Background: The microorganisms colonizing the gastrointestinal tract of animals, collectively referred to as the gut microbiome, affect numerous host behaviors dependent on the central nervous system (CNS). Studies comparing germ-free mice to normally colonized mice have demonstrated influences of the microbiome on anxiety-related behaviors, voluntary activity, and gene expression in the CNS. Additionally, there is epidemiologic evidence supporting an intergenerational influence of the maternal microbiome on neurodevelopment of offspring and behavior later in life.
View Article and Find Full Text PDFThe gut microbiota (GM) influences multiple processes during host development and maintenance. To study these events, fecal microbiota transfer (FMT) to germ-free (GF) recipients is often performed. Mouse models of disease are also susceptible to GM-dependent effects, and cryo-repositories often store feces from donated mouse strains.
View Article and Find Full Text PDFThe biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework.
View Article and Find Full Text PDFThere is limited understanding of how the microbiota colonizing various maternal tissues contribute to the development of the neonatal gut microbiota (GM). To determine the contribution of various maternal microbiotic sites to the offspring microbiota in the upper and lower gastrointestinal tract (GIT) during early life, litters of mice were sacrificed at 7, 9, 10, 11, 12, 14, and 21 days of age, and fecal and ileal samples were collected. Dams were euthanized alongside their pups, and oral, vaginal, ileal, and fecal samples were collected.
View Article and Find Full Text PDFBrucellosis is a globally significant zoonotic disease. Human patients with brucellosis develop recurrent fever and focal complications, including arthritis and neurobrucellosis. The current study investigated the role of innate lymphoid cells (ILCs) in the pathogenesis of focal brucellosis caused by Brucella melitensis.
View Article and Find Full Text PDFA modified KSOM for rat embryo culture (KSOM-R), which has enriched taurine, glycine, glutamic acid, and alanine, promoted rat embryo development in vitro. Since mice and rats share similar amino acid profiles in their female reproductive tracts, this study explored whether KSOM-R would also have a positive effect on mouse embryo development and if KSOM-R modifications could extend its shelf time at 2-8 °C for consistency. We first examined the effects of newly made (≤1 month at 2-8 °C) antibiotics-free KSOM-R (mKSOM-R), antibiotics-free KSOM (mKSOM) and KSOM on the development of in vivo or in vitro derived C57BL/6NJ zygotes.
View Article and Find Full Text PDFTo test causal relationships between complex gut microbiota (GM) and host outcomes, researchers frequently transfer GM between donor and recipient mice via embryo transfer (ET) rederivation, cross-fostering (CF), and co-housing. In this study, we assess the influence of the transfer method and the differences in baseline donor and recipient microbiota richness, on transfer efficiency. Additionally, recipient mice were subjected to DSS-induced chronic colitis to determine whether disease severity was affected by GM transfer efficiency or features within the GM.
View Article and Find Full Text PDFThe gut microbiome of humans and animals is critical to host health. Mice are used to investigate the microbiome and its influences; however, the predictive value of such studies is hindered by cage effects due to coprophagy. Our objectives were to evaluate the influence of cage density on the statistical power to detect treatment-dependent effects of a selective pressure on microbiome composition.
View Article and Find Full Text PDFGastrointestinal microbiota are affected by a wide variety of extrinsic and intrinsic factors. In the husbandry of laboratory mice and design of experiments, controlling these factors where possible provides more reproducible results. However, the microbiome is dynamic, particularly in the weeks immediately after weaning.
View Article and Find Full Text PDFAccumulating studies show that the host microbiome influences the development or progression of many diseases. The eukaryotic virome, as a key component of the microbiome, plays an important role in host health and disease in humans and animals, including research animals designed to model human disease. To date, the majority of research on the microbiome has focused on bacterial populations, while less attention has been paid to the viral component.
View Article and Find Full Text PDFThe intestinal microbiota of an organism can significantly alter outcome data in otherwise identical experiments. Occasionally, animals may require sedation or anesthesia for scientific or health-related purposes, and certain anesthetics, such as ketamine, can profoundly affect the gastrointestinal system. While many factors can alter the gut microbiome (GM), the effects of anesthetics on the composition or diversity of the GM have not been established.
View Article and Find Full Text PDFThe mouse is the most commonly used model species in biomedical research. Just as human physical and mental health are influenced by the commensal gut bacteria, mouse models of disease are influenced by the fecal microbiome (FM). The source of mice represents one of the strongest influences on the FM and can influence the phenotype of disease models.
View Article and Find Full Text PDFThe gut microbiome (GM), a complex community of bacteria, viruses, protozoa, and fungi located in the gut of humans and animals, plays significant roles in host health and disease. Animal models are widely used to investigate human diseases in biomedical research and the GM within animal models can change due to the impact of many factors, such as the vendor, husbandry, and environment. Notably, variations in GM can contribute to differences in disease model phenotypes, which can result in poor reproducibility in biomedical research.
View Article and Find Full Text PDFInflammatory bowel disease (IBD) is associated with both impaired intestinal blood flow and increased risk of cardiovascular disease, but the functional role of perivascular nerves that control vasomotor function of mesenteric arteries (MAs) perfusing the intestine during IBD is unknown. Because perivascular sensory nerves and their transmitters calcitonin gene-related peptide (CGRP) and substance P (SP) are important mediators of both vasodilation and inflammatory responses, our objective was to identify IBD-related deficits in perivascular sensory nerve function and vascular neurotransmitter signaling. In MAs from an interleukin-10 knockout (IL-10) mouse model, IBD significantly impairs electrical field stimulation (EFS)-mediated sensory vasodilation and inhibition of sympathetic vasoconstriction, despite decreased sympathetic nerve density and vasoconstriction.
View Article and Find Full Text PDFJust as the gut microbiota (GM) is now recognized as an integral mediator of environmental influences on human physiology, susceptibility to disease, and response to pharmacological intervention, so too does the GM of laboratory mice affect the phenotype of research using mouse models. Multiple experimental factors have been shown to affect the composition of the GM in research mice, as well as the model phenotype, suggesting that the GM represents a major component in experimental reproducibility. Moreover, several recent studies suggest that manipulation of the GM of laboratory mice can substantially improve the predictive power or translatability of data generated in mouse models to the human conditions under investigation.
View Article and Find Full Text PDFBiomedical research relies on the use of animal models, and the animals used in those models receive medical care, including antibiotics for brief periods of time to treat conditions such as dermatitis, fight wounds, and suspected bacterial pathogens of unknown etiology. As many mouse model phenotypes are sensitive to changes in the gut microbiota, our goal was to examine the effect of antibiotics commonly administered to mice. Therefore, four treatment groups (subcutaneous enrofloxacin for 7 days, oral enrofloxacin for 14 days, oral trimethoprim-sulfamethoxazole for 14 days, and topical triple antibiotic ointment for 14 days) alongside a fifth control group receiving no treatment (n = 12/group) were included in our study.
View Article and Find Full Text PDFColorectal cancer (CRC) risk is influenced by host genetics, sex, and the gut microbiota. Using a genetically susceptible mouse model of CRC induced via inoculation with pathobiont Helicobacter spp. and demonstrating variable tumor incidence, we tested the ability of the Th17-enhancing commensal Candidatus Savagella, more commonly denoted as Segmented Filamentous Bacteria (SFB), to influence the incidence and severity of colitis-associated CRC in male and female mice.
View Article and Find Full Text PDFOur bodies and those of our animal research subjects are colonized by bacterial communities that occupy virtually every organ system, including many previously considered sterile. These bacteria reside as complex communities that are collectively referred to as microbiota. Prior to the turn of the century, characterization of these communities was limited by a reliance on culture of organisms on a battery of selective media.
View Article and Find Full Text PDFBackground: Colorectal cancer (CRC) is a multifactorial disease resulting from both genetic predisposition and environmental factors including the gut microbiota (GM), but deciphering the influence of genetic variants, environmental variables, and interactions with the GM is exceedingly difficult. We previously observed significant differences in intestinal adenoma multiplicity between C57BL/6 J-Apc (B6-Min/J) from The Jackson Laboratory (JAX), and original founder strain C57BL/6JD-Apc (B6-Min/D) from the University of Wisconsin.
Methods: To resolve genetic and environmental interactions and determine their contributions we utilized two genetically inbred, independently isolated Apc mouse colonies that have been separated for over 20 generations.
J Am Assoc Lab Anim Sci
July 2020
The gut microbiota (GM) is the sum of hundreds of distinct microbial species that can equal or outnumber their host's somatic cells. The GM influences a multitude of physiologic and immunologic processes in the host, and changes in the GM have been shown to alter the phenotypes of animal models. Previous studies using rodents have also shown that the composition of the GM is affected by many factors, including diet, husbandry, housing, and the genetic background of the animals.
View Article and Find Full Text PDFRodent models are invaluable to understanding health and disease in many areas of biomedical research. Unfortunately, many models suffer from lack of phenotype reproducibility. Our laboratory has shown that differences in gut microbiota (GM) can modulate phenotypes of models of colon cancer and inflammatory bowel disease.
View Article and Find Full Text PDFPosttranscriptional gene regulation by RNA-binding proteins, such as HuR (), fine-tune gene expression in T cells, leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3' untranslated region adenylate and uridylate-rich elements. It was previously demonstrated that HuR facilitates Th2 cytokine expression by mRNA stabilization.
View Article and Find Full Text PDFStudies indicate that the gut microbiota (GM) can significantly influence both local and systemic host physiologic processes. With rising concern for optimization of experimental reproducibility and translatability, it is essential to consider the GM in study design. However, GM profiles can vary between rodent producers making consistency between models challenging.
View Article and Find Full Text PDFUsing animal models, the gut microbiota has been shown to play a critical role in the health and disease of many organ systems. Unfortunately, animal model studies often lack reproducibility when performed at different institutions. Previous studies in our laboratory have shown that the gut microbiota of mice can vary with a number of husbandry factors leading us to speculate that differing environments may alter gut microbiota, which in turn may influence animal model phenotypes.
View Article and Find Full Text PDF