Metformin Alters The Gut Microbiome Of Individuals With Treatment-naive Type 2 Diabetes, Contributing To The Therapeutic Effects Of The Drug
Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin–microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects. Nathan, D.M. et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 32, 193–203 (2009). Collado, M.C., Derrien, M., Isolauri, E., de Vos, W.M. & Salminen, S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl. Environ. Microbiol. 73, 7767–7770 (2007). We thank C. Arvidsson, S. Nordin-Larsson, C. Wennberg, and U. Enqvist for superb mouse husbandry Continue reading >>
Gut Microbiome Changes Linked To Numerous Biomarkers Of Type 2 Diabetes
Gut microbiome changes linked to numerous biomarkers of type 2 diabetes Gut microbiome changes linked to numerous biomarkers of type 2 diabetes Low-carb breakfast synonymous with more thoughtful behaviour in new study 13 June 2017 A new study has identified links between alterations in gut microbial populations and multiple markers of obesity and type 2 diabetes. Changes to the gut microbiome and its associated genes are increasingly thought to be involved in obesity and type 2 diabetes through complex mechanisms that are not fully elucidated. Until now, scientists have focused on understanding the role of one gut microbial shift on one marker. This new research suggests that microbiome changes may in fact exert a more or less incidental influence on almost everything. Researchers have found over 27 metabolic markers, including body fat , HbA1c , insulin resistance (HOMA-IR), appetite regulation and inflammatory factors, that correlate with microbiome changes, suggesting that such a ripple effect exists. The team of scientists from Shanghai Jiao Tong University School of Medicine analysed gut DNA sequencing data in different populations: lean versus obese young Chinese as well as in adult Chinese who underwent bariatric surgery . They isolated groups of genes pertaining to specific microbe species with the aim to determine how much of a genetic control of obesity originated from the gut microbiome. The findings, which appeared in the journal Nature Medicine, show that there is about 200 of those microbial gene clusters that could impact more than 100 of known core genes playing a role in obesity. Researchers discovered what function serves certain of those identified gut microbial genes and, unsurprisingly, some have been found to play a role in fat accumulation while Continue reading >>
Type 2 Diabetes And Your Microbiome
The rapid increase in cases of people with Type 2 Diabetes Mellitus (T2DM) has made it a widespread metabolic condition. It is well known that diabetes is influenced by genetic makeup and lifestyle. However, the new kid on the block, otherwise known as the microbiome, may also act as a potential and very important, modifiable risk factor. Genes in the human microbiome produce multitudes of compounds that can influence diabetes, including molecules of inflammation, hormones and neurotransmitters. Studies have shown associations both between the development of T2DM and its complications. Gut microbiota associated with developing T2DM The association between gut bacteria and obesity has been well established. The microbiota influences the calories that the body absorbs, and the bacterial group that generates more energy, known as Firmicutes, is found in high populations in obese individuals. Given the strong association T2DM has with obesity, it is not surprising that the microbiome also affects this disorder. T2DM is a condition very closely linked with abnormal energy metabolism and inflammation in fat tissues. These two factors have been found to be related to the presence of certain gut bacteria. Furthermore, In T2DM, people are unable to process insulin properly, otherwise known as insulin resistance. Majority of the gut microflora are one of two types: Bacteroidetes and Firmicutes. In the case of T2DM, high ratios of the bacteria Firmicutes to Bacteroidetes have been found, compared to healthy people. These microbiota influence carbohydrate metabolism, and affect the production of short-chain fatty acids. Specifically, the production of short chain fatty acid, acetate is increased while butyrate is decreased. Low levels of this fatty acid may encourage low-grade inf Continue reading >>
How Your Gut Microbiome May Affect Diabetes
How Your Gut Microbiome May Affect Diabetes Is your gut health the answer to better insulin function and blood sugar control in type 2 diabetes? Experts say the gut microbiome is one factor among many that can play a role in diabetes risk. If youve been diagnosed withprediabetesor type 2 diabetes, your doctor has likely told you to focus on healthy eating habits and exercise to help prevent the development, or progression, of the disease. Chances are youve probably also heard that caring for your gut health is the X factor that may decrease the risk of developing full-blown type 2 diabetes . Perhaps you also have heard that it could even reverse the disease as well. So, whats the truth? Your gutmicrobiomeis the collection of microbes in your gastrointestinal (GI) tract that may impact your immunity, your ability to extract energy from food, your metabolism, and more. They play an important role in your health but not the only role. If you look at diabetes and obesity, over 600 million people in the world are obese, and over 400 million have diabetes. There are multiple factors implicated in both diseases, including genetics, culture, environment, and lifestyle, says RuchiMathur, MD , director of Anna and Max Webb & Family Diabetes Outpatient Treatment and Education Centerat Cedars-Sinai inLosAngeles. Gut microbes may play one piece of a very large and complicated puzzle, but theyre not the be-all and end-all, she says. Even what we know about the gutmicrobiome is still in the early stages. We know disruptions in the gutmicrobiometouch almost all diseases we see in medicine. We know these (diabetes) patients may have a different gutmicrobiome than others, says Eugene Yen, MD , a physician in the division ofgastroenterologyatNorthShoreUniversityHealthSysteminEvanston, Il Continue reading >>
For Diabetics, A High-fiber Diet Feeds Gut Microbes, Lowering Blood Sugar
For diabetics, a high-fiber diet feeds gut microbes, lowering blood sugar lenty of fiber: Thats long been the recommendation for a healthy diet. But why? The main rationale has been that fiber is made up of undigestible bulk that prevents people from eating unhealthy food and helps keep the digestive tract regular. But new research suggests that dietary fibers actually play a critical role in feeding the trillions of microbes that reside in our bodies, known collectively as the microbiome . And that specifically for people with type 2 diabetes, a high-fiber diet along with a favorable gut microbiome can keep patients blood sugar and body weight under control. Researchers in China were able to pinpoint the specific good bacteria that ferment fiber into acids, andultimately improves insulin regulation. These bugs, according to lead investigator Liping Zhao, chair of applied microbiology at Rutgers University, create an acidic microenvironment in the gut that helps beneficial, blood-sugar-lowering bacteria proliferate and might even keep pathogens at bay. Access to exclusive, in-depth pharma, biotech, business and policy coverage. Join now. The study really gets at the mechanistic reasons of why these fiber-rich, plant-based diets may be helpful, especially in patients with type 2 diabetes, said Dr. Clare Lee, an endocrinologist at Johns Hopkins University who also studies the link between diabetes and the microbiome. She was not involved in the study. Its an exciting step towards understanding potential mechanisms that can help us prevent and treat diabetes, she said. Fiber, of course, has long been shown to improve blood sugar, and diabetics are encouraged to eat plenty of it. But the benefits of fiber may be much more complex than scientists previously understood. Leaf Continue reading >>
Gut Bacteria Found To Trigger Gene That Protects Against Type 1 Diabetes
Gut bacteria found to trigger gene that protects against type 1 diabetes Early antibiotic use could affect the development of the gut microbiome and increase prevalence of autoimmune diseases(Credit: AnatomyInsider/Depositphotos ) Researchers have discovered that a powerful guardian gene known to protect against a variety of autoimmune diseases, including type 1 diabetes, is triggered by the bacteria in our gut. This finding offers a clue to the complex interaction between our genes, immune system and gut microbiota. Scientists at the Harvard Medical School set out to investigate what factors influence the activity of a powerful gene complex known as the human leukocyte antigen (HLA). It has been known for some time that specific variants of HLA genes in humans and major histocompatibility complexes (MHC) in mice can protect against diseases such as type 1 diabetes, but how that influence is exerted has been a mystery. The team focused on gut bacteria as being a potential catalyst for modulating the genes' activity. In a series of experiments, non-obese diabetic (NOD) mice engineered to carry a guardian gene were treated with gut bacteria killing antibiotics at various times in their development. The mice treated with antibiotics during the first six weeks of life were found to subsequently develop symptoms of early stage type 1 diabetes despite holding the protective guardian gene. On the other hand, when treated with antibiotics at between six and 10 weeks of age, the mice still displayed signs of genetic diabetic resistance. These results imply that early-life formation of gut microbiota has a significant effect on gene modulation influencing immune system behavior. The experiment also delivered antibiotics to mother mice in the 10 days before giving birth and disco Continue reading >>
Role Of The Gastrointestinal Tract Microbiome In The Pathophysiology Of Diabetes Mellitus
Copyright © 2017 Muhammad U. Sohail et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The incidence of diabetes mellitus is rapidly increasing throughout the world. Although the exact cause of the disease is not fully clear, perhaps, genetics, ethnic origin, obesity, age, and lifestyle are considered as few of many contributory factors for the disease pathogenesis. In recent years, the disease progression is particularly linked with functional and taxonomic alterations in the gastrointestinal tract microbiome. A change in microbial diversity, referred as microbial dysbiosis, alters the gut fermentation profile and intestinal wall integrity and causes metabolic endotoxemia, low-grade inflammation, autoimmunity, and other affiliated metabolic disorders. This article aims to summarize the role of the gut microbiome in the pathogenesis of diabetes. Additionally, we summarize gut microbial dysbiosis in preclinical and clinical diabetes cases reported in literature in the recent years. 1. Introduction The gastrointestinal tract (GIT) harbors a dense and diverse microbial community, which includes archaea, bacteria, protozoans, and viruses, and is commonly referred to as microbiome. There are approximately 100 trillion bacteria that occupy the GIT mucosal surface, constantly interacting with metabolically and immunologically active cells. These microbes not only act as the first line of defense against foreign particles but also initiate a vast array of immunological activities that augment mucosal and systemic immunity [1]. The GIT microbiome displays very diverse physiological features: digestion Continue reading >>
Understanding The Microbiome
Its one of the hottest topics in sciencebut could it lead to a diabetes cure? We know more bacteria are good for you. The more diverse your microbiome, the less likely you are to have type 1. Dont look now, but youre covered in bacteriainside and out. The human body plays host to thousands of different species of microscopic organisms. All of the bacteria that live inside us are collectively known as the microbiome, and its a world as diverse and complicated as any rainforest. These organisms live in and on our hair and skin, and especially in our digestive system. Researchers estimate our bodies contain 100 trillion single-celled bacteria and just 10 trillion human cells. All of these passengers arent just along for the ride. We now know that some of the bacteria inside us perform necessary tasks. The microbiome breaks down the food you eat and makes essential vitamins, says Stanford University geneticist Mike Snyder, PhD. Other bacteria are unpleasant or harmful, producing toxins, eating away at our teeth, or making our armpits stink. Still others may be an evolutionary advantage gone wrong: By helping the body wring more calories out of food, for example, some species of gut bacteria may contribute to obesity and type 2 diabetes . The idea that the trillions of bacteria inside our bodies could have a dramatic effect on our health is relatively new. In the past decade, research into this world within has become one of the hottest fields in science, driven by new gene sequencing technologies that let researchers quickly and inexpensively catalog and identify the thousands of different species living inside us. As they learn more about how the microbiome works, some scientists have begun to wonder whether our bacteria are in a state of upheaval. Technological advances Continue reading >>
Connections Between The Human Gut Microbiome And Gestational Diabetes Mellitus
The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21–29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM. Larval stage zebrafish are an increasingly popular model for neurobiological studies. With a brain that contains an estimated 105 neurons, larvae are similar in complexity to adult Drosophila, another established neuroscience model. In both systems, researchers can deploy a wide range of genetic tools in efforts to decode patterns of neural structure and connectivity. In larval zebrafish, optical transparency and constrained physical dimensions (fitting within a Continue reading >>
Research Shows Swapping Gut Bacteria Can Reverse Type 2 Diabetes And Other Diseases Hot
The quality, quantity, and composition of the bacteria in your gut have enormous influence on your brain. Dr. David Perlmutter explores this phenomenon in great detail in his new book, Brain Maker: The Power of Gut Microbes to Heal and Protect Your Brain-for Life. Dr. Perlmutter is a board-certified neurologist and a fellow of the American College of Nutrition (ACN). He also has a clinic in Naples, Florida, and he's been very active in publishing his findings in peer-reviewed medical journals. His previous book, Grain Brain, topped the New York Times bestseller list for 54 weeks. In my view, Dr. Perlmutter is probably the leading natural medicine neurologist in the US. Certainly, most neurologists fail to consider how lifestyle impacts the neurological disorders they diagnose and treat every day, and prevention is an area of utmost importance as we still do not have effective treatments for many of the most common brain disorders. "We're now recognizing from research at our most well-respected institutions from around the globe that the gut bacteria are wielding this very powerful sword of Damocles," he says. They determine whether we're going to have a healthy brain or not, whether our brain is going to function well or not, and whether our brain is going to become diseased or not. Who knew that we'd be referring back to the gut?" Microbiome Research Shreds Notion of Reductionism It turns out that this notion of reductionism—where your body is reduced to its individual parts—is completely nonsensical and grossly flawed. As explained by Dr. Perlmutter, every system in your body interrelates in a way that ultimately causes the manifestation of either health or disease. In a previous interview, Dr. Perlmutter discussed specific dietary factors that influence your brai Continue reading >>
The App That Helps You Plan Your Meals To Avoid Diabetes
The app that helps you plan your meals to avoid diabetes Based on Israeli research on how foods affect individuals blood sugar differently, DayTwo kit and app helps plan your optimum personal menu. DayTwo helps users choose the right meals for balanced blood sugar. Photo by Iakov Filimonov/Shutterstock.com Already available in Israel and soon in the United States, DayTwo is the worlds first health-improvement and disease-prevention solution based on the groundbreaking gut microbiome research of Prof. Eran Segal and Dr. Eran Elinav from the Weizmann Institute of Science. Both scientists are involved in the company, located in Adanim near Hod Hasharon. The gut microbiome bacteria residing in everyones intestines interacts with the digestive and immune systems, and its diversity holds certain clues. DayTwo and the Weizmann researchers developed an algorithm for predicting individualized blood-glucose response to thousands of different foods and meals based on gut microbiome information and other personal parameters. DayTwo cofounder and CEO Lihi Segal. Photo: courtesy Cofounder and CEO Lihi Segal explains how the DayTwo process works. You come online to our site and go through the registration process where you fill in a questionnaire about your medical history, physical characteristics, lifestyle and diet. We then FedEx the kit to you. The DayTwo kit contains instructions for taking a small stool sample and sending it to DayTwos lab, where the DNA of your bodys microbiome is sequenced using next-generation metagenomics. That data is plugged into an advanced machine-learning algorithm. In about six to eight weeks, you will receive your microbiome report and a mobile (initially only iOS) or web application where you can access, for six months, personalized recommendations Continue reading >>
Metformin Alters Microbiota, Improving Insulin Sensitivity
For Professionals Research Updates Type 2 Diabetes Metformin Alters Microbiota, Improving Insulin Sensitivity Given the strength of the findings, people who take metformin for their diabetes appear to have an enriched gut microflora that fosters a more efficient response to glucose metabolism. With Juan S. Escobar, PhD,and Caroline Apovian, MD The use of metformin in people with diabetes appears to favorably alter their gut microbiome, resulting in an improved glucose metabolism. The primary effect of metformin aims to stimulate levels of certain bacteria to enrich the microbiota milieu,1according to a team of researchers including the Johns Hopkins Bloomberg School of Public Health in Baltimore, MD. "In particular, my colleagues and I found that mucin-degrading Akkermansia muciniphila and several butyrate-producing bacteria were positively associated with metformin use," said study researcher Juan S. Escobar, PhD, of the Vidarium Research Center in Medellin, Colombia.These results echo findings from an earlier study.2 "Although we are not the first to demonstrate alterations in the gut microbial community associated with intake of this medication, our study is unique in matching cases and control on sex, age and body mass index, which makes our findings robust," Dr. Escobar said told EndocrineWeb. Even so, he cannot claim a causal relationship yet, as the study was based on observational data. However, the findings may have some clinical relevance, he said, both for preventing disease and helping clinicians tailor treatments not only for those with type 2 diabetes but for other diseases associated with dysfunction in the gut microbiota. "Alterations in the microbiome have been shown to be central in many chronic diseases," he said, ''including obesity, cardiovascular Continue reading >>
The Gut Microbiome As A Target For Prevention And Treatment Of Hyperglycaemia In Type 2 Diabetes: From Current Human Evidence To Future Possibilities.
Department of Clinical Sciences in Malm, Lund University Diabetes Centre, Lund University, Jan Waldenstrms gata 35, 205 02, Malm, Sweden. Department of Clinical Sciences in Malm, Lund University Diabetes Centre, Lund University, Jan Waldenstrms gata 35, 205 02, Malm, Sweden. [email protected]. Diabetologia. 2017 Jun;60(6):943-951. doi: 10.1007/s00125-017-4278-3. Epub 2017 Apr 22. The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. During the last decade, evidence has accumulated to support a role for gut microbiota (analysed from faecal samples) in glycaemic control and type 2 diabetes. Mechanistic studies in mice support a causal role for gut microbiota in metabolic diseases, although human data favouring causality is insufficient. As it may be challenging to sort the human evidence from the large number of animal studies in the field, there is a need to provide a review of human studies. Thus, the aim of this review is to cover the current and future possibilities and challenges of using the gut microbiota, with its capacity to be modified, in the development of preventive and treatment strategies for hyperglycaemia and type 2 diabetes in humans. We discuss what is known about the composition and functionality of human gut microbiota in type 2 diabetes and summarise recent evidence of current treatment strategies that involve, or are based on, modification of gut microbiota (diet, probiotics, metformin and bariatri Continue reading >>
Can Probiotics Help Lower Blood Sugar Levels In Diabetics?
Individuals with diabetes have to be fairly cautious with what they are consuming and how they are consuming. Their blood sugar levels tend to fluctuate often. For instance, if a diabetic person consumes a piece of cake in a party, his blood sugar levels might shoot up overnight. While diet, exercise, and medications have their own significance in the management of diabetes, the drastic increase in the rates of diabetes has led scientists to explore alternative therapies. One of these therapies includes the use of probiotics in diabetes. Luckily, probiotics have been so far shown to regulate the blood glucose levels and benefit people with diabetes. Probiotics raise insulin and incretin and lower blood sugar levels Insulin is a hormone released by pancreas (a gut organ) that functions to move the ingested glucose into the target cells, thereby lowering the blood glucose levels. In individuals with diabetes, insulin is either completely absent (such as in type 1 diabetes) or the target organs are unresponsive (like in type 2 diabetes). Probiotics can raise the levels of insulin as well as another intestinal hormone called incretin that works to increase insulin levels in the body after a meal, allowing the blood glucose levels to drop. German experts conducted a study to determine the antidiabetic potential of the probiotic, Lactobacillus reuteri. [1] What did they discover? After daily administration of L. reuteri for a month, the subjects were found to have raised insulin and incretin levels. Probiotics reduce oxidative stress and glucose levels Oxidative stress or damage is a state in which excess of oxidants or highly reactive and damaging molecules (called free radicals) overcome the body’s natural antioxidant potential. This oxidative stress plays a vital role in Continue reading >>
Role Of The Gut Microbiome In Diabetes
With the rapid expansion of research into the role of the gut microbiome in all aspects of health, there is accumulating evidence linking it with both type 1 and type 2 diabetes. Investigations are currently underway into a wide array of topics relevant to the disease, and recent technological advances have made microbiome analysis more efficient and cost-effective. The intestinal microbiome represents one of the largest areas of contact of the human body with non-human substances, Emory Hsu, MD, endocrinology fellow at Emory University School of Medicine, Atlanta, Georgia, told Endocrinology Advisor. It is affected in large part by environmental exposure, diet, medications, maternal transmission, and systemic disease. In a paper published in BMC Medicine in 2013, Spanish researchers presented the first study demonstrating an association between type 1 diabetes and significant alterations in the composition of gut microbiota, which the authors said could be associated with participants' glycemic levels.1 Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children, they reported. Another 2013 study found similar differences in adult patients with prediabetes and newly diagnosed type 2 diabetes vs those with normal glucose tolerance, and further showed a significant association between microbiota diversity and fasting plasma glucose and C-reactive protein.2 Subsequent studies have begun to shed light on the temporal relationship between diabetes pathogenesis and the microbiome, including a trial comparing veterans with normal glucose tolerance to those with prediabetes. The findings suggest a role for microbiota in early stages of diabetes development and that specific taxa are ass Continue reading >>
