The Role of Viruses in the Pathogenesis of Immune-Mediated Gastro-Intestinal Diseases

Abstract

Immune-mediated gastrointestinal (GI) diseases, including achalasia, celiac disease, and inflammatory bowel diseases, pose significant challenges in diagnosis and management due to their complex etiology and diverse clinical manifestations. While genetic predispositions and environmental factors have been extensively studied in the context of these conditions, the role of viral infections and virome dysbiosis remains a subject of growing interest. This review aims to elucidate the involvement of viral infections in the pathogenesis of immune-mediated GI diseases, focusing on achalasia and celiac disease, as well as the virome dysbiosis in IBD. Recent evidence suggests that viral pathogens, ranging from common respiratory viruses to enteroviruses and herpesviruses, may trigger or exacerbate achalasia and celiac disease by disrupting immune homeostasis in the GI tract. Furthermore, alterations in the microbiota and, specifically, in the virome composition and viral-host interactions have been implicated in perpetuating chronic intestinal inflammation in IBD. By synthesizing current knowledge on viral contributions to immune-mediated GI diseases, this review aims to provide insights into the complex interplay between viral infections, host genetics, and virome dysbiosis, shedding light on novel therapeutic strategies aimed at mitigating the burden of these debilitating conditions on patients' health and quality of life.

Keywords: Crohn’s disease; achalasia; celiac disease; inflammatory bowel disease; ulcerative colitis; virome; virus.

Figure 1

Intestine immune response to viral infection.

Figure 2

Alterations in the gut virome are associated with the initiation and severity of IBDs. Virome changes impact intestinal mucosa integrity: phages indirectly stimulate the immune response by releasing bacterial products following lysis or transcytosis, which activate pattern recognition receptors on IECs or immune cells. Moreover, virome factors disrupt barrier integrity and influence intestinal physiology through interactions with commensals. Phages modify host bacterial dynamics, leading to dysbiosis and contributing to IBD pathogenesis. Furthermore, phages shape immunity, prompting type-I interferon responses in immune cells, thereby exacerbating intestinal inflammation and disease severity.