PubMed

Related Articles Branched chain amino acid metabolic reprogramming in heart failure. Biochim Biophys Acta. 2016 Sep 14; Authors: Sun H, Wang Y Abstract Metabolic remodeling is a hall-mark of cardiac maturation and pathology. The switch of substrate utilization from glucose to fatty acid is observed during post-natal maturation period in developing heart, but the process is reversed from fatty acids to glucose in the failing hearts across different clinic and experimental models. Majority of the current investigations have been focusing on the regulatory mechanism and functional impact of this metabolic reprogramming involving fatty acids and carbohydrates. Recent progress in metabolomics and transcriptomic analysis, however, revealed another significant remodeled metabolic branch associated with cardiac development and disease, i.e. Branched-Chain Amino Acid (BCAA) catabolism. These findings have established BCAA catabolic deficiency as a novel metabolic feature in failing hearts with potentially significant impact on the progression of pathological remodeling and dysfunction. In this review, we will evaluate the current evidence and potential implication of these discoveries in the context of heart diseases and novel therapies. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz. PMID: 27639835 [PubMed - as supplied by publisher]

Urinary exposure marker discovery for toxicants using ultra-high pressure liquid chromatography coupled with Orbitrap high resolution mass spectrometry and three untargeted metabolomics approaches. Anal Chim Acta. 2016 Oct 5;939:73-83 Authors: Hsu JY, Hsu JF, Chen YR, Shih CL, Hsu YS, Chen YJ, Tsai SH, Liao PC Abstract Human biomonitoring is the assessment of actual internal contamination of chemicals by measuring exposure markers, chemicals or their metabolites, in human urine, blood, serum, and other body fluids. However, the metabolism of chemicals within an organism is extremely complex. Therefore, the identification of metabolites is often difficult and laborious. Several untargeted metabolomics methods have been developed to perform objective searching/filtering of accurate-mass-based LC-MS data to facilitate metabolite identification. In this study, three metabolomics data processing approaches were used for chemical exposure marker discovery in urine with an LTQ-Orbitrap high-resolution mass spectrometry (HRMS) dataset; di-isononyl phthalate (DINP) was used as an example. The data processing techniques included the SMAIT, mass defect filtering (MDF), and XCMS Online. Sixteen, 83, and 139 probable DINP metabolite signals were obtained using the SMAIT, MDF, and XCMS procedures, respectively. Fourteen probable metabolite signals mined simultaneously by the three metabolomics approaches were confirmed as DINP metabolites by structural information provided by LC-MS/MS. Among them, 13 probable metabolite signals were validated as exposure-related markers in a rat model. Six (m/z 319.155, 361.127, 373.126, 389.157, 437.112 and 443.130) of the 13 exposure-related DINP metabolite signals have not previously been reported in the literature. Our data indicate that SMAIT provided an efficient method to discover effectively and systematically urinary exposure markers of toxicant. The DINP metabolism information can provide valuable information for further investigations of DINP toxicity, toxicokinetics, exposure assessment, and human health effects. PMID: 27639145 [PubMed - as supplied by publisher]

Multidimensional NMR approaches towards highly resolved, sensitive and high-throughput quantitative metabolomics. Curr Opin Biotechnol. 2016 Sep 13;43:49-55 Authors: Marchand J, Martineau E, Guitton Y, Dervilly-Pinel G, Giraudeau P Abstract Multi-dimensional NMR is an appealing approach for dealing with the challenging complexity of biological samples in metabolomics. This article describes how spectroscopists have recently challenged their imagination in order to make 2D NMR a powerful tool for quantitative metabolomics, based on innovative pulse sequences combined with meticulous analytical chemistry approaches. Clever time-saving strategies have also been explored to make 2D NMR a high-throughput tool for metabolomics, relying on alternative data acquisition schemes such as ultrafast NMR. Currently, much work is aimed at drastically boosting the NMR sensitivity thanks to hyperpolarisation techniques, which have been used in combination with fast acquisition methods and could greatly expand the application potential of NMR metabolomics. PMID: 27639136 [PubMed - as supplied by publisher]

Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease. J Neurosci Res. 2016 Nov;94(11):1094-107 Authors: Weinstock NI, Wrabetz L, Feltri ML, Shin D Abstract Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression when performed presymptomatically but carries a significant risk of morbidity and mortality. Accurate presymptomatic diagnosis is therefore critical to facilitate the efficacy of existing transplant approaches and to avoid unnecessary treatment of children who will not develop KD. Unfortunately, current diagnostic criteria, including GALC activity, genetic analysis, and psychosine measurement, are insufficient for secure presymptomatic diagnosis. This study performs a global metabolomic analysis to identify pathogenetic metabolic pathways and novel biomarkers implicated in the authentic mouse model of KD known as twitcher. At a time point before onset of signs of disease, twitcher hindbrains had metabolic profiles similar to WT, with the exception of a decrease in metabolites related to glucose energy metabolism. Many metabolic pathways were altered after early signs of disease in the twitcher, including decreased phospholipid turnover, restricted mitochondrial metabolism of branched-chain amino acids, increased inflammation, and changes in neurotransmitter metabolism and osmolytes. Hypoxanthine, a purine derivative, is increased before signs of disease appear, suggesting its potential as a biomarker for early diagnosis of KD. Additionally, given the early changes in glucose metabolism in the pathogenesis of KD, diagnostic modalities that report metabolic function, such as positron emission tomography, may be useful in KD. © 2016 Wiley Periodicals, Inc. PMID: 27638595 [PubMed - in process]

[Metabolome analysis of solid tumors]. Pathologe. 2016 Sep 15; Authors: Budczies J Abstract Metabolomics, the newest of the omics sciences that also include genomics, transcriptomics and proteomics, has matured into a reliable high-throughput technology. Gas chromatography combined with time-of-flight mass spectrometry (GC-TOFMS) is a suitable method to analyze the central metabolism in fresh frozen tumor tissue samples. Bioinformatics methods, including the PROFILE clustering developed by us, permit integrated analysis and fast interpretation of metabolomics data in the context of enzymatic reactions and metabolic pathways. The metabolome analyses of three solid tumor types presented here, together with the results of other authors, show that metabolites are suitable as biomarkers and provide diverse options for translation into the clinical setting. PMID: 27638539 [PubMed - as supplied by publisher]

Enhanced cytotoxic and apoptosis inducing activity of lycopene oxidation products in different cancer cell lines. Food Chem Toxicol. 2016 Sep 13; Authors: Arathi BP, Sowmya PR, Kuriakose GC, Vijay K, Baskaran V, Jayabaskaran C, Lakshminarayana R Abstract Currently, upon understanding the metabolomics of carotenoids, it is important to address the key role of carotenoid derived products. In this regard, aim of the study was to elucidate and explore the role of lycopene (LYC) oxidative products generated through autoxidation (AOL) or chemical (KMnO4) oxidation (COL) against proliferation of selected cancer cells. Preliminary, we investigated the effect of LYC on cell viability of various cancer cell lines (PC-3, MCF-7, A431, HepG2, HeLa and A549). Based on the results of LYC treatment on cell cytotoxicity levels, MCF-7, PC-3 and HeLa cell lines were further tested with AOL and COL products. The decreased cell viability with depleted GSH and increased MDA levels were observed when treated with COL products than control, LYC and AOL. In addition, COL products increased ROS levels and percent apoptosis. The typical morphological changes and nuclear condensations showed that COL products have anti-proliferation and apoptosis inducing activity. Based on results, we hypothesized that ROS generation by LYC oxidation products may be one of intermediate step involved in apoptosis. The redox status and therapeutic approach of COL products in modulating ROS and induction of apoptosis in cancer cells were reported for the first time, to our knowledge. To conclude, COL products involves in cancer growth inhibition efficiently than intact LYC and AOL. Hence, there is a great potential for synthesizing or producing such carotenoid oxidation products to augment cancer complication. PMID: 27637924 [PubMed - as supplied by publisher]

Metabolomics as read-across tool: A case study with phenoxy herbicides. Regul Toxicol Pharmacol. 2016 Sep 13; Authors: van Ravenzwaay B, Sperber S, Lemke O, Fabian E, Faulhammer F, Kamp H, Mellert W, Strauss V, Strigun A, Peter E, Spitzer M, Walk T Abstract New technologies, such as metabolomics, can address chemical grouping and read across from a biological perspective. In a virtual case study, we selected MCPP as target substance and MCPA and 2,4-DP as source substances with the goal to waive a 90-day study with MCPP. In order to develop a convincing case to show how biological data can substantiate read across, we used metabolomics on blood samples from the 28-day studies to show the qualitative and quantitative similarity of the substances. The 28-day metabolome evaluation of source substances and the target substance indicate liver and kidneys as target organs. 2,4-DP was identified as the best source substance. Using the information of the 90-day 2,4-DP study, we predicted MCPP's toxicity profile at 2500 ppm: reduced food consumption and body weight gain, liver and kidney weight increases with clinical-pathology changes and a moderate red blood cell parameter reduction. NOEL prediction for MCPP was below that of 2,4-DP (<500 ppm), and similar to that of MCPA (≥150 ppm). Qualitatively, these predictions are comparable to the results of the real MCPP 90-day study in rats (reduced food consumption and body weight gain, weight increases and clinical-pathology changes in liver and kidneys, reduced red blood cells values). Quantitatively, the predicted NOAEL (150 ppm) is similar to the actual study (NOEL = 75 ppm, NOAEL ≤ 500 ppm). Thus, the 90-day rat toxicity study of MCPP could have been waived and substituted by the 90-day results of 2,4-DP by using metabolome data of 28 day studies. PMID: 27637788 [PubMed - as supplied by publisher]

Role of Metabolomics in Traumatic Brain Injury Research. Neurosurg Clin N Am. 2016 Oct;27(4):465-72 Authors: Wolahan SM, Hirt D, Braas D, Glenn TC Abstract Metabolomics is an important member of the omics community in that it defines which small molecules may be responsible for disease states. This article reviews the essential principles of metabolomics from specimen preparation, chemical analysis, to advanced statistical methods. Metabolomics in traumatic brain injury has so far been underutilized. Future metabolomics-based studies focused on the diagnoses, prognoses, and treatment effects need to be conducted across all types of traumatic brain injury. PMID: 27637396 [PubMed - in process]

Toward a Global Roadmap for Precision Medicine in Psychiatry: Challenges and Opportunities. OMICS. 2016 Sep 16; Authors: Dalvie S, Koen N, McGregor N, O'Connell K, Warnich L, Ramesar R, Nievergelt CM, Stein DJ Abstract Mental disorders represent a major public health burden worldwide. This is likely to rise in the next decade, with the highest increases predicted to occur in low- and middle-income countries. Current psychotropic medication treatment guidelines focus on uniform approaches to the treatment of heterogeneous disorders and achieve only partial therapeutic success. Developing a global precision medicine approach in psychiatry appears attractive, given the value of this approach in other fields of medicine, such as oncology and infectious diseases. In this horizon scanning analysis, we review the salient opportunities and challenges for precision medicine in psychiatry over the next decade. Variants within numerous genes involved in a range of pathways have been implicated in psychotropic drug response and might ultimately be used to guide choice of pharmacotherapy. Multipronged approaches such as multi-omics (genomics, proteomics, metabolomics) analyses and systems diagnostics together with high-throughput sequencing and genotyping technologies hold promise for identifying precise and targeted treatments in mental disorders. To date, however, the vast majority of pharmacogenomics work has been undertaken in high-income countries on a relatively small proportion of the global population, and many other challenges face the field. Opportunities and challenges for establishing a global roadmap for precision medicine in psychiatry are discussed in this article. PMID: 27636104 [PubMed - as supplied by publisher]

Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers. Bioanalysis. 2016 Sep 16; Authors: Kaluarachchi MR, Boulangé CL, Garcia-Perez I, Lindon JC, Minet EF Abstract AIM: Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events. RESULTS: A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC-MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases. Perturbation of metabolites involved in chronic obstructive pulmonary disease, cardiovascular diseases and cancer were identified and discussed. CONCLUSION: Combining multiplatform metabolic phenotyping with knowledge-based mapping gives mechanistic insights into disease development, which can be applied to next-generation tobacco and nicotine products for comparative risk assessment. PMID: 27635669 [PubMed - as supplied by publisher]

Reference point insensitive molecular data analysis. Bioinformatics. 2016 Sep 15; Authors: Altenbuchinger M, Rehberg T, Zacharias HU, Stämmler F, Dettmer K, Weber D, Hiergeist A, Gessner A, Holler E, Oefner PJ, Spang R Abstract MOTIVATION: In biomedicine, every molecular measurement is relative to a reference point, like a fixed aliquot of RNA extracted from a tissue, a defined number of blood cells, or a defined volume of biofluid. Reference points are often chosen for practical reasons. For example, we might want to assess the metabolome of a diseased organ but can only measure metabolites in blood or urine. In this case the observable data only indirectly reflects the disease state. The statistical implications of these discrepancies in reference points have not yet been discussed. RESULTS: Here we show that reference point discrepancies compromise the performance of regression models like the LASSO. As an alternative, we suggest zero-sum regression for a reference point insensitive analysis. We show that zero-sum regression is superior to the LASSO in case of a poor choice of reference point both in simulations and in an application that integrates intestinal microbiome analysis with metabolomics. Moreover, we describe a novel coordinate descent based algorithm to fit zero-sum elastic nets. AVAILABILITY: The R-package "zeroSum" can be downloaded at https://github.com/rehbergT/zeroSum Moreover, we provide all R-scripts and data used to produce the results of this manuscript as supplementary material. CONTACT: Michael.Altenbuchinger@ukr.de, Thorsten.Rehberg@ukr.de, and Rainer.Spang@ukr.de SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online. PMID: 27634945 [PubMed - as supplied by publisher]

Transitioning From Descriptive to Mechanistic Understanding of the Microbiome: The Need for a Prospective Longitudinal Approach to Predicting Disease. J Pediatr. 2016 Sep 12; Authors: Martin VJ, Leonard MM, Fiechtner L, Fasano A PMID: 27634626 [PubMed - as supplied by publisher]

Caveats of Untargeted Metabolomics for Biomarker Discovery. J Am Coll Cardiol. 2016 Sep 20;68(12):1294-6 Authors: Baig F, Pechlaner R, Mayr M PMID: 27634120 [PubMed - in process]

Comprehensive Metabolomic Characterization of Coronary Artery Diseases. J Am Coll Cardiol. 2016 Sep 20;68(12):1281-93 Authors: Fan Y, Li Y, Chen Y, Zhao YJ, Liu LW, Li J, Wang SL, Alolga RN, Yin Y, Wang XM, Zhao DS, Shen JH, Meng FQ, Zhou X, Xu H, He GP, Lai MD, Li P, Zhu W, Qi LW Abstract BACKGROUND: Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. OBJECTIVES: The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD. METHODS: A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography-quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics. RESULTS: We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305). CONCLUSIONS: Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression. PMID: 27634119 [PubMed - in process]

The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress. Brain. 2016 Sep 15; Authors: Chao de la Barca JM, Simard G, Amati-Bonneau P, Safiedeen Z, Prunier-Mirebeau D, Chupin S, Gadras C, Tessier L, Gueguen N, Chevrollier A, Desquiret-Dumas V, Ferré M, Bris C, Kouassi Nzoughet J, Bocca C, Leruez S, Verny C, Miléa D, Bonneau D, Lenaers G, Martinez MC, Procaccio V, Reynier P Abstract Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q(2) cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as the greater expression of C/EBP homologous protein and the increased XBP1 splicing, in fibroblasts from affected patients, all these changes being reversed by the endoplasmic reticulum stress inhibitor, TUDCA (tauroursodeoxycholic acid). Thus, our metabolomic analysis reveals a pharmacologically-reversible endoplasmic reticulum stress in complex I-related Leber's hereditary optic neuropathy fibroblasts, a finding that may open up new therapeutic perspectives for the treatment of Leber's hereditary optic neuropathy with endoplasmic reticulum-targeting drugs. PMID: 27633772 [PubMed - as supplied by publisher]

Related Articles CD147 reprograms fatty acid metabolism in hepatocellular carcinoma cells through Akt/mTOR/SREBP1c and P38/PPARα pathways. J Hepatol. 2015 Dec;63(6):1378-89 Authors: Li J, Huang Q, Long X, Zhang J, Huang X, Aa J, Yang H, Chen Z, Xing J Abstract BACKGROUND & AIMS: CD147 is a transmembrane glycoprotein which is highly expressed in various human cancers including hepatocellular carcinoma (HCC). A drug Licartin developed with (131)Iodine-labeled antibody against CD147 has been approved by the Chinese Food and Drug Administration (FDA) and enters into clinical use for HCC treatment. Increasing lines of evidence indicate that CD147 is implicated in the metabolism of cancer cells, especially glycolysis. However, the molecular mechanism underlying the relationship between CD147 and aberrant tumor lipid metabolism remains elusive. METHODS: We systematically investigated the role of CD147 in the regulation of lipid metabolism, including de novo lipogenesis and fatty acid β-oxidation, in HCC cells and explored the underlying molecular mechanisms. RESULTS: Bioinformatic analysis and experimental evidence demonstrated that CD147 significantly contributed to the reprogramming of fatty acid metabolism in HCC cells mainly through two mechanisms. On one hand, CD147 upregulated the expression of sterol regulatory element binding protein 1c (SREBP1c) by activating the Akt/mTOR signaling pathway, which in turn directly activated the transcription of major lipogenic genes FASN and ACC1 to promote de novo lipogenesis. On the other hand, CD147 downregulated peroxisome proliferator-activated receptor alpha (PPARα) and its transcriptional target genes CPT1A and ACOX1 by activating the p38 MAPK signaling pathway to inhibit fatty acid β-oxidation. Moreover, in vitro and in vivo assays indicated that the CD147-mediated reprogramming of fatty acid metabolism played a critical role in the proliferation and metastasis of HCC cells. CONCLUSION: Our findings demonstrate that CD147 is a critical regulator of fatty acid metabolism, which provides a strong line of evidence for this molecule to be used as a drug target in cancer treatment. PMID: 26282231 [PubMed - indexed for MEDLINE]

Related Articles Haberlea rhodopensis: pharmaceutical and medical potential as a food additive. Nat Prod Res. 2016;30(5):507-29 Authors: Todorova R, Atanasov AT Abstract This review discusses the potential of Haberlea rhodopensis as a food additive. The following are described: plant distribution, reproduction, cultivation, propagation and resurrection properties; extraction, isolation and screening of biologically active compounds; metabolite changes during dehydration; phytotherapy-related properties such as antioxidant potential and free radical-scavenging activities, antioxidant skin effect, antibacterial activity, cytotoxic activity and cancer-modulating effect, radioprotective effect, chemoprotective effect, immunologic effect; present use in homoeopathy and cosmetics, pharmacological and economical importance; perspectives based on the ethnobotanical data for medicinal, cosmetic or ritual attributes. H. rhodopensis showed unique medical and pharmaceutical potential, related to antioxidant, antimicrobial, antimutagenic, anticancer, radioprotective, chemoprotective and immunological properties. H. rhodopensis extracts lack any cytotoxic activity and could be used in phytotherapy. The metabolic profiling of H. rhodopensis extracts revealed the presence of biologically active compounds, possessing antiradical and other physiological activities, useful for design of in vitro synthesised analogues and drugs. PMID: 25849378 [PubMed - indexed for MEDLINE]

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Gut Microbiota: A Contributing Factor to Obesity. Front Cell Infect Microbiol. 2016;6:95 Authors: Harakeh SM, Khan I, Kumosani T, Barbour E, Almasaudi SB, Bahijri SM, Alfadul SM, Ajabnoor GM, Azhar EI Abstract Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 10(14) microorganisms reside within the lower human intestine and many of these 10(14) microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity. PMID: 27625997 [PubMed - in process]

Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view. Sci Rep. 2016;6:32826 Authors: Turroni S, Fiori J, Rampelli S, Schnorr SL, Consolandi C, Barone M, Biagi E, Fanelli F, Mezzullo M, Crittenden AN, Henry AG, Brigidi P, Candela M Abstract The recent characterization of the gut microbiome of traditional rural and foraging societies allowed us to appreciate the essential co-adaptive role of the microbiome in complementing our physiology, opening up significant questions on how the microbiota changes that have occurred in industrialized urban populations may have altered the microbiota-host co-metabolic network, contributing to the growing list of Western diseases. Here, we applied a targeted metabolomics approach to profile the fecal metabolome of the Hadza of Tanzania, one of the world's few remaining foraging populations, and compared them to the profiles of urban living Italians, as representative of people in the post-industrialized West. Data analysis shows that during the rainy season, when the diet is primarily plant-based, Hadza are characterized by a distinctive enrichment in hexoses, glycerophospholipids, sphingolipids, and acylcarnitines, while deplete in the most common natural amino acids and derivatives. Complementary to the documented unique metagenomic features of their gut microbiome, our findings on the Hadza metabolome lend support to the notion of an alternate microbiome configuration befitting of a nomadic forager lifestyle, which helps maintain metabolic homeostasis through an overall scarcity of inflammatory factors, which are instead highly represented in the Italian metabolome. PMID: 27624970 [PubMed - in process]