Animal models to study acute and chronic intestinal inflammation in mammals

Abstract

Acute and chronic inflammatory diseases of the intestine impart a significant and negative impact on the health and well-being of human and non-human mammalian animals. Understanding the underlying mechanisms of inflammatory disease is mandatory to develop effective treatment and prevention strategies. As inflammatory disease etiologies are multifactorial, the use of appropriate animal models and associated metrics of disease are essential. In this regard, animal models used alone or in combination to study acute and chronic inflammatory disease of the mammalian intestine paired with commonly used inflammation-inducing agents are reviewed. This includes both chemical and biological incitants of inflammation, and both non-mammalian (i.e. nematodes, insects, and fish) and mammalian (i.e. rodents, rabbits, pigs, ruminants, dogs, and non-human primates) models of intestinal inflammation including germ-free, gnotobiotic, as well as surgical, and genetically modified animals. Importantly, chemical and biological incitants induce inflammation via a multitude of mechanisms, and intestinal inflammation and injury can vary greatly according to the incitant and animal model used, allowing studies to ascertain both long-term and short-term effects of inflammation. Thus, researchers and clinicians should be aware of the relative strengths and limitations of the various animal models used to study acute and chronic inflammatory diseases of the mammalian intestine, and the scope and relevance of outcomes achievable based on this knowledge. The ability to induce inflammation to mimic common human diseases is an important factor of a successful animal model, however other mechanisms of disease such as the amount of infective agent to induce disease, invasion mechanisms, and the effect various physiologic changes can have on inducing damage are also important features. In many cases, the use of multiple animal models in combination with both chemical and biological incitants is necessary to answer the specific question being addressed regarding intestinal disease. Some incitants can induce acute responses in certain animal models while others can be used to induce chronic responses; this review aims to illustrate the strengths and weaknesses in each animal model and to guide the choice of an appropriate acute or chronic incitant to facilitate intestinal disease.

Human mini-guts: new insights into intestinal physiology and host–pathogen interactions

“…As discussed, a major hurdle that has contributed to the lack of specific treatments for many enteric-pathogen-caused illnesses is the absence of a physiologically relevant preclinical intestinal model of pathogen-induced human disease. Although numerous animal models have been used to study human enteric pathogens, they have not provided a breakthrough in understanding the complexity of intestinal damage nor led to the development of successful therapeutic interventions 75 . Both HIOs and enteroid or colonoid cultures are quickly gaining a role as an indispensable model for host–pathogen interactions.…”

Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota

“…Despite being tremendously complex and involving a variety of immune cells, blood vessels, and molecular mediators, inflammatory processes can be distinguished into two somewhat different types [2; 3] termed herein clinical and subclinical chronic inflammation (SCI). In contrast to clinical inflammation resulting for instance from injury or bacterial infection, SCI appears as a much milder but persistent response of the host’s immune system [4].…”

Impacts of resistant starch and wheat bran consumption on enteric inflammation in relation to colonic bacterial community structures and short-chain fatty acid concentrations in mice

“…Citrobacter rodentium is a Gram negative bacterium that incites epithelial cell hyperplasia and inflammation within the murine colonic mucosa, and it is commonly used to study intestinal inflammation in mice [23]. Colitis incited by C. rodentium is a self-limiting process in mice, with peak infection occurring ≈7–14 days post-inoculation (p.i.)…”

“…Infections with C. rodentium induce a pro-inflammatory immune response that is characterized by an initial Th17 response, followed by a Th1 response towards recovery [27, 29]. This bacterium is commonly used as an inducer of acute inflammation in the murine intestine [23], but few studies have examined the impacts of DFs on the pathobiology of C. rodentium -induced intestinal inflammation. Generally, research investigating the therapeutic potential of DFs has focused on the alterations to the microbiota in models that do not exhibit acute inflammation [30–32].…”