Animal models: are they useful for the investigation of gastrointestinal disease?

ABSTRACT Campylobacter jejuni is a major cause of food-borne human bacterial gastroenteritis but animal models for C. jejuni mediated disease remain limited because C. jejuni poorly colonizes immunocompetent, conventionally-reared (Conv-R) mice. Thus, a reliable rodent model (i.e. persistent colonization) is desirable in order to evaluate C. jejuni-mediated gastrointestinal disease and mechanisms of pathogenicity. As the nature and complexity of the microbiota likely impacts colonization resistance for C. jejuni, Conv-R and gnotobiotic C3H/HeN mice were used to evaluate the persistence of C. jejuni colonization and development of disease. A total of four C. jejuni isolates readily and persistently colonized ASF mice and induced mild mucosal inflammation in the proximal colon, but C. jejuni did not stably colonize nor induce lesions in Conv-R mice. This suggests that the pathogenesis of C. jejuni is influenced by the microbiota, and that ASF mice offer a reproducible model to study the influence of the microbiota on the ability of C. jejuni to colonize the gut and to mediate gastroenteritis.

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Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00206.2015 ◽

2015 ◽

Vol 309 (12) ◽

pp. G927-G941 ◽

Cited By ~ 28

Author(s):

Calvin S. Pohl ◽

Julia E. Medland ◽

Adam J. Moeser

Keyword(s):

Animal Models ◽

Life Stress ◽

Early Life ◽

Disease Susceptibility ◽

Gastrointestinal Disease ◽

Adult Life ◽

Early Life Stress ◽

Early Postnatal Development ◽

Disease States ◽

Fundamental Understanding

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted.

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Could Naturally Occurring Coronaviral Diseases in Animals Serve as Models for COVID-19? A Review Focusing on the Bovine Model

Pathogens ◽

10.3390/pathogens9120991 ◽

2020 ◽

Vol 9 (12) ◽

pp. 991

Author(s):

Jonas Johansson Wensman ◽

Maria Stokstad

Keyword(s):

Animal Models ◽

Current Knowledge ◽

Gastrointestinal Disease ◽

Animal Health ◽

Virus Species ◽

Adult Cattle ◽

Naturally Occurring ◽

Basic Studies ◽

Welfare Production

The current pandemic of COVID-19 has highlighted the importance of basic studies on coronaviruses (CoVs) in general, and severe acute respiratory syndrome CoV type 2 (SARS-CoV-2) in particular. CoVs have for long been studied in veterinary medicine, due to their impact on animal health and welfare, production, and economy. Several animal models using coronaviral disease in the natural host have been suggested. In this review, different animal models are discussed, with the main focus on bovine CoV (BCoV). BCoV is endemic in the cattle population worldwide and has been known and studied for several decades. SARS-CoV-2 and BCoV are both betacoronaviruses, where BCoV is highly similar to human coronavirus (HCoV) OC43, encompassing the same virus species (Betacoronavirus 1). BCoV causes respiratory and gastrointestinal disease in young and adult cattle. This review summarizes the current knowledge of the similarities and dissimilarities between BCoV and SARS-CoV-2, as well as discussing the usage of BCoV as a model for human CoVs, including SARS-CoV-2.

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Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00422.2013 ◽

2014 ◽

Vol 306 (11) ◽

pp. G917-G928 ◽

Cited By ~ 38

Author(s):

Peng Lu ◽

Chhinder P. Sodhi ◽

Hongpeng Jia ◽

Shahab Shaffiey ◽

Misty Good ◽

...

Keyword(s):

Animal Models ◽

Necrotizing Enterocolitis ◽

Gastrointestinal Disease ◽

Coagulation Necrosis ◽

Rapid Progression ◽

Feeding Intolerance ◽

Future Directions ◽

Cellular Events ◽

Current Thinking ◽

Underlying Mechanisms

Necrotizing enterocolitis is the leading cause of morbidity and mortality from gastrointestinal disease in premature infants and is characterized by initial feeding intolerance and abdominal distention followed by the rapid progression to coagulation necrosis of the intestine and death in many cases. Although the risk factors for NEC development remain well accepted, namely premature birth and formula feeding, the underlying mechanisms remain incompletely understood. Current thinking indicates that NEC develops in response to an abnormal interaction between the mucosal immune system of the premature host and an abnormal indigenous microflora, leading to an exaggerated mucosal inflammatory response and impaired mesenteric perfusion. In seeking to understand the molecular and cellular events leading to NEC, various animal models have been developed. However, the large number and variability between the available animal models and the unique characteristics of each has raised important questions regarding the validity of particular models for NEC research. In an attempt to provide some guidance to the growing community of NEC researchers, we now seek to review the key features of the major NEC models that have been developed in mammalian and nonmammalian species and to assess the advantages, disadvantage, challenges and major scientific discoveries yielded by each. A strategy for model validation is proposed, the principal models are compared, and future directions and challenges within the field of NEC research are explored.

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Reductionist thinking and animal models in neuropsychiatric research

Behavioral and Brain Sciences ◽

10.1017/s0140525x18001231 ◽

2019 ◽

Vol 42 ◽

Cited By ~ 1

Author(s):

Nicole M. Baran

Keyword(s):

Animal Models ◽

Mental Disorders ◽

Environmental Factors ◽

Neuropsychiatric Disorders ◽

Model Organisms ◽

Developmental Genetic ◽

Term Study ◽

Genetic And Environmental Factors ◽

Mechanisms Of Plasticity

AbstractReductionist thinking in neuroscience is manifest in the widespread use of animal models of neuropsychiatric disorders. Broader investigations of diverse behaviors in non-model organisms and longer-term study of the mechanisms of plasticity will yield fundamental insights into the neurobiological, developmental, genetic, and environmental factors contributing to the “massively multifactorial system networks” which go awry in mental disorders.

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Inflammational Animal Models for Schizophrenia

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000216 ◽

2015 ◽

Vol 223 (3) ◽

pp. 157-164 ◽

Cited By ~ 1

Author(s):

Georg Juckel

Keyword(s):

Animal Model ◽

Animal Models ◽

Immune Activation ◽

Microglial Activation ◽

Treatment Options ◽

Early Adulthood ◽

Brain Regions ◽

Synaptic Connections ◽

Preventive Interventions ◽

Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

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