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Singapore Scientists Reveal Gut Microbes’ Hidden Role in Anxiety

The AHA! Team — Thu, 24 Apr 2025 20:21:06 +0000

Duke-NUS Medical School via EurekAlert! – Could the key to easing anxiety be hidden in our gut? Scientists from Duke-NUS Medical School and the National Neuroscience Institute have discovered a crucial connection between gut microbes and anxiety-related behaviour. Their research, published today in EMBO Molecular Medicine, suggests that microbial metabolites– specifically indoles–play a direct role in regulating brain activity linked to anxiety. This finding opens up exciting possibilities for new probiotic-based therapies to improve mental health. The prevalence of mental health disorders has been rising over the years. According to the latest nationwide study, 1 in 7 people in Singapore has experienced a mental health disorder, which includes depressive and anxiety disorders[1]. In 2019, mental health disorders were one of the top four leading causes of disease burden in Singapore[2]. The research team thus set out to investigate the role microbes play in anxious behaviour. In pre-clinical studies, the scientists observed that in a germ-free environment, those which were not exposed to live microbes, showed significantly more anxiety-related behaviour than those with typical resident live microbes. Further investigation revealed that the increased anxiety was associated with heightened activity in a brain region involved in processing emotions such as fear and anxiety, the basolateral amygdala (BLA). This was further identified to be related to specialised proteins within brain cells known as the calcium dependent SK2 channels, associated with anxiety behaviour. In conditions when the body and brain are exposed to live microbe metabolites, the SK2 channels act like a clutch, thus preventing neurons from becoming overly excited and firing too frequently. Associate Professor Shawn Je from Duke-NUS’ Neuroscience and Behavioural Disorders Programme and one of the lead authors, explained: “Our findings reveal the specific and intricate neural process that link microbes to mental health. Those without any live microbes showed higher levels of anxious behavior than those with live bacteria. Essentially, the lack of these microbes disrupted the way their brains functioned, particularly in areas that control fear and anxiety, leading to anxious behavior.” The mice showed significantly less anxiety-related behavior To better understand the role of microbes in this process, the researchers introduced live microbes into germ-free mice[3]. This reduced the elevated neuronal activity in the basolateral amygdala and thus SK2 channel activity. As a result, the mice showed significantly less anxiety-related behavior—their emotional responses became like those exposed to microbes. The researchers also tried treatment with indoles, microbial metabolites produced by certain microbes. When the germ-free mice were given indoles, they showed reduced activity in the basolateral amygdala and displayed less anxiety-related behaviour. This demonstrated that our indigenous microbes produce metabolites, which suggest a direct link between our microbiota and maintaining mental balance. Professor Sven Pettersson from the Department of Research, National Neuroscience Institute of Singapore, who is also a lead author of the study, said: “Establishing hunger signals and controlling hunger is an evolutionarily conserved defence mechanism. The physiological switch at birth, can therefore, be viewed as a first major wave of anxiety exposure for the newborn, which simply says, “If you don’t eat, you will die.” Additionally, birth is associated with exposure to breast milk, known to contain microbes that can produce molecules known as indoles. Indoles are known to be secreted in plants when they are exposed to stress or malnutrition (draught) and in this paper we report a similar mechanism in which indoles can regulate anxiety levels in mammals. That is, different levels of circulating microbial plasma indoles in the blood may reflect different sensitivity and vulnerability to stressful situations and therefore variable risk of experiencing anxiety-related situations.” The implications of these observations are multiple: The implications of these observations are multiple: for example, it opens for the therapeutic potential of targeting the gut-brain axis to treat anxiety-related disorders by restoring the microbe composition through dietary supplementation with indoles or by introducing indole-producing gut microbes as probiotics. “In other words, it opens for tailor-made therapies in line with 21st-century precision medicine. Studies such as this illustrate the close hereditary relationship that exists between our indigenous microbes and the higher complexity of life,” concludes Pettersson. Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, said: “Our findings underscore the deep evolutionary links between microbes, nutrition and brain function. This has huge potential for people suffering from stress-related conditions, such as sleep disorders or those unable to tolerate standard psychiatric medications. It’s a reminder that mental health is not just in the brain–it’s in the gut too.” The team now hopes to explore clinical trials to determine whether indole-based probiotics or supplements can be effectively used in humans as a natural anxiety treatment. If successful, this could mark the beginning of a new era in mental health care—one where gut microbes help keep our minds at ease. Referrences [1] Institute of Mental Health, Singapore Mental Health study https://www.imh.com.sg/Newsroom/News-Releases/Documents/SMHS%202016_Media%20Release_FINAL_web%20upload.pdf [2] Ministry of Health 28 October 2020 Global Burden of Disease 2019 Study Findings https://www.moh.gov.sg/news-highlights/details/global-burden- of-disease-2019-study-findings [3] The study was conducted according to the National Advisory Committee for Laboratory Animal Research (NACLAR) guidelines. Journal EMBO Molecular Medicine DOI 10.1038/s44321-024-00179-y To read the original article click here.

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Microbiome to Blame for Weight Gain After You Quit Smoking

AHA Publisher — Wed, 15 Dec 2021 08:00:47 +0000

Jon Schiller via Israel21c – It’s estimated that more than a billion people smoke cigarettes despite its role in causing disease. Recent studies have shown that 70 percent of smokers are interested in quitting but are concerned that they will gain weight. For years, the cause of weight gain as the result of quitting smoking has been unclear. In a recent study published in Nature, Weizmann Institute of Science researchers say the culprit may be weight-modulating compounds released by gut microbes. The researchers found that mice regularly exposed to cigarette smoke failed to gain weight, despite consuming a diet high in fat and sugar. When the smoke exposure stopped, the mice rapidly gained weight. But when the mice were given broad-spectrum antibiotics that depleted their microbiome, they gained much less weight after undergoing smoking cessation, staying slim for months regardless of their diet. The scientists believe that smoking-related compounds such as nicotine penetrated the gut of the smoke-exposed mice, altering the gut’s bacterial composition and, consequently, the body’s metabolism. They also assessed the microbiomes of 96 smoking and nonsmoking people. They found marked alterations in the microbiome of smokers, as well as microbial metabolite changes similar to those found in the smoke-exposed mice. “Our findings exemplify how the host and microbiome act as partners in regulating weight and metabolism,” said immunologist Prof. Eran Elinav, who headed the research team. “The compounds we have identified may lead to new treatments that will help people avoid weight gain when quitting smoking. Moreover, these compounds may be further developed into therapies to fight obesity even among nonsmokers.” To read the original article click here.

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New Study Reveals How Gut Microbes May Contribute to the Beneficial Effects of Breastfeeding

AHA Publisher — Thu, 02 Dec 2021 08:00:37 +0000

DTU (Technical University of Denmark) via News-Medical – It is widely acknowledged that breastfeeding benefits the health of infants. However, there is still a lack of solid evidence to document what happens in the gut of breastfed babies and how gut microbes may contribute to these beneficial effects. It has long been known that certain gut bacteria—bifidobacteria—are prevalent in the gut of breastfed infants. Although these bifidobacteria are considered beneficial, the reason why has so far been unclear. A new study has shown that the types of bifidobacteria, which utilize components of breastmilk to grow in the gut of infants, contain a particular enzyme. This enzyme enables the bacteria to produce small molecules that are believed to have a beneficial effect on the immune system. Researchers from the National Food Institute, Technical University of Denmark, and the Department of Nutrition, Exercise and Sports at the University of Copenhagen led the study, which has been published in Nature Microbiology. Unintended Discovery The idea for the project arose five years ago, when the driving forces behind the project, Martin Frederik Laursen and Henrik Munch Roager, made a discovery by coincidence while they were colleagues in the Research Group for Gut, Microbes and Health at the National Food Institute. The discovery piqued their curiosity to such an extent that they launched the project, which has been completed with a very small budget, a strong drive and persistence, and—importantly—support from within the research group. “It all started on a winter morning five years ago when we stumbled upon the fact that infant stool samples contained remarkably high levels of a certain molecule. And now we know that this particular molecule could be key in our understanding of how bifidobacteria help strengthening breastfed children’s immune system,” says Henrik Munch Roager, who was the principal investigator on the study and is now Associate Professor at the Department of Nutrition, Exercise and Sports at the University of Copenhagen. The researchers’ focus has been to understand the reason why such high concentrations of these substances—the so-called aromatic lactic acids—are present in breastfed infants’ faeces, and how they potentially could affect the health of infants. “Experiments in the lab have shown us that the aromatic lactic acids, which the bifidobacteria produce in the gut, can affect the activity of immune cells in what we would consider to be a beneficial direction in relation to a well-balanced immune response. This could prove relevant when for example the infant’s immune system is fighting an infection,” senior researcher Martin Frederik Laursen from the National Food Institute explains. Raises More Interesting Questions The study design did not allow the researcher to look at the incidence of disease among the infants who participated. Therefore, a natural follow-up study would look at the connections between the aromatic lactic acids, the development of the immune system early in life and their role in preventing disease. “More studies are needed to be able to prove whether the immune effects observed in the laboratory, also apply to infants and to what extent these effects provide protection against infections and immune-related diseases later in life,” says Martin Frederik Laursen and adds: “Furthermore, we do not know if there is a window where this effect of breastfeeding is particularly important in order to achieve the optimal effect on the immune system. Naturally, it is interesting and relevant to investigate this further.” Knowledge Might Be Useful for Improving Infant Formulas The researchers hope that down the line, the results of the study can pave the way for new, targeted ways of strengthening children’s immune systems in early life. “The results of the study are useful for supporting measures aimed at helping children develop a balanced gut microbiota, which supports a well-functioning immune system. Such measures include supporting breastfeeding and developing new types of infant formula and probiotics that promote the presence of these bifidobacteria in life early,” says Henrik Munch Roager. Caption: The studied bifidobacteria utilize certain carbohydrates (human milk oligosaccharides) in breastmilk to grow in the gut where they transform aromatic amino acids (which are also found in breastmilk) into aromatic lactic acids. The production of these aromatic lactic acids in the gut probably has a beneficial effect on the infants’ immune system. Caption: During the course of the study, Henrik Munch Roager (left) and Martin Frederik Laursen both became dads (again). Source: DTU (Technical University of Denmark) Journal reference: Laursen, M.F., et al. (2021) Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut. Nature Microbiology. doi.org/10.1038/s41564-021-00970-4. To read the original article click here.

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A Fermented-Food Diet Increases Microbiome Diversity and Lowers Inflammation, Study Finds

AHA Publisher — Tue, 20 Jul 2021 07:00:26 +0000

Stanford Medicine via EurekAlert – A diet rich in fermented foods enhances the diversity of gut microbes and decreases molecular signs of inflammation, according to researchers at the Stanford School of Medicine. In a clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The two diets resulted in different effects on the gut microbiome and the immune system. Eating foods such as yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks, and kombucha tea led to an increase in overall microbial diversity, with stronger effects from larger servings. “This is a stunning finding,” said Justin Sonnenburg, PhD, an associate professor of microbiology and immunology. “It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults.” In addition, four types of immune cells showed less activation in the fermented-food group. The levels of 19 inflammatory proteins measured in blood samples also decreased. One of these proteins, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress. “Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and director of nutrition studies at the Stanford Prevention Research Center. “This finding was consistent across all participants in the study who were assigned to the higher fermented food group.” Microbe diversity stable in fiber-rich diet By contrast, none of these 19 inflammatory proteins decreased in participants assigned to a high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits. On average, the diversity of their gut microbes also remained stable. “We expected high fiber to have a more universally beneficial effect and increase microbiota diversity,” said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology and immunology. “The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity.” The study will be published online July 12 in Cell. Justin and Erica Sonnenburg and Christopher Gardner are co-senior authors. The lead authors are Hannah Wastyk, a PhD student in bioengineering, and former postdoctoral scholar Gabriela Fragiadakis, PhD, who is now an assistant professor of medicine at UC-San Francisco. A wide body of evidence has demonstrated that diet shapes the gut microbiome, which can affect the immune system and overall health. According to Gardner, low microbiome diversity has been linked to obesity and diabetes. “We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases,” Gardner said. The researchers focused on fiber and fermented foods due to previous reports of their potential health benefits. While high-fiber diets have been associated with lower rates of mortality, the consumption of fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer and cardiovascular disease. The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose. The findings paint a nuanced picture of the influence of diet on gut microbes and immune status. On one hand, those who increased their consumption of fermented foods showed similar effects on their microbiome diversity and inflammatory markers, consistent with prior research showing that short-term changes in diet can rapidly alter the gut microbiome. On the other hand, the limited change in the microbiome within the high-fiber group dovetails with the researchers’ previous reports of a general resilience of the human microbiome over short time periods. Designing a Suite of Dietary and Microbial Strategies The results also showed that greater fiber intake led to more carbohydrates in stool samples, pointing to incomplete fiber degradation by gut microbes. These findings are consistent with other research suggesting that the microbiome of people living in the industrialized world is depleted of fiber-degrading microbes. “It is possible that a longer intervention would have allowed for the microbiota to adequately adapt to the increase in fiber consumption,” Erica Sonnenburg said. “Alternatively, the deliberate introduction of fiber-consuming microbes may be required to increase the microbiota’s capacity to break down the carbohydrates.” In addition to exploring these possibilities, the researchers plan to conduct studies in mice to investigate the molecular mechanisms by which diets alter the microbiome and reduce inflammatory proteins. They also aim to test whether high-fiber and fermented foods synergize to influence the microbiome and immune system of humans. Another goal is to examine whether the consumption of fermented food decreases inflammation or improves other health markers in patients with immunological and metabolic diseases, and in pregnant women and older individuals. “There are many more ways to target the microbiome with food and supplements, and we hope to continue to investigate how different diets, probiotics and prebiotics impact the microbiome and health in different groups,” Justin Sonnenburg said. To read the original article click here.

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Friendly Gut Bacteria Emerged as an Invaluable Ally in the Battle Against Malnutrition

AHA Publisher — Mon, 03 May 2021 07:00:36 +0000

SciDev.Net via News-Medical Net – Treating malnutrition by boosting gut microbes produces better results than traditional nutritional supplements. Friendly gut bacteria have emerged as an invaluable ally in the war against malnutrition after a research study in Bangladesh showed that bacteria-targeting food supplements were more effective than standard nutritional supplements in improving the health of undernourished children. The supplement – made from ingredients such as chickpeas, soy, bananas, and peanuts and developed to boost normal gut microbes – helped Bangladeshi children with malnutrition gain more weight than those receiving a standard nutritional supplement, the study found. Published on 22 April in the New England Journal of Medicine, the study showed that the supplement also increased certain protein levels in the blood which are linked with the health of bone, cartilage and brain. Last year, 144 million children were too short for their age due to malnutrition, while 47 million were too light for their height, according to the World Health Organization. The friendly bacteria study showed that children with malnutrition have defects in the development of their gut microbiota – the bacteria, virus and fungi that are normally found in the digestive system. According to the study, the effects of the current therapies for childhood malnutrition showed “limited efficacy” in taking care of the long-term consequences of inadequate nutrition and in repairing the gut microbiota. In the study, researchers from the Washington University School of Medicine in US and the International Centre for Diarrhoeal Disease Research, Bangladesh, assessed the efficacy of a food supplement they developed, called microbiota-directed complementary food prototype (MDCF-2), which targets friendly gut bacteria, in comparison to a ready-to-use supplementary food (RSUF) among slum-dwelling children aged 12-18 months in Bangladesh who had moderate acute malnutrition. The supplements were provided twice daily for three months and after that the children were monitored for a month. They found that children treated with the new supplement put on more weight and grew more compared with children who were just given the normal supplement. The new supplement was linked to changes in the blood levels of 70 proteins and 21 bacterial units that influenced growth, as well as brain development. “This study demonstrated that MDCF-2 was able to repair immature microbiota, promote weight gain and increase plasma biomarkers related to bone formation, neurodevelopment, and immune function.” (Ishita Mostafa, Study Author and Assistant Scientist, Nutrition and Clinical Services Division of the International Centre for Diarrhoeal Disease Research, Bangladesh) “These foods [MDCF-2], consumed during the complementary feeding period by malnourished children could provide an effective, affordable, culturally acceptable, and sustainable approach to treatment,” she tells SciDev.Net. “Larger trials will need to be performed in different geographic regions to further assess the efficacy of this therapeutic approach for treating childhood undernutrition,” she says. According to Rahuldeb Sarkar, consultant of respiratory medicine and critical care, Medway Hospital, Kent, UK, it is exciting that the new approach may promote brain development. “We should really aim for more upstream intervention that can prevent occurrence of malnutrition in the first place. Until it is achieved, this intervention can potentially mitigate the harms associated with malnutrition to affected children,” he tells SciDev.Net. “Most importantly, this new food supplement potentially promotes the brain development among undernourished children, which is exciting.” To read the original article click here.

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Study Uncovers Strong Links Between a Person’s Diet, Gut Microbes and Health

AHA Publisher — Tue, 12 Jan 2021 08:00:22 +0000

University of Trento via News-Medical Net – Diets rich in certain plant-based foods are linked with the presence of gut microbes that are associated with a lower risk of developing conditions such as obesity, type 2 diabetes and cardiovascular disease, according to recent results from a large-scale international study that included researchers from King’s College London, the Harvard T.H. Chan School of Public Health, Massachusetts General Hospital (MGH), the University of Trento, Italy, and health science start-up company ZOE. Key Takeaways The largest and most detailed study of its kind uncovered strong links between a person’s diet, the microbes in their gut (microbiome) and their health. International study uses metagenomics and blood chemical profiling to uncover a panel of 15 gut microbes associated with lower risks (and 15 with higher risks) for common illnesses such as diabetes and heart disease. Some of the identified microbes are so novel that they have not yet been named. These findings could be used to provide personalized dietary advice for better health, based on gut microbiome testing. The PREDICT 1 study analyzed detailed data on the composition of participants’ gut microbiomes, their dietary habits, and cardiometabolic blood biomarkers. The researchers found evidence that the microbiome is linked with specific foods and diets, and that, in turn, certain microbes in the gut are linked to biomarkers of metabolic disease. Surprisingly, the microbiome has a greater association to these markers than other factors, such as genetics. Their report, authored by Dr. Francesco Asnicar (University of Trento) and Dr. Sarah Berry (King’s College London) and coordinated by Tim Spector (King’s College London) and Nicola Segata (University of Trento), appears in Nature Medicine. As a nutritional scientist, finding novel microbes that are linked to specific foods, as well as metabolic health, is exciting. Given the highly personalised composition of each individuals’ microbiome, our research suggests that we may be able to modify our gut microbiome to optimize our health by choosing the best foods for our unique biology.” (Dr. Sarah Berry, Reader in Nutrition Sciences, King’s College London) For example, the findings reveal that having a microbiome rich in Prevotella copri and Blastocystis species was associated with maintaining a favorable blood sugar level after a meal. Other species were linked to lower post-meal levels of blood fats and markers of inflammation. Professor Tim Spector, Epidemiologist from King’s College London, who started the PREDICT study program and is scientific founder of ZOE explains, “When you eat, you’re not just nourishing your body, you’re feeding the trillions of microbes that live inside your gut.” Researchers also discovered that the makeup of subjects’ gut microbiome was strongly associated with specific nutrients, foods, food groups and overall diet composition. The researchers found robust microbiome-based biomarkers of obesity, as well as markers for cardiovascular disease and impaired glucose tolerance, which are key risk factors for COVID. These findings can be used to help create personalized eating plans designed specifically to improve one’s health. “I am very excited that we have been able to translate this cutting edge science into an at-home test in the time it has taken for the research to be peer reviewed and published,” says Spector. “Through ZOE, we can now offer the public an opportunity to discover which of these microbes they have living in their gut. After taking ZOE’s at-home test, participants will receive personalized recommendations for what to eat, based on comparing their results with the thousands of participants in the PREDICT studies. By using machine learning, we can then share with you our calculations of how your body will respond to any food, in real-time through an app.” The researchers found in subjects who ate a diet rich in healthy, plant-based foods were more likely to have high levels of ‘good’ gut microbes. Conversely, diets containing more highly processed plant-based foods were more likely to be associated with the ‘bad’ gut microbes. “We were surprised to see such large, clear groups of what we informally call ‘good’ and ‘bad’ microbes emerging from our analysis,” affirmed Nicola Segata, PhD, professor and principal investigator of the Computational Metagenomics Lab at the University of Trento, Italy and leader of the microbiome analysis in the study. “It is also exciting to see that microbiologists know so little about many of these microbes that they are not even named yet. This is now a big area of focus for us, as we believe they may open new insights in the future into how we could use the gut microbiome as a modifiable target to improve human metabolism and health.” PREDICT 1 was an international collaboration to study links between diet, the microbiome, and biomarkers of cardiometabolic health. The researchers gathered microbiome sequence data, detailed long-term dietary information, and results of hundreds of cardiometabolic blood markers from just over 1,100 participants in the U.K. and the U.S. PREDICT 2 completed its primary investigations in 2020 with a further 1,000 U.S participants, and PREDICT 3 launched a few months ago. To read the original article click here.

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