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Potential application of helminth therapy for resolution of neuroinflammation in neuropsychiatric disorders

  • Amir AbdoliEmail author
  • Hoda Mirzaian Ardakani
Review Article

Abstract

Neuropsychiatric disorders (NPDs) are among the major debilitating disorders worldwide with multiple etiological factors. However, in recent years, psychoneuroimmunology uncovered the role of inflammatory condition and autoimmune disorders in the etiopathogenesis of different NPDs. Hence, resolution of inflammation is a new therapeutic target of NPDs. On the other hand, Helminth infections are among the most prevalent infectious diseases in underdeveloped countries, which usually caused chronic infections with minor clinical symptoms. Remarkably, helminths are among the master regulator of inflammatory reactions and epidemiological studies have shown an inverse association between prevalence of autoimmune disorders with these infections. As such, changes of intestinal microbiota are known to be associated with inflammatory conditions in various NPDs. Conversely, helminth colonization alters the intestinal microbiota composition that leads to suppression of intestinal inflammation. In animal models and human studies, helminths or their antigens have shown to be protected against severe autoimmune and allergic disorders, decline the intensity of inflammatory reactions and improved clinical symptoms of the patients. Therefore, “helminthic therapy” have been used for modulation of immune disturbances in different autoimmunity illnesses, such as Multiple Sclerosis (MS) and Inflammatory Bowel Disease (IBD). Here, it is proposed that “helminthic therapy” is able to ameliorate neuroinflammation of NPDs through immunomodulation of inflammatory reactions and alteration of microbiota composition. This review discusses the potential application of “helminthic therapy” for resolution of neuroinflammation in NPDs.

Keywords

Inflammation Helminth therapy Neuropsychiatric disorders Autoimmune disorders Microbiota 

Abbreviations

NPDs

neuropsychiatric disorders

MS

Multiple Sclerosis

IBD

Inflammatory Bowel Disease

CNS

central nervous system

NMDA

N-Methyl-D-aspartic acid

IFN-γ

interferon-γ

TNF-α

tumor necrosis factor-α

IL

interleukin

TGF-β

transforming growth factor-β

TH

T helper

T1D

type 1 diabetes

RA

rheumatoid arthritis

ELE

systemic lupus erythematosus

UC

ulcerative colitis

CD

Crohn’s disease

HR

hazard ratio

OR

odd ratios

MGB axis

microbiota-gut-brain axis

ADHD

attention-deficit hypersensitivity disorder

Treg

regulatory T cells

Breg

regulatory B cells

DCreg

regulatory dendritic cells

EAE

experimental autoimmune encephalomyelitis

TNBS

Trinitrobenzene sulfonic acid

DSS

Dextran sodium sulfate

DNBS

Dinitrobenzene sulfonic acid

NSAIDs

Nonsteroidal anti-inflammatory drugs

TCT

T cell transfer model of colitis

NOD

Non-obese diabetic

CIA

Collagen-induced arthritis

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Aarts E, Ederveen THA, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, Smeekens SP, Netea MG, Buitelaar JK, Franke B, van Hijum SAFT, Arias Vasquez A (2017) Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS ONE 12:e0183509.  https://doi.org/10.1371/journal.pone.0183509 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Abdoli A (2017) Hypothesis: high salt intake as an inflammation amplifier might be involved in the pathogenesis of neuropsychiatric disorders. Clin Exp Neuroimmunol 8:146–157.  https://doi.org/10.1111/cen3.12389 CrossRefGoogle Scholar
  3. Abdoli A (2019) Therapeutic potential of helminths and helminth-derived antigens for resolution of inflammation in inflammatory bowel disease. Arch Med Res 50(1): 58-59.  https://doi.org/10.1016/j.arcmed.2019.03.001
  4. Abdoli A, Pirestani M (2014) Are pregnant women with chronic helminth infections more susceptible to congenital infections? Front Immunol 5.  https://doi.org/10.3389/fimmu.2014.00053
  5. Abdoli A, Rasti S (2017) Cardioprotective manifestations of chronic helminth infections: new aspects of an old disease. Heart 103:1651.  https://doi.org/10.1136/heartjnl-2017-311768 CrossRefPubMedGoogle Scholar
  6. Allen JE, Maizels RM (2011) Diversity and dialogue in immunity to helminths. Nat Rev Immunol 11:375–388CrossRefPubMedGoogle Scholar
  7. Alper E, Mehmet Emin C (2016) Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders. Clin Psychopharmacol Neurosci 14:231–237CrossRefGoogle Scholar
  8. Arroyo-López C (2019) Helminth therapy for autism under gut-brain axis-hypothesis. Med Hypotheses 125:110–118CrossRefPubMedGoogle Scholar
  9. Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640CrossRefPubMedGoogle Scholar
  10. Baune BT et al (2012) Inflammatory biomarkers predict depressive, but not anxiety symptoms during aging: the prospective Sydney memory and aging study. Psychoneuroendocrinology 37:1521–1530.  https://doi.org/10.1016/j.psyneuen.2012.02.006 CrossRefPubMedGoogle Scholar
  11. Benros ME, Eaton WW, Mortensen PB (2014a) The Epidemiologic Evidence Linking Autoimmune Diseases and Psychosis. Biol Psychiatr 75:300–306.  https://doi.org/10.1016/j.biopsych.2013.09.023
  12. Benros ME, Eaton WW, Mortensen PB (2014b) The epidemiologic evidence linking autoimmune diseases and psychosis. Biol Psychiatr 75:300–306CrossRefGoogle Scholar
  13. Bergink V, Gibney SM, Drexhage HA (2014) Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biol Psychiatry 75:324–331CrossRefPubMedGoogle Scholar
  14. Black C, Miller B (2015) Meta-analysis of Cytokines and Chemokines in Suicidality: Distinguishing Suicidal Versus Nonsuicidal Patients. Biol Psychiatr 78:28–37CrossRefGoogle Scholar
  15. Boeschoten RE, Braamse AMJ, Beekman ATF, Cuijpers P, van Oppen P, Dekker J, Uitdehaag BMJ (2017) Prevalence of depression and anxiety in multiple sclerosis: a systematic review and meta-analysis. J Neurol Sci 372:331–341.  https://doi.org/10.1016/j.jns.2016.11.067 CrossRefPubMedGoogle Scholar
  16. Borovčanin M, Jovanović I, Đukić-Dejanović S, Radosavljević G, Arsenijević N, Lukić ML (2016) Possible role of TGH β pathways in schizophrenia. Serbian J Exp Clin Res 17:3–8CrossRefGoogle Scholar
  17. Broadhurst MJ, Ardeshir A, Kanwar B, Mirpuri J, Gundra UM, Leung JM, Wiens KE, Vujkovic-Cvijin I, Kim CC, Yarovinsky F, Lerche NW, McCune JM, Loke P' (2012) Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon. PLoS Pathogens 8:e1003000.  https://doi.org/10.1371/journal.ppat.1003000 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cantacessi C, Giacomin P, Croese J, Zakrzewski M, Sotillo J, McCann L, Nolan MJ, Mitreva M, Krause L, Loukas A (2014) Impact of experimental hookworm infection on the human gut microbiota. J Infect Dis 210:1431–1434CrossRefPubMedPubMedCentralGoogle Scholar
  19. Chen M-H, Su T-P, Chen Y-S, Hsu J-W, Huang K-L, Chang W-H, Bai Y-M (2013) Allergic rhinitis in adolescence increases the risk of depression in later life: a nationwide population-based prospective cohort study. J Affect Disord 145:49–53CrossRefPubMedGoogle Scholar
  20. Cheng AM, Jaint D, Thomas S, Wilson J, Parker W (2015) Overcoming evolutionary mismatch by self-treatment with helminths: current practices and experience. J Evol Med 3:1–22CrossRefGoogle Scholar
  21. Cho M, Lee C, Yu H (2011) Amelioration of intestinal colitis by macrophage migration inhibitory factor isolated from intestinal parasites through toll-like receptor 2 Parasite Immunol 33:265–275Google Scholar
  22. Cooke A, Tonks P, Jones FM, O'SHEA H, Hutchings P, Fulford AJ (1999) Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol 21:169–176CrossRefPubMedGoogle Scholar
  23. Correale J, Farez M (2007) Association between parasite infection and immune responses in multiple sclerosis. Annals Neurol 61:97–108.  https://doi.org/10.1002/ana.21067 CrossRefGoogle Scholar
  24. Correale J, Farez MF (2011) The impact of parasite infections on the course of multiple sclerosis. J Neuroimmunol 23:6–11.  https://doi.org/10.1016/j.jneuroim.2011.01.002
  25. Croese J, O’Neil J, Masson J, Cooke S, Melrose W, Pritchard D, Speare R (2006) A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors. Gut 55:136–137.  https://doi.org/10.1136/gut.2005.079129 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Croese J et al (2015) Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy Clin Immunol 135:508–516 e505CrossRefPubMedGoogle Scholar
  27. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712.  https://doi.org/10.1038/nrn3346 CrossRefPubMedGoogle Scholar
  28. Daveson AJ et al (2011) Effect of hookworm infection on wheat challenge in celiac disease–a randomised double-blinded placebo controlled trial. PloS One 6:e17366CrossRefPubMedPubMedCentralGoogle Scholar
  29. Davison K (2012) Autoimmunity in psychiatry brit. J Psychiatr 200:353–355CrossRefGoogle Scholar
  30. Debnath M, Berk M (2014) Th17 pathway–mediated immunopathogenesis of schizophrenia: mechanisms and implications. Schizophr Bull 40:1412–1421CrossRefPubMedPubMedCentralGoogle Scholar
  31. Debnath M, Doyle KM, Langan C, McDonald C, Leonard B, Cannon DM (2011) Recent advances in psychoneuroimmunology: Inflammation in psychiatric disorders. Transl Neurosci 2:121–137.  https://doi.org/10.2478/s13380-011-0019-0 CrossRefGoogle Scholar
  32. Dickerson F, Severance E, Yolken R (2017) The microbiome, immunity, and schizophrenia and bipolar disorder brain. Behav Immun 62:46–52.  https://doi.org/10.1016/j.bbi.2016.12.010 CrossRefGoogle Scholar
  33. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatr 67:446–457.  https://doi.org/10.1016/j.biopsych.2009.09.033
  34. Driss V, el Nady M, Delbeke M, Rousseaux C, Dubuquoy C, Sarazin A, Gatault S, Dendooven A, Riveau G, Colombel JF, Desreumaux P, Dubuquoy L, Capron M (2016) The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils. Mucosal Immunol 9:322–335CrossRefPubMedGoogle Scholar
  35. Ducasse D, Olié E, Guillaume S, Artéro S, Courtet P (2015) A meta-analysis of cytokines in suicidal behavior. Brain Behav Immun 46:203–211CrossRefPubMedGoogle Scholar
  36. Dybdal D, Tolstrup JS, Sildorf SM, Boisen KA, Svensson J, Skovgaard AM, Teilmann GK (2018) Increasing risk of psychiatric morbidity after childhood onset type 1 diabetes: a population-based cohort study. Diabetologia 61:831–838.  https://doi.org/10.1007/s00125-017-4517-7 CrossRefPubMedGoogle Scholar
  37. Elliott D, Weinstock J (2017) Nematodes and human therapeutic trials for inflammatory disease. Parasite Immunol 39:e12407CrossRefGoogle Scholar
  38. Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban JF Jr, Weinstock JV (2003) Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol:43Google Scholar
  39. Elliott DE, Setiawan T, Metwali A, Blum A, Urban JF Jr, Weinstock JV (2004) Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur J Immunol 34:2690–2698Google Scholar
  40. Everts B, Smits HH, Hokke CH, Yazdanbakhsh M (2010) Helminths and dendritic cells: sensing and regulating via pattern recognition receptors, Th2 and Treg responses. Eur J Immunol 40:1525–1537CrossRefPubMedGoogle Scholar
  41. Fang X, Zhang Y, Fan W, Tang W, Zhang C (2017) Interleukin-17 alteration in first-episode psychosis: a meta-analysis. Mol Neuropsychiatry 3:135–140CrossRefPubMedPubMedCentralGoogle Scholar
  42. Fernandes BS et al (2016) C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 3:1147–1156.  https://doi.org/10.1016/S2215-0366(16)30370-4 CrossRefPubMedGoogle Scholar
  43. Finlay CM, Walsh KP, Mills KH (2014) Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases. Immunol Rev 259:206–230CrossRefPubMedGoogle Scholar
  44. Fleming J, Weinstock J (2015) Clinical trials of helminth therapy in autoimmune diseases: rationale and findings. Parasite Immunol 37:277–292CrossRefPubMedGoogle Scholar
  45. Fleming JO et al (2011) Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study. Mult Scler J 17:743–754.  https://doi.org/10.1177/1352458511398054 CrossRefGoogle Scholar
  46. Fleming P, Bai JW, Pratt M, Sibbald C, Lynde C, Gulliver WP (2017) The prevalence of anxiety in patients with psoriasis: a systematic review of observational studies and clinical trials. J Eur Acad Dermatol Venereol 31:798–807.  https://doi.org/10.1111/jdv.13891 CrossRefPubMedGoogle Scholar
  47. Fond G, Lançon C, Auquier P, Boyer L (2018) C-reactive protein as a peripheral biomarker in schizophrenia. An Updated Systematic Review. Front Psychiatr 9:392Google Scholar
  48. Frolkis AD et al (2018) Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression. Gut 2018:317182.  https://doi.org/10.1136/gutjnl-2018-317182 CrossRefGoogle Scholar
  49. Fuller-Thomson E, Sulman J (2006) Depression and inflammatory bowel disease: Findings from two nationally representative Canadian surveys. Inflamm Bowel Dis 12:697–707.  https://doi.org/10.1097/00054725-200608000-00005 CrossRefPubMedGoogle Scholar
  50. Gallego JA et al (2018) Cytokines in cerebrospinal fluid of patients with schizophrenia spectrum disorders: new data and an updated meta-analysis. Schizophr Res 202:64–71.  https://doi.org/10.1016/j.schres.2018.07.019 CrossRefPubMedGoogle Scholar
  51. Geiss T, Schaefert RM, Berens S, Hoffmann P, Gauss A (2018) Risk of depression in patients with inflammatory bowel disease. J Dig Dis 19:456–467.  https://doi.org/10.1111/1751-2980.12644 CrossRefPubMedGoogle Scholar
  52. Giacomin P et al (2016) Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease. Sci Rep 6:36797CrossRefPubMedPubMedCentralGoogle Scholar
  53. Gilsanz P, Karter AJ, Beeri MS, Quesenberry CP, Whitmer RA (2018a) The bidirectional association between depression and severe hypoglycemic and hyperglycemic events in type 1 diabetes. Diabetes Care 41:446–452.  https://doi.org/10.2337/dc17-1566 CrossRefPubMedGoogle Scholar
  54. Gilsanz P, Schnaider Beeri M, Karter AJ, Quesenberry CP, Adams AS, Whitmer RA (2019) Depression in type 1 diabetes and risk of dementia. Aging Ment health 23(7):880–886.  https://doi.org/10.1080/13607863.2018.1455167
  55. Gracie DJ, Guthrie EA, Hamlin PJ, Ford AC (2018) Bi-directionality of brain–gut interactions in patients with inflammatory bowel disease. Gastroenterology 154:1635–1646 e1633CrossRefPubMedGoogle Scholar
  56. Graff LA, Walker JR, Bernstein CN (2009) Depression and Anxiety in Inflammatory Bowel Disease:A Review of Comorbidity and Management. Inflamm Bowel Dis 15:1105–1118.  https://doi.org/10.1002/ibd.20873 CrossRefPubMedGoogle Scholar
  57. Graham AL, Allen JE, Read AF (2005) Evolutionary causes and consequences of immunopathology. Annu Rev Ecol Evol Syst 36:373–397Google Scholar
  58. Gray SM (2012) Bloch MH. Systematic review of proinflammatory cytokines in obsessive-compulsive disorder Curr Psychiatry Rep. 14:220–228.  https://doi.org/10.1007/s11920-012-0272-0 CrossRefPubMedGoogle Scholar
  59. Gruden-Movsesijan A, Ilic N, Mostarica-Stojkovic M, StosiC-Grujicic S, Milic M, SOFRONIC-MILOSAVLJEVIC l (2010) Mechanisms of modulation of experimental autoimmune encephalomyelitis by chronic Trichinella spiralis infection in Dark Agouti rats. Parasite Immunol 32:450–459CrossRefPubMedGoogle Scholar
  60. Haapakoski R, Mathieu J, Ebmeier KP, Alenius H, Kivimäki M (2015) Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder brain. Behav Immun 49:206–215.  https://doi.org/10.1016/j.bbi.2015.06.001 CrossRefGoogle Scholar
  61. Hannestad J, DellaGioia N, Bloch M (2011) The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36:2452CrossRefPubMedPubMedCentralGoogle Scholar
  62. Harnett W (2014) Secretory products of helminth parasites as immunomodulators. Mol Biochem Parasitol 195:130–136CrossRefPubMedGoogle Scholar
  63. Haroon E, Raison CL, Miller AH (2012) Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology 37:137–162CrossRefPubMedGoogle Scholar
  64. Harris NL, Loke P. (2017) Recent Advances in Type-2-Cell-Mediated Immunity. Insights from Helminth. Infect Immun 47:1024–1036.  https://doi.org/10.1016/j.immuni.2017.11.015
  65. He Y et al (2010) The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent. BMC Immunol 11:28CrossRefPubMedPubMedCentralGoogle Scholar
  66. Hewitson JP, Grainger JR, Maizels RM (2009) Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity. Mol Biochem Parasitol 167:1–11CrossRefPubMedPubMedCentralGoogle Scholar
  67. Hiles SA, Baker AL, de Malmanche T, Attia J (2012) A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity brain. Behav Immun 26:1180–1188.  https://doi.org/10.1016/j.bbi.2012.06.001 CrossRefGoogle Scholar
  68. Hoang H, Laursen B, Stenager EN, Stenager E (2016) Psychiatric co-morbidity in multiple sclerosis: The risk of depression and anxiety before and after MS diagnosis. Mult Scler J 22:347–353.  https://doi.org/10.1177/1352458515588973 CrossRefGoogle Scholar
  69. Hoerauf A (2010) Microflora, helminths, and the immune system—who controls whom? N Engl J Med 363:1476–1478CrossRefPubMedGoogle Scholar
  70. Hollander E et al. (2018) Randomized crossover feasibility trial of helminthic Trichuris suis ova versus placebo for repetitive behaviors in adult autism spectrum disorder. World J Biol Psychiatry:1–9.  https://doi.org/10.1080/15622975.2018.1523561
  71. Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118:1311–1321CrossRefPubMedPubMedCentralGoogle Scholar
  72. Hotez PJ et al (2014) The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases. Plos Negl Trop Dis 8:e2865CrossRefPubMedPubMedCentralGoogle Scholar
  73. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186CrossRefPubMedGoogle Scholar
  74. Inga Jácome MC et al (2016) Peripheral Inflammatory Markers Contributing to Comorbidities in Autism. Behav Sci 6:29CrossRefGoogle Scholar
  75. Kahl J, Brattig N, Liebau E (2018) The untapped pharmacopeic potential of helminths trend ParasitolGoogle Scholar
  76. Kang D-W, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, Pollard EL, Roux S, Sadowsky MJ, Lipson KS, Sullivan MB, Caporaso JG, Krajmalnik-Brown R (2017) Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 5:10.  https://doi.org/10.1186/s40168-016-0225-7 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Kang D-W et al (2019) Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep 9:5821CrossRefPubMedPubMedCentralGoogle Scholar
  78. Khan W, Blennerhasset P, Varghese A, Chowdhury S, Omsted P, Deng Y, Collins S (2002) Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun 70:5931–5937CrossRefPubMedPubMedCentralGoogle Scholar
  79. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB (2015) Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry 2:258–270CrossRefPubMedPubMedCentralGoogle Scholar
  80. Khor B, Gardet A, Xavier RJ (2011) Genetics and pathogenesis of inflammatory bowel disease. Nature 474:307CrossRefPubMedPubMedCentralGoogle Scholar
  81. Köhler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, Krogh J (2014) Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71:1381–1391CrossRefPubMedGoogle Scholar
  82. Köhler CA et al (2017) Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand 135:373–387.  https://doi.org/10.1111/acps.12698 CrossRefPubMedGoogle Scholar
  83. Kou HH, Parker W (2018) Intestinal worms eating neuropsychiatric disorders? Apparently so. Brain Res 1693:218–221.  https://doi.org/10.1016/j.brainres.2018.01.023 CrossRefPubMedGoogle Scholar
  84. Kowalski J, Blada P, Kucia K, Madej A, Herman Z (2001) Neuroleptics normalize increased release of interleukin-1β and tumor necrosis factor-α from monocytes in schizophrenia. Schizophr Res 50:169–175CrossRefPubMedGoogle Scholar
  85. Kurina LM, Goldacre MJ, Yeates D, Gill LE (2001) Depression and anxiety in people with inflammatory bowel disease. J Epidemiol Community Health 55:716–720.  https://doi.org/10.1136/jech.55.10.716 CrossRefPubMedPubMedCentralGoogle Scholar
  86. La Flamme AC, Ruddenklau K, Bäckström BT (2003) Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun 71:4996–5004CrossRefPubMedPubMedCentralGoogle Scholar
  87. Langdon K, Phie J, Thapa CB, Biros E, Loukas A, Haleagrahara N (2019) Helminth-based therapies for rheumatoid arthritis: A systematic review and meta-analysis. Int Immunopharmacol 66:366–372CrossRefPubMedGoogle Scholar
  88. Lee SC et al (2014) Helminth colonization is associated with increased diversity of the gut microbiota. PLoS Negl Trop Dis 8:e2880CrossRefPubMedPubMedCentralGoogle Scholar
  89. Liu Q, Sundar K, Mishra PK, Mousavi G, Liu Z, Gaydo A, Alem F, Lagunoff D, Bleich D, Gause WC (2009) Helminth infection can reduce insulitis and type 1 diabetes through CD25-and IL-10-independent mechanisms. Infect Immun 77:5347–5358CrossRefPubMedPubMedCentralGoogle Scholar
  90. Liu Y, Ho RC-M, Mak A (2012) Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord 139:230–239.  https://doi.org/10.1016/j.jad.2011.08.003 CrossRefPubMedGoogle Scholar
  91. Liu J, Morey R, Wilson J, Parker W (2017) Practices and outcomes of self-treatment with helminths based on physicians' observations. J Helminthol 91:267–277CrossRefPubMedGoogle Scholar
  92. Lopresti AL, Maker GL, Hood SD, Drummond PD (2014) A review of peripheral biomarkers in major depression: The potential of inflammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry 48:102–111.  https://doi.org/10.1016/j.pnpbp.2013.09.017 CrossRefPubMedGoogle Scholar
  93. Lynch SV, Pedersen O (2016) The Human Intestinal Microbiome in Health and Disease. N Engl J Med 375:2369–2379.  https://doi.org/10.1056/NEJMra1600266 CrossRefPubMedGoogle Scholar
  94. Maes M, Bosmans E, Calabrese J, Smith R, Meltzer HY (1995) Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. J Psychiatr Res 29:141–152CrossRefPubMedGoogle Scholar
  95. Maizels RM (2016) Parasitic helminth infections and the control of human allergic and autoimmune disorders. Clin Microbiol Infect 22:481–486CrossRefPubMedGoogle Scholar
  96. Maizels RM, McSorley HJ (2016) Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol 138:666–675.  https://doi.org/10.1016/j.jaci.2016.07.007 CrossRefPubMedPubMedCentralGoogle Scholar
  97. Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ (2015) Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20:440–446.  https://doi.org/10.1038/mp.2014.59 CrossRefPubMedGoogle Scholar
  98. Mathis D, Benoist C (2011) Microbiota and autoimmune disease: the hosted self. Cell Host Microbe 10:297–301CrossRefPubMedGoogle Scholar
  99. McSorley HJ et al (2011) Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. PloS One 6:e24092CrossRefPubMedPubMedCentralGoogle Scholar
  100. Miller AH, Raison CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 16:22–34CrossRefPubMedPubMedCentralGoogle Scholar
  101. Miller BJ, Buckley P, Seabolt W, Mellor A (2011) Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatr 70:663–671.  https://doi.org/10.1016/j.biopsych.2011.04.013
  102. Mo HM, Liu WQ, Lei JH, Cheng YL, Li YL (2007) Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent development of colitis in mice. Exp Parasitol 116:385–389Google Scholar
  103. Modabbernia A, Taslimi S, Brietzke E, Ashrafi M (2013) Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol Psychiatry 74:15–25.  https://doi.org/10.1016/j.biopsych.2013.01.007 CrossRefPubMedGoogle Scholar
  104. Moots R, Al-Saffar Z, Hutchinson D, Golding S, Young S, Bacon P, McLaughlin P (1999) Old drug, new tricks: haloperidol inhibits secretion of proinflammatory cytokines. Ann Rheum Dis 58:585–587CrossRefPubMedPubMedCentralGoogle Scholar
  105. Moreels T, Nieuwendijk R, De Man J, Winter D, Herman A, Van Marck E, Pelckmans P (2004) Concurrent infection with Schistosoma mansoni attenuates inflammation induced changes in colonic morphology, cytokine levels, and smooth muscle contractility of trinitrobenzene sulphonic acid induced colitis in rats. Gut 53:99–107CrossRefPubMedPubMedCentralGoogle Scholar
  106. Munkholm K, Braüner JV, Kessing LV, Vinberg M (2013a) Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res 47:1119–1133CrossRefPubMedGoogle Scholar
  107. Munkholm K, Vinberg M, Kessing LV (2013b) Cytokines in bipolar disorder: a systematic review and meta-analysis. J Affect Disord 144:16–27CrossRefPubMedGoogle Scholar
  108. Nguyen TT, Kosciolek T, Eyler LT, Knight R, Jeste DV (2018) Overview and systematic review of studies of microbiome in schizophrenia and bipolar disorder. J Psychiatr Res 99:50–61.  https://doi.org/10.1016/j.jpsychires.2018.01.013 CrossRefPubMedPubMedCentralGoogle Scholar
  109. Noto C, Rizzo LB, Mansur RB, McIntyre RS, Maes M, Brietzke E (2014) Targeting the inflammatory pathway as a therapeutic tool for major depression. Neuroimmunomodulation 21:131–139CrossRefPubMedGoogle Scholar
  110. Okada H, Kuhn C, Feillet H, Bach JF (2010) The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol 160:1–9CrossRefPubMedPubMedCentralGoogle Scholar
  111. Osada Y, Shimizu S, Kumagai T, Yamada S, Kanazawa T (2009) Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators. Int J Parasitol 39:457–464CrossRefPubMedGoogle Scholar
  112. O'Shea JJ, Ma A, Lipsky P (2002) Cytokines and autoimmunity. Nat Rev Immunol 2:37–45.  https://doi.org/10.1038/nri702 CrossRefPubMedGoogle Scholar
  113. Park S, Miller BJ (2019) Meta-analysis of cytokine and C-reactive protein levels in high-risk psychosis. Schizophr Res.  https://doi.org/10.1016/j.schres.2019.03.012
  114. Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC (2015) Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation. Clin Ther 37:984–995.  https://doi.org/10.1016/j.clinthera.2015.04.002 CrossRefPubMedPubMedCentralGoogle Scholar
  115. Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E (2008) Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatr 63:801–808CrossRefGoogle Scholar
  116. Ramanan D et al (2016) Helminth infection promotes colonization resistance via type 2 immunity. Science 352:608–612CrossRefPubMedPubMedCentralGoogle Scholar
  117. Rapin A, Harris NL (2018) Helminth–bacterial interactions: cause and consequence. Trend Immunol 39(9):724–733Google Scholar
  118. Reich DS, Lucchinetti CF, Calabresi PA (2018) Multiple Sclerosis. N Engl J Med 378:169–180.  https://doi.org/10.1056/NEJMra1401483 CrossRefPubMedGoogle Scholar
  119. Reyes JL et al (2016) IL-22 restrains tapeworm-mediated protection against experimental colitis via regulation of IL-25 expression. PLOS Pathogens 12:e1005481CrossRefPubMedPubMedCentralGoogle Scholar
  120. Reynolds LA et al (2014) Commensal-pathogen interactions in the intestinal tract gut. Microbes 5:522–532.  https://doi.org/10.4161/gmic.32155 CrossRefGoogle Scholar
  121. Reynolds LA, Finlay BB, Maizels RM (2015) Cohabitation in the intestine: interactions among helminth parasites, Bacterial Microbiota, and Host Immunity. J Immunol 195:4059–4066.  https://doi.org/10.4049/jimmunol.1501432
  122. Rivest S (2009) Regulation of innate immune responses in the brain. Nat Rev Immunol 9:429–439.  https://doi.org/10.1038/nri2565 CrossRefPubMedGoogle Scholar
  123. Roberts AL, Kubzansky LD, Malspeis S, Feldman CH, Costenbader KH (2018) Association of Depression With Risk of Incident Systemic Lupus Erythematosus in Women Assessed Across 2 Decades. JAMA Psychiatry 75:1225–1233.  https://doi.org/10.1001/jamapsychiatry.2018.2462
  124. Rodgers D, Pineda M, Suckling C, Harnett W, Harnett M (2015) Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus. Lupus 24:1437–1442CrossRefPubMedPubMedCentralGoogle Scholar
  125. Rogler G (2017) Resolution of inflammation in inflammatory bowel disease lancet. Gastroenterol Hepatol 2:521–530Google Scholar
  126. Rossi S et al (2017) Neuroinflammation drives anxiety and depression in relapsing-remitting multiple sclerosis. Neurology 89:1338–1347.  https://doi.org/10.1212/wnl.0000000000004411 CrossRefPubMedGoogle Scholar
  127. Roy T, Lloyd CE (2012) Epidemiology of depression and diabetes: A systematic review. J Affect Disord 142:S8–S21.  https://doi.org/10.1016/S0165-0327(12)70004-6 CrossRefPubMedGoogle Scholar
  128. Rzepecka J et al (2015) Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome. J Autoimmun 60:59–73CrossRefPubMedPubMedCentralGoogle Scholar
  129. Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133:775–787CrossRefPubMedGoogle Scholar
  130. Salinas-Carmona MC, De la Cruz-Galicia G, Pérez-Rivera I, Solís-Soto JM, Segoviano-Ramirez JC, Vázquez AV, Garza MA (2009) Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorated by Nippostrongylus brasiliensis infections. Autoimmunity 42:25–32Google Scholar
  131. Sandborn WJ et al (2013) Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn's disease. Aliment Pharmacol Ther 38:255–263.  https://doi.org/10.1111/apt.12366
  132. Sandhu KV, Sherwin E, Schellekens H, Stanton C, Dinan TG, Cryan JF (2017) Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry. Transl Res 179:223–244.  https://doi.org/10.1016/j.trsl.2016.10.002 CrossRefPubMedGoogle Scholar
  133. Saunders KA, Raine T, Cooke A, Lawrence CE (2007) Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun 75:397–407CrossRefPubMedGoogle Scholar
  134. Schnoeller C, Rausch S, Pillai S, Avagyan A, Wittig BM, Loddenkemper C, Hamann A, Hamelmann E, Lucius R, Hartmann S (2008) A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages. J Immunol 180:4265–4272CrossRefPubMedGoogle Scholar
  135. Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M, Fabry Z (2003) Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol 15:59–69CrossRefPubMedGoogle Scholar
  136. Siegmann E-M, Müller HH, Luecke C, Philipsen A, Kornhuber J, Grömer TW (2018) Association of Depression and Anxiety Disorders With Autoimmune Thyroiditis: A Systematic Review and Meta-analysis. JAMA Psychiatry 75:577–584CrossRefPubMedPubMedCentralGoogle Scholar
  137. Siniscalco D, Antonucci N (2013) Possible use of Trichuris suis ova in autism spectrum disorders therapy. Med Hypotheses 81:1–4Google Scholar
  138. Slyepchenko A, Maes M, Köhler CA, Anderson G, Quevedo J, Alves GS, Berk M, Fernandes BS, Carvalho AF (2016) T helper 17 cells may drive neuroprogression in major depressive disorder: proposal of an integrative model. Neurosci Biobehav Rev 64:83–100CrossRefPubMedGoogle Scholar
  139. Smallwood TB, Giacomin PR, Loukas A, Mulvenna JP, Clark RJ, Miles JJ (2017) Helminth immunomodulation in autoimmune disease. Front Immunol 8:453CrossRefPubMedPubMedCentralGoogle Scholar
  140. Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie AN, van Rooijen N, Fallon PG (2007) Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol 178:4557–4566CrossRefPubMedGoogle Scholar
  141. Smith KJ, Béland M, Clyde M, Gariépy G, Pagé V, Badawi G, Rabasa-Lhoret R, Schmitz N (2013) Association of diabetes with anxiety: a systematic review and meta-analysis. J Psychosom Res 74:89–99.  https://doi.org/10.1016/j.jpsychores.2012.11.013 CrossRefPubMedGoogle Scholar
  142. Sommer IE, Begemann M, Kahn R (2012) Nonsteroidal anti-inflammatory drugs in schizophrenia: ready for practice or a good start? A meta-analysis. J Clin Psychiatry 73:1478–1419CrossRefGoogle Scholar
  143. Sommer IE, van Westrhenen R, Begemann MJ, de Witte LD, Leucht S, Kahn RS (2014) Efficacy of Anti-inflammatory Agents to Improve Symptoms in Patients With Schizophrenia: An Update. Schizophr Bullet 40:181–191CrossRefGoogle Scholar
  144. Son JS et al (2015) Comparison of fecal microbiota in children with autism spectrum disorders and neurotypical siblings in the simons simplex collection. PloS One 10:e0137725CrossRefPubMedPubMedCentralGoogle Scholar
  145. Strati F, Cavalieri D, Albanese D, de Felice C, Donati C, Hayek J, Jousson O, Leoncini S, Renzi D, Calabrò A, de Filippo C (2017) New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 5:24.  https://doi.org/10.1186/s40168-017-0242-1 CrossRefPubMedPubMedCentralGoogle Scholar
  146. Summers RW, Elliott DE, Qadir K, Urban JF Jr, Thompson R, Weinstock JV (2003) Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 98:2034–2041Google Scholar
  147. Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV (2005) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128:825–832Google Scholar
  148. Sutton TL et al (2008) Anti-inflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model. Infect Immun 76:4772–4782Google Scholar
  149. Tomasik J, Rahmoune H, Guest PC, Bahn S (2016) Neuroimmune biomarkers in schizophrenia. Schizophr Res 176:3–13.  https://doi.org/10.1016/j.schres.2014.07.025 CrossRefPubMedGoogle Scholar
  150. Tourjman V, Kouassi É, Koué M-È, Rocchetti M, Fortin-Fournier S, Fusar-Poli P, Potvin S (2013) Antipsychotics' effects on blood levels of cytokines in schizophrenia: a meta-analysis. Schizophr Res 151:43–47CrossRefPubMedGoogle Scholar
  151. Upthegrove R, Manzanares-Teson N, Barnes NM (2014) Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophr Res 155:101–108CrossRefPubMedGoogle Scholar
  152. Valkanova V, Ebmeier KP, Allan CL (2013) CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord 150:736–744.  https://doi.org/10.1016/j.jad.2013.06.004 CrossRefPubMedGoogle Scholar
  153. van Dooren FEP, Nefs G, Schram MT, Verhey FRJ, Denollet J, Pouwer F (2013) Depression and Risk of Mortality in People with Diabetes Mellitus: A Systematic Review and Meta-Analysis. PLoS ONE 8:e57058.  https://doi.org/10.1371/journal.pone.0057058 CrossRefPubMedPubMedCentralGoogle Scholar
  154. Veenstra AA, Tang J, Kern TS (2013) Antagonism of CD11b with neutrophil inhibitory factor (NIF) inhibits vascular lesions in diabetic retinopathy. PLoS One 8:e78405CrossRefPubMedPubMedCentralGoogle Scholar
  155. Voldsgaard A et al (2015) Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect. Mult Scler J 21:1723–1729.  https://doi.org/10.1177/1352458514568173
  156. Walsh KP, Brady MT, Finlay CM, Boon L, Mills KH (2009) Infection with a helminth parasite attenuates autoimmunity through TGF-β-mediated suppression of Th17 and Th1 responses. J Immunol 183:1577–1586CrossRefPubMedGoogle Scholar
  157. Wammes LJ, Mpairwe H, Elliott AM, Yazdanbakhsh M (2014) Helminth therapy or elimination: epidemiological, immunological, and clinical considerations. Lancet Infect Dis 14:1150–1162CrossRefPubMedGoogle Scholar
  158. Wang Y, Kasper LH (2014) The role of microbiome in central nervous system disorders. Brain Behav Immun 38:1–12.  https://doi.org/10.1016/j.bbi.2013.12.015 CrossRefPubMedGoogle Scholar
  159. Weinstock JV, Elliott DE (2013) Translatability of helminth therapy in inflammatory bowel diseases. Int J Parasitol 43:245–251CrossRefPubMedGoogle Scholar
  160. Williamson LL et al (2016) Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection. Brain Behav Immun 51:14–28CrossRefPubMedGoogle Scholar
  161. Wiria AE, Djuardi Y, Supali T, Sartono E, Yazdanbakhsh M (2012) Helminth infection in populations undergoing epidemiological transition: a friend or foe? In: Semin Immunopathol, vol 6. Springer, pp 889–901Google Scholar
  162. Xia C-M, Zhao Y, Jiang L, Jiang J, Zhang S-C (2011) Schistosoma japonicum ova maintains epithelial barrier function during experimental colitis. World J Gastroenterol 17:4810Google Scholar
  163. Yasuda K, Takeuchi Y, Hirota K (2019) The pathogenicity of Th17 cells in autoimmune diseases. Semin Immunopathol 41(3):283–297.  https://doi.org/10.1007/s00281-019-00733-8
  164. Zaccone P, Fehérvári Z, Jones FM, Sidobre S, Kronenberg M, Dunne DW, Cooke A (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol 33:1439–1449Google Scholar
  165. Zaiss Mario M et al (2015) The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation. Immunity 43:998–1010.  https://doi.org/10.1016/j.immuni.2015.09.012 CrossRefPubMedPubMedCentralGoogle Scholar
  166. Zhang S (2018) The role of transforming growth factor β in T helper 17 differentiation. Immunology 155:24–35CrossRefPubMedPubMedCentralGoogle Scholar
  167. Zhao Y, Zhang S, Jiang L, Jiang J, Liu H (2009) Preventive effects of Schistosoma japonicum ova on trinitrobenzenesulfonic acid-induced colitis and bacterial translocation in mice. J Gastroenterol Hepatol 24:1775–1780Google Scholar
  168. Zheng X, Hu X, Zhou G, Lu Z, Qiu W, Bao J, Dai Y (2008) Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. J Neuroimmunol 194:107–114Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Parasitology and Mycology, School of MedicineJahrom University of Medical SciencesJahromIran
  2. 2.Zoonoses Research Center, School of MedicineJahrom University of Medical SciencesJahromIran
  3. 3.Research Center for Noncommunicable Diseases, School of MedicineJahrom University of Medical SciencesJahromIran
  4. 4.Department of Parasitology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran

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