Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
Kristoffer Forslund,Falk Hildebrand,Falk Hildebrand,Trine Nielsen,Gwen Falony,Gwen Falony,Shinichi Sunagawa,Edi Prifti,Sara Vieira-Silva,Sara Vieira-Silva,Valborg Gudmundsdottir,Helle Krogh Pedersen,Manimozhiyan Arumugam,Karsten Kristiansen,Anita Y. Voigt,Anita Y. Voigt,Henrik Vestergaard,Rajna Hercog,Paul I. Costea,Jens Roat Kultima,Junhua Li,Torben Jørgensen,Torben Jørgensen,Florence Levenez,Joël Doré,H. Bjørn Nielsen,Søren Brunak,Søren Brunak,Jeroen Raes,Jeroen Raes,Jeroen Raes,Torben Hansen,Torben Hansen,Jun Wang,S. Dusko Ehrlich,S. Dusko Ehrlich,Peer Bork,Oluf Pedersen +37 more
TLDR
A unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa is reported, highlighting the need to disentangle gut microbiota signatures of specific human diseases from those of medication.Abstract:
In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.read more
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The Human Intestinal Microbiome in Health and Disease
Susan V. Lynch,Oluf Pedersen +1 more
TL;DR: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.
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Population-level analysis of gut microbiome variation
Gwen Falony,Marie Joossens,Marie Joossens,Sara Vieira-Silva,Jun Wang,Youssef Darzi,Youssef Darzi,Karoline Faust,Karoline Faust,Alexander Kurilshikov,Marc Jan Bonder,Mireia Valles-Colomer,Doris Vandeputte,Doris Vandeputte,Raul Y. Tito,Raul Y. Tito,Samuel Chaffron,Samuel Chaffron,Leen Rymenans,Leen Rymenans,Chloë Verspecht,Lise De Sutter,Lise De Sutter,Gipsi Lima-Mendez,Kevin D'hoe,Kevin D'hoe,Karl Jonckheere,Karl Jonckheere,Daniel Homola,Daniel Homola,Roberto Garcia,Roberto Garcia,Ettje F. Tigchelaar,Linda Eeckhaudt,Linda Eeckhaudt,Jingyuan Fu,Liesbet Henckaerts,Alexandra Zhernakova,Cisca Wijmenga,Jeroen Raes,Jeroen Raes +40 more
TL;DR: Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations, and proposed disease marker genera associated to host covariates were found associated to microbiota compositional variation with a 92% replication rate.
Journal ArticleDOI
Gut microbiota in human metabolic health and disease.
Yong Fan,Oluf Pedersen +1 more
TL;DR: How the gut microbiota and derived microbial compounds may contribute to human metabolic health and to the pathogenesis of common metabolic diseases are discussed, and examples of microbiota-targeted interventions aiming to optimize metabolic health are highlighted.
Journal ArticleDOI
Human gut microbes impact host serum metabolome and insulin sensitivity
Helle Krogh Pedersen,Valborg Gudmundsdottir,Henrik Nielsen,Tuulia Hyötyläinen,Tuulia Hyötyläinen,Trine G. Nielsen,Benjamin A. H. Jensen,Kristoffer Forslund,Falk Hildebrand,Falk Hildebrand,Edi Prifti,Edi Prifti,Gwen Falony,Florence Levenez,Joël Doré,Ismo Mattila,Ismo Mattila,Damian R. Plichta,Päivi Pöhö,Päivi Pöhö,Lars Hellgren,Manimozhiyan Arumugam,Shinichi Sunagawa,Sara Vieira-Silva,Torben Jørgensen,Torben Jørgensen,Jacob Bak Holm,Kajetan Trošt,Karsten Kristiansen,Susanne Brix,Jeroen Raes,Jeroen Raes,Jun Wang,Torben Hansen,Torben Hansen,Peer Bork,Søren Brunak,Søren Brunak,Matej Orešič,Matej Orešič,Matej Orešič,S. Dusko Ehrlich,S. Dusko Ehrlich,Oluf Pedersen +43 more
TL;DR: It is shown how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals and suggested that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
Journal ArticleDOI
The mechanisms of action of metformin
TL;DR: Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut.
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