Inflammation-Associated Microbiota Composition Across Domestic Animals

Domestic animals represent important resources for understanding shared mechanisms underlying complex natural diseases that arise due to both genetic and environmental factors. Intestinal inflammation, particularly inflammatory bowel disease (IBD), is a significant health challenge in humans and domestic animals. While the etiology of IBD is multifactorial, imbalance of symbiotic gut microbiota has been hypothesized to play a central role in disease pathophysiology. Advances in genomic sequencing and analytical pipelines have enabled researchers to decipher the composition of the intestinal microbiota during health and in the context of naturally occurring diseases. This review compiles microbiome genomic data across domestic species and highlights a common occurrence of gut microbiome dysbiosis during idiopathic intestinal inflammation in multiple species, including dogs, cats, horses, cows, and pigs. Current microbiome data obtained from animals with intestinal inflammation are mostly limited to taxonomical analyses in association with broad clinical phenotype. In general, a pathogen or pathosymbiont were not detected. Rather, functional potential of the altered microbiota has been suggested to be one of the key etiologic factors. Among the domestic species studied, canine analyses are currently the most advanced with incorporation of functional profiling of microbiota. Canine IBD parallels features of the disease in humans, thus canines represent a strong natural model for human IBD. While deeper analyses of metagenomic data, coupled with host molecular analyses are needed, comparative studies across domestic species can reveal shared microbial alterations and regulatory mechanisms that will improve our understanding of intestinal inflammation in both animals and humans

Differential food protein-induced inflammatory responses in swine lines selected for reactivity to soy antigens

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151332/1/all13757.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151332/2/all13757_am.pd

Role of Retinoic Acid in Regulation of Intestinal T cells

Epidemiological studies have shown that vitamin A is essential micronutrient for proper immune function. However, the detailed mechanisms by which vitamin A and its active metabolite retinoic acid (RA) regulate the immune cells are largely unknown. We investigated the novel regulatory role of RA in the intestinal immune system. RA has been known to regulate CD4+ T cell migration and differentiation. We discovered that RA also regulates T cell survival by induction of an apoptosis-inducing purinergic receptor P2X7. RA induces P2X7 expression by direct binding to the intragenic enhancer of P2X7 gene in CD4+ T cells, rendering them highly susceptible to P2X7-mediated cell death which is triggered by extracellular ATP and NAD. This tolerogenic mechanism was shown to be especially important in the intestine where RA concentration and extracellular ATP/NAD concentrations were believed to be high, by demonstrating aberrant expansion of Th1/Th17 cells in the intestine of P2X7-null mice as well as amelioration of CD4+ T cell-induced-colitis with administration of NAD. We concluded that this RA-P2X7 axis is a novel immune homeostatic mechanism by which over-population of effector T cells is prevented. As illustrated well in this study, effects of RA is cell type-specific and pleiotropic. It is important to recognize that cell- and microenvironment-specific factors cooperate with RA to produce certain physiological outcomes as exemplified in part I of our study which show that RA, P2X7, and extracellular NAD work together to induce apoptosis of T cells. In addition, detailed immune phenotyping is necessary to better understand the roles of RA in a certain immunological context. Our study provided novel information to the existing knowledge regarding the complex roles of RA in the immune system. Uncovering the intricate relationship between this micronutrient and immune system will likely produce more exciting findings in the future

RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells

Langerhans cells (LC) and langerin-expressing conventional dendritic cells are made from distinct progenitors and enriched in the distinct microenvironments of the skin. Here the authors show that these immune cells are regulated by retinoic acid receptor alpha (RARα) via simultaneous induction of LC-promoting Runx3 and repression of LC-inhibiting C/EBPβ

Succinylated Chitosan Derivative Has Local Protective Effects on Intestinal Inflammation

We have previously reported on the anti-inflammatory effects of a water-soluble chitosan derivative, zwitterionic chitosan (ZWC). In the present study, we hypothesized that orally administered ZWC would provide local anti-inflammatory effects in the intestinal lumen. ZWC indeed showed anti-inflammatory effects in various in vitro models including peritoneal macrophages, engineered THP1 monocytes, and Caco-2 cells. In Caco-2 cells, ZWC applied before the lipopolysaccharide (LPS) challenge was more effective than when it was applied after it in preventing LPS-induced cell damage. When administered to mice via drinking water as a prophylactic measure, ZWC protected the animals from 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, helping them to recover the body weight, restore the gross and histological appearance of the colon, and generate FoxP3⁺ T cells. In contrast, orally administered ZWC did not protect the animals from LPS-induced systemic inflammation. These results indicate that orally administered ZWC reaches the colon with minimal absorption through the upper gastrointestinal tract and provides a local anti-inflammatory effect