Bacteriophage-Mediated Perturbation of Defined Bacterial Communities in an
            <i>In Vitro</i>
            Model of the Human Gut

Attai, Hedieh; Wilde, Jacob; Liu, Roland; Chopyk, Jessica; Garcia, Andrew G.; Allen‐Vercoe, Emma; Pride, David T.

doi:10.1128/spectrum.01135-22

Cited by 10 publications

(14 citation statements)

References 34 publications

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“…However, we believe this is unlikely, as the PEG precipitation protocol involved centrifugation and resuspension in PBS to reduce metabolite carryover. Each of these purified viromes were subjected to culture to identify whether any cultivable bacteria were present, which provides broader confidence that these were pure viromes as we have used in prior studies [35].…”

Section: Discussionmentioning

confidence: 99%

“…While much of the focus has been placed on the bacteria of the gut, which are known to shape a host metabolism, disease, and even behavior [49][50][51], it is becoming clear that the viral community also plays a role in many of these conditions [11,13,14]. Prior studies inform us that viruses in the gut have the capacity to shape their concomitant bacterial communities [22,25,35]. By extension, if bacterial communities can affect metabolic phenotypes [8], viromes can help to shape them as well.…”

Section: Discussionmentioning

confidence: 99%

“…Using previously described techniques [35], we purified and then transplanted fecal viromes into mice on different diet types via oral gavage. In order to determine whether viruses directly affected mouse phenotypes, we recorded mouse body weights throughout 4 weeks of study.…”

Section: Discussionmentioning

confidence: 99%

“…To sequence the fecal viromes of donor and recipient mice, viral DNA and RNA was extracted using an adapted "NetoVIR" protocol [35], adapted from [36]. First, 0.05 g of fecal material was homogenized in 500 μL of 0.5x PBS for 1 min, centrifuged at 17,000 x g for 3 min.…”

Section: Virome Shotgun Sequencingmentioning

confidence: 99%

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Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice

Borin

Liu

Wang

et al. 2023

Preprint

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Background: The gastrointestinal microbiome plays a significant role in numerous host processes and has an especially large impact on modulating the host metabolism. Prior studies have shown that when mice receive fecal transplants from obese donors that were fed high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes. These studies demonstrate the prominent role that the gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, studies have not measured the impact of gut viruses on these phenotypes. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow. By characterizing the mice gut bacterial biota and weight-gain phenotypes over time, we demonstrate that viruses can shape the gut bacterial community and affect weight gain or loss. Results: We gavaged mice longitudinally over 4 weeks while measuring their body weights and collecting fecal samples for 16S rRNA amplicon sequencing. We evaluated mice that were fed normal chow or high-fat diets, and gavaged each group with either chow-derived fecal viromes, HFD-derived fecal viromes, or phosphate buffered saline controls. We found a significant effect of gavage type, where mice fed chow but gavaged with HFD-derived viromes gained significantly more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained significantly less weight than their counterparts receiving HFD-derived viromes. These results were replicated in two separate experiments and the phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Notably, there were differences in Lachnospirales and Clostridia in mice fed chow but gavaged with HFD-derived fecal viromes, and in Peptostreptococcales, Oscillospirales, and Lachnospirales in mice fed HFD but gavaged with chow-derived fecal viromes. Due to methodological limitations, we were unable to identify specific bacterial species or strains that were responsible for respective phenotypic changes. Conclusions: This study confirms that virome-mediated perturbations can alter the fecal microbiome in an in vivo model and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Virome Shotgun Sequencingmentioning

confidence: 99%

See 2 more Smart Citations

Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice

Borin

Liu

Wang

et al. 2023

Preprint

Self Cite

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“…An important selling point of phage therapy is that phage cocktails act in species-specific manner and do not disrupt the overall (bacterial) microbiome composition (10, 37, 38). In our work, we confirm that the phage cocktails specifically targeting E. coli Mt1B1 and E. faecalis KB1 do not affect the overall bacterial community structure.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophages targeting protective commensals impair resistance againstSalmonellaTyphimurium infection in gnotobiotic mice

Strempel

Weiß

Wittmann

et al. 2022

Preprint

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Gut microbial communities protect the host against a variety of major human gastrointestinal pathogens. Bacteriophages (phages) are ubiquitous in nature and frequently ingested via food and drinking water. Moreover, they are an attractive tool for microbiome engineering due to the lack of known serious adverse effects on the host. However, the functional role of phages within the gastrointestinal microbiome remain poorly understood. Here, we investigated the effects of microbiota-directed phages on infection with the human enteric pathogen Salmonella enterica serovar Typhimurium (S. Tm), using a gnotobiotic mouse model (OMM12) for colonization resistance (CR). We show that phage cocktails targeting Escherichia coli and Enterococcus faecalis acted in a strain-specific manner. They transiently reduced the population density of their respective target before establishing coexistence for up to 9 days. Infection susceptibility to S. Tm was markedly increased at an early time point after phage challenge. Surprisingly, OMM12 mice were more susceptible 7 days after a single phage inoculation, when the targeted bacterial populations were back to pre-phage administration density. The presence of phages that dynamically modulates the density of protective members of the gut microbiota provides opportunities for invasion of bacterial pathogens.

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The Robogut: A Bioreactor Model of the Human Colon for Evaluation of Gut Microbial Community Ecology and Function

et al. 2023

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The human colon is inhabited by a complex community of microbes. These microbes are integral to host health and physiology. Understanding how and when the microbiome causally influences host health will require microbiome models that can be tightly controlled and manipulated. While in vivo models are unrivalled in their ability to study host-microbial interplay, in vitro models are gaining in popularity as methods to study the ecology and function of the gut microbiota, and benefit from tight controllability and reproducibility, as well as reduced ethical constraints. In this set of protocols, we describe the Robogut, a single-stage bioreactor system designed to replicate the conditions of the distal human colon, to culture whole microbial communities derived from stool and/or colonic biopsy samples, with consideration of methods to create culture medium formulations and to build, run, and sample the bioreactor apparatus. Cleaning and maintenance of the bioreactor system are also described.

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Bacteriophage-Mediated Perturbation of Defined Bacterial Communities in an In Vitro Model of the Human Gut

Abstract: Bacteriophages are relatively ubiquitous in the environment and are highly abundant in the human microbiome. Phages can be commonly transmitted between close contacts, but the impact that such transmissions may have on their bacteria counterparts in our microbiomes is unknown.

Cited by 10 publications

References 34 publications

Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice

Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice

Bacteriophages targeting protective commensals impair resistance againstSalmonellaTyphimurium infection in gnotobiotic mice

The Robogut: A Bioreactor Model of the Human Colon for Evaluation of Gut Microbial Community Ecology and Function

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