Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model DOI Creative Commons
Xiaotian Mao,

Sabina Birgitte Larsen,

Line Fisker Zachariassen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 20, 2023

Abstract Metabolic syndrome encompasses amongst other conditions like obesity, type-2 diabetes, and metabolic dysfunction associated fatty liver disease (MAFLD), which are all with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat by restoring the GM. FMT is generally safe, but motivated case reports, accidental transfer of pathogenic bacteria remains a concern. As safer alternative, fecal virome (FVT, sterile-filtrated feces) advantage over in that mainly bacteriophages transferred FVT from lean male donors shown promise alleviating effects high-fat diet preclinical mouse study. However, still carries risk eukaryotic viral infections. To address this, we here apply recently developed modification methodologies inactivate or remove component while maintaining an active enteric bacteriophage community. Modified FVTs were compared unmodified saline animal model diet-induced obesity using C57BL/6N mice. In contrast obese control group, mice administered modified FVT, nearly depleted viruses (0.1%), exhibited enhanced blood glucose clearance, although without concurrent reduction weight gain. The improved pathology reduced proportions immune cells adipose tissue non-uniform response. GM analysis suggested bacteriophage-mediated modulation had influenced these outcomes. When optimized, this may pave way for developing safe bacteriophage-based therapies targeting through restoration.

Language: Английский

Choice of Ultrafilter Affects Recovery Rate of Bacteriophages DOI Creative Commons
Frej Larsen, Simone Margaard Offersen, Viktoria Rose Li

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(10), P. 2051 - 2051

Published: Oct. 5, 2023

Studies into the viral fraction of complex microbial communities, like in mammalian gut, have recently garnered much interest. Yet there is still no standardized protocol for extracting viruses from such samples, and protocols that exist employ procedures skew community sample one way or another. The first step extraction pipeline often consists basic filtering macromolecules bacteria, yet even this affects a strain-specific manner. In study, we investigate based on ultrafiltration how choice ultrafilter might influence extracted community. Clinical samples (feces, vaginal swabs, tracheal suction samples) were spiked with mock known phages (T4, c2, Φ6, Φ29, Φx174, Φ2972), filtered, quantified using spot plaque assays to estimate loss recovery. enveloped Φ6 phage especially severely affected by filter, but also tailed as T4 c2 reduced infectivity after ultrafiltration. We conclude pore size ultrafilters may affect recovery strain- sample-dependent manner, suggesting need greater thought when selecting filters virus extraction.

Language: Английский

Citations

9

Detection, isolation and characterization of phage-host complexes using BONCAT and click chemistry DOI Creative Commons
Patrick Hellwig, Anna Dittrich,

Robert Heyer

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 3, 2024

Phages are viruses that infect prokaryotes and can shape microbial communities by lysis, thus offering applications in various fields. However, challenges exist sampling, isolation accurate prediction of the host specificity phages as well identification newly replicated virions response to environmental challenges.

Language: Английский

Citations

3

Virus-host interactions predictor (VHIP): Machine learning approach to resolve microbial virus-host interaction networks DOI Creative Commons
G Eric Bastien, Rachel Cable,

Cecelia Batterbee

et al.

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(9), P. e1011649 - e1011649

Published: Sept. 18, 2024

Viruses of microbes are ubiquitous biological entities that reprogram their hosts' metabolisms during infection in order to produce viral progeny, impacting the ecology and evolution microbiomes with broad implications for human environmental health. Advances genome sequencing have led discovery millions novel viruses an appreciation great diversity on Earth. Yet, knowledge only "who is there?" we fall short our ability infer impacts at population, community, ecosystem-scales. To do this, need a more explicit understanding they infect?" Here, developed machine learning model (ML), Virus-Host Interaction Predictor (VHIP), predict virus-host interactions (infection/non-infection) from input virus host genomes. This ML was trained tested high-value manually curated set 8849 pairs corresponding sequence data. The resulting dataset, 'Virus Host Range network' (VHRnet), core VHIP functionality. Each data point underlies training testing represents lab-tested pair VHRnet, which meaningful signals adaptation were computed genomic sequences. departs existing prediction models its multiple rather than predicting single most likely or clade. As result, able complexity networks natural systems. has 87.8% accuracy rate between species level can be applied population genomes reconstructed metagenomic datasets.

Language: Английский

Citations

3

The role of phages for microdiverse bacterial communities in proglacial stream biofilms DOI Creative Commons
Hannes Peter, Grégoire Michoud, Susheel Bhanu Busi

et al.

Frontiers in Microbiomes, Journal Year: 2024, Volume and Issue: 2

Published: Jan. 15, 2024

Viruses modulate the diversity and activity of microbial communities. However, little is known about their role for structure stream bacterial biofilm Here, we present insights into composition viral communities in various streams draining three proglacial floodplains Switzerland. Proglacial are characterized by extreme environmental conditions, including near-freezing temperatures ultra-oligotrophy. These conditions select few but well-adapted clades, which dominate occupy niches via microdiversification. We used metagenomic sequencing to reveal a diverse assemblage these streams. Across different streams, community was tightly coupled that hosts, underscored generally high host specificity. Combining predictions phage-host interactions with auxiliary metabolic genes (AMGs), identify specific AMGs shared phages infecting microdiverse clade members. Our work provides step towards better understanding complex among bacteria general influenced glacier meltwaters microdiversity particular.

Language: Английский

Citations

2

Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model DOI Creative Commons
Xiaotian Mao,

Sabina Birgitte Larsen,

Line Fisker Zachariassen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 20, 2023

Abstract Metabolic syndrome encompasses amongst other conditions like obesity, type-2 diabetes, and metabolic dysfunction associated fatty liver disease (MAFLD), which are all with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat by restoring the GM. FMT is generally safe, but motivated case reports, accidental transfer of pathogenic bacteria remains a concern. As safer alternative, fecal virome (FVT, sterile-filtrated feces) advantage over in that mainly bacteriophages transferred FVT from lean male donors shown promise alleviating effects high-fat diet preclinical mouse study. However, still carries risk eukaryotic viral infections. To address this, we here apply recently developed modification methodologies inactivate or remove component while maintaining an active enteric bacteriophage community. Modified FVTs were compared unmodified saline animal model diet-induced obesity using C57BL/6N mice. In contrast obese control group, mice administered modified FVT, nearly depleted viruses (0.1%), exhibited enhanced blood glucose clearance, although without concurrent reduction weight gain. The improved pathology reduced proportions immune cells adipose tissue non-uniform response. GM analysis suggested bacteriophage-mediated modulation had influenced these outcomes. When optimized, this may pave way for developing safe bacteriophage-based therapies targeting through restoration.

Language: Английский

Citations

6