Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy DOI Creative Commons

Rosina Pryor,

Povilas Norvaišas, Γεώργιος Μαρίνος

et al.

Cell, Journal Year: 2019, Volume and Issue: 178(6), P. 1299 - 1312.e29

Published: Aug. 29, 2019

Metformin is the first-line therapy for treating type 2 diabetes and a promising anti-aging drug. We set out to address fundamental question of how gut microbes nutrition, key regulators host physiology, affect effects metformin. Combining two tractable genetic models, bacterium E. coli nematode C. elegans, we developed high-throughput four-way screen define underlying host-microbe-drug-nutrient interactions. show that integrate cues from metformin diet through phosphotransferase signaling pathway converges on transcriptional regulator Crp. A detailed experimental characterization downstream Crp in combination with metabolic modeling microbiota metformin-treated diabetic patients predicts production microbial agmatine, lipid metabolism lifespan. Our screening platform paves way identifying exploitable drug-nutrient-microbiome interactions improve health longevity targeted microbiome therapies.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI3OGQ0MjNhNTMzNGQyZmYxYTZiNTdlNmY2MmYxMzM3ZSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4NzgzMjE5fQ.C3wdcP1TL3PapJWq4aI9LqsiS4q6cpUWw-FQ7fy9lgDmKHFywjogOw_G7SPvpjQAddWJFM3HFiFp6aC-1emmlgxKYfkZob882qDP8r0K1SoLm87Cbli3lc1G7hM9SeBcggAoLXUh0eD50eoNMejy-aonZO3owgKn92ybO60X8R38WWtkT-dE_vYa7x1RJIluwBYG7ocgruTrQ13ku0YQCB8I7s963G-jxU4aVCrfH2_2dj3oHNkmUYfkHx-WxMZiw6prSCAo2MxN0khMxAHYyi5KTpJGSVJwcQVLnY4qxocw4p080sYc1DSUlXTBVUq_Z11m6HKwvf0_D0Iarevc_A(mp4, (44.92 MB) Download video

Language: Английский

Gut microbial metabolites in obesity, NAFLD and T2DM DOI
Emanuel E. Canfora, Ruth C. R. Meex, Koen Venema

et al.

Nature Reviews Endocrinology, Journal Year: 2019, Volume and Issue: 15(5), P. 261 - 273

Published: Jan. 22, 2019

Language: Английский

Citations

1104

Facing up to the global challenges of ageing DOI
Linda Partridge, Joris Deelen, P. Eline Slagboom

et al.

Nature, Journal Year: 2018, Volume and Issue: 561(7721), P. 45 - 56

Published: Aug. 30, 2018

Language: Английский

Citations

1083

Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer DOI
Jakob Wirbel, Paul Theodor Pyl, Ece Kartal

et al.

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(4), P. 679 - 689

Published: April 1, 2019

Language: Английский

Citations

973

Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation DOI
Andrew Maltez Thomas, Paolo Manghi, Francesco Asnicar

et al.

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(4), P. 667 - 678

Published: April 1, 2019

Language: Английский

Citations

739

Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration DOI Open Access
Emily R. Leeming, Abigail Johnson, Tim D. Spector

et al.

Nutrients, Journal Year: 2019, Volume and Issue: 11(12), P. 2862 - 2862

Published: Nov. 22, 2019

The human gut is inhabited by trillions of microorganisms composing a dynamic ecosystem implicated in health and disease. composition the microbiota unique to each individual tends remain relatively stable throughout life, yet daily transient fluctuations are observed. Diet key modifiable factor influencing microbiota, indicating potential for therapeutic dietary strategies manipulate microbial diversity, composition, stability. While diet can induce shift these changes appear be temporary. Whether prolonged permanent alterations unknown, mainly due lack long-term interventions, or follow-ups short-term interventions. It possible that habitual diets have greater influence on than acute strategies. This review presents current knowledge around response interventions identifies major factors contribute diet. Overall, further research include microbiome measures required before clinical recommendations made modulation health.

Language: Английский

Citations

652

The Gut Virome Database Reveals Age-Dependent Patterns of Virome Diversity in the Human Gut DOI Creative Commons
Ann Gregory, Olivier Zablocki, Ahmed A. Zayed

et al.

Cell Host & Microbe, Journal Year: 2020, Volume and Issue: 28(5), P. 724 - 740.e8

Published: Aug. 24, 2020

Language: Английский

Citations

523

Gut Microbiota and Cancer: From Pathogenesis to Therapy DOI Open Access
Silvia Vivarelli, Rossella Salemi, Saverio Candido

et al.

Cancers, Journal Year: 2019, Volume and Issue: 11(1), P. 38 - 38

Published: Jan. 3, 2019

Cancer is a multifactorial pathology and it represents the second leading cause of death worldwide. In recent years, numerous studies highlighted dual role gut microbiota in preserving host’s health. Gut resident bacteria are able to produce number metabolites bioproducts necessary protect gut’s homeostasis. Conversely, several subpopulations may expand during pathological dysbiosis therefore high levels toxins capable, turn, trigger both inflammation tumorigenesis. Importantly, can interact with host either modulating directly epithelium or immune system. Numerous populating bacteria, called probiotics, have been identified as protective against genesis tumors. Given their capability homeostasis, probiotics currently tested help fight cancer patients subjected chemotherapy radiotherapy. Most recently, three independent show that specific species potentiate positive outcome anti-cancer immunotherapy. The highly significant studies, uncovering tight association between tumorigenesis, well therapy, here described. Lactobacillus rhamnosus GG (LGG), most studied probiotic model cancer, also reported. Overall, according findings summarized, novel strategies integrating such LGG, conventional therapies strongly encouraged.

Language: Английский

Citations

496

Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health DOI
Marina Fassarella, Ellen E. Blaak, John Penders

et al.

Gut, Journal Year: 2020, Volume and Issue: 70(3), P. 595 - 605

Published: Oct. 13, 2020

The human gut microbiome is a complex ecosystem, densely colonised by thousands of microbial species. It varies among individuals and depends on host genotype environmental factors, such as diet antibiotics. In this review, we focus stability resilience essential ecological characteristics the its relevance for health. Microbial diversity, metabolic flexibility, functional redundancy, microbe–microbe host–microbe interactions seem to be critical maintaining resilience. equilibrium ecosystem can disrupted perturbations, antibiotic therapy, causing significant decreases in richness diversity well impacting As consequence, unbalanced states or even unhealthy stable develop, potentially leading supporting diseases. Accordingly, strategies have been developed manipulate order prevent revert caused including faecal microbiota transplantation, supplementation with probiotics non-digestible carbohydrates, more extensive dietary modifications. Nevertheless, an increasing number studies has evidenced interindividual variability extent direction response which attributed unique each individual’s microbiome. From clinical, translational perspective, ability improve prior restore afterwards, would offer benefits. To effective, therapeutic approach will likely need personalised subgroup-based understanding individual genetics, diet, other factors that might involved.

Language: Английский

Citations

470

Extensive transmission of microbes along the gastrointestinal tract DOI Creative Commons
Thomas Schmidt, Matthew R. Hayward, Luís Pedro Coelho

et al.

eLife, Journal Year: 2019, Volume and Issue: 8

Published: Feb. 12, 2019

The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to intestine considered a rare aberrant event, and hallmark disease. By studying salivary fecal microbial strain populations 310 in 470 individuals from five countries, we found that transmission to, subsequent colonization of, large microbes common extensive among healthy individuals. We evidence for vast majority be transferable, with increased levels colorectal cancer rheumatoid arthritis patients and, more generally, described as opportunistic pathogens. This establishes cavity an endogenous reservoir gut strains, oral-fecal important process shapes microbiome health

Language: Английский

Citations

433

Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism DOI
Ilaria Elia, Marcia C. Haigis

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(1), P. 21 - 32

Published: Jan. 4, 2021

Language: Английский

Citations

430