Human gut microbes impact host serum metabolome and insulin sensitivity

@article{Pedersen2016HumanGM,
  title={Human gut microbes impact host serum metabolome and insulin sensitivity},
  author={Helle Krogh Pedersen and Valborg Gudmundsdottir and Henrik Bj{\o}rn Nielsen and Tuulia Hyotylainen and Trine Nielsen and Benjamin Anderschou Holbech Jensen and Kristoffer Forslund and Falk Hildebrand and Edi Prifti and Gwen Falony and Emmanuelle Le Chatelier and Florence Levenez and Jo{\"e}l Dor{\'e} and Ismo Mattila and Damian Rafal Plichta and P{\"a}ivi P{\"o}h{\"o} and Lars Ingvar Hellgren and Manimozhiyan Arumugam and Shinichi Sunagawa and Sara Vieira-Silva and Torben J{\o}rgensen and Jacob Bak Holm and Kajetan Tro{\vs}t and MetaHIT consortium and Karsten Kristiansen and Susanne Brix and Jeroen Raes and Jun Wang and Torben Hansen and Peer Bork and S{\o}ren Brunak and Matej Ore{\vs}ič and Stanislav Dusko Ehrlich and Oluf Pedersen},
  journal={Nature},
  year={2016},
  volume={535},
  pages={376-381}
}
Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes… 
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References

SHOWING 1-10 OF 73 REFERENCES
Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)
TLDR
Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.
The gut microbiota modulates host energy and lipid metabolism in mice[S]
TLDR
It is shown that the gut microbiota affects both host energy and lipid metabolism and highlights its role in the development of metabolic diseases.
Branched-chain amino acids in metabolic signalling and insulin resistance
TLDR
Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review, and a BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM.
Gut metagenome in European women with normal, impaired and diabetic glucose control
TLDR
This work uses shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control, and develops a mathematical model based on metagenomic profiles that identified T2D with high accuracy.
A branched chain amino acid metabolite drives vascular transport of fat and causes insulin resistance
TLDR
PPARGC1a is leveraged, a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.
Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans.
TLDR
A relationship between lipid acyl chain content and diabetes risk is identified and how lipid profiling could aid in clinical risk assessment is demonstrated.
Ceramides in insulin resistance and lipotoxicity.
  • S. Summers
  • Biology, Medicine
    Progress in lipid research
  • 2006
...
...