Autism Res. 2022 Feb;15(2):340-352. doi: 10.1002/aur.2656.Epub 2021 Dec 23.

Jong Yeob Kim ¹, Min Je Choi ¹, Sungji Ha ², Jimin Hwang ³, Ai Koyanagi ^4 5, Elena Dragioti ⁶, Joaquim Radua ^7 8 9, Lee Smith ¹⁰, Louis Jacob ^4 11, Gonzalo Salazar de Pablo ^12 13 14, Seung Won Lee ¹⁵, Dong Keon Yon ¹⁶, Trevor Thompson ¹⁷, Samuele Cortese ^{18 19 20 21}, Gianluca Lollo ²², Chih-Sung Liang ^23 24, Che-Sheng Chu ^{25 26 27 28}, Paolo Fusar-Poli ^{12 29 30 31}, Keun-Ah Cheon ², Jae Il Shin ³², Marco Solmi ^{12 18 33 34 35}

Author information

¹Yonsei University College of Medicine, Seoul, South Korea.

²Department of Child and Adolescent Psychiatry, Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.

³Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

⁴Research and Development Unit, Parc Sanitari Sant Joan de Déu/CIBERSAM, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.

⁵ICREA, Barcelona, Spain.

⁶Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.

⁷Mental Health Research Networking Center (CIBERSAM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

⁸Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

⁹Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.

¹⁰Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK.

¹¹Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.

¹²Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

¹³Child and Adolescent Mental Health Services, South London & Maudsley NHS Trust, London, UK.

¹⁴Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

¹⁵Department of Data Science, Sejong University College of Software Convergence, Seoul, South Korea.

¹⁶Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea.

¹⁷Centre for Chronic Illness and Ageing, University of Greenwich, London, UK.

¹⁸Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life sciences & Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.

¹⁹Solent NHS Trust, Southampton, UK.

²⁰Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.

²¹Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, New York, USA.

²²Department of Gastroenterology, Ospedale Regionale di Bellinzona e Valli (Ente Ospedaliero Cantonale: EOC), Bellinzona, Switzerland.

²³Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan.

²⁴Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

²⁵Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

²⁶Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

²⁷Society of Psychophysiology, Non-invasive Neuromodulation Consortium for Mental Disorders, Taipei, Taiwan.

²⁸Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

²⁹OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.

³⁰Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

³¹National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.

³²Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea.

³³Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada.

³⁴Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada.

³⁵Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, Ontario, Canada.

Abstract

Children with autism spectrum disorder (ASD) are frequently diagnosed with co-occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random-effects meta-analysis. We searched PubMed, Embase, and PsycInfo (last search on January 25, 2021), and manually searched relevant publications. We included observational studies measuring the association between ASD and IBD. The primary outcome was the association (odds ratio, OR) between ASD and later development of IBD. Sensitivity analyses were conducted by quality, confounding adjustment, and study design. We performed meta-regression analyses and assessed heterogeneity, publication bias, and quality of studies with the Newcastle-Ottawa Scale. Overall, we included six studies consisting of eight datasets, including over 11 million participants. We found that ASD was significantly associated with subsequent incident IBD (any IBD, OR = 1.66, 95% confidence interval[CI] = 1.25-2.21, p < 0.001; ulcerative colitis, OR = 1.91, 95%CI = 1.41-2.6, p < 0.001; Crohn's disease, OR = 1.47, 95%CI = 1.15-1.88, p = 0.002). ASD and IBD were also associated regardless of temporal sequence of diagnosis (any IBD, OR = 1.57, 95%CI = 1.28-1.93, p < 0.001; ulcerative colitis, OR = 1.7, 95%CI = 1.36-2.12, p < 0.001; Crohn's disease, OR = 1.37, 95%CI = 1.12-1.69, p = 0.003). Sensitivity analyses confirmed the findings of the main analysis. Meta-regression did not identify any significant moderators. Publication bias was not detected. Quality was high in four datasets and medium in four. In conclusion, our findings highlight the need to screen for IBD in individuals with ASD, and future research should identify who, among those with ASD, has the highest risk of IBD, and elucidate the shared biological mechanisms between ASD and IBD. LAY SUMMARY: This systematic review and meta-analysis of eight observational datasets found that individuals with autism spectrum disorder (ASD) are more likely to develop any inflammatory bowel disease, ulcerative colitis, or Crohn's disease. Our findings highlight the need to screen for inflammatory bowel disease in patients with ASD and elucidate the shared biological mechanisms between the two disorders.