depression. Transl Psychiatry (2015) 5:e532.10.1038/tp.2015.25
    1. Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry (2010) 9:155–61.10.1002/j.2051-5545.2010.tb00298.x
    1. Carpenter LL, Moreno FA, Kling MA, Anderson GM, Regenold WT, Labiner DM, et al. Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients. Biol Psychiatry (2004) 56:418–26.10.1016/j.biopsych.2004.06.025
    1. Dorr AE, Debonnel G. Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. J Pharmacol Exp Ther (2006) 318:890–8.10.1124/jpet.106.104166
    1. Manta S, El Mansari M, Debonnel G, Blier P. Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems. Int J Neuropsychopharmacol (2013) 16:459–70.10.1017/S1461145712000387
    1. Moret C, Briley M. The importance of norepinephrine in depression. Neuropsychiatr Dis Treat (2011) 7:9–13.10.2147/NDT.S19619
    1. Pisapia J, Baltuch G. Vagus nerve stimulation. In: Hamani C, Holtzheimer P, Lozano AM, Mayberg H, editors. Neuromodulation in Psychiatry. John Wiley & Sons, Ltd; (2016). p. 325–34.
    1. Roosevelt RW, Smith DC, Clough RW, Jensen RA, Browning RA. Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat. Brain Res (2006) 1119:124–32.10.1016/j.brainres.2006.08.04
    1. Manta S, Dong J, Debonnel G, Blier P. Enhancement of the function of rat serotonin and norepinephrine neurons by sustained vagus nerve stimulation. J Psychiatry Neurosci (2009) 34:272–80.10.1503/jpn.090175
    1. Follesa P, Biggio F, Gorini G, Caria S, Talani G, Dazzi L, et al. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res (2007) 1179:28–34.10.1016/j.brainres.2007.08.045
    1. Furmaga H, Shah A, Frazer A. Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats. Biol Psychiatry (2011) 70:937–45.10.1016/j.biopsych.2011.07.020
    1. Conway CR, Chibnall JT, Gebara MA, Price JL, Snyder AZ, Mintun MA, et al. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression. Brain Stimul (2013) 6:788–97.10.1016/j.brs.2012.11.006
    1. de Araujo IE, Ferreira JG, Tellez LA, Ren X, Yeckel CW. The gut–brain dopamine axis: a regulatory system for caloric intake. Physiol Behav (2012) 106:394–9.10.1016/j.physbeh.2012.02.026
    1. Kumaria A, Tolias CM. Is there a role for vagus nerve stimulation therapy as a treatment of traumatic brain injury? Br J Neurosurg (2012) 26:316–20.10.3109/02688697.2012.663517
    1. Revesz D, Tjernstrom M, Ben-Menachem E, Thorlin T. Effects of vagus nerve stimulation on rat hippocampal progenitor proliferation. Exp Neurol (2008) 214:259–65.10.1016/j.expneurol.2008.08.012
    1. Yuan T-F, Li J, Ding F, Arias-Carrion O. Evidence of adult neurogenesis in non-human primates and human. Cell Tissue Res (2014) 358:17–23.10.1007/s00441-014-1980-z
    1. Bellono NW, Bayrer JR, Leitch DB, Castro J, Zhang C, O’Donnell TA, et al. Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways. Cell (2017) 170:185–98.e.10.1016/j.cell.2017.05.034
    1. Browning KN. Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology. Front Neurosci (2015) 9:413.10.3389/fnins.2015.00413
    1. Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJL, et al. Burden of depressive disorders by country, sex, age, and year: findings from the Global Burden of Disease Study 2010. PLoS Med (2013) 10:e1001547.10.1371/journal.pmed.1001547
    1. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health (2013) 34:119–38.10.1146/annurev-publhealth-031912-114409
    1. Sobocki P, Jönsson B, Angst J, Rehnberg C. Cost of depression in Europe. J Ment Health Policy Econ (2006) 9:87–98.
    1. Jeon SW, Kim YK. Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? World J Psychiatry (2016) 6:283–93.10.5498/wjp.v6.i3.283
    1. Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience (2013) 246:199–229.10.1016/j.neuroscience.2013.04.060
    1. Schiepers OJG, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry (2005) 29:201–17.10.1016/j.pnpbp.2004.11.003
    1. Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Müller B, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry (2006) 11:680–4.10.1038/sj.mp.4001805
    1. Byrne G, Rosenfeld G, Leung Y, Qian H, Raudzus J, Nunez C, et al. Prevalence of anxiety and depression in patients with inflammatory bowel disease. Can J Gastroenterol Hepatol (2017) 2017:6496727.10.1155/2017/6496727
    1. Cámara RJA, Schoepfer AM, Pittet V, Begré S, von Känel R, Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS) Group Mood and nonmood components of perceived stress and exacerbation of Crohn’s disease. Inflamm Bowel Dis (2011) 17:2358–65.10.1002/ibd.21623
    1. Schlaepfer TE, Frick C, Zobel A, Maier W, Heuser I, Bajbouj M, et al. Vagus nerve stimulation for depression: efficacy and safety in a European study. Psychol Med (2008) 38:651–61.10.1017/S0033291707001924
    1. Berry SM, Broglio K, Bunker M, Jayewardene A, Olin B, Rush AJ. A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression. Med Devices (Auckl) (2013) 6:17–35.10.2147/MDER.S41017
    1. Nahas Z, Marangell LB, Husain MM, Rush AJ, Sackeim HA, Lisanby SH, et al. Two-year outcome of vagus nerve stimulation (VNS) for treatment of major depressive episodes. J Clin Psychiatry (2005) 66:1097–104.10.4088/JCP.v66n0902
    1. Aaronson ST, Sears P, Ruvuna F, Bunker M, Conway CR, Dougherty DD, et al. A 5-year observational study of patients with treatment-resistant depression treated with vagus nerve stimulation or treatment as usual: comparison of response, remission, and suicidality. Am J Psychiatry (2017) 174:640–8.10.1176/appi.ajp.2017.16010034
    1. Suarez EC, Krishnan RR, Lewis JG. The relation of severity of depressive symptoms to monocyte-associated proinflammatory cytokines and chemokines in apparently healthy men. Psychosom Med (2003) 65:362–8.10.1097/01.PSY.0000035719.79068.2B
    1. Corcoran C, Connor TJ, O’Keane V, Garland MR. The effects of vagus nerve stimulation on pro- and anti-inflammatory cytokines in humans: a preliminary report. Neuroimmunomodulation (2005) 12:307–9.10.1159/000087109
    1. O’Keane V, Dinan TG, Scott L, Corcoran C. Changes in hypothalamic–pituitary–adrenal axis measures after vagus nerve stimulation therapy in chronic depression. Biol Psychiatry (2005) 58:963–8.10.1016/j.biopsych.2005.04.049
    1. Cerf-Bensussan N, Gaboriau-Routhiau V. The immune system and the gut microbiota: friends or foes? Nat Rev Immunol (2010) 10:nri2850.10.1038/nri2850
    1. Principi N, Esposito S. Gut microbiota and central nervous system development. J Infect (2016) 73:536–46.10.1016/j.jinf.2016.09.010
    1. Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol (2013) 6:39–51.10.1177/1756283X12459294
    1. Sánchez B, Delgado S, Blanco-Míguez A, Lourenço A, Gueimonde M, Margolles A. Probiotics, gut microbiota, and their influence on host health and disease. Mol Nutr Food Res (2017) 6110.1002/mnfr.201600240
    1. Sanz Y. Microbiome and gluten. Ann Nutr Metab (2015) 67(Suppl 2):28–41.10.1159/000440991
    1. Cai J, Zhang L, Jones RA, Correll JB, Hatzakis E, Smith PB, et al. Antioxidant drug tempol promotes functional metabolic changes in the gut microbiota. J Proteome Res (2016) 15:563–71.10.1021/acs.jproteome.5b00957
    1. Lange K, Buerger M, Stallmach A, Bruns T. Effects of antibiotics on gut microbiota. Dig Dis (2016) 34:260–8.10.1159/000443360
    1. Alcock J, Maley CC, Aktipis CA. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays (2014) 36:940–9.10.1002/bies.201400071
    1. Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research. Appl Environ Microbiol (2008) 74:4985–96.10.1128/AEM.00753-08
    1. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A (2011) 108:16050–5.10.1073/pnas.1102999108
    1. Hasler G, Nugent AC, Carlson PJ, Carson RE, Geraci M, Drevets WC. Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography. Arch Gen Psychiatry (2008) 65:1166–75.10.1001/archpsyc.65.10.1166
    1. Hasler G, van der Veen JW, Geraci M, Shen J, Pine D, Drevets WC. Prefrontal cortical gamma-aminobutyric acid levels in panic disorder determined by proton magnetic resonance spectroscopy. Biol Psychiatry (2009) 65:273–5.10.1016/j.biopsych.2008.06.023
    1. Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology (2011) 141:.e1–3.10.1053/j.gastro.2011.04.052
    1. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry (2013) 74:720–6.10.1016/j.biopsych.2013.05.001
    1. Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry (2016) 21:786–96.10.1038/mp.2016.44
    1. Kok BE, Coffey KA, Cohn MA, Catalino LI, Vacharkulksemsuk T, Algoe SB, et al. How positive emotions build physical health: perceived positive social connections account for the upward spiral between positive emotions and vagal tone. Psychol Sci (2013) 24:1123–32.10.1177/0956797612470827
    1. Pilkington K, Kirkwood G, Rampes H, Richardson J. Yoga for depression: the research evidence. J Affect Disord (2005) 89:13–24.10.1016/j.jad.2005.08.013
    1. Tyagi A, Cohen M. Yoga and heart rate variability: a comprehensive review of the literature. Int J Yoga (2016) 9:97–113.10.4103/0973-6131.183712
    1. Chu I-H, Wu W-L, Lin I-M, Chang Y-K, Lin Y-J, Yang P-C. Effects of yoga on heart rate variability and depressive symptoms in women: a randomized controlled trial. J Altern Complement Med (2017) 23:310–6.10.1089/acm.2016.0135
    1. Streeter CC, Gerbarg PL, Saper RB, Ciraulo DA, Brown RP. Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder. Med Hypotheses (2012) 78:571–9.10.1016/j.mehy.2012.01.021
    1. Zope S, Zope R. Sudarshan Kriya yoga: breathing for health. Int J Yoga (2013) 6:4–10.10.4103/0973-6131.105935
    1. Sharma A, Barrett MS, Cucchiara AJ, Gooneratne NS, Thase ME. A breathing-based meditation intervention for patients with major depressive disorder following inadequate response to antidepressants: a randomized pilot study. J Clin Psychiatry (2017) 78:e59–63.10.4088/JCP.16m10819
    1. Woolery A, Myers H, Sternlieb B, Zeltzer L. A yoga intervention for young adults with elevated symptoms of depression. Altern Ther Health Med (2004) 10:60–3.
    1. Khattab K, Khattab AA, Ortak J, Richardt G, Bonnemeier H. Iyengar yoga increases cardiac parasympathetic nervous modulation among healthy yoga practitioners. Evid Based Complement Altern Med (2007) 4:511–7.10.1093/ecam/nem087
    1. Hasler G. Can the neuroeconomics revolution revolutionize psychiatry? Neurosci Biobehav Rev (2012) 36:64–78.10.1016/j.neubiorev.2011.04.011
    1. Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress (2013) 26:537–47.10.1002/jts.21848
    1. Zoellner LA, Bedard-Gilligan MA, Jun JJ, Marks LH, Garcia NM. The evolving construct of posttraumatic stress disorder (PTSD): DSM-5 criteria changes and legal implications. Psychol Inj Law (2013) 6:277–89.10.1007/s12207-013-9175-6
    1. Williamson JB, Porges EC, Lamb DG, Porges SW. Maladaptive autonomic regulation in PTSD accelerates physiological aging. Front Psychol (2014) 5:1571.10.3389/fpsyg.2014.01571
    1. Agorastos A, Boel JA, Heppner PS, Hager T, Moeller-Bertram T, Haji U, et al. Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder. Stress (2013) 16:300–10.10.3109/10253890.2012.751369
    1. Grupe D, Wielgosz J, Nitschke J, Davidson R. 15. respiratory sinus arrhythmia and ventromedial prefrontal function in veterans with posttraumatic stress symptoms. Biol Psychiatry (2017) 81:S7.10.1016/j.biopsych.2017.02.026
    1. Chang H-A, Chang C-C, Tzeng N-S, Kuo TB, Lu R-B, Huang S-Y. Decreased cardiac vagal control in drug-naïve patients with posttraumatic stress disorder. Psychiatry Investig (2013) 10:121–30.10.4306/pi.2013.10.2.121
    1. Noble LJ, Gonzalez IJ, Meruva VB, Callahan KA, Belfort BD, Ramanathan KR, et al. Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats. Transl Psychiatry (2017) 7:e1217.10.1038/tp.2017.191
    1. Hayes JP, Hayes SM, Mikedis AM. Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biol Mood Anxiety Disord (2012) 2:9.10.1186/2045-5380-2-9
    1. Marin M-F, Camprodon JA, Dougherty DD, Milad MR. Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond. Depress Anxiety (2014) 31:269–78.10.1002/da.22252
    1. Maren S, Phan KL, Liberzon I. The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat Rev Neurosci (2013) 14:417–28.10.1038/nrn3492
    1. Akiki TJ, Averill CL, Wrocklage KM, Schweinsburg B, Scott JC, Martini B, et al. The association of PTSD symptom severity with localized hippocampus and amygdala abnormalities. Chronic Stress (Thousand Oaks) (2017) 1.
    1. Pape H-C, Pare D. Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev (2010) 90:419–63.10.1152/physrev.00037.2009
    1. Marek R, Strobel C, Bredy TW, Sah P. The amygdala and medial prefrontal cortex: partners in the fear circuit. J Physiol (2013) 591:2381–91.10.1113/jphysiol.2012.248575
    1. Thayer JF, Sternberg E. Beyond heart rate variability: vagal regulation of allostatic systems. Ann N Y Acad Sci (2006) 1088:361–72.10.1196/annals.1366.014
    1. Neumeister P, Feldker K, Heitmann CY, Buff C, Brinkmann L, Bruchmann M, et al. Specific amygdala response to masked fearful faces in post-traumatic stress relative to other anxiety disorders. Psychol Med (2017):1–11.10.1017/S0033291717002513
    1. Nelson MD, Tumpap AM. Posttraumatic stress disorder symptom severity is associated with left hippocampal volume reduction: a meta-analytic study. CNS Spectr (2017) 22:363–72.10.1017/S1092852916000833
    1. Levy-Gigi E, Szabo C, Richter-Levin G, Kéri S. Reduced hippocampal volume is associated with overgeneralization of negative context in individuals with PTSD. Neuropsychology (2015) 29:151–61.10.1037/neu0000131
    1. George MS, Sackeim HA, Rush AJ, Marangell LB, Nahas Z, Husain MM, et al. Vagus nerve stimulation: a new tool for brain research and therapy. Biol Psychiatry (2000) 47:287–95.10.1016/S0006-3223(99)00308-X
    1. Hassert DL, Miyashita T, Williams CL. The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala. Behav Neurosci (2004) 118:79–88.10.1037/0735-7044.118.1.79
    1. Berlau DJ, McGaugh JL. Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdala. Neurobiol Learn Mem (2006) 86:123–32.10.1016/j.nlm.2005.12.008
    1. Peña DF, Childs JE, Willett S, Vital A, McIntyre CK, Kroener S. Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the ventromedial prefrontal cortex to the amygdala. Front Behav Neurosci (2014) 8:327.10.3389/fnbeh.2014.00327
    1. Capone F, Assenza G, Di Pino G, Musumeci G, Ranieri F, Florio L, et al. The effect of transcutaneous vagus nerve stimulation on cortical excitability. J Neural Transm (Vienna) (2015) 122:679–85.10.1007/s00702-014-1299-7
    1. Zobel A, Joe A, Freymann N, Clusmann H, Schramm J, Reinhardt M, et al. Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach. Psychiatry Res (2005) 139:165–79.10.1016/j.pscychresns.2005.02.010
    1. Perez SM, Carreno FR, Frazer A, Lodge DJ. Vagal nerve stimulation reverses aberrant dopamine system function in the methylazoxymethanol acetate rodent model of schizophrenia. J Neurosci (2014) 34:9261–7.10.1523/JNEUROSCI.0588-14.2014
    1. Hemmings SMJ, Malan-Müller S, van den Heuvel LL, Demmitt BA, Stanislawski MA, Smith DG, et al. The microbiome in posttraumatic stress disorder and trauma-exposed controls: an exploratory study. Psychosom Med (2017) 79:936–46.10.1097/PSY.0000000000000512
    1. Reber SO, Langgartner D, Foertsch S, Postolache TT, Brenner LA, Guendel H, et al. Chronic subordinate colony housing paradigm: a mouse model for mechanisms of PTSD vulnerability, targeted prevention, and treatment-2016 Curt Richter Award Paper. Psychoneuroendocrinology (2016) 74:221–30.10.1016/j.psyneuen.2016.08.031
    1. Reber SO, Siebler PH, Donner NC, Morton JT, Smith DG, Kopelman JM, et al. Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. Proc Natl Acad Sci U S A (2016) 113:E3130–9.10.1073/pnas.1600324113
    1. Huang R, Wang K, Hu J. Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients (2016) 8:E483.10.3390/nu8080483
    1. Pirbaglou M, Katz J, de Souza RJ, Stearns JC, Motamed M, Ritvo P. Probiotic supplementation can positively affect anxiety and depressive symptoms: a systematic review of randomized controlled trials. Nutr Res (2016) 36:889–98.10.1016/j.nutres.2016.06.009
    1. Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry (2017) 1610.1186/s12991-017-0138-2
    1. McKean J, Naug H, Nikbakht E, Amiet B, Colson N. Probiotics and subclinical psychological symptoms in healthy participants: a systematic review and meta-analysis. J Altern Complement Med (2017) 23:249–58.10.1089/acm.2016.0023
    1. Earley MD, Chesney MA, Frye J, Greene PA, Berman B, Kimbrough E. Mindfulness intervention for child abuse survivors: a 2.5-year follow-up. J Clin Psychol (2014) 70:933–41.10.1002/jclp.22102
    1. Kearney DJ, McDermott K, Malte C, Martinez M, Simpson TL. Association of participation in a mindfulness program with measures of PTSD, depression and quality of life in a veteran sample. J Clin Psychol (2012) 68:101–16.10.1002/jclp.20853
    1. Stephenson KR, Simpson TL, Martinez ME, Kearney DJ. Changes in mindfulness and posttraumatic stress disorder symptoms among veterans enrolled in mindfulness-based stress reduction. J Clin Psychol (2017) 73:201–17.10.1002/jclp.22323
    1. Krygier JR, Heathers JAJ, Shahrestani S, Abbott M, Gross JJ, Kemp AH. Mindfulness meditation, well-being, and heart rate variability: a preliminary investigation into the impact of intensive Vipassana meditation. Int J Psychophysiol (2013) 89:305–13.10.1016/j.ijpsycho.2013.06.017
    1. Hilton L, Maher AR, Colaiaco B, Apaydin E, Sorbero ME, Booth M, et al. Meditation for posttraumatic stress: systematic review and meta-analysis. Psychol Trauma (2017) 9:453–60.10.1037/tra0000180
    1. Luo Q. Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells. Infect Immun (2014) 82:509–21.10.1128/IAI.01106-13
    1. Price M, Spinazzola J, Musicaro R, Turner J, Suvak M, Emerson D, et al. Effectiveness of an extended yoga treatment for women with chronic posttraumatic stress disorder. J Altern Complement Med (2017) 23:300–9.10.1089/acm.2015.0266
    1. Descilo T, Vedamurtachar A, Gerbarg PL, Nagaraja D, Gangadhar BN, Damodaran B, et al. Effects of a yoga breath intervention alone and in combination with an exposure therapy for post-traumatic stress disorder and depression in survivors of the 2004 South-East Asia tsunami. Acta Psychiatr Scand (2010) 121:289–300.10.1111/j.1600-0447.2009.01466.x
    1. Telles S, Singh N, Joshi M, Balkrishna A. Post traumatic stress symptoms and heart rate variability in Bihar flood survivors following yoga: a randomized controlled study. BMC Psychiatry (2010) 10:18.10.1186/1471-244X-10-18
    1. Sack M, Hopper JW, Lamprecht F. Low respiratory sinus arrhythmia and prolonged psychophysiological arousal in posttraumatic stress disorder: heart rate dynamics and individual differences in arousal regulation. Biol Psychiatry (2004) 55:284–90.10.1016/S0006-3223(03)00677-2
    1. Norouzinia M, Chaleshi V, Alizadeh AHM, Zali MR. Biomarkers in inflammatory bowel diseases: insight into diagnosis, prognosis and treatment. Gastroenterol Hepatol Bed Bench (2017) 10:155–67.
    1. Jonkers D, Stockbrügger R. Probiotics and inflammatory bowel disease. J R Soc Med (2003) 96:167–71.10.1177/014107680309600403
    1. Bonaz B, Sinniger V, Pellissier S. The vagus nerve in the neuro-immune axis: implications in the pathology of the gastrointestinal tract. Front Immunol (2017) 8:1452.10.3389/fimmu.2017.01452
    1. Yamamoto-Furusho JK, Fonseca-Camarillo G. Genetic markers associated with clinical outcomes in patients with inflammatory bowel disease. Inflamm Bowel Dis (2015) 21:2683–95.10.1097/MIB.0000000000000500
    1. Kaplan GG, Ng SC. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology (2017) 152:313.e–21.e.10.1053/j.gastro.2016.10.020
    1. Fonseca-Camarillo G, Yamamoto-Furusho JK. Immunoregulatory pathways involved in inflammatory bowel disease. Inflamm Bowel Dis (2015) 21:2188–93.10.1097/MIB.0000000000000477
    1. Rogler G, Vavricka S. Exposome in IBD: recent insights in environmental factors that influence the onset and course of IBD. Inflamm Bowel Dis (2015) 21:400–8.10.1097/MIB.0000000000000229
    1. Nourian M, Chaleshi V, Pishkar L, Azimzadeh P, Baradaran Ghavami S, Balaii H, et al. Evaluation of tumor necrosis factor (TNF)-α mRNA expression level and the rs1799964 polymorphism of the TNF-α gene in peripheral mononuclear cells of patients with inflammatory bowel diseases. Biomed Rep (2017) 6:698–702.10.3892/br.2017.908
    1. de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol (2005) 6:844–51.10.1038/ni1229
    1. Meregnani J, Clarençon D, Vivier M, Peinnequin A, Mouret C, Sinniger V, et al. Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease. Auton Neurosci (2011) 160:82–9.10.1016/j.autneu.2010.10.007
    1. Marshall R, Taylor I, Lahr C, Abell TL, Espinoza I, Gupta NK, et al. Bioelectrical stimulation for the reduction of inflammation in inflammatory bowel disease. Clin Med Insights Gastroenterol (2015) 8:55–9.10.4137/CGast.S31779
    1. Miller AH, Raison CL. Are anti-inflammatory therapies viable treatments for psychiatric disorders? Where the rubber meets the road. JAMA Psychiatry (2015) 72:527–8.10.1001/jamapsychiatry.2015.22
    1. Lowry CA, Smith DG, Siebler PH, Schmidt D, Stamper CE, Hassell JE, et al. The microbiota, immunoregulation, and mental health: implications for public health. Curr Environ Health Rep (2016) 3:270–86.10.1007/s40572-016-0100-5
    1. Schultz M, Veltkamp C, Dieleman LA, Grenther WB, Wyrick PB, Tonkonogy SL, et al. Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflamm Bowel Dis (2002) 8:71–80.10.1097/00054725-200203000-00001
    1. Madsen KL. Inflammatory bowel disease: lessons from the IL-10 gene-deficient mouse. Clin Investig Med (2001) 24:250–7.
    1. Gupta P, Andrew H, Kirschner BS, Guandalini S. Is Lactobacillus GG helpful in children with Crohn’s disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr (2000) 31:453–7.10.1097/00005176-200010000-00024
    1. Ganji-Arjenaki M, Rafieian-Kopaei M. Probiotics are a good choice in remission of inflammatory bowel diseases: a meta analysis and systematic review. J Cell Physiol (2018) 233:2091–103.10.1002/jcp.25911
    1. Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis (2017) 11:3–25.10.1093/ecco-jcc/jjw168
    1. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis (2017) 11:649–70.10.1093/ecco-jcc/jjx008
    1. Currò D, Ianiro G, Pecere S, Bibbò S, Cammarota G. Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders. Br J Pharmacol (2017) 174:1426–49.10.1111/bph.13632
    1. Mizrahi MC, Reicher-Atir R, Levy S, Haramati S, Wengrower D, Israeli E, et al. Effects of guided imagery with relaxation training on anxiety and quality of life among patients with inflammatory bowel disease. Psychol Health (2012) 27:1463–79.10.1080/08870446.2012.691169
    1. Berrill JW, Sadlier M, Hood K, Green JT. Mindfulness-based therapy for inflammatory bowel disease patients with functional abdominal symptoms or high perceived stress levels. J Crohns Colitis (2014) 8:945–55.10.1016/j.crohns.2014.01.018
    1. Dossett ML, Korzenik JR, Baim M, Denninger JW, Mehta DH. A case report of improvement in Crohn’s disease-related symptoms following participation in a comprehensive mind-body program. Glob Adv Health Med (2016) 5:122–5.10.7453/gahmj.2015.118
    1. Gerbarg PL, Jacob VE, Stevens L, Bosworth BP, Chabouni F, DeFilippis EM, et al. The effect of breathing, movement, and meditation on psychological and physical symptoms and inflammatory biomarkers in inflammatory bowel disease: a randomized controlled trial. Inflamm Bowel Dis (2015) 21:2886–96.10.1097/MIB.0000000000000568
    1. Cotton S, Humenay Roberts Y, Tsevat J, Britto MT, Succop P, McGrady ME, et al. Mind-body complementary alternative medicine use and quality of life in adolescents with inflammatory bowel disease. Inflamm Bowel Dis (2010) 16:501–6.10.1002/ibd.21045
    1. Cramer H, Schäfer M, Schöls M, Köcke J, Elsenbruch S, Lauche R, et al. Randomised clinical trial: yoga vs written self-care advice for ulcerative colitis. Aliment Pharmacol Ther (2017) 45:1379–89.10.1111/apt.14062
    1. Kuo B, Bhasin M, Jacquart J, Scult MA, Slipp L, Riklin EIK, et al. Genomic and clinical effects associated with a relaxation response mind-body intervention in patients with irritable bowel syndrome and inflammatory bowel disease. PLoS One (2015) 10:e0123861.10.1371/journal.pone.0123861
    1. DeBenedittis G, Cigada M, Bianchi A, Signorini MG, Cerutti S. Autonomic changes during hypnosis: a heart rate variability power spectrum analysis as a marker of sympatho-vagal balance. Int J Clin Exp Hypn (1994) 42:140–52.10.1080/00207149408409347

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