Gut. 2020 Oct 16;gutjnl-2020-322429. doi: 10.1136/gutjnl-2020-322429.Online ahead of print.

Ho-Su Lee ^# 1 2, Evy Lobbestael ^# 3, Séverine Vermeire ^4 5, João Sabino ^4 5, Isabelle Cleynen ⁶

Author information

• ¹Department of Human Genetics, KU Leuven, Leuven, Belgium.
• ²Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea.
• ³Laboratory for Neurobiology and Gene Therapy, KU Leuven, Leuven, Belgium.
• ⁴Department of Chronic diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
• ⁵Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
• ⁶Department of Human Genetics, KU Leuven, Leuven, Belgium isabelle.cleynen@kuleuven.be.

^#Contributed equally.

Abstract

Inflammatory bowel disease and Parkinson's disease are chronic progressive disorders that mainly affect different organs: the gut and brain, respectively. Accumulating evidence has suggested a bidirectional link between gastrointestinal inflammation and neurodegeneration, in accordance with the concept of the 'gut-brain axis'. Moreover, recent population-based studies have shown that inflammatory bowel disease might increase the risk of Parkinson's disease. Although the precise mechanisms underlying gut-brain interactions remain elusive, some of the latest findings have begun to explain the link. Several genetic loci are shared between both disorders with a similar direction of effect on the risk of both diseases. The most interesting example is LRRK2 (leucine-rich repeat kinase 2), initially identified as a causal gene in Parkinson's disease, and recently also implicated in Crohn's disease. In this review, we highlight recent findings on the link between these seemingly unrelated diseases with shared genetic susceptibility. We discuss supporting and conflicting data obtained from epidemiological and genetic studies along with remaining questions and concerns. In addition, we discuss possible biological links including the gut-brain axis, microbiota, autoimmunity, mitochondrial function and autophagy.