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肠道病毒组转移可改善肥胖雄性小鼠与代谢综合征相关的症状。

Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice.

机构信息

Section of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.

Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.

出版信息

Nat Commun. 2024 Jun 3;15(1):4704. doi: 10.1038/s41467-024-49152-w.


DOI:10.1038/s41467-024-49152-w
PMID:38830845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11148109/
Abstract

Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.

摘要

代谢综合征包括肥胖症和 2 型糖尿病等疾病,与肠道微生物组(GM)失调有关。通过恢复 GM,粪便微生物群移植(FMT)已被探索用于治疗代谢综合征;然而,人们仍然担心会意外转移致病微生物。作为一种更安全的选择,粪便病毒群移植(FVT,无菌过滤粪便)在传递物上主要是噬菌体,相对于 FMT 具有优势。来自瘦型雄性供体的 FVT 在一项临床前小鼠研究中显示出有希望减轻高脂肪饮食的代谢影响。然而,FVT 仍存在真核病毒感染的风险。为了解决这个问题,最近开发的方法被应用于去除或失活 FVT 病毒成分中的真核病毒。在雄性 C57BL/6N 小鼠的饮食诱导肥胖模型中,对改良的 FVT 与未改良的 FVT 和生理盐水进行了比较。与肥胖对照组相比,给予改良 FVT(几乎耗尽真核病毒)的小鼠表现出血糖清除增强,但体重未减轻。未改良的 FVT 可改善肝脏病理,并减少脂肪组织中免疫细胞的比例,但反应不均匀。GM 分析表明,噬菌体介导的 GM 调节影响结果。优化这些方法可能会导致通过 GM 恢复开发针对代谢综合征的安全噬菌体为基础的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/1269ceb93a62/41467_2024_49152_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/5797d4798cd7/41467_2024_49152_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/821012ce8814/41467_2024_49152_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/18ecaaea53e7/41467_2024_49152_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/f8bbbdf1ed6a/41467_2024_49152_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/4a6a28d64b57/41467_2024_49152_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/1269ceb93a62/41467_2024_49152_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/5797d4798cd7/41467_2024_49152_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/821012ce8814/41467_2024_49152_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/18ecaaea53e7/41467_2024_49152_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/f8bbbdf1ed6a/41467_2024_49152_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/4a6a28d64b57/41467_2024_49152_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce96/11148109/1269ceb93a62/41467_2024_49152_Fig6_HTML.jpg

相似文献

[1]
Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice.

Nat Commun. 2024-6-3

[2]
Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model.

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[3]
Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments.

Microbiome. 2024-7-1

[4]
Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations.

FEMS Microbiol Rev. 2020-7-1

[5]
Fecal virome transfer improves proliferation of commensal gut and unexpectedly enhances the fertility rate in laboratory mice.

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[6]
Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice.

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[7]
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J Microbiol Immunol Infect. 2023-10

[8]
Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation.

BMC Biol. 2020-11-20

[9]
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Biomed Pharmacother. 2024-8

[10]
Effects of fecal microbiota transplantation and fecal virome transplantation on LPS-induced intestinal injury in broilers.

Poult Sci. 2024-2

引用本文的文献

[1]
Gut microbiome dysregulation in noninfectious uveitis.

Front Immunol. 2025-7-29

[2]
An Exploration of the Relationship Between Gut Virome and Cardiovascular Disease: A Comprehensive Review.

Rev Cardiovasc Med. 2025-6-24

[3]
The gut virome and human health: From diversity to personalized medicine.

Eng Microbiol. 2025-2-7

[4]
Bacteriophage-driven DNA inversions shape bacterial functionality and long-term co-existence in .

Gut Microbes. 2025-12

[5]
The human phageome: niche-specific distribution of bacteriophages and their clinical implications.

Appl Environ Microbiol. 2025-6-18

[6]
Fecal microbiota transplantation: application scenarios, efficacy prediction, and factors impacting donor-recipient interplay.

Front Microbiol. 2025-3-25

[7]
Effects of bacteriophages on gut microbiome functionality.

Gut Microbes. 2025-12

[8]
Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis.

Gut Microbes. 2024

本文引用的文献

[1]
Phage-inducible chromosomal minimalist islands (PICMIs), a novel family of small marine satellites of virulent phages.

Nat Commun. 2024-1-22

[2]
Fecal virus transplantation has more moderate effect than fecal microbiota transplantation on changing gut microbial structure in broiler chickens.

Poult Sci. 2024-2

[3]
A Mammalian Cell's Guide on How to Process a Bacteriophage.

Annu Rev Virol. 2023-9-29

[4]
Recipient-independent, high-accuracy FMT-response prediction and optimization in mice and humans.

Microbiome. 2023-8-14

[5]
Nutritional and host environments determine community ecology and keystone species in a synthetic gut bacterial community.

Nat Commun. 2023-8-8

[6]
Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice.

Gut Microbes. 2023

[7]
Function of in type 2 diabetes and related diseases.

Front Microbiol. 2023-6-15

[8]
Immunogenicity of bacteriophages.

Trends Microbiol. 2023-10

[9]
Fecal virome transfer improves proliferation of commensal gut and unexpectedly enhances the fertility rate in laboratory mice.

Gut Microbes. 2023

[10]
iPHoP: An integrated machine learning framework to maximize host prediction for metagenome-derived viruses of archaea and bacteria.

PLoS Biol. 2023-4

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