Consistent alterations of human fecal microbes after transplanted to germ-free mice

Li, Yanze; Cao, Wen-Jun; Gao, Na; Zhao, Xing‐Ming

doi:10.1101/495663

Cited by 3 publications

(3 citation statements)

References 127 publications

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“…These results underlie the importance of characterizing the establishment of taxa of interest in HMA animal models in human-to-animal microbiota transplantation experiments, as the human taxa suspected to be the cause of a human health outcome might not be able to colonize the animal model being used. In fact, a recent study evaluating >1700 samples from human-to-GF mouse transplant studies in the published literature reported that, on average, <50% of species level taxa identified in the human donors are able to establish in GF mice 48 .…”

Section: Discussionmentioning

confidence: 99%

Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models

et al. 2020

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The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice. However, the domestic pig is a relevant model that is currently underutilized for human microbiome investigations. In this study, we performed a direct comparison of the engraftment of fecal bacterial communities from human donors between human microbiota-associated (HMA) piglet and mouse models under identical dietary conditions. Analysis of 16S rRNA genes using amplicon sequence variants (ASVs) revealed that with the exception of early microbiota from infants, the more mature microbiotas tested established better in the HMA piglets compared to HMA mice. Of interest was the greater transplantation success of members belonging to phylum Firmicutes in the HMA piglets compared to the HMA mice. Together, these results provide evidence for the HMA piglet model potentially being more broadly applicable for donors with more mature microbiotas while the HMA mouse model might be more relevant for developing microbiotas such as those of infants. This study also emphasizes the necessity to exercise caution in extrapolating findings from HMA animals to humans, since up to 28% of taxa from some donors failed to colonize either model.

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Section: Discussionmentioning

confidence: 99%

Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models

et al. 2020

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“… 27 However, there are and will be limitations as recently illustrated in a study involving 1700 transfers of human-to-GF mouse transfers, where less than half of the bacterial species identified in the human donors were able to colonize in GF mice. 28 This can be attributed to several factors such as donor-to-donor variations in colonization efficiency due to individual donor characteristics that influence microbiota behavior such as differences in dietary habits, genetics, and lifestyle. 29 In addition, some human species such as some Firmicutes and Faecalibacterium spp .…”

Section: Part a Methods For Studying The Causal Role Of Gut Microbiotamentioning

confidence: 99%

Approaches to discern if microbiome associations reflect causation in metabolic and immune disorders

et al. 2022

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Our understanding of microorganisms residing within our gut and their roles in the host metabolism and immunity advanced greatly over the past 20 years. Currently, microbiome studies are shifting from association and correlation studies to studies demonstrating causality of identified microbiome signatures and identification of molecular mechanisms underlying these interactions. This transformation is crucial for the efficient translation into clinical application and development of targeted strategies to beneficially modulate the intestinal microbiota. As mechanistic studies are still quite challenging to perform in humans, the causal role of microbiota is frequently evaluated in animal models that need to be appropriately selected. Here, we provide a comprehensive overview on approaches that can be applied in addressing causality of host-microbe interactions in five major animal model organisms ( Caenorhabditis elegans, Drosophila melanogaster , zebrafish, rodents, and pigs). We particularly focused on discussing methods available for studying the causality ranging from the usage of gut microbiota transfer, diverse models of metabolic and immune perturbations involving nutritional and chemical factors, gene modifications and surgically induced models, metabolite profiling up to culture-based approached. Furthermore, we addressed the impact of the gut morphology, physiology as well as diet on the microbiota composition in various models and resulting species specificities. Finally, we conclude this review with the discussion on models that can be applied to study the causal role of the gut microbiota in the context of metabolic syndrome and host immunity. We hope this review will facilitate important considerations for appropriate animal model selection.

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“…the engraftment of human cells) differ in their gut physical conditions, nutrient availability, and immune responses, all of which could impose distinct selective pressures on the colonizing microbes 7 . As a result, colonization dynamics of human microbes could differ across mouse models 11,14 . We have previously shown that these differences are often manifested at low taxonomic levels: for example, different Bacteroides species were enriched in immunocompetent vs. immunodeficient mice, demonstrating environmental selection at the species level 11 .…”

Section: Introductionmentioning

confidence: 99%

Mice with a humanized immune system are resilient to transplantation of human microbiota

Zhou

Chow

Geyer

et al. 2021

Preprint

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Human gut microbiota has co-evolved with human, and plays important roles in regulating the development and functioning of the host immune system. To study the human-specific microbiome-immunune interaction in an animal model is challenging as the animal model needs to capture both the human-specific immune functions and the human-specific microbiome composition. Here we combined two widely-used humanization procedures to generate a humanized mouse model (HMA-huCD34) with functional human leukocytes developed from engrafted huCD34+ cells and human fecal microbes introduced through fecal microbiota transplantation, and investigated how the two introduced human components interact. We found that the engrafted human leukocytes are resilient to the transplanted human microbes, while reciprocally the transplanted microbial community in the huCD34 mice was significantly different from mice without a humanized immune system. By tracking the colonization of human fecal Bacteroides strains in the mouse gut, we found that the composition of the strain population changes over time, the trajectory of which depends upon the type of mouse. On the other hand, different from Bacteroides, Akkermansia muciniphila exhibited consistent and rapid fixation of a single donor strain in all tested mice, suggesting strong purifying selection common to all mouse types. Our prospect study illustrated the complex interactions between the transplanted microbiome and different host factors, and suggested that the humanized mouse model may not faithfully reproduce the human-specific microbiome-immune interaction.

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Consistent alterations of human fecal microbes after transplanted to germ-free mice

Cited by 3 publications

References 127 publications

Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models

Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models

Approaches to discern if microbiome associations reflect causation in metabolic and immune disorders

Mice with a humanized immune system are resilient to transplantation of human microbiota

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