scholarly journals A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens

2021 ◽  
Vol 11 ◽  
Author(s):  
Henriette Arnesen ◽  
Linn Emilie Knutsen ◽  
Bente Wabakken Hognestad ◽  
Grethe Marie Johansen ◽  
Mats Bemark ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Real Life ◽  
Domestic Animal ◽  
Microbial Colonization ◽  
Housing System ◽  
Laboratory Mice ◽  
Natural Behavior ◽  
Immunological Phenotype ◽  
Living Mouse ◽  
Microbial Environment

Laboratory mice are typically housed under extremely clean laboratory conditions, far removed from the natural lifestyle of a free-living mouse. There is a risk that this isolation from real-life conditions may lead to poor translatability and misinterpretation of results. We and others have shown that feral mice as well as laboratory mice exposed to naturalistic environments harbor a more diverse gut microbiota and display an activated immunological phenotype compared to hygienic laboratory mice. We here describe a naturalistic indoors housing system for mice, representing a farmyard-type habitat typical for house mice. Large open pens were installed with soil and domestic animal feces, creating a highly diverse microbial environment and providing space and complexity allowing for natural behavior. Laboratory C57BL/6 mice were co-housed in this system together with wild-caught feral mice, included as a source of murine microbionts. We found that mice feralized in this manner displayed a gut microbiota structure similar to their feral cohabitants, such as higher relative content of Firmicutes and enrichment of Proteobacteria. Furthermore, the immunophenotype of feralized mice approached that of feral mice, with elevated levels of memory T-cells and late-stage NK cells compared to laboratory-housed control mice, indicating antigenic experience and immune training. The dietary elements presented in the mouse pens could only moderately explain changes in microbial colonization, and none of the immunological changes. In conclusion, this system enables various types of studies using genetically controlled mice on the background of adaptation to a high diversity microbial environment and a lifestyle natural for the species.

scholarly journals Parallel signatures of mammalian domestication and human industrialization in the gut microbiota

2019 ◽  
Author(s):  
Aspen T. Reese ◽  
Katia S. Chadaideh ◽  
Caroline E. Diggins ◽  
Mark Beckel ◽  
Peggy Callahan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Diversity ◽  
Dominant Role ◽  
Domestic Animals ◽  
Domestic Animal ◽  
Microbial Interactions ◽  
Laboratory Mice ◽  
Wild Mammals ◽  
Traditional Societies ◽  
Ecological Shifts

AbstractDomestication may have had convergent effects on the microbiota of domesticates and humans through analogous ecological shifts. Comparing the gut microbiota of domestic and related wild mammals plus humans and chimpanzees, we found consistent shifts in composition in domestic animals and in humans from industrialized but not traditional societies. Reciprocal diet switches in mice and canids demonstrated that diet played a dominant role in shaping the domestic gut microbiota, with stronger responses in the member of the wild-domestic pair with higher dietary and microbial diversity. Laboratory mice recovered wild-like microbial diversity and responsiveness with experimental colonization. We conclude that domestication and industrialization have similarly impacted the gut microbiota, emphasizing the utility of domestic animal models and diets for understanding host-microbial interactions in rapidly changing environments.

scholarly journals BOARD INVITED REVIEW: The pig microbiota and the potential for harnessing the power of the microbiome to improve growth and health1

2019 ◽  
Vol 97 (9) ◽  
pp. 3741-3757 ◽  
Author(s):  
Nirosh D Aluthge ◽  
Dana M Van Sambeek ◽  
Erin E Carney-Hinkle ◽  
Yanshuo S Li ◽  
Samodha C Fernando ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Therapeutic Potential ◽  
Animal Health ◽  
Microbial Colonization ◽  
Critical Importance ◽  
Specific Host ◽  
Microbiome Research ◽  
Health And Disease ◽  
The Impact

Abstract A variety of microorganisms inhabit the gastrointestinal tract of animals including bacteria, archaea, fungi, protozoa, and viruses. Pioneers in gut microbiology have stressed the critical importance of diet:microbe interactions and how these interactions may contribute to health status. As scientists have overcome the limitations of culture-based microbiology, the importance of these interactions has become more clear even to the extent that the gut microbiota has emerged as an important immunologic and metabolic organ. Recent advances in metagenomics and metabolomics have helped scientists to demonstrate that interactions among the diet, the gut microbiota, and the host to have profound effects on animal health and disease. However, although scientists have now accumulated a great deal of data with respect to what organisms comprise the gastrointestinal landscape, there is a need to look more closely at causative effects of the microbiome. The objective of this review is intended to provide: 1) a review of what is currently known with respect to the dynamics of microbial colonization of the porcine gastrointestinal tract; 2) a review of the impact of nutrient:microbe effects on growth and health; 3) examples of the therapeutic potential of prebiotics, probiotics, and synbiotics; and 4) a discussion about what the future holds with respect to microbiome research opportunities and challenges. Taken together, by considering what is currently known in the four aforementioned areas, our overarching goal is to set the stage for narrowing the path towards discovering how the porcine gut microbiota (individually and collectively) may affect specific host phenotypes.

scholarly journals The gut microbiome of laboratory mice: considerations and best practices for translational research

2021 ◽  
Author(s):  
Aaron C. Ericsson ◽  
Craig L. Franklin
Keyword(s):  
Human Physiology ◽  
Best Practices ◽  
Gut Microbiota ◽  
Translational Research ◽  
Mouse Models ◽  
Gut Microbiome ◽  
Predictive Power ◽  
Environmental Influences ◽  
Pharmacological Intervention ◽  
Laboratory Mice

AbstractJust 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. This review provides readers with information related to these various factors and practices, and recommendations regarding methods by which issues with poor reproducibility or translatability can be transformed into discoveries.

scholarly journals Successional stages in infant gut microbiota maturation

2021 ◽  
Author(s):  
Leen Beller ◽  
Ward Deboutte ◽  
Gwen Falony ◽  
Sara Vieira Silva ◽  
Raul Tito ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Early Life ◽  
Microbial Colonization ◽  
Maturation Stage ◽  
Gut Flora ◽  
Microbiome Composition ◽  
Gut Colonization ◽  
Maturation Stages ◽  
Colonization Process ◽  
First Year Of Life

Background: Disturbances in the primary colonization of the infant gut can result in life-long consequences and have been associated with a range of host conditions. Although early life factors have been shown to affect the infant gut microbiota development, our current understanding of the human gut colonization in early life remains limited. To gain more insights in the unique dynamics of this rapidly evolving ecosystem, we investigated the microbiota over the first year of life in eight densely sampled infants (total number of samples, n=303). To evaluate gut microbiota maturation transition towards an adult configuration, we compared the microbiome composition of the infants to the Flemish Gut Flora Project population (n=1,106). Results: We observed the infant gut microbiota to mature through three distinct, conserved stages of ecosystem development. Across these successional gut microbiota maturation stages, genus predominance was observed to shift from Escherichia over Bifidobacterium to Bacteroides. Both disease and antibiotic treatment were observed to be associated occasionally with gut microbiota maturation stage regression, a transient setback in microbiota maturation dynamics. Although the studied microbiota trajectories evolved to more adult-like constellations, microbiome community typing against the background of the Flemish Gut Flora Project (FGFP) cohort clustered all infant samples within the (in adults) potentially dysbiotic Bact2 enterotype. Conclusion: We confirmed similarities between infant gut microbial colonization and adult dysbiosis. A profound knowledge about the primary gut colonization process in infants might provide crucial insights into how the secondary colonization of a dysbiotic adult gut can be redirected.

scholarly journals Intestinal IgA Regulates Expression of a Fructan Polysaccharide Utilization Locus in Colonizing Gut Commensal Bacteroides thetaiotaomicron

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Payal Joglekar ◽  
Hua Ding ◽  
Pablo Canales-Herrerias ◽  
Pankaj Jay Pasricha ◽  
Justin L. Sonnenburg ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Ex Vivo ◽  
Microbial Colonization ◽  
Bacteroides Thetaiotaomicron ◽  
Content Type ◽  
Microbial Utilization ◽  
Polysaccharide Utilization Locus ◽  
The Impact

ABSTRACT Gut-derived immunoglobulin A (IgA) is the most abundant antibody secreted in the gut that shapes gut microbiota composition and functionality. However, most of the microbial antigens targeted by gut IgA remain unknown, and the functional effects of IgA targeting these antigens are currently understudied. This study provides a framework for identifying and characterizing gut microbiota antigens targeted by gut IgA. We developed a small intestinal ex vivo culture assay to harvest lamina propria IgA from gnotobiotic mice, with the aim of identifying antigenic targets in a model human gut commensal, Bacteroides thetaiotaomicron VPI-5482. Colonization by B. thetaiotaomicron induced a microbe-specific IgA response that was reactive against diverse antigens, including capsular polysaccharides, lipopolysaccharides, and proteins. IgA against microbial protein antigens targeted membrane and secreted proteins with diverse functionalities, including an IgA specific against proteins of the polysaccharide utilization locus (PUL) that are necessary for utilization of fructan, which is an important dietary polysaccharide. Further analyses demonstrated that the presence of dietary fructan increased the production of fructan PUL-specific IgA, which then downregulated the expression of fructan PUL in B. thetaiotaomicron, both in vivo and in vitro. Since the expression of fructan PUL has been associated with the ability of B. thetaiotaomicron to colonize the gut in the presence of dietary fructans, our work suggests a novel role for gut IgA in regulating microbial colonization by modulating their metabolism. IMPORTANCE Given the significant impact that gut microbes have on our health, it is essential to identify key host and environmental factors that shape this diverse community. While many studies have highlighted the impact of diet on gut microbiota, little is known about how the host regulates this critical diet-microbiota interaction. In our present study, we discovered that gut IgA targeted a protein complex involved in the utilization of an important dietary polysaccharide: fructan. While the presence of dietary fructans was previously thought to allow unrestricted growth of fructan-utilizing bacteria, our work shows that gut IgA, by targeting proteins responsible for fructan utilization, provides the host with tools that can restrict the microbial utilization of such polysaccharides, thereby controlling their growth.

scholarly journals Gut microbiota induce IGF-1 and promote bone formation and growth

2016 ◽  
Vol 113 (47) ◽  
pp. E7554-E7563 ◽  
Author(s):  
Jing Yan ◽  
Jeremy W. Herzog ◽  
Kelly Tsang ◽  
Caitlin A. Brennan ◽  
Maureen A. Bower ◽  
...  
Keyword(s):  
Bone Formation ◽  
Gut Microbiota ◽  
Bone Mass ◽  
Bone Growth ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Skeletal Growth ◽  
Microbial Colonization ◽  
Adult Mice ◽  
Specific Pathogen

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.

scholarly journals Lactobacillus reuteri DSM 17938 feeding of healthy newborn mice regulates immune responses while modulating gut microbiota and boosting beneficial metabolites

2019 ◽  
Vol 317 (6) ◽  
pp. G824-G838 ◽  
Author(s):  
Yuying Liu ◽  
Xiangjun Tian ◽  
Baokun He ◽  
Thomas K. Hoang ◽  
Christopher M. Taylor ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Oral Administration ◽  
Relative Abundance ◽  
Lactobacillus Reuteri ◽  
Tca Cycle ◽  
Microbial Colonization ◽  
Plasma Metabolites ◽  
Early Administration ◽  
Newborn Mice ◽  
Breastfed Infants

Early administration of Lactobacillus reuteri DSM 17938 (LR) prevents necrotizing enterocolitis and inhibits regulatory T-cell (Treg)-deficiency-associated autoimmunity in mice. In humans, LR reduces crying time in breastfed infants with colic, modifies severity in infants with acute diarrheal illnesses, and improves pain in children with functional bowel disorders. In healthy breastfed newborns with evolving microbial colonization, it is unclear if early administration of LR can modulate gut microbiota and their metabolites in such a way as to promote homeostasis. We gavaged LR (107 colony-forming units/day, daily) to C57BL/6J mice at age of day 8 for 2 wk. Both male and female mice were investigated in these experiments. We found that feeding LR did not affect clinical phenotype or inflammatory biomarkers in plasma and stool, but LR increased the proportion of Foxp3+ regulatory T cells (Tregs) in the intestine. LR also increased bacterial diversity and the relative abundance of p_Firmicutes, f_Lachnospiraceae, f_Ruminococcaceae, and genera Clostridium and Candidatus arthromitus, while decreasing the relative abundance of p_Bacteriodetes, f_Bacteroidaceae, f_Verrucomicrobiaceae, and genera Bacteroides, Ruminococcus, Akkermansia, and Sutterella. Finally, LR exerted a major impact on the plasma metabolome, upregulating amino acid metabolites formed via the urea, tricarboxylic acid, and methionine cycles and increasing tryptophan metabolism. In conclusion, early oral administration of LR to healthy breastfed mice led to microbial and metabolic changes which could be beneficial to general health. NEW & NOTEWORTHY Oral administration of Lactobacillus reuteri DSM 17938 (LR) to healthy breastfed mice promotes intestinal immune tolerance and is linked to proliferation of beneficial gut microbiota. LR upregulates plasma metabolites that are involved in the urea cycle, the TCA cycle, methionine methylation, and the polyamine pathway. Herein, we show that LR given to newborn mice specifically increases levels of tryptophan metabolites and the purine nucleoside adenosine that are known to enhance tolerance to inflammatory stimuli.

Development of the microbiome-gut-brain axis and its effect on behavior

2020 ◽  
Author(s):  
Rebecca C. Knickmeyer
Keyword(s):  
Gut Microbiota ◽  
Critical Period ◽  
Animal Studies ◽  
Environmental Chemicals ◽  
Microbial Colonization ◽  
Long Term Effects ◽  
Community Influences ◽  
Mutualistic Relationship ◽  
System 2

Humans coexist in a mutualistic relationship with the gut microbiota, a complex ecologic community of commensal, symbiotic, and pathogenic microorganisms inhabiting the gastrointestinal tract. This chapter reviews evidence from both human and animal studies that the composition of this community influences development of the host brain. Infancy represents a critical period in the establishment of the gut microbiome and early alterations in microbial colonization may have long-term effects on mental health. Several mechanisms through which the microbiota could affect brain development are discussed including 1) activation of the peripheral immune system, 2) production of neuroactive metabolites, and 3) processing of nutrients and environmental chemicals. The chapter concludes with a discussion of whether modulation of the gut microbiota represents a tractable strategy for treating or preventing complex neurodevelopmental disorders.

scholarly journals Effect of an Intermittent Meat Protein Diet on Colon Homeostasis

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 424-424
Author(s):  
Xiaohui Li ◽  
Chunbao Li ◽  
Guanghong Zhou
Keyword(s):  
Body Weight ◽  
Gut Microbiota ◽  
Proinflammatory Cytokines ◽  
Dietary Protein ◽  
Real Life ◽  
Protein Diet ◽  
Microbiota Composition ◽  
Gut Health ◽  
Junction Protein ◽  
Gut Microbiota Composition

Abstract Objectives The level of dietary protein is a major factor determining gut health. The level of dietary protein is fluctuated in real life, which may affect colon homeostasis. However, it is still less known about it. Here, we investigated how an intermittent protein diet affected inflammatory, gut barrier and microbiota. Methods Six-week-old male C57BL/6J mice received either a casein or pork protein with (i) 20% protein (C), (ii) 5% protein, (iii) 40% protein, or intermittent diet, a diet alternating weekly between 5% protein and 40% protein ((iv) ending on 40% protein or (v) ending on 5% protein)) for up to 16 weeks. The gene expression of inflammatory cytokines, tight junction protein and gut microbiota composition were measured. Results The intermittent intake of casein decreased body weight, but intermittent pork protein diet didn't affect body weight. In casein group, the proinflammatory factors were highly upregulated in intermittent group ending on 5% protein, but the proinflammatory cytokines of intermittent group ending on 40% protein were not significantly affected. However, the two intermittent pork protein groups reduced the expression of proinflammatory cytokines. Additionally, intermittent diet altered gut microbiota composition. Intermittent casein group ending on 40% protein increased richness of gut microbiota, but intermittent pork protein group ending on 5% protein decreased richness and microbial diversity. Conclusions Intermittent diet indeed altered microbiota structure and colon health. In addition to protein level and source, dietary pattern is also an important parameter for host health. Funding Sources This work was funded by Ministry of Science and Technology (10000 Talent Project).

scholarly journals Alterations in human gut microbiome composition and metabolism after exposure to glyphosate and Roundup and/or a spore-based formulation using the SHIME® technology

2021 ◽  
Author(s):  
Robin Mesnage ◽  
Marta Calatayud ◽  
Cindy Duysburgh ◽  
Massimo Marzorati ◽  
Michael Antoniou
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Large Scale ◽  
Epidemiological Studies ◽  
Human Gut ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Ammonium Production ◽  
Profiling Techniques ◽  
Microbial Environment

Despite extensive research into the toxicology of the herbicide glyphosate, there are still major unknowns regarding its effects on the human gut microbiome. As a step in addressing this knowledge gap, we describe for the first time the effects of glyphosate and a Roundup glyphosate-based herbicide on infant gut microbiota using SHIME technology, which mimics the entire gastrointestinal tract. SHIME microbiota culture was undertaken in the presence of a concentration of 100 mg/L (corresponding to a dose of 1.6 mg/kg/day) glyphosate and the same glyphosate equivalent concentration of Roundup, which is in the range of the US chronic reference dose, and subjected to molecular profiling techniques to assess outcomes. Roundup and to a lesser extent glyphosate caused an increase in fermentation activity, resulting in acidification of the microbial environment. This was also reflected by an increase in lactate and acetate production concomitant to a decrease in the levels of propionate, valerate, caproate and butyrate. Ammonium production reflecting proteolytic activities was increased by Roundup exposure. Global metabolomics revealed large scale disturbances in metabolite profiles, including an increased abundance of long chain polyunsaturated fatty acids (n3 and n6). Although changes in bacterial composition measured by qPCR and 16S rRNA sequencing were less clear, our results suggested that lactobacilli had their growth stimulated as a result of microenvironment acidification. Co-treatment with the spore-based probiotic formulation MegaSporeBiotic reverted some of the changes in short-chain fatty acid levels. Altogether, our results suggest that glyphosate can exert effects on human gut microbiota at permitted regulatory levels of exposure, highlighting the need for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on human gut microbiome function.

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