Diet, Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites
Abstract
Diet, genetics, and the gut microbiome are determinants of metabolic status, in part through production of metabolites by the gut microbiota. To understand the mechanisms linking these factors, we performed LC-MS-based metabolomic analysis of cecal contents and plasma from C57BL/6J, 129S1/SvImJ, and 129S6/SvEvTac mice on chow or a high-fat diet (HFD) and HFD-treated with vancomycin or metronidazole. Prediction of the functional metagenome of gut bacteria by PICRUSt analysis of 16S sequences revealed dramatic differences in microbial metabolism. Cecal and plasma metabolites showed multifold differences reflecting the combined and integrated effects of diet, antibiotics, host background, and the gut microbiome. Eighteen plasma metabolites correlated positively or negatively with host insulin resistance across strains and diets. Over 1,000 still-unidentified metabolite peaks were also highly regulated by diet, antibiotics, and genetic background. Thus, diet, host genetics, and the gut microbiota interact to create distinct responses in plasma metabolites, which can contribute to regulation of metabolism and insulin resistance.
Keywords: TMAO; antibiotics; bile acids; cecal metabolomics; diabetes; diet; gut microbiome; obesity; serum lipids; serum metabolomics, genetics and the gut microbiome.
Tropical rainforest, Queensland, Australia. Photo by Dr. Rohan Davis.
Analytical equipment. Photo by Atanas G. Atanasov.
Hep-2 signal activated cells. Image by Dr. Vassilis Doucas.
Flower blossoms at gardens by the bay Singapore-photo by Dr. Hemanth Kumar Boyina.
Saffron plants, Zapponeta (Foggia), South of Italy. Photo by Dr. Grazia D'Onofrio.
Blood cells colored with fluorescence dye. Photo by Dr. Davide Barreca.
The Botanical Garden of Department of Pharmacognosy, University of Vienna, Austria. Photo by Atanas G. Atanasov.
Lagoon of the seven cities, a twin lake in the crater of a dormant volcano in the western part of the São Miguel island (Azores, Portugal). Photo by Dr. Ana Sanches Silva.
Central Australian desert scene. Photo by Dr. Rohan Davis.
HEK293T cells. Photo by Atanas G. Atanasov.
Tropical rainforest, Queensland, Australia. Photo by Dr. Rohan Davis.
Australian ocean scene. Photo by Dr. Rohan Davis.
Laboratory equipment. Photo by Atanas G. Atanasov.
Rhododendron arboreum flower. Photo by Devesh Tewari.
The Valley of Flowers, Himalaya, India. Photo by Dr. Rajeshwari Singh.
Bryce Canyon, Utah, USA. Photo by Dr. Anupam Bishayee.
Euphorbia prolifera Buch. (Ham) Ex. Photo by Devesh Tewari.
Foothills of Himalaya, India. Photo by Devesh Tewari.
The Valley of Flowers, Himalaya, India. Photo by Dr. Rajeshwari Singh.
Eco-School Festival, Leiria-Portugal, Spring 2018
Polygonum maritimum (L.) (Polygonaceae)- Ourdania beach (Ain Temouchent- west Algeria)- taken by PhD. EL HACI Imad Abdelhamid
Flower blossoms at gardens by the bay Singapore-photo by Dr. Hemanth Kumar Boyina.