Worms, flies and four-legged friends: the applicability of biological models to the understanding of intestinal inflammatory diseases

Abstract

Diseases of intestinal inflammation, including Crohn’s disease, ulcerative colitis and necrotizing enterocolitis, cause substantial acute and chronic disability in a large proportion of the population. Crohn’s disease and ulcerative colitis, which are collectively referred to as inflammatory bowel disease (IBD), lead to recurrent episodes of intestinal dysfunction and systemic illness, whereas necrotizing enterocolitis is characterized by the development of dramatic and all too often fatal intestinal necrosis in infants. To determine the molecular underpinnings of these disorders, investigators have explored a variety of animal models that vary widely in their complexity. These experimental systems include the invertebrate nematode Caenorhabditis elegans, the more complex invertebrate Drosophila melanogaster, and vertebrate systems including mice, rats and other mammals. This review explores the experimental models that are used to mimic and evaluate the pathogenic mechanisms leading to these diseases of intestinal inflammation. We then highlight, as an example, how the use of different experimental models that focus on the role of Toll-like receptor 4 (TLR4) signaling in the gut has revealed important distinctions between the pathogenesis of IBD and necrotizing enterocolitis. Specifically, TLR4-mediated signaling plays a protective role in the development of Crohn’s disease and ulcerative colitis, whereas this signaling pathway plays a causative role in the development of necrotizing enterocolitis in the newborn small intestine by adversely affecting intestinal injury and repair mechanisms.

Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans

“…C. elegans can be used as a model to study the pathophysiology of intestinal inflammation ( e.g . inflammatory bowel disease and necrotic enterocolitis; Lin & Hackam, ) and other diseases associated with metabolic syndrome, such as non‐alcoholic fatty liver disease (Walker et al, ).…”

Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

“…In this regard, the existing homologies between the immunologic phenotype of the nematode C. elegans and humans suggested the applicability of this roundworm to IBD immunological studies; host-microbiome immune interactions can be simulated feeding the worm with specific bacterial strains. In addition, this species is particularly useful in imaging studies due to its peculiarity of being transparent during the entire life-span (Lin & Hackam, 2011).…”

Guts, germs and glucose: understanding the effects of prematurity on the interaction between bacteria and nutrient absorption across the intestine

“…However, despite numerous theories that have been advanced in order to define the causes of NEC, the precise underpinnings of this disease remain incompletely understood (1 – 3) . One consistent feature in infants who develop NEC is the observation that this devastating disease develops almost exclusively after feeds have been initiated and in the setting of microbial colonisation of the intestine, raising the distinct possibility that an underlying inability of the premature infant to tolerate bacterial products and feeds may be central in NEC pathogenesis (4) . In this issue, Bering et al .…”