Coordinated regulation of the metabolome and lipidome at the host-microbial interface.

The creative use of gnotobiotic animals, coupled with the development of modern metagenomic sequencing platforms and metabolomic profiling of biospecimens, has bestowed new insight into the remarkably intricate interface between the host mammal and its resident microbiota. As mutual benefactors, each partner exhibits evidence of adaptation: the host provides a hospitable habitat, giving consideration to its own species of origin, diet, genotype, geographical location, presence or absence of disease, and use of medications; the microbiota, in turn, configures its constituency, collective genome (microbiome), transcriptome, and metabolome to optimally suit its ecological niche. In this review, we discuss the mechanisms through which the gut microbiota and its host collaborate to regulate lipid metabolism, thereby influencing the metabolic response to nutrient intake and ultimately, the development of obesity and associated diseases such as lipotoxicity. These studies therefore demonstrate that the gut microbiota is an "environmental" influence whose synergistic interdependence with its host strongly suggests that we are in fact "supraorganisms."

[1]  B. Wostmann,et al.  Effects of Microbial Flora on Cardiac Output and Other Elements of Blood Circulation.∗ , 1963, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[2]  R. Knight,et al.  The Human Microbiome Project , 2007, Nature.

[3]  Mary Ann Moran,et al.  Analyzing Gene Expression from Marine Microbial Communities using Environmental Transcriptomics , 2009, Journal of visualized experiments : JoVE.

[4]  Henry Buchwald,et al.  Bariatric surgery: a systematic review and meta-analysis. , 2004, JAMA.

[5]  A. Neish,et al.  REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY Microbes in Gastrointestinal Health and Disease , 2009 .

[6]  L. Fulton,et al.  Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. , 2008, Cell host & microbe.

[7]  Oxygen consumption and thyroid hormones in germfree mice fed glucose-amino acid liquid diet. , 1982, The Journal of nutrition.

[8]  W. R. Wikoff,et al.  Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites , 2009, Proceedings of the National Academy of Sciences.

[9]  Rob Knight,et al.  Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation , 2009, Proceedings of the National Academy of Sciences.

[10]  P. Turnbaugh,et al.  Microbial ecology: Human gut microbes associated with obesity , 2006, Nature.

[11]  E. N. Bergman Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. , 1990, Physiological reviews.

[12]  Jeffrey I. Gordon,et al.  Reciprocal Gut Microbiota Transplants from Zebrafish and Mice to Germ-free Recipients Reveal Host Habitat Selection , 2006, Cell.

[13]  G. Sweeney,et al.  Cardiac remodeling in obesity. , 2008, Physiological reviews.

[14]  Elaine Holmes,et al.  A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model , 2007, Molecular systems biology.

[15]  James R. Knight,et al.  Genome sequencing in microfabricated high-density picolitre reactors , 2005, Nature.

[16]  J. Gordon,et al.  A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Gordon,et al.  Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. , 2008, Cell host & microbe.

[18]  Qingming Luo,et al.  Mass spectrometry in systems biology: an overview. , 2008, Mass spectrometry reviews.

[19]  O. Paliy,et al.  High-Throughput Quantitative Analysis of the Human Intestinal Microbiota with a Phylogenetic Microarray , 2009, Applied and Environmental Microbiology.

[20]  J. Gordon,et al.  IgA response to symbiotic bacteria as a mediator of gut homeostasis. , 2007, Cell host & microbe.

[21]  R. Knight,et al.  Evolution of Mammals and Their Gut Microbes , 2008, Science.

[22]  R. Knight,et al.  Worlds within worlds: evolution of the vertebrate gut microbiota , 2008, Nature Reviews Microbiology.

[23]  R. Gerszten,et al.  Application of metabolomics to cardiovascular biomarker and pathway discovery. , 2008, Journal of the American College of Cardiology.

[24]  Elaine Holmes,et al.  Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes , 2008, Molecular systems biology.

[25]  M. Crowell,et al.  Human gut microbiota in obesity and after gastric bypass , 2009, Proceedings of the National Academy of Sciences.

[26]  J. Ferrières,et al.  Metabolic Endotoxemia Initiates Obesity and Insulin Resistance , 2007, Diabetes.

[27]  Masashi Yanagisawa,et al.  Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41 , 2008, Proceedings of the National Academy of Sciences.

[28]  Z. Ramadan,et al.  Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model , 2008, Molecular systems biology.

[29]  J. Gordon,et al.  Molecular analysis of commensal host-microbial relationships in the intestine. , 2001, Science.

[30]  E. Mardis,et al.  An obesity-associated gut microbiome with increased capacity for energy harvest , 2006, Nature.

[31]  M. McCarthy,et al.  Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice , 2006, Proceedings of the National Academy of Sciences.

[32]  William C Stanley,et al.  Myocardial substrate metabolism in the normal and failing heart. , 2005, Physiological reviews.

[33]  M. Pop,et al.  Metagenomic Analysis of the Human Distal Gut Microbiome , 2006, Science.

[34]  T. Olivecrona,et al.  Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting. , 1996, The Biochemical journal.

[35]  G. Abrams,et al.  Effect of the Normal Microbial Flora on Gastrointestinal Motility.∗ , 1967, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[36]  D. Russell The enzymes, regulation, and genetics of bile acid synthesis. , 2003, Annual review of biochemistry.

[37]  T. Midtvedt,et al.  Intestinal and gastric bypass. Changes in intestinal microecology after surgical treatment of morbid obesity in man. , 1981, Scandinavian journal of gastroenterology.

[38]  E. Ford,et al.  Gluconeogenesis from caecal propionate in the horse , 1985, British Journal of Nutrition.

[39]  F. Bäckhed,et al.  Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota , 2009, PloS one.

[40]  J. Borén,et al.  The assembly and secretion of apolipoprotein B-containing lipoproteins. , 1999, Current opinion in lipidology.

[41]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[42]  S. Salminen,et al.  Early differences in fecal microbiota composition in children may predict overweight. , 2008, The American journal of clinical nutrition.

[43]  R. Sartor,et al.  Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseases , 2008, Journal of internal medicine.

[44]  Jeffrey I. Gordon,et al.  Mechanisms underlying the resistance to diet-induced obesity in germ-free mice , 2007, Proceedings of the National Academy of Sciences.

[45]  T. Hernandez-Boussard,et al.  Probiotics Improve Outcomes After Roux-en-Y Gastric Bypass Surgery: A Prospective Randomized Trial , 2009, Journal of Gastrointestinal Surgery.

[46]  G. Macfarlane,et al.  Collaborative JPEN‐Clinical Nutrition Scientific Publications Role of intestinal bacteria in nutrient metabolism , 1997 .

[47]  R. Zechner,et al.  Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism , 2002, Current opinion in lipidology.

[48]  H. Pospisil,et al.  Acute-Phase Serum Amyloid A as a Marker of Insulin Resistance in Mice , 2008, Experimental diabetes research.

[49]  M. Membrez,et al.  Gut decontamination with norfloxacin and ampicillin enhances insulin sensitivity in mice. , 2008, Nestle Nutrition workshop series. Paediatric programme.

[50]  R. Bibiloni,et al.  Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice , 2008, Diabetes.

[51]  Ting Wang,et al.  The gut microbiota as an environmental factor that regulates fat storage. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[52]  M. Sakurai,et al.  A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Christina K. Chan,et al.  Adipocyte-Derived Serum Amyloid A3 and Hyaluronan Play a Role in Monocyte Recruitment and Adhesion , 2007, Diabetes.

[54]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[55]  M. Membrez,et al.  Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[56]  I. Yano,et al.  Relationship of fat deposition and intestinal microflora in VMH rats. , 1988, International journal of obesity.

[57]  Ian J. Brown,et al.  Human metabolic phenotype diversity and its association with diet and blood pressure , 2008, Nature.

[58]  Haifeng Lu,et al.  Symbiotic gut microbes modulate human metabolic phenotypes , 2008, Proceedings of the National Academy of Sciences.

[59]  Nathan Blow,et al.  Metabolomics: Biochemistry's new look , 2008, Nature.

[60]  Jeffrey I. Gordon,et al.  Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[61]  B. Wostmann The germfree animal in nutritional studies. , 1981, Annual review of nutrition.

[62]  Elaine Holmes,et al.  Probiotic Modulation of Symbiotic Gut Microbial–host Metabolic Interactions in a Humanized Microbiome Mouse Model , 2022 .

[63]  E. Purdom,et al.  Diversity of the Human Intestinal Microbial Flora , 2005, Science.

[64]  B. Roe,et al.  A core gut microbiome in obese and lean twins , 2008, Nature.

[65]  Dominique Gauguier,et al.  Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models , 2007, Nature Genetics.

[66]  H. Towle Glucose and cAMP: Adversaries in the regulation of hepatic gene expression , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[67]  N. Pace,et al.  Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. , 2008, Cell host & microbe.

[68]  S. O'keefe,et al.  Nutrition and colonic health: the critical role of the microbiota , 2008, Current opinion in gastroenterology.

[69]  Weidong Deng,et al.  The use of molecular techniques based on ribosomal RNA and DNA for rumen microbial ecosystem studies: a review , 2008, Molecular Biology Reports.

[70]  E. Abel,et al.  Diabetic cardiomyopathy revisited. , 2007, Circulation.

[71]  I. Wilson,et al.  Gut microorganisms, mammalian metabolism and personalized health care , 2005, Nature Reviews Microbiology.

[72]  F. Bäckhed,et al.  Host-Bacterial Mutualism in the Human Intestine , 2005, Science.

[73]  R. Wilson,et al.  Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut , 2007, Proceedings of the National Academy of Sciences.

[74]  Les Dethlefsen,et al.  The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing , 2008, PLoS biology.

[75]  Patrice D Cani,et al.  The role of the gut microbiota in energy metabolism and metabolic disease. , 2009, Current pharmaceutical design.

[76]  F. Bäckhed,et al.  Obesity alters gut microbial ecology. , 2005, Proceedings of the National Academy of Sciences of the United States of America.