Amino acids link gut microbiome to obesity

Researchers at Lund University in Sweden have discovered a new link between gut bacteria and obesity. They found that certain amino acids in our blood can be connected to both obesity and the composition of the gut microbiome.

Increasing number of research studies indicate that our gut microbiome does play an important role in our health. It affects our metabolism and can be linked to obesity, cardiovascular disease and type 2 diabetes.

Previous studies have shown that people with these diseases have varying occurrence of different metabolites, i.e. small molecules or metabolic residues, in the bloodstream. The aim of the new study was therefore to identify metabolites in the blood that can be linked to obesity (high body mass index, BMI) and to investigate whether these obesity-related metabolites affect the composition of the bacterial flora in stool samples.

The researchers analysed blood plasma and stool samples from 674 participants in the Malmö Offspring Study. They found 19 different metabolites that could be linked to the person’s BMI; glutamate and so-called BCAA (branched-chain and aromatic amino acids) had the strongest connection to obesity. They also found that the obesity-related metabolites were linked to four different intestinal bacteria (Blautia, Dorea and Ruminococcus in the Lachnospiraceae family, and SHA98).

“The differences in BMI were largely explained by the differences in the levels of glutamate and branched-chain and aromatic amino acids. This indicates that the metabolites and gut bacteria interact, rather than being independent of each other”, says Marju Orho-Melander, professor of genetic epidemiology at Lund University.

By far the strongest risk factor for obesity in the study, glutamate, has been associated with obesity in previous studies, and BCAA has been used to predict the future onset of type 2 diabetes and cardiovascular disease.

“This means that future studies should focus more on how the composition of gut bacteria can be modified to reduce the risk of obesity and associated metabolic diseases and cardiovascular disease”, says Marju Orho-Melander. “To get there, we first need to understand what a healthy normal gut flora looks like, and what factors impact the bacterial composition. This requires large population studies, like the Malmö Offspring Study, as well as intervention studies”, she concludes.

Citation: Ottosson, Filip, Louise Brunkwall, Ulrika Ericson, Peter M. Nilsson, Peter Almgren, Céline Fernandez, Olle Melander, and Marju Orho-Melander. “Connection between BMI related plasma metabolite profile and gut microbiota.” The Journal of Clinical Endocrinology & Metabolism, 2018. doi:10.1210/jc.2017-02114.

Adapted from press release by the Lund University.

Metformin influences gut microbiome

A recent study at Sahlgrenska Academy and University of Girona indicates thatcontrol of blood glucose by metformin is achieved partly through modulation of the gut microbiota. Results of the study are published in journal Nature Medicine.

Fredrik Bäckhed’s research group at Sahlgrenska Academy has previously shown that the gut microbiota is altered in patients with type 2 diabetes and after bariatric surgery. By conducting a clinical study in patients with new onset diabetes, the group could clarify how the gut microbiomeis affected by metformin.

Sequencing of the microbiome of 22 patients before and after treatment compared with a placebo treated group of patients showed that the gut microbiome was altered dramatically within two months of treatment. Through experiments in the laboratory, the researchers demonstrated that metformin increases the growth of several bacterial species that are linked to improved metabolism.

Citation: Wu, Hao, Eduardo Esteve, Valentina Tremaroli, Muhammad Tanweer Khan, Robert Caesar, Louise Mannerås-Holm, Marcus Ståhlman, Lisa M. Olsson, Matteo Serino, Mercè Planas-Fèlix, Gemma Xifra, Josep M. Mercader, David Torrents, Rémy Burcelin, Wifredo Ricart, Rosie Perkins, José Manuel Fernàndez-Real, and Fredrik Bäckhed. “Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.” Nature Medicine, 2017.
Adapted from press release by  the University of Gothenburg.

ResistoMap developed to track world wide microbial drug resistance

Scientists from the Federal Research and Clinical Center of Physical-Chemical Medicine, the Moscow Institute of Physics and Technology, and Data Laboratory have created the ResistoMap, an interactive visualization of gut resistome. Gut resistome is human gut microbiota potential to resist antibiotics and includes the set of all antibiotic resistance genes in the genomes of human gut microbes. Their ResistoMap will help identify national trends in antibiotic use and control antibiotic resistance on the global scale. This research is published in journal Bioinformatics.

Resistomap - interactive world map of human gut resistome
Resistomap –  an interactive world map of human gut microbiota potential to resist antibiotics.
Credit: Bioinformatics

Microbial drug resistance is caused by the extensive uncontrolled use of antibiotics in medicine and agriculture. It has been predicted that by 2050 around 10 million people will die annually due to reasons associated with drug resistance.

The ResistoMap has two main interactive work fields: a geographic map and a heat map. A user can choose the antibiotic group or country of interest to be displayed on the heat map and obtain a resistome cross section. The data can be filtered by the country of origin, gender, age, and diagnosis. The current version of the interactive map developed by the authors draws on a dataset that includes over 1600 individuals from 12 studies covering 15 countries. However, the dataset can be expanded by additional input from users reflecting the findings of new published studies in a unified format.

Using the ResistoMap, researchers fee that it is possible to estimate the global variation of the resistance to different groups of antibiotics and explore the associations between specific drugs and clinical factors or other metadata. For example, the Danish gut metagenomes tend to demonstrate the lowest resistome among the European groups, whereas the French samples have the highest levels, particularly of the fluoroquinolones, a group of broad-spectrum anti-bacterial drugs. This is in agreement with the fact that France has the highest total antibiotic use across Western Europe, while the use of antimicrobial drugs in Denmark and Germany is moderate, both in health care and agriculture. At the opposite end of the spectrum, Chinese and Russian populations appear to have increased levels of resistome, which is likely due to looser regulation policies, frequent prescription of broad-spectrum antibiotics, and their over-the-counter availability without prescription. The lowest levels of microbiota resistome are observed in the native population of Venezuela who have no documented contacts with populations of the developed countries. ResistoMap-informed analysis reveals certain novel trends that await further interpretation from the clinical standpoint.

Konstantin Yarygin, one of the creators of the visualization tool, says, “We anticipate that the exploratory analysis of global gut resistome enabled by the ResistoMap will provide new insights into how the use of antibiotics in medicine and agriculture could be optimized.”

Citation: Yarygin, Konstantin S., Boris A. Kovarsky, Tatyana S. Bibikova, Damir S. Melnikov, Alexander V. Tyakht, and Dmitry G. Alexeev. “ResistoMap—online visualization of human gut microbiota antibiotic resistome.” Bioinformatics, 2017.
Research funding: Russian Scientific Foundation.
Adapted from press release by the Moscow Institute of Physics and Technology.

Role of diet and gut microbiome in the major depressive disorder

An international group of researchers headed by André Carvalho has published in Psychotherapy and Psychosomatic a paper that provides new data and prospects for the links between the intestinal flora and several disorders, notably depression.

Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of the major depressive disorder. The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis. New evidence implicates these pathways in the onset of the major depressive disorder. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with depression, including but not limited to irritable bowel syndrome, chronic fatigue syndrome, obesity, and type 2 diabetes mellitus.

The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in depression and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of major depressive disorder, including but not limited to immune activation, oxidative and nitrosative stress, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies.

Authors conclude that intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between depression and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.

Citation: Slyepchenko, Anastasiya, Michael Maes, Felice N. Jacka, Cristiano A. Köhler, Tatiana Barichello, Roger S. Mcintyre, Michael Berk, Iria Grande, Jane A. Foster, Eduard Vieta, and André F. Carvalho. “Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities.” Psychotherapy and Psychosomatics 86, no. 1 (2016): 31-46. doi:10.1159/000448957.
Adapted from press release by Karger medical and scientific publishers.