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.

The study findings provide evidence that administration of butyrate in a dose-dependent manner can improve the weight gain of infected mice, enhance clearance of the infection, reduce inflammation through altered cytokine expression, and enhance tissue repair and mucus secretion. Moreover, butyrate treatment also affected the abundance of bacterial populations in both noninflamed and inflamed intestines. Notably, this investigation provides foundational information that can be used to determine the effects of prebiotics and other functional foods on the production of butyrate by enteric bacteria and their impact on intestinal health and host well-being.

Identifying the connection among diet, the intestinal microbiome, and host health is currently an area of intensive research, but the potential of dietary fiber (DF) consumption to ameliorate intestinal inflammation has not been extensively studied. We examined the impacts of the DFs, wheat bran (WB) and resistant starch (RS) on host enteric health. A murine model of acute Th1/Th17 colitis (i.e. incited by Citrobacter rodentium) was used. Diets enriched with RS increased weight gain in mice inoculated with C. rodentium compared to mice consuming a conventional control (CN) diet. Short-chain fatty acid (SCFA) quantities in the cecum and distal colon were higher in mice consuming DFs, and these mice exhibited higher butyrate concentrations in the distal colon during inflammation. Histopathologic scores of inflammation in the proximal colon on day 14 post-inoculation (p.i.) (peak infection) and 21 p.i. (late infection) were lower in mice consuming DF-enriched diets compared to the CN diet. Consumption of WB reduced the expression of Th1/Th17 cytokines. As well, the expression of bacterial recognition and response genes such as Relmβ, RegIIIγ, and Tlr4 increased in mice consuming the RS-enriched diets. Furthermore, each diet generated a region-specific bacterial community, suggesting a link between selection for specific bacterial communities, SCFA concentrations, and inflammation in the murine colon. Collectively, data indicated that the consumption of DF-rich diets ameliorates the effects of C. rodentium-induced enteritis by modifying the host microbiota to increase SCFA production, and bacterial recognition and response mechanisms to promote host health.

The impact of physiological stress on lipid metabolism, the metabolome, and systemic responses was examined in chickens. To incite a stress response, birds were continuously administered corticosterone (CORT) in their drinking water at three doses (0 mg/L, 10 mg/L, and 30 mg/L), and they were sampled 1, 5, and 12 days after commencement of CORT administration. Corticosterone administration to birds differentially regulated lipogenesis genes (i.e. FAS, ACC, ME, and SREBF1), and histopathological examination indicated lipid deposition in hepatocytes. In addition, CORT affected water-soluble metabolite profiles in the liver, as well as in kidney tissue and breast muscle; thirteen unique metabolites were distinguished in CORT-treated birds and this was consistent with the dysregulation of lipid metabolism due to physiological stress. Acute phase responses (APRs) were also altered by CORT, and in particular, expression of SAA1 was decreased and expression of CP was increased. Furthermore, CORT administration caused lymphoid depletion in the bursa of Fabricius and elevated IL6 and TGFβ2 mRNA expression after 5 and 12 days of CORT administration. Collectively, incitement of physiological stress via administration of CORT in chickens modulated host metabolism and systemic responses, which indicated that energy potentials are diverted from muscle anabolism during periods of stress.

Salmonella enterica serovar Typhimurium is a prevalent incitant of enteritis in human beings and animals. It has been proposed that host defense responses incited by Salmonella allow the bacterium to overcome colonization resistance. Piglets (n=24) were orally inoculated with S. enterica Typhimurium DT104 or buffer alone, and the host and microbial responses were temporally examined at acute (2 days post-inoculation [dpi]), subacute (6 dpi), and recovery (10 dpi) stages of salmonellosis. At the acute stage of disease, body temperatures were elevated, and feed consumption and weight gain were reduced. Densities of Salmonella associated with gut mucosa decreased over time, with higher densities of the bacterium in the ileum and the large intestine. Moreover, substantive histopathologic changes were observed as a function of time, with prominent epithelial injury and neutrophil infiltration observed at 2 dpi. Correspondingly, a variety of host metrics were temporally affected in piglets with salmonellosis (e.g. TNFα, IFNγ, PR39, βD2, iNOS, IL8, REGIIIγ). The enteric microbiota was characterized using culture-independent and -dependent methods in concert, and taxon- and location-specific changes to the microbiota were observed in infected piglets. Bacteroides spp. (e.g. B. uniformis, B. fragilis), Streptococcus spp. (e.g. S. gallolyticus), and various Gammaproteobacteria were highly associated with inflamed tissues, while bacteria within Ruminococcaceae and Veillonellaceae were mainly associated with healthy mucosa. In conclusion, the study findings showed that S. Typhimurium incited temporal and spatial modifications to the swine autochthonous microbiota, and to host defense responses, that were consistent with overcoming colonization resistance to incite salmonellosis in swine. IMPORTANCE Limited information is available on host and enteric microbiota responses incited by Salmonellaenterica Typhimurium in swine, and possible mechanisms by which the bacterium overcomes colonization resistance to incite salmonellosis. Temporal characterization of a variety of host metrics in piglets (e.g. physiologic, histopathologic, and immunologic) showed the importance of studying the progression of salmonellosis. A number of host responses integrally associated with disease development were identified. Utilization of next-generation sequence analysis to characterize the enteric microbiota was found to lack sufficient resolution; however, culture-dependent and -independent methods in combination identified taxon- and location-specific changes to bacterial communities in infected piglets. The study identified bacteria and host responses associated with salmonellosis, which will be beneficial in understanding colonization resistance and for the development of effective alternatives to antibiotics to mitigate salmonellosis.

A model of physiological stress mediated by the administration of corticosterone (CORT) was used to investigate the impact of stress on the intestinal microbiota of chickens. Birds were administered CORT in their drinking water at 0, 10 (low dose CORT; LDC), and 30 (high dose CORT; HDC) mg/L. Digesta from the small intestine and ceca were examined after 1, 5, and 12 days post-initiation of CORT administration by 16S rRNA gene sequencing. A decrease in phylogenetic diversity and altered composition of bacteria were observed for HDC in the small intestine. Analysis by ANOVA-Like Differential Expression 2 (ALDEx2) showed that densities of Clostridium sensu stricto 1 bacteria were increased in the small intestine for LDC and HDC. Quantitative PCR confirmed that CORT administration increased densities of Clostridium perfringens in the small intestine, but only HDC was associated with increased densities of the bacterium in ceca. Predictive functional analysis by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2) showed pathways of carbohydrate metabolism to be enriched with CORT, and amino acid synthesis to be enriched in control birds in the small intestine. In conclusion, physiological stress mediated by CORT modulated bacterial communities in the small intestine and increased densities of C. perfringens. This implicates stress as an important mediator of this important enteric pathogen in poultry.