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Institute for Food and Health

Freising, Germany

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News Article | November 28, 2016
Site: www.eurekalert.org

Gut bacteria play a little-understood role in the body's energy balance, which is influenced by diet. However, the crucial nutritional components are unknown. A team at the Technical University of Munich (TUM) was able to demonstrate for the very first time that mice without gastrointestinal microbiota grow obese when fed with dietary fat from plant sources, but not from animal sources. One of the important findings of the study is that cholesterol from the animal dietary fat plays a crucial role in what goes on in the intestines. Obesity, diabetes, and related illnesses are among the most widespread health problems in Western societies, and an increasing number of people are also suffering from them in emerging economies. According to a study published in the specialist journal The Lancet in spring, more than 600 million people around the world are now obese. Besides the well-established fact that obesity is a result of an imbalance between calorie intake and energy consumption, it has been known for a long time that the colonization of the intestines with bacteria (gastrointestinal microbiota) also has an effect on the energy metabolism. More recent studies have shown how changes in the intestinal flora due to differences in diet have an impact on the energy metabolism, thereby facilitating obesity and diabetes. Therefore, fats and their influence on the gut flora were compared for a new study that has been published in Molecular Metabolism. For this study, germ-free mice that did not host any microbiota in their intestines were fed a high-fat diet for four weeks, which was either made using lard or palm oil. As a control, the same feed was given to mice with a normal gut flora. A diet with a high quantity of animal fat does not necessarily lead to obesity The findings led to three crucial conclusions: The first observation was that the germ-free mice which were fed a lot of animal fat (lard) did not gain body fat. At the same time, a different group which received a diet enriched with fats from plant sources (palm oil) fully developed diet-induced obesity. On the other hand, the control groups with a normal gut flora became obese regardless of whether they were fed lard or palm oil. Hence, it was the type of dietary fat alone which made the crucial difference for the germ-free mice: Diet-induced obesity only occurred with fats from plant sources, not from animal sources. "The feed with high levels of lard stimulated the metabolism in the body of the germ-free mice," says Professor Martin Klingenspor from the Chair for Molecular Nutritional Medicine at the Else Kroener-Fresenius Center for Nutritional Medicine (EKFZ) at TUM explained, presenting the second, central finding. "What this means is that a large percentage of the nutritional energy is combusted in metabolism," said Klingenspor. Hence, the basal metabolic rate was increased accordingly in the germ-free mice. Furthermore, animal fat is harder to absorb and process: "Because they were less able to utilize the feed with the lard, the germ-free mice modified their metabolism to use more carbohydrates because dietary fat was only available in limited amounts," Klingenspor concluded from the findings of the study. The two types of dietary fat used in the study differ fundamentally: Palm oil is practically free from cholesterol, while lard is rich in cholesterol. Because it has been linked to an increased risk of heart attack, cholesterol has a negative connotation. But despite this bad reputation, cholesterol, which is a sterol, is also essential for life, because it is a vital component of cell membranes and a precursor to steroid hormones and bile acids. The plant-based fats fed to the mice in this current study contain phytosterols such as sitosterol, which inhibit the absorption of cholesterol in the intestine. On the other hand, the supply and availability of cholesterol in animal fats is greatly increased. Could the cholesterol in lard therefore lower the fat storage capacity and increase the basal metabolic rate in the germ-free mice? The accompanying analysis conducted on the metabolites (intermediate products created during metabolism) for this purpose and on the corresponding metabolic paths in the intestines of the mice yielded unexpected results: Steroids, steroid hormones, and bile acids, which are all chemical derivatives of cholesterol, showed noticeable changes which were linked to the intake of the lard-containing feed. Higher concentrations of steroid hormones could explain the increased basal metabolic rate: The level of estradiol was increased, which is a steroid hormone that plays a vital role in weight loss, as it boosts energy consumption. At the same time, it also plays a role in the bile acid metabolism, resulting in less fat being stored. A reduction in bile acids in the intestines was in fact measurable. These changes in the cholesterol and its metabolic products can be explained by the absence of the microbiota. This is because in mice with a normal gut flora, the microbiota are involved in cholesterol metabolism, thereby assisting with the efficient utilization of the animal fats. This, however, leads to obesity. Therefore, the interdisciplinary team led by Professor Klingenspor, Professor Dirk Haller from the Chair for Nutrition and Immunology, Dr Tom Clavel as the head of the junior research group 'Intestinal Microbiome' at ZIEL -Institute for Food and Health, Professor Hannelore Daniel from the Chair for Nutritional Physiology, Professor Karl-Heinz Engel from the Chair for General Food Technology, and Professor Philippe Schmitt-Kopplin from the Chair of Analytical Food Chemistry concluded the study with an investigation on what happens in the gastrointestinal flora and how this influences the metabolism in conjunction with the type of diet. This led the scientists to their third conclusion: In the test groups with a normal gut flora, a comparison of the palm oil group with the lard feed group showed subtle differences in their bacterial composition. In the mice that were fed with lard, the abundance of specific bacterial strains was associated with changes in bile acid levels in the gut. One of these strains is actually known to metabolize cholesterol. Hence, diet-induced changes of the gut microbiota lead to modified sterol and bile acid metabolism. These cholesterol metabolites impact on fat resorption and energy expenditure and play a role in determining whether diet-induced obesity develops - or not. Contact: Prof. Dr. Martin Klingenspor Technical University of Munich Else Kroener-Fresenius Center for Nutritional Medicine Chair for Molecular Nutritional Medicine Phone: +49 8161 71 2386 Mail: mk@tum.de


MUNICH, 24-Nov-2016 — /EuropaWire/ — Gut bacteria play a little-understood role in the body’s energy balance, which is influenced by diet. However, the crucial nutritional components are unknown. A team at the Technical University of Munich (TUM) was able to demonstrate for the very first time that mice without gastrointestinal microbiota grow obese when fed with dietary fat from plant sources, but not from animal sources. One of the important findings of the study is that cholesterol from the animal dietary fat plays a crucial role in what goes on in the intestines. Obesity, diabetes, and related illnesses are among the most widespread health problems in Western societies, and an increasing number of people are also suffering from them in emerging economies. According to a study published in the specialist journal The Lancet in spring, more than 600 million people around the world are now obese. Besides the well-established fact that obesity is a result of an imbalance between calorie intake and energy consumption, it has been known for a long time that the colonization of the intestines with bacteria (gastrointestinal microbiota) also has an effect on the energy metabolism. More recent studies have shown how changes in the intestinal flora due to differences in diet have an impact on the energy metabolism, thereby facilitating obesity and diabetes. Therefore, fats and their influence on the gut flora were compared for a new study that has been published in Molecular Metabolism. For this study, germ-free mice that did not host any microbiota in their intestines were fed a high-fat diet for four weeks, which was either made using lard or palm oil. As a control, the same feed was given to mice with a normal gut flora. A DIET WITH A HIGH QUANTITY OF ANIMAL FAT DOES NOT NECESSARILY LEAD TO OBESITY The findings led to three crucial conclusions: The first observation was that the germ-free mice which were fed a lot of animal fat (lard) did not gain body fat. At the same time, a different group which received a diet enriched with fats from plant sources (palm oil) fully developed diet-induced obesity. On the other hand, the control groups with a normal gut flora became obese regardless of whether they were fed lard or palm oil. Hence, it was the type of dietary fat alone which made the crucial difference for the germ-free mice: Diet-induced obesity only occurred with fats from plant sources, not from animal sources. “The feed with high levels of lard stimulated the metabolism in the body of the germ-free mice,” Professor Martin Klingenspor from the Chair for Molecular Nutritional Medicine at the Else Kröner-Fresenius Center for Nutritional Medicine (EKFZ) at TUM explained, presenting the second, central finding. “What this means is that a large percentage of the nutritional energy is combusted in metabolism,” said Klingenspor. Hence, the basal metabolic rate was increased accordingly in the germ-free mice. Furthermore, animal fat is harder to absorb and process: “Because they were less able to utilize the feed with the lard, the germ-free mice modified their metabolism to use more carbohydrates because dietary fat was only available in limited amounts,” Klingenspor concluded from the findings of the study. The two types of dietary fat used in the study differ fundamentally: Palm oil is practically free from cholesterol, while lard is rich in cholesterol. Because it has been linked to an increased risk of heart attack, cholesterol has a negative connotation. But despite this bad reputation, cholesterol, which is a sterol, is also essential for life, because it is a vital component of cell membranes and a precursor to steroid hormones and bile acids. The plant-based fats fed to the mice in this current study contain phytosterols such as sitosterol, which inhibit the absorption of cholesterol in the intestine. On the other hand, the supply and availability of cholesterol in animal fats is greatly increased. Could the cholesterol in lard therefore lower the fat storage capacity and increase the basal metabolic rate in the germ-free mice? The accompanying analysis conducted on the metabolites (intermediate products created during metabolism) for this purpose and on the corresponding metabolic paths in the intestines of the mice yielded unexpected results: Steroids, steroid hormones, and bile acids, which are all chemical derivatives of cholesterol, showed noticeable changes which were linked to the intake of the lard-containing feed. Higher concentrations of steroid hormones could explain the increased basal metabolic rate: The level of estradiol was increased, which is a steroid hormone that plays a vital role in weight loss, as it boosts energy consumption. At the same time, it also plays a role in the bile acid metabolism, resulting in less fat being stored. A reduction in bile acids in the intestines was in fact measurable. These changes in the cholesterol and its metabolic products can be explained by the absence of the microbiota. This is because in mice with a normal gut flora, the microbiota are involved in cholesterol metabolism, thereby assisting with the efficient utilization of the animal fats. This, however, leads to obesity. Therefore, the interdisciplinary team led by Professor Klingenspor, Professor Dirk Haller from the Chair for Nutrition and Immunology, Dr Tom Clavel as the head of the junior research group “Intestinal Microbiome” at ZIEL -Institute for Food and Health, Professor Hannelore Daniel from the Chair for Nutritional Physiology, Professor Karl-Heinz Engel from the Chair for General Food Technology, and Professor Philippe Schmitt-Kopplin from the Chair of Analytical Food Chemistry concluded the study with an investigation on what happens in the gastrointestinal flora and how this influences the metabolism in conjunction with the type of diet. This led the scientists to their third conclusion: In the test groups with a normal gut flora, a comparison of the palm oil group with the lard feed group showed subtle differences in their bacterial composition. In the mice that were fed with lard, the abundance of specific bacterial strains was associated with changes in bile acid levels in the gut. One of these strains is actually known to metabolize cholesterol. Hence, diet-induced changes of the gut microbiota lead to modified sterol and bile acid metabolism. These cholesterol metabolites impact on fat resorption and energy expenditure and play a role in determining whether diet-induced obesity develops — or not. Prof. Dr. Martin Klingenspor Technical University of Munich Else Kröner-Fresenius Center for Nutritional Medicine Chair for Molecular Nutritional Medicine Phone: +49 8161 71 2386 E-Mail: mk@tum.de


News Article | October 6, 2016
Site: phys.org

The Sequence Read Archive, a public database for deposition of sequences, currently stores over 100,000 gene sequence datasets which previously could not be evaluated in their whole. Credit: Fotolia/ Dreaming Andy Sequencing data from biological samples such as the skin, intestinal tissues, or soil and water are usually archived in public databases. This allows researchers from all over the globe to access them. However, this has led to the creation of extremely large quantities of data. To be able to explore all these data, new evaluation methods are necessary. Scientists at the Technical University of Munich (TUM) have developed a bioinformatics tool which allows to search all bacterial sequences in databases in just a few mouse clicks and find similarities or check whether a particular sequence exists. Microbial communities are essential components of ecosystems around the world. They play a key role in key biological functions, ranging from carbon to nitrogen cycles in the environment to the regulation of immune and metabolic processes in animals and humans. That is why many scientists are currently investigatin microbial communities in great detail. The Sanger sequencing method developed in 1975 used to be the gold standard to decipher the DNA code for 30 years. Recently, next generation sequencing technologies, or NGS as they are called, have led to a new revolution: With minimal personnel requirements, current devices can, within 24 hours, generate as much data as a hundred runs of the very first DNA sequencing method. Today, the sequencing analysis of bacterial 16S rRNA genes is the most frequently used identification method for bacteria. The 16S rRNA genes are seen as ideal molecular markers for reconstructing the degree of relationship between organisms, as their sequence of nucleotides (the building blocks of DNA) has been relatively conserved throughout evolution and can be used to infer phylogenetic relationships between microorganisms. The acronym rRNA stands for ribosomal ribonucleic acid. The Sequence Read Archive (SRA), a public database for deposition of sequences, currently stores over 100,000 such 16S rRNA gene sequence datasets. This is because the new technical procedures for DNA sequencing have caused the volume and complexity of genome research data over the past few years to grow exponentially. The SRA is home to datasets which previously could not be evaluated in their whole. "Over all these years, a tremendous amount of sequences from human environments such as the intestine or skin, but also from soils or the ocean has been accumulated", explains Dr. Thomas Clavel from the Institute for Food and Health (ZIEL) at the TU Munich. "We have now created a tool which allows these databases to be searched in a relatively short amount of time in order to study the diversity and habitats of bacteria", says Clavel—"with this tool, a scientists can conduct a query within a few hours in order to find out in which type of samples the bacterium he is interested in can be found—for example a pathogen from a hospital. This was not possible before." The new platform is called Integrated Microbial Next Generation Sequencing (IMNGS) and can be accessed via the main website http://www.imngs.org. A detailed description of how IMGS functions using the intestinal bacterium Acetatifactor muris has been published in the current online issue of "Scientific Reports". Registered users can carry out queries filtered by the origin of the bacterial data, or also download entire sequences. Such bioinformatics approach may soon become indispensable in routine daily clinical diagnostics. However, one critical aspect is that many members of complex microbial communities remain to be described. "Improving the quality of sequence datasets by collecting new reference sequences is a great challenge ahead", says Clavel—"moreover, the quality of datasets is not yet good enough: the description of individual samples in databases is incomplete, and hence the comparison possibilities using IMNGS are currently still limited." However, Clavel imagines that a collaboration with clinics could be a catalyst for progress, provided the database is filled more meticulously. "If we had very well-maintained databases, we could use innovative tools such as IMNGS to possibly help diagnosis of chronic illnesses more rapidly", says Clavel. Explore further: Study establishes the first public collection of bacteria from the intestine of mice More information: Ilias Lagkouvardos et al, IMNGS: A comprehensive open resource of processed 16S rRNA microbial profiles for ecology and diversity studies, Scientific Reports (2016). DOI: 10.1038/srep33721


Smirnov K.S.,Helmholtz Center Munich | Maier T.V.,Helmholtz Center Munich | Walker A.,Helmholtz Center Munich | Heinzmann S.S.,Helmholtz Center Munich | And 6 more authors.
International Journal of Medical Microbiology | Year: 2016

The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. © 2016 Elsevier GmbH.


Stelzl T.,TU Munich | Stelzl T.,Institute for Food and Health | Baranov T.,TU Munich | Baranov T.,Institute for Food and Health | And 6 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2016

The intestinal peptide transporter PEPT1 provides bulk quantities of amino acids to epithelial cells. PEPT1 is a high-capacity and lowaffinity solute carrier of the SLC15 family found in apical membranes of enterocytes in small intestine and distal colon. Surprisingly, murine PEPT1 (mPEPT1) has an apparent molecular mass of ~95 kDa in the small intestine but ~105 kDa in the large intestine. Here we describe studies on mPEPT1 protein glycosylation and how glycans affect transport function. Putative N-glycosylation sites of mPEPT1 were altered by site-directed mutagenesis followed by expression in Xenopus laevis oocytes. Replacement of six asparagine residues (N) at positions N50, N406, N439, N510, N515, and N532 by glutamine (Q) resulted in a decrease of the mPEPT1 mass by around 35 kDa. Electrophysiology revealed all glycosylation-deficient transporters to be functional with comparable expression levels in oocyte membranes. Strikingly, the mutant protein with N50Q exhibited a twofold decreased affinity for Gly-Sar but a 2.5-fold rise in the maximal inward currents compared with the wild-type protein. Elevated maximal transport currents were also recorded for cefadroxil and tri-Lalanine. Tracer flux studies performed with [14C]-Gly-Sar confirmed the reduction in substrate affinity and showed twofold increased maximal transport rates for the N50Q transporter. Elimination of individual N-glycosylation sites did not alter membrane expression in oocytes or overall transport characteristics except for the mutant protein N50Q. Because transporter surface density was not altered in N50Q, removal of the glycan at this location appears to accelerate the substrate turnover rate. © 2016 the American Physiological Society.

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