Selective colonization ability of human fecal microbes in different mouse gut environments

Zhou, Wei; Chow, Kin-Hoe; Fleming, Elizabeth; Oh, Julia

doi:10.1038/s41396-018-0312-9

Cited by 44 publications

(45 citation statements)

References 88 publications

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“…There are several documented regimens for depleting gut bacteria in mice with antibiotics 26,27,28,29,30,31 . We chose our cocktail of antibiotics due to their known capacity to target a broad range of bacteria in the gut and because we found several examples of successful bacterial depletion in the literature.…”

Section: Discussionmentioning

confidence: 99%

A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

Daharsh

Zhang

Ramer‐Tait

et al. 2019

JoVE

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Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut microbiome. NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice are one of the best animals for humanization due to their high level of immunodeficiency. However, germ-free NSG mice, and various other important germ-free mice models are not currently commercially available. Further, many research settings do not have access to gnotobiotic facilities, and working under gnotobiotic conditions can often be expensive and time consuming. Importantly, germ-free mice have several immune deficiencies that exist even after the engraftment of microbes. Therefore, we developed a protocol that does not require germ-free animals or gnotobiotic facilities. To generate double hu-mice, NSG mice were treated with radiation prior to surgery to create bone-marrow, liver, thymus-humanized (hu-BLT) mice. The mice were then treated with broad spectrum antibiotics to deplete the pre-existing murine gut microbiome. After antibiotic treatment, the mice were given fecal transplants with healthy human donor samples via oral gavage. Double hu-BLT mice had unique 16S rRNA gene profiles based on the individual human donor sample that was transplanted. Importantly, the transplanted human-like microbiome was stable in the double hu-BLT mice for the duration of the study up to 14.5 weeks post-transplant.

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Section: Discussionmentioning

confidence: 99%

A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

Daharsh

Zhang

Ramer‐Tait

et al. 2019

JoVE

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“…In addition, there was no significant difference between the individuals caught in the wild or fed on a controlled diet across two time periods. Several factors can influence the success of colonization by exogenous microbes and the presence of a native microbiota offering resistance is one of the main lines of defense, especially in the case of hosts with high diversity communities 69 , as may be the case in this study. In addition, we acknowledge that an investigation of the effects of the individuals caught in the wild or fed on a controlled diet requires a greater understanding of the composition of the wild diet of the two colonies that were sampled here, but there is little data on the general biology of this omnivorous species, which further increases the importance of the 18S rRNA data from the present study.…”

Section: Found That Formentioning

confidence: 74%

Development but not diet alters microbial communities in the Neotropical arboreal trap jaw ant Daceton armigerum: an exploratory study

Ramalho

Duplais

Orivel

et al. 2020

Sci Rep

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To better understand the evolutionary significance of symbiotic interactions in nature, microbiome studies can help to identify the ecological factors that may shape host-associated microbial communities. In this study we explored both 16S and 18S rRNA microbial communities of D. armigerum from both wild caught individuals collected in the Amazon and individuals kept in the laboratory and fed on controlled diets. We also investigated the role of colony, sample type, development and caste on structuring microbial communities. Our bacterial results (16S rRNA) reveal that (1) there are colony level differences between bacterial communities; (2) castes do not structure communities; (3) immature stages (brood) have different bacterial communities than adults; and 4) individuals kept in the laboratory with a restricted diet showed no differences in their bacterial communities from their wild caught nest mates, which could indicate the presence of a stable and persistent resident bacterial community in this host species. The same categories were also tested for microbial eukaryote communities (18S rRNA), and (5) developmental stage has an influence on the diversity recovered; (6) the diversity of taxa recovered has shown this can be an important tool to understand additional aspects of host biology and species interactions.

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“…Their immunodeficiency may contribute to their pre-existing low diversity gut microbiome status before human fecal material transplant. In a study by Zhou et al, NSG and C57BL6/J mice whose native microbiota were depleted by antibiotics followed by FMT had no significant differences in diversity but did observe significant differences in which species colonized[39]. A study done by Ericsson et al showed that it is easier to transfer high diversity fecal donor samples into low diversity recipients, which could help to explain the success of engraftment and stability in our model[30].…”

Section: Discussionmentioning

confidence: 91%

Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice

Daharsh

Ramer‐Tait

2019

Preprint

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BackgroundHumanized mice featuring a functional human immune system are an important pre-clinical model for examining immune responses to human-specific pathogens. This model has been widely utilized to study human diseases that are otherwise impossible or difficult to investigate in humans or with other animal models. However, one limitation of using humanized mice is their native murine gut microbiome, which significantly differs from the one found in humans. These differences may be even greater for mice housed and bred in specific pathogen free conditions. Given the importance of the gut microbiome to human health and disease, these differences may profoundly impact the ability to translate the results from humanized mice studies to human disease. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We therefore created double humanized mice with both a functional human immune system and stable human-like gut microbiome.ResultsSurgery was performed on NOD.Cg-PrkdcscidII2rgtm1Wjl/SzJ (NSG) mice to create bone-marrow, liver, thymus (BLT) humanized mice. After immune reconstitution, mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and then transplanted with fecal material from healthy human donors. Characterization of 173 fecal samples obtained from 45 humanized mice revealed that double humanized mice had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors compared to humanized mice.ConclusionsHere, we describe successful engraftment of a stable human microbiome in BLT humanized mice to further improve this preclinical humanized mouse model. These double humanized mice represent a unique and tractable new model to study the complex relationships between the human gut microbiome, human immune system, and human disease in vivo.

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Selective colonization ability of human fecal microbes in different mouse gut environments

Cited by 44 publications

References 88 publications

A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

Development but not diet alters microbial communities in the Neotropical arboreal trap jaw ant Daceton armigerum: an exploratory study

Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice

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