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Effect of gut microbiota on host whole metabolome 总被引:1,自引:0,他引:1
Takeo Moriya Yoshinori Satomi Shumpei Murata Hiroshi Sawada Hiroyuki Kobayashi 《Metabolomics : Official journal of the Metabolomic Society》2017,13(9):101
Introduction
Recent advances in microbiome research have revealed the diverse participation of gut microbiota in a number of diseases. Bacteria-specific endogenous small molecules are produced in the gut, are transported throughout the whole body by circulation, and play key roles in disease establishment. However, the factors and mechanisms underlying these microbial influences largely remain unknown.Objectives
The purpose of this study was to use metabolomics to better understand the influence of microbiota on host physiology.Methods
Germ-free mice (GF) were orally administered with the feces of specific pathogen-free (SPF) mice and were maintained in a vinyl isolator for 4 weeks for establishing the so-called ExGF mice. Comparative metabolomics was performed on luminal contents, feces, urine, plasma, and tissues of GF and ExGF mice.Results
The metabolomics profile of 1716 compounds showed marked difference between GF and ExGF for each matrix. Intestinal differences clearly showed the contribution of microbiota to host digestive activities. In addition, colonic metabolomics revealed the efficient conversion of primary to secondary metabolites by microbiota. Furthermore, metabolomics of tissues and excrements demonstrated the effect of microbiota on the accumulation of metabolites in tissues and during excretion. These effects included known bacterial effects (such as bile acids and amino acids) as well as novel ones, including a drastic decrease of sphingolipids in the host.Conclusion
The diverse effects of microbiota on different sites of the host metabolome were revealed and novel influences on host physiology were demonstrated. These findings should contribute to a deeper understanding of the influence of gut microbiota on disease states and aid in the development of effective intervention strategies.2.
Background
Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague.Objective
The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota.Methods
A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review.Results
Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT).Conclusion
Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.3.
Christopher W. Armstrong Neil R. McGregor Donald P. Lewis Henry L. Butt Paul R. Gooley 《Metabolomics : Official journal of the Metabolomic Society》2017,13(1):8
Introduction
The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota.Objectives
Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites.Methods
A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput 1H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9?±?1.8 SE years old) and twenty-five non-ME/CFS female (33.0?±?1.6 SE years old).Results
The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA. In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients.Conclusion
Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism.4.
Background
Visceral pain is a complex and heterogeneous disorder, which can range from the mild discomfort of indigestion to the agonizing pain of renal colic. Regulation of visceral pain involves the spinal cord as well as higher order brain structures. Recent findings have linked the microbiota to gastrointestinal disorders characterized by abdominal pain suggesting the ability of microbes to modulate visceral hypersensitivity and nociception to pain.Main body
In this review we describe the neuroanatomical basis of visceral pain signaling and the existing evidence of its manipulation exerted by the gut microbiota. We included an updated overview of the potential therapeutic effects of dietary intervention, specifically probiotics and prebiotics, in alleviating hypersensitivity to visceral pain stimuli.Conclusions
The gut microbiota dramatically impacts normal visceral pain sensation and affects the mechanisms mediating visceral nociception. Furthermore, manipulation of the gut microbiota using prebiotics and probiotics plays a potential role in the regulation of visceral pain disorders.5.
Julia B. Honneffer Jörg M. Steiner Jonathan A. Lidbury Jan S. Suchodolski 《Metabolomics : Official journal of the Metabolomic Society》2017,13(3):26
Introduction
The fecal microbiota are relevant to the health and disease of many species. The importance of the fecal metabolome has more recently been appreciated, but our knowledge of the microbiota and metabolome at other sites along the gastrointestinal tract remains deficient.Objective
To analyze the gastrointestinal microbiota and metabolome of healthy domestic dogs at four anatomical sites.Methods
Samples of the duodenal, ileal, colonic, and rectal contents were collected from six adult dogs after humane euthanasia for an unrelated study. The microbiota were characterized using Illumina sequencing of 16S rRNA genes. The metabolome was characterized by mass spectrometry-based methods.Results
Prevalent phyla throughout the samples were Proteobacteria, Firmicutes, Fusobacteria, and Bacteroidetes, consistent with previous findings in dogs and other species. A total of 530 unique metabolites were detected; 199 of these were identified as previously named compounds, but 141 of them had at least one significantly different site-pair comparison. Noteworthy examples include relative concentrations of amino acids, which decreased from the small to large intestine; pyruvate, which peaked in the ileum; and several phenol-containing carboxylic acid compounds that increased in the large intestine.Conclusion
The microbiota and metabolome vary significantly at different sites along the canine gastrointestinal tract.6.
Amy McMillan Adebola E. Orimadegun Mark W. Sumarah Justin Renaud Magdalena Muc da Encarnacao Gregory B. Gloor Olusegun O. Akinyinka Gregor Reid Stephen J. Allen 《Metabolomics : Official journal of the Metabolomic Society》2017,13(2):13
Introduction
Severe acute malnutrition (SAM) is a major cause of child mortality worldwide, however the pathogenesis of SAM remains poorly understood. Recent studies have uncovered an altered gut microbiota composition in children with SAM, suggesting a role for microbes in the pathogenesis of malnutrition.Objectives
To elucidate the metabolic consequences of SAM and whether these changes are associated with changes in gut microbiota composition.Methods
We applied an untargeted multi-platform metabolomics approach [gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS)] to stool and plasma samples from 47 Nigerian children with SAM and 11 control children. The composition of the stool microbiota was assessed by 16S rRNA gene sequencing.Results
The plasma metabolome discriminated children with SAM from controls, while no significant differences were observed in the microbial or small molecule composition of stool. The abundance of 585 features in plasma were significantly altered in malnourished children (Wilcoxon test, FDR corrected P?<?0.1), representing approximately 15% of the metabolome. Consistent with previous studies, children with SAM exhibited a marked reduction in amino acids/dipeptides and phospholipids, and an increase in acylcarnitines. We also identified numerous metabolic perturbations which have not been reported previously, including increased disaccharides, truncated fibrinopeptides, angiotensin I, dihydroxybutyrate, lactate, and heme, and decreased bioactive lipids belonging to the eicosanoid and docosanoid family.Conclusion
Our findings provide a deeper understanding of the metabolic consequences of malnutrition. Further research is required to determine if specific metabolites may guide improved management, and/or act as novel biomarkers for assessing response to treatment.7.
Madhusmita Dehingia Supriyo Sen Bhuwan Bhaskar Tulsi K. Joishy Manab Deka Narayan C. Talukdar Mojibur R. Khan 《Metabolomics : Official journal of the Metabolomic Society》2017,13(6):69
Introduction
The human gut microbes and their metabolites are involved in multiple host metabolic pathways. Dysbiosis in the gut microbiota and altered metabolite profiles were reported in diseased state. In a region like Assam, where 12.4% of the populations are tribal population, evaluating the influence of ethnicity on gut microbiota and metabolites has become important to further differentiate it from the diseased state.Objective
To study the influence of ethnicity on fecal metabolite profile and their association with the gut microbiota composition.Methods
In this study, we determined the untargeted fecal metabolites from five ethnic groups of Assam (Tai-Aiton, Bodo, Karbi, Tea-tribe and Tai-Phake) using GC–MS and compared them among the tribes for common and unique metabolites. Metabolites of microbial origin were related with the available metagenomic data on gut bacterial profiles of the same ethnic groups and functional analysis were carried out based on HMDB.Results
The core fecal metabolite profile of the Tea-tribe contained aniline, benzoate and acetaldehyde. PLS-DA based on the metabolites suggested that the individuals grouped based on their ethnicity. PCA plot of the data on bacterial abundance at the level of genus indicated clustering of individuals based on ethnicity. Positive correlations were observed between propionic acid and the genus Clostridium (R?=?0.43 and p?=?0.03), butyric acid and the genus Lactobacillus (R?=?0.45 and p?=?0.024), acetic acid and the genus Bacteroides (R?=?0.63 and p?=?0.001) and methane and the genus Escherichia (R?=?0.58 and p?=?0.002).Conclusion
Results of this study indicated that ethnicity influences both gut bacterial profile and their metabolites.8.
Xiaojiao Zheng Fengjie Huang Aihua Zhao Sha Lei Yunjing Zhang Guoxiang Xie Tianlu Chen Chun Qu Cynthia Rajani Bing Dong Defa Li Wei Jia 《BMC biology》2017,15(1):120
Background
Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way.Results
We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites. A high-fat diet (HFD) intervention resulted in a rapid and significant increase in the intestinal BA pool within 12 h, followed by an alteration in microbial composition at 24 h, providing supporting evidence that BAs are major dietary factors regulating gut microbiota. Feeding mice with BAs along with a normal diet induced an obese phenotype and obesity-associated gut microbial composition, similar to HFD-fed mice. Inhibition of hepatic BA biosynthesis under HFD conditions attenuated the HFD-induced gut microbiome alterations. Both inhibition of BAs and direct suppression of microbiota improved obese phenotypes.Conclusions
Our study highlights a liver–BA–gut microbiome metabolic axis that drives significant modifications of BA and microbiota compositions capable of triggering metabolic disorders, suggesting new therapeutic strategies targeting BA metabolism for metabolic diseases.9.
Alexander V. Tyakht Alexander I. Manolov Alexandra V. Kanygina Dmitry S. Ischenko Boris A. Kovarsky Anna S. Popenko Alexander V. Pavlenko Anna V. Elizarova Daria V. Rakitina Julia P. Baikova Valentina G. Ladygina Elena S. Kostryukova Irina Y. Karpova Tatyana A. Semashko Andrei K. Larin Tatyana V. Grigoryeva Mariya N. Sinyagina Sergei Y. Malanin Petr L. Shcherbakov Anastasiya Y. Kharitonova Igor L. Khalif Marina V. Shapina Igor V. Maev Dmitriy N. Andreev Elena A. Belousova Yulia M. Buzunova Dmitry G. Alexeev Vadim M. Govorun 《BMC genomics》2018,19(1):968
Background
Crohn’s disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated.Methods
We performed a metagenomic study investigating the gut microbiota of patients with Crohn’s disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability.Results
The abnormal shifts in the microbial community structures in Crohn’s disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes.Conclusions
The genomic diversity of Crohn’s disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn’s disease and the development of new strategies for the prevention and treatment of this disease.10.
Background
Microbial communities are influenced by environmental factors including host genetics. We investigated the relationship between host bitter taste receptor genotype hTAS2R38 and oral microbiota, together with the influence of geographical location.Methods
hTAS2R38 polymorphisms and 16S bacterial gene sequencing from oral samples were analyzed from a total of 45 healthy volunteers from different geographical locations.Results
Genetic variation in the bitter taste receptor TAS2R38 reflected in the microbial composition of oral mucosa in Finnish and Spanish subjects. Multivariate analysis showed significant differences in the microbial composition between country and also dependent on taste genotype. Oral microbiota was shown to be more stable to the geographical location impact among AVI-homozygotes than PAV-homozygotes or heterozygotes (PAV/AVI).Conclusion
Geographical location and genetic variation in the hTAS2R38 taste receptor impact oral mucosa microbial composition. These findings provide an advance in the knowledge regarding the interactions between taste receptor genes and oral microbiota. This study suggests the role of host-microbiota interactions on the food taste perception in food choices, nutrition, and eating behavior.11.
Background
Annual hibernation is an adaptation that helps many animals conserve energy during food shortage in winter. This natural cycle is also accompanied by a remodeling of the intestinal immune system, which is an aspect of host biology that is both influenced by, and can itself influence, the microbiota. In amphibians, the bacteria in the intestinal tract show a drop in bacterial counts. The proportion of pathogenic bacteria is greater in hibernating frogs than that found in nonhibernating frogs. This suggests that some intestinal gut microbes in amphibians can be maintained and may contribute to the functions in this closed ecosystem during hibernation. However, these results were derived from culture-based approaches that only covered a small portion of bacteria in the intestinal tract.Methods
In this study, we use a more comprehensive analysis, including bacterial appearance and functional prediction, to reveal the global changes in gut microbiota during artificial hibernation via high-throughput sequencing technology.Results
Our results suggest that artificial hibernation in the brown tree frog (Polypedates megacephalus) could reduce microbial diversity, and artificially hibernating frogs tend to harbor core operational taxonomic units that are rarely distributed among nonhibernating frogs. In addition, artificial hibernation increased significantly the relative abundance of the red-leg syndrome-related pathogenic genus Citrobacter. Furthermore, functional predictions via PICRUSt and Tax4Fun suggested that artificial hibernation has effects on metabolism, disease, signal transduction, bacterial infection, and primary immunodeficiency.Conclusions
We infer that artificial hibernation may impose potential effects on primary immunodeficiency and increase the risk of bacterial infections in the brown tree frog.12.
Background
We investigated whether the long-term consumption of a symbiotic formulation with Lactobacillus fermentum (probiotic) and β-glucan from cauliflower mushroom (prebiotic) would delay the progression of post-menopausal symptoms in ovariectomized (OVX) rats and explored their mechanisms of action, including changes in gut microbiota.Methods
OVX rats were fed with high-fat diets containing 1% dextrin (control), 1% lyophilized cauliflower mushroom extract (CFM), 0.1% L. fermentum JS (LFE), 1% CFM plus 0.1% LFE (CFLF), or 30 μg 17β-estradiol/kg body weight (positive-control) for 8 weeks.Results
CFM contained 95.8% β-glucans. OVX increased the ratio of Firmicutes and Bacteroidetes in the large intestines. Only CFLF lowered tail skin temperature without increasing serum 17β-estradiol and uterine index. Visceral fat mass was lower in CFLF and positive-control groups by increasing daily energy expenditure and fat oxidation. Dyslipidemia induced by OVX was improved by CFM and CFLF as much as in the positive-control group. Homeostasis model assessment estimate of insulin resistance was lower in CFLF than in the positive-control. Hepatic insulin signaling (pAkt?GSK-3β) was potentiated in the ascending order of the control, LFE, CFM, CFLF, and positive-control. AMPK phosphorylation showed similar patterns of hepatic insulin signaling but LFE increased it more than CFM. The changes in gut microbiota were prevented by CFLF in OVX rats, and the ratio of Firmicutes and Bacteroidetes in the CFLF was similar to the positive-control group.Conclusion
OVX changed gut microbiota and was associated with menopausal symptoms; however, the synbiotics, CFM and LFE, prevented menopausal symptoms and improved the gut microbiota in estrogen-deficient rats.13.
Samir Rezki Claire Campion Philippe Simoneau Marie-Agnès Jacques Ashley Shade Matthieu Barret 《Plant and Soil》2018,422(1-2):67-79
Background and aims
Seeds are involved in the transmission of microorganisms from one plant generation to another and consequently may act as the initial inoculum source for the plant microbiota. In this work, we assessed the structure and composition of the seed microbiota of radish (Raphanus sativus) across three successive plant generations.Methods
Structure of seed microbial communities were estimated on individual plants through amplification and sequencing of genes that are markers of taxonomic diversity for bacteria (gyrB) and fungi (ITS1). The relative contribution of dispersal and ecological drift in inter-individual fluctuations were estimated with a neutral community model.Results
Seed microbial communities of radish display a low heritability across plant generations. Fluctuations in microbial community profiles were related to changes in community membership and composition across plant generations, but also to variation between individual plants. Ecological drift was an important driver of the structure of seed bacterial communities, while dispersal was involved in the assembly of the fungal fraction of the seed microbiota.Conclusions
These results provide a first glimpse of the governing processes driving the assembly of the seed microbiota.14.
Hui Yang Ming Yang Shaoming Fang Xiaochang Huang Maozhang He Shanlin Ke Jun Gao Jinyuan Wu Yunyan Zhou Hao Fu Congying Chen Lusheng Huang 《BMC microbiology》2018,18(1):215
Background
There are growing evidences showing that gut microbiota should play an important role in host appetite and feeding behavior. However, what kind of microbe(s) and how they affect porcine appetite remain unknown.Results
In this study, 280 commercial Duroc pigs were raised in a testing station with the circadian feeding behavior records for a continuous period of 30–100?kg. We first analyzed the influences of host gender and genetics in porcine average daily feed intake (ADFI), but no significant effect was observed. We found that the Prevotella-predominant enterotype had a higher ADFI than the Treponema enterotype-like group. Furthermore, 12 out of the 18 OTUs positively associated with the ADFI were annotated to Prevotella, and Prevotella was the hub bacteria in the co-abundance network. These results suggested that Prevotella might be a keystone bacterial taxon for increasing host feed intake. However, some bacteria producing short-chain fatty acids (SCFAs) and lactic acid (e.g. Ruminococcaceae and Lactobacillus) showed negative associations with the ADFI. Predicted function capacity analysis showed that the genes for amino acid biosynthesis had significantly different enrichment between pigs with high and low ADFI.Conclusions
The present study provided important information on the profound effect of gut microbiota on porcine appetite and feeding behavior. This will profit us to regulate porcine appetite through modulating the gut microbiome in the pig industry.15.
J. C. Martínez-Ávila A. García Bartolomé I. García I. Dapía Hoi Y. Tong L. Díaz P. Guerra J. Frías A. J. Carcás Sansuan A. M. Borobia 《Metabolomics : Official journal of the Metabolomic Society》2018,14(5):70
Introduction
Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route.Objectives
Our objective was to evaluate the utility of pharmacometabolomics in the detection of zonisamide metabolites that could be related to its disposition and therefore, to its efficacy and toxicity.Methods
This study was nested to a bioequivalence clinical trial with 28 healthy volunteers. Each participant received a single dose of zonisamide on two separate occasions (period 1 and period 2), with a washout period between them. Blood samples of zonisamide were obtained from all patients at baseline for each period, before volunteers were administered any medication, for metabolomics analysis.Results
After a Lasso regression was applied, age, height, branched-chain amino acids, steroids, triacylglycerols, diacyl glycerophosphoethanolamine, glycerophospholipids susceptible to methylation, phosphatidylcholines with 20:4 FA (arachidonic acid) and cholesterol ester and lysophosphatidylcholine were obtained in both periods.Conclusion
To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.16.
Antonella Del-Corso Mario Cappiello Roberta Moschini Francesco Balestri Umberto Mura 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):2
Introduction
While the evolutionary adaptation of enzymes to their own substrates is a well assessed and rationalized field, how molecules have been originally selected in order to initiate and assemble convenient metabolic pathways is a fascinating, but still debated argument.Objectives
Aim of the present study is to give a rationale for the preferential selection of specific molecules to generate metabolic pathways.Methods
The comparison of structural features of molecules, through an inductive methodological approach, offer a reading key to cautiously propose a determining factor for their metabolic recruitment.Results
Starting with some commonplaces occurring in the structural representation of relevant carbohydrates, such as glucose, fructose and ribose, arguments are presented in associating stable structural determinants of these molecules and their peculiar occurrence in metabolic pathways.Conclusions
Among other possible factors, the reliability of the structural asset of a molecule may be relevant or its selection among structurally and, a priori, functionally similar molecules.17.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.18.
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N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99