Download PDF
Semin Neurol 2023; 43(04): 572-582
DOI: 10.1055/s-0043-1771467
Review Article

The Interface between Inflammatory Bowel Disease, Neuroinflammation, and Neurological Disorders

Grace E. Hey
1   Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
,
Vinata Vedam-Mai
1   Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
,
Matthew Beke
1   Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
2   Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida
,
Manuel Amaris
3   Department of Gastroenterology, University of Florida, Gainesville, Florida
,
Adolfo Ramirez-Zamora
1   Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Inflammatory Bowel Disease (IBD) is a complex, chronic inflammatory condition affecting the gastrointestinal tract. IBD has been associated with a variety of neurologic manifestations including peripheral nerve involvement, increased risk of thrombotic, demyelinating and events. Furthermore, an evolving association between IBD and neurodegenerative disorders has been recognized, and early data suggests an increased risk of these disorders in patients diagnosed with IBD. The relationship between intestinal inflammatory disease and neuroinflammation is complex, but the bidirectional interaction between the brain-gut-microbiome axis is likely to play an important role in the pathogenesis of these disorders. Identification of common mechanisms and pathways will be key to developing potential therapies. In this review, we discuss the evolving interface between IBD and neurological conditions, with a focus on clinical, mechanistic, and potentially therapeutic implications.

Keywords

inflammatory bowel disease - Parkinson's disease - gut microbiome - brain–gut axis - ulcerative colitis - Crohn's disease


Publication History

Article published online:
10 August 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Nguyen GC, Chong CA, Chong RY. National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States. J Crohn's Colitis 2014; 8 (04) 288-295
    CrossrefPubMedGoogle Scholar
  • 2 Molodecky NA, Soon IS, Rabi DM. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142 (01) 46-54.e42 , quiz e30
    CrossrefPubMedGoogle Scholar
  • 3 Ahluwalia B, Magnusson MK, Öhman L. Mucosal immune system of the gastrointestinal tract: maintaining balance between the good and the bad. Scand J Gastroenterol 2017; 52 (11) 1185-1193
    CrossrefPubMedGoogle Scholar
  • 4 Perez-Lopez A, Behnsen J, Nuccio SP, Raffatellu M. Mucosal immunity to pathogenic intestinal bacteria. Nat Rev Immunol 2016; 16 (03) 135-148
    CrossrefPubMedGoogle Scholar
  • 5 Wallace KL, Zheng LB, Kanazawa Y, Shih DQ. Immunopathology of inflammatory bowel disease. World J Gastroenterol 2014; 20 (01) 6-21
    CrossrefPubMedGoogle Scholar
  • 6 Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448 (7152): 427-434
    CrossrefPubMedGoogle Scholar
  • 7 de Souza HSP, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol 2016; 13 (01) 13-27
    CrossrefPubMedGoogle Scholar
  • 8 Cushing K, Higgins PDR. Management of Crohn disease: a review. JAMA 2021; 325 (01) 69-80
    CrossrefPubMedGoogle Scholar
  • 9 Mosli MH, Zou G, Garg SK. et al. C-reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. Am J Gastroenterol 2015; 110 (06) 802-819 , quiz 820
    CrossrefPubMedGoogle Scholar
  • 10 Chang JT. Pathophysiology of inflammatory bowel diseases. N Engl J Med 2020; 383 (27) 2652-2664
    CrossrefPubMedGoogle Scholar
  • 11 Illig D, Kotlarz D. Dysregulated inflammasome activity in intestinal inflammation - Insights from patients with very early onset IBD. Front Immunol 2022; 13: 1027289
    CrossrefPubMedGoogle Scholar
  • 12 Xu XR, Liu CQ, Feng BS, Liu ZJ. Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease. World J Gastroenterol 2014; 20 (12) 3255-3264
    CrossrefPubMedGoogle Scholar
  • 13 Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009; 9 (05) 313-323
    CrossrefPubMedGoogle Scholar
  • 14 Manichanh C, Rigottier-Gois L, Bonnaud E. et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 2006; 55 (02) 205-211
    CrossrefPubMedGoogle Scholar
  • 15 Swidsinski A, Ladhoff A, Pernthaler A. et al. Mucosal flora in inflammatory bowel disease. Gastroenterology 2002; 122 (01) 44-54
    CrossrefPubMedGoogle Scholar
  • 16 Duerr RH, Taylor KD, Brant SR. et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314 (5804): 1461-1463
    CrossrefPubMedGoogle Scholar
  • 17 Jostins L, Ripke S, Weersma RK. et al; International IBD Genetics Consortium (IIBDGC). Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491 (7422): 119-124
    CrossrefPubMedGoogle Scholar
  • 18 de Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol 2016; 13 (01) 13-27
    CrossrefPubMedGoogle Scholar
  • 19 Sauceda C, Bayne C, Sudqi K. et al. Stool multi-omics for the study of host-microbe interactions in inflammatory bowel disease. Gut Microbes 2022; 14 (01) 2154092
    CrossrefPubMedGoogle Scholar
  • 20 Bernstein CN, Shanahan F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut 2008; 57 (09) 1185-1191
    CrossrefPubMedGoogle Scholar
  • 21 Ng SC, Bernstein CN, Vatn MH. et al; Epidemiology and Natural History Task Force of the International Organization of Inflammatory Bowel Disease (IOIBD). Geographical variability and environmental risk factors in inflammatory bowel disease. Gut 2013; 62 (04) 630-649
    CrossrefPubMedGoogle Scholar
  • 22 Hviid A, Svanström H, Frisch M. Antibiotic use and inflammatory bowel diseases in childhood. Gut 2011; 60 (01) 49-54
    CrossrefPubMedGoogle Scholar
  • 23 Benjamin JL, Hedin CR, Koutsoumpas A. et al. Smokers with active Crohn's disease have a clinically relevant dysbiosis of the gastrointestinal microbiota. Inflamm Bowel Dis 2012; 18 (06) 1092-1100
    CrossrefPubMedGoogle Scholar
  • 24 Nerich V, Jantchou P, Boutron-Ruault MC. et al. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther 2011; 33 (08) 940-945
    CrossrefPubMedGoogle Scholar
  • 25 Graham DB, Xavier RJ. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature 2020; 578 (7796): 527-539
    CrossrefPubMedGoogle Scholar
  • 26 Furey TS, Sethupathy P, Sheikh SZ. Redefining the IBDs using genome-scale molecular phenotyping. Nat Rev Gastroenterol Hepatol 2019; 16 (05) 296-311
    CrossrefPubMedGoogle Scholar
  • 27 Crowley E, Muise A. Inflammatory bowel disease: what very early onset disease teaches us. Gastroenterol Clin North Am 2018; 47 (04) 755-772
    CrossrefPubMedGoogle Scholar
  • 28 Round JL, Palm NW. Causal effects of the microbiota on immune-mediated diseases. Sci Immunol 2018; 3 (20) eaao1603
    CrossrefPubMedGoogle Scholar
  • 29 Schirmer M, Garner A, Vlamakis H, Xavier RJ. Microbial genes and pathways in inflammatory bowel disease. Nat Rev Microbiol 2019; 17 (08) 497-511
    CrossrefPubMedGoogle Scholar
  • 30 Skelly AN, Sato Y, Kearney S, Honda K. Mining the microbiota for microbial and metabolite-based immunotherapies. Nat Rev Immunol 2019; 19 (05) 305-323
    CrossrefPubMedGoogle Scholar
  • 31 Herrick MK, Tansey MG. Is LRRK2 the missing link between inflammatory bowel disease and Parkinson's disease?. NPJ Parkinsons Dis 2021; 7 (01) 26
    CrossrefPubMedGoogle Scholar
  • 32 Frolkis AD, Vallerand IA, Shaheen AA. et al. Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression. Gut 2019; 68 (09) 1606-1612
    CrossrefPubMedGoogle Scholar
  • 33 Gracie DJ, Guthrie EA, Hamlin PJ, Ford AC. Bi-directionality of brain-gut interactions in patients with inflammatory bowel disease. Gastroenterology 2018; 154 (06) 1635-1646.e3
    CrossrefPubMedGoogle Scholar
  • 34 Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 2012; 9 (05) 286-294
    CrossrefPubMedGoogle Scholar
  • 35 Fothergill LJ, Furness JB. Diversity of enteroendocrine cells investigated at cellular and subcellular levels: the need for a new classification scheme. Histochem Cell Biol 2018; 150 (06) 693-702
    CrossrefPubMedGoogle Scholar
  • 36 Gribble FM, Reimann F. Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu Rev Physiol 2016; 78: 277-299
    CrossrefPubMedGoogle Scholar
  • 37 Ferrante M, de Hertogh G, Hlavaty T. et al. The value of myenteric plexitis to predict early postoperative Crohn's disease recurrence. Gastroenterology 2006; 130 (06) 1595-1606
    CrossrefPubMedGoogle Scholar
  • 38 Villanacci V, Bassotti G, Nascimbeni R. et al. Enteric nervous system abnormalities in inflammatory bowel diseases. Neurogastroenterol Motil 2008; 20 (09) 1009-1016
    CrossrefPubMedGoogle Scholar
  • 39 Sokol H, Polin V, Lavergne-Slove A. et al. Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease. Gut 2009; 58 (09) 1218-1225
    CrossrefPubMedGoogle Scholar
  • 40 Geboes K, Collins S. Structural abnormalities of the nervous system in Crohn's disease and ulcerative colitis. Neurogastroenterol Motil 1998; 10 (03) 189-202
    CrossrefPubMedGoogle Scholar
  • 41 Margolis KG, Stevanovic K, Karamooz N. et al. Enteric neuronal density contributes to the severity of intestinal inflammation. Gastroenterology 2011; 141 (02) 588-598 , 598.e1–598.e2
    CrossrefPubMedGoogle Scholar
  • 42 Mashaghi A, Marmalidou A, Tehrani M, Grace PM, Pothoulakis C, Dana R. Neuropeptide substance P and the immune response. Cell Mol Life Sci 2016; 73 (22) 4249-4264
    CrossrefPubMedGoogle Scholar
  • 43 O'Connor TM, O'Connell J, O'Brien DI, Goode T, Bredin CP, Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol 2004; 201 (02) 167-180
    CrossrefPubMedGoogle Scholar
  • 44 Kulka M, Sheen CH, Tancowny BP, Grammer LC, Schleimer RP. Neuropeptides activate human mast cell degranulation and chemokine production. Immunology 2008; 123 (03) 398-410
    CrossrefPubMedGoogle Scholar
  • 45 He SH. Key role of mast cells and their major secretory products in inflammatory bowel disease. World J Gastroenterol 2004; 10 (03) 309-318
    CrossrefPubMedGoogle Scholar
  • 46 Casado-Bedmar M, Heil SDS, Myrelid P, Söderholm JD, Keita ÅV. Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis. Neurogastroenterol Motil 2019; 31 (03) e13503
    CrossrefPubMedGoogle Scholar
  • 47 Raithel M, Winterkamp S, Pacurar A, Ulrich P, Hochberger J, Hahn EG. Release of mast cell tryptase from human colorectal mucosa in inflammatory bowel disease. Scand J Gastroenterol 2001; 36 (02) 174-179
    CrossrefPubMedGoogle Scholar
  • 48 Turner D, Ricciuto A, Lewis A. et al; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021; 160 (05) 1570-1583
    CrossrefPubMedGoogle Scholar
  • 49 Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG Clinical Guideline: management of Crohn's disease in adults. Am J Gastroenterol 2018; 113 (04) 481-517
    CrossrefPubMedGoogle Scholar
  • 50 Ko CW, Singh S, Feuerstein JD, Falck-Ytter C, Falck-Ytter Y, Cross RK. American Gastroenterological Association Institute Clinical Guidelines Committee. AGA clinical practice guidelines on the management of mild-to-moderate ulcerative colitis. Gastroenterology 2019; 156 (03) 748-764
    CrossrefPubMedGoogle Scholar
  • 51 Ford AC, Achkar JP, Khan KJ. et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol 2011; 106 (04) 601-616
    CrossrefPubMedGoogle Scholar
  • 52 Marshall JK, Thabane M, Steinhart AH, Newman JR, Anand A, Irvine EJ. Rectal 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2010; (01) CD004115
    PubMedGoogle Scholar
  • 53 Ford AC, Khan KJ, Achkar JP, Moayyedi P. Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol 2012; 107 (02) 167-176 , author reply 177
    CrossrefPubMedGoogle Scholar
  • 54 Feagan BG, Macdonald JK. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2012; 10: CD000543
    PubMedGoogle Scholar
  • 55 Sandborn WJ, Travis S, Moro L. et al. Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology 2012; 143 (05) 1218-1226 .e2
    CrossrefPubMedGoogle Scholar
  • 56 Ford AC, Bernstein CN, Khan KJ. et al. Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 2011; 106 (04) 590-599 , quiz 600
    CrossrefPubMedGoogle Scholar
  • 57 Rubin DT, Cohen RD, Sandborn WJ. et al. Budesonide multimatrix is efficacious for mesalamine-refractory, mild to moderate ulcerative colitis: a randomised, placebo-controlled trial. J Crohn's Colitis 2017; 11 (07) 785-791
    CrossrefPubMedGoogle Scholar
  • 58 Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S. AGA Institute Clinical Guidelines Committee. AGA Clinical Practice Guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology 2020; 158 (05) 1450-1461
    CrossrefPubMedGoogle Scholar
  • 59 Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of inflammatory bowel disease. Neurology 1995; 45 (3, Pt 1): 416-421
    CrossrefPubMedGoogle Scholar
  • 60 Ferro JM, Oliveira SN, Correia L. Neurologic manifestations of inflammatory bowel diseases. Neurologic Aspects of Systemic Disease Part II. Elsevier; 2014:595–605. Handbook of Clinical Neurology
    PubMedGoogle Scholar
  • 61 Gondim FAA, Brannagan III TH, Sander HW, Chin RL, Latov N. Peripheral neuropathy in patients with inflammatory bowel disease. Brain 2005; 128 (Pt 4): 867-879
    CrossrefPubMedGoogle Scholar
  • 62 Loftus Jr EV. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 2004; 126 (06) 1504-1517
    CrossrefPubMedGoogle Scholar
  • 63 Talbot RW, Heppell J, Dozois RR, Beart Jr RW. Vascular complications of inflammatory bowel disease. Mayo Clin Proc 1986; 61 (02) 140-145
    CrossrefPubMedGoogle Scholar
  • 64 Xiao Z, Pei Z, Yuan M, Li X, Chen S, Xu L. Risk of stroke in patients with inflammatory bowel disease: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis 2015; 24 (12) 2774-2780
    CrossrefPubMedGoogle Scholar
  • 65 Chen Y, Wang X. Increased risk of stroke among patients with inflammatory bowel disease: a PRISMA-compliant meta-analysis. Brain Behav 2021; 11 (06) e02159
    CrossrefPubMedGoogle Scholar
  • 66 Tanislav C, Trommer K, Labenz C, Kostev K. Inflammatory bowel disease as a precondition for stroke or TIA: a matter of Crohn's disease rather than ulcerative colitis. J Stroke Cerebrovasc Dis 2021; 30 (07) 105787
    CrossrefPubMedGoogle Scholar
  • 67 Kristensen SL, Lindhardsen J, Ahlehoff O. et al. Increased risk of atrial fibrillation and stroke during active stages of inflammatory bowel disease: a nationwide study. Europace 2014; 16 (04) 477-484
    CrossrefPubMedGoogle Scholar
  • 68 Zhao L, Xiong Q, Stary CM. et al. Bidirectional gut-brain-microbiota axis as a potential link between inflammatory bowel disease and ischemic stroke. J Neuroinflammation 2018; 15 (01) 339
    CrossrefPubMedGoogle Scholar
  • 69 Golovics PA, Verdon C, Wetwittayakhlang P. et al. Increased prevalence of myocardial infarction and stable stroke proportions in patients with inflammatory bowel diseases in Quebec in 1996-2015. J Clin Med 2022; 11 (03) 686
    CrossrefPubMedGoogle Scholar
  • 70 Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating diseases in patients with inflammatory bowel disease. Gastroenterology 2005; 129 (03) 819-826
    CrossrefPubMedGoogle Scholar
  • 71 Wong M, Ziring D, Korin Y. et al. TNFalpha blockade in human diseases: mechanisms and future directions. Clin Immunol 2008; 126 (02) 121-136
    CrossrefPubMedGoogle Scholar
  • 72 Kemanetzoglou E, Andreadou E. CNS demyelination with TNF-α blockers. Curr Neurol Neurosci Rep 2017; 17 (04) 36
    CrossrefPubMedGoogle Scholar
  • 73 Lis K, Kuzawińska O, Bałkowiec-Iskra E. Tumor necrosis factor inhibitors - state of knowledge. Arch Med Sci 2014; 10 (06) 1175-1185
    CrossrefPubMedGoogle Scholar
  • 74 Braga SFF, Clark KJ. Overview of TNF inhibitors for treating inflammatory bowel disease. US Pharm 2021; 46 (05) 34-37
    PubMedGoogle Scholar
  • 75 Marchi N, Granata T, Janigro D. Inflammatory pathways of seizure disorders. Trends Neurosci 2014; 37 (02) 55-65
    CrossrefPubMedGoogle Scholar
  • 76 Bonaz B, Picq C, Sinniger V, Mayol JF, Clarençon D. Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway. Neurogastroenterol Motil 2013; 25 (03) 208-221
    CrossrefPubMedGoogle Scholar
  • 77 Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation. J Physiol 2016; 594 (20) 5781-5790
    CrossrefPubMedGoogle Scholar
  • 78 Bonaz B, Sinniger V, Pellissier S. Therapeutic potential of vagus nerve stimulation for inflammatory bowel diseases. Front Neurosci 2021; 15: 650971
    CrossrefPubMedGoogle Scholar
  • 79 van IJzendoorn SCD, Derkinderen P. The intestinal barrier in Parkinson's disease: current state of knowledge. J Parkinsons Dis 2019; 9 (Suppl. 02) S323-S329
    CrossrefPubMedGoogle Scholar
  • 80 Gray MT, Woulfe JM. Striatal blood-brain barrier permeability in Parkinson's disease. J Cereb Blood Flow Metab 2015; 35 (05) 747-750
    CrossrefPubMedGoogle Scholar
  • 81 Lema Tomé CM, Tyson T, Rey NL, Grathwohl S, Britschgi M, Brundin P. Inflammation and α-synuclein's prion-like behavior in Parkinson's disease – Is there a link?. Mol Neurobiol 2013; 47 (02) 561-574
    CrossrefPubMedGoogle Scholar
  • 82 Sprenger FS, Stefanova N, Gelpi E. et al. Enteric nervous system α-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology 2015; 85 (20) 1761-1768
    CrossrefPubMedGoogle Scholar
  • 83 Liu B, Fang F, Pedersen NL. et al. Vagotomy and Parkinson disease: a Swedish register-based matched-cohort study. Neurology 2017; 88 (21) 1996-2002
    CrossrefPubMedGoogle Scholar
  • 84 Lee HS, Lobbestael E, Vermeire S, Sabino J, Cleynen I. Inflammatory bowel disease and Parkinson's disease: common pathophysiological links. Gut 2021; 70 (02) 408-417
    PubMedGoogle Scholar
  • 85 Park S, Kim J, Chun J. et al. Patients with inflammatory bowel disease are at an increased risk of Parkinson's disease: a South Korean Nationwide Population-Based Study. J Clin Med 2019; 8 (08) 1191
    CrossrefPubMedGoogle Scholar
  • 86 Zhu Y, Yuan M, Liu Y. et al. Association between inflammatory bowel diseases and Parkinson's disease: systematic review and meta-analysis. Neural Regen Res 2022; 17 (02) 344-353
    CrossrefPubMedGoogle Scholar
  • 87 Weimers P, Halfvarson J, Sachs MC. et al. Inflammatory bowel disease and Parkinson's disease: a nationwide Swedish cohort study. Inflamm Bowel Dis 2019; 25 (01) 111-123
    CrossrefPubMedGoogle Scholar
  • 88 Zhu F, Li C, Gong J, Zhu W, Gu L, Li N. The risk of Parkinson's disease in inflammatory bowel disease: a systematic review and meta-analysis. Dig Liver Dis 2019; 51 (01) 38-42
    CrossrefPubMedGoogle Scholar
  • 89 Choi K, Lee HJ, Han K, Koh SJ, Im JP, Kim JS. Depression in patients with inflammatory bowel disease is associated with increased risk of dementia and Parkinson's disease: a nationwide, population-based study. Front Med (Lausanne) 2022; 9: 1014290
    CrossrefPubMedGoogle Scholar
  • 90 Lin JC, Lin CS, Hsu CW, Lin CL, Kao CH. Association between Parkinson's disease and inflammatory bowel disease: a nationwide Taiwanese retrospective cohort study. Inflamm Bowel Dis 2016; 22 (05) 1049-1055
    CrossrefPubMedGoogle Scholar
  • 91 Cui G, Li S, Ye H. et al. Are neurodegenerative diseases associated with an increased risk of inflammatory bowel disease? A two-sample Mendelian randomization study. Front Immunol 2022; 13: 956005
    CrossrefPubMedGoogle Scholar
  • 92 Peter I, Dubinsky M, Bressman S. et al. Anti-tumor necrosis factor therapy and incidence of Parkinson disease among patients with inflammatory bowel disease. JAMA Neurol 2018; 75 (08) 939-946
    CrossrefPubMedGoogle Scholar
  • 93 Pinel Ríos J, Madrid Navarro CJ, Pérez Navarro MJ. et al. Association of Parkinson's disease and treatment with aminosalicylates in inflammatory bowel disease: a cross-sectional study in a Spain drug dispensation records. BMJ Open 2019; 9 (06) e025574
    CrossrefPubMedGoogle Scholar
  • 94 Racette BA, Gross A, Vouri SM, Camacho-Soto A, Willis AW, Searles Nielsen S. Immunosuppressants and risk of Parkinson disease. Ann Clin Transl Neurol 2018; 5 (07) 870-875
    CrossrefPubMedGoogle Scholar
  • 95 Coates MD, Ba DM, Liu G, Dalessio S, Leslie DL, Huang X. Revisiting the association between inflammatory bowel disease and Parkinson's disease. Inflamm Bowel Dis 2022; 28 (06) 850-854
    CrossrefPubMedGoogle Scholar
  • 96 Freuer D, Meisinger C. Association between inflammatory bowel disease and Parkinson's disease: a Mendelian randomization study. NPJ Parkinsons Dis 2022; 8 (01) 55
    CrossrefPubMedGoogle Scholar
  • 97 Kim GH, Lee YC, Kim TJ. et al. Risk of neurodegenerative diseases in patients with inflammatory bowel disease: a nationwide population-based cohort study. J Crohn's Colitis 2022; 16 (03) 436-443
    CrossrefPubMedGoogle Scholar
  • 98 Zhu W, Tao M, Hong Y. et al. Dysfunction of vesicular storage in young-onset Parkinson's patient-derived dopaminergic neurons and organoids revealed by single cell electrochemical cytometry. Chem Sci (Camb) 2022; 13 (21) 6217-6223
    CrossrefPubMedGoogle Scholar
  • 99 Witoelar A, Jansen IE, Wang Y. et al; International Parkinson's Disease Genomics Consortium (IPDGC), North American Brain Expression Consortium (NABEC), and United Kingdom Brain Expression Consortium (UKBEC) Investigators. Genome-wide pleiotropy between Parkinson disease and autoimmune diseases. JAMA Neurol 2017; 74 (07) 780-792
    CrossrefPubMedGoogle Scholar
  • 100 Franke A, McGovern DPB, Barrett JC. et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 2010; 42 (12) 1118-1125
    CrossrefPubMedGoogle Scholar
  • 101 Herrick MK, Tansey MG. Is LRRK2 the missing link between inflammatory bowel disease and Parkinson's disease?. NPJ Parkinsons Dis 2021; 7 (01) 26
    CrossrefPubMedGoogle Scholar
  • 102 Hui KY, Fernandez-Hernandez H, Hu J. et al. Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's disease and Parkinson's disease. Sci Transl Med 2018; 10 (423) eaai7795
    CrossrefPubMedGoogle Scholar
  • 103 Dogra N, Jakhmola-Mani R, Potshangbam AM, Buch S, Pande Katare D. CXCR4 as possible druggable target linking inflammatory bowel disease and Parkinson's disease. Metab Brain Dis 2023; 38 (03) 1079-1096
    CrossrefPubMedGoogle Scholar
  • 104 Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol 2011; 106 (04) 563-573
    CrossrefPubMedGoogle Scholar
  • 105 Hantikainen E, Roos E, Bellocco R. et al. Dietary fat intake and risk of Parkinson disease: results from the Swedish National March Cohort. Eur J Epidemiol 2022; 37 (06) 603-613
    CrossrefPubMedGoogle Scholar
  • 106 Ananthakrishnan AN, Khalili H, Konijeti GG. et al. A prospective study of long-term intake of dietary fiber and risk of Crohn's disease and ulcerative colitis. Gastroenterology 2013; 145 (05) 970-977
    CrossrefPubMedGoogle Scholar
  • 107 Agim ZS, Cannon JR. Dietary factors in the etiology of Parkinson's disease. BioMed Res Int 2015; 2015: 672838
    PubMedGoogle Scholar
  • 108 Ananthakrishnan AN, Khalili H, Higuchi LM. et al. Higher predicted vitamin D status is associated with reduced risk of Crohn's disease. Gastroenterology 2012; 142 (03) 482-489
    CrossrefPubMedGoogle Scholar
  • 109 Higuchi LM, Khalili H, Chan AT, Richter JM, Bousvaros A, Fuchs CS. A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. Am J Gastroenterol 2012; 107 (09) 1399-1406
    CrossrefPubMedGoogle Scholar
  • 110 Doiron M, Dupré N, Langlois M, Provencher P, Simard M. Smoking history is associated to cognitive impairment in Parkinson's disease. Aging Ment Health 2017; 21 (03) 322-326
    CrossrefPubMedGoogle Scholar
  • 111 Fang X, Han D, Cheng Q. et al. Association of levels of physical activity with risk of Parkinson disease: a systematic review and meta-analysis. JAMA Netw Open 2018; 1 (05) e182421
    CrossrefPubMedGoogle Scholar
  • 112 Khalili H, Ananthakrishnan AN, Konijeti GG. et al. Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses' Health Study cohorts. BMJ 2013; 347 (04) f6633
    CrossrefPubMedGoogle Scholar
  • 113 Ali T, Madhoun MF, Orr WC, Rubin DT. Assessment of the relationship between quality of sleep and disease activity in inflammatory bowel disease patients. Inflamm Bowel Dis 2013; 19 (11) 2440-2443
    CrossrefPubMedGoogle Scholar
  • 114 Bohnen NI, Hu MTM. Sleep disturbance as potential risk and progression factor for Parkinson's disease. J Parkinsons Dis 2019; 9 (03) 603-614
    CrossrefPubMedGoogle Scholar
  • 115 Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (N Y) 2010; 6 (05) 339-346
    PubMedGoogle Scholar
  • 116 Guo S, Al-Sadi R, Said HM, Ma TY. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol 2013; 182 (02) 375-387
    CrossrefPubMedGoogle Scholar
  • 117 Abd-El-Basset EM, Rao MS, Alshawaf SM, Ashkanani HK, Kabli AH. Tumor necrosis factor (TNF) induces astrogliosis, microgliosis and promotes survival of cortical neurons. AIMS Neurosci 2021; 8 (04) 558-584
    CrossrefPubMedGoogle Scholar
  • 118 Zhang B, Wang HE, Bai YM. et al. Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut 2021; 70 (01) 85-91
    CrossrefPubMedGoogle Scholar
  • 119 Szandruk-Bender M, Wiatrak B, Szeląg A. The risk of developing Alzheimer's disease and Parkinson's disease in patients with inflammatory bowel disease: a meta-analysis. J Clin Med 2022; 11 (13) 3704
    CrossrefPubMedGoogle Scholar
  • 120 Zhang MN, Shi YD, Jiang HY. The risk of dementia in patients with inflammatory bowel disease: a systematic review and meta-analysis. Int J Colorectal Dis 2022; 37 (04) 769-775
    CrossrefPubMedGoogle Scholar
  • 121 Wang D, Zhang X, Du H. Inflammatory bowel disease: a potential pathogenic factor of Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2022; 119: 110610
    CrossrefPubMedGoogle Scholar
  • 122 Adewuyi EO, O'Brien EK, Nyholt DR, Porter T, Laws SM. A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer's disease and gastrointestinal tract disorders. Commun Biol 2022; 5 (01) 691
    CrossrefPubMedGoogle Scholar
  • 123 Liu N, Wang Y, He L, Sun J, Wang X, Li H. Inflammatory bowel disease and risk of dementia: an updated meta-analysis. Front Aging Neurosci 2022; 14: 962681
    CrossrefPubMedGoogle Scholar
  • 124 Gopinath A, Mackie P, Hashimi B. et al. DAT and TH expression marks human Parkinson's disease in peripheral immune cells. NPJ Parkinsons Dis 2022; 8 (01) 72
    CrossrefPubMedGoogle Scholar
  • 125 Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis?. NPJ Parkinsons Dis 2017; 3 (01) 3
    CrossrefPubMedGoogle Scholar