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News Article | May 22, 2017
Site: news.yahoo.com

In the past 30 years, there has been a massive decline in the development of strategies to treat anxiety and mood disorders. Focusing less narrowly on the brain itself and more on gut bacteria could redefine the way we approach mental health. The stall in conventional treatments has happened despite tremendous advances in neuroscience, genetics and brain imaging technologies. In both animals and humans the neurobiology of fear and anxiety is being exquisitely dissected at a cellular level, yet translating these efforts to usable treatments has been challenging, with many pharmaceutical companies prioritising their efforts into other disease areas. Trending: How taking care of your gut bacteria could improve your anxiety At the same time, there is an amazing growth in industrial and academic innovation focused on deriving health benefits from the microbiome, the collective genes of the trillions of microbes that inhabit our gut. There is a growing realisation that these gut critters play a fundamental role in shaping all aspects of physiology, including brain function and the way our bodies manage stress. This could be the start of the psychobiotic revolution. We are only at the beginning of trying to understand how this happens, but these are exciting times. Many mechanisms have been shown to be involved, including activating a long wandering nerve called the vagus nerve, which sends and receives signals from the body's internal organs to the brain, immune activation, and production of chemicals such as short chain fatty acids, vitamins and neurotransmitters. Don't miss: Long lost jars discovered in ancient Egyptian tomb shed light on how mummies were embalmed Interestingly, most of the common neurotransmitters in the human brain which anti-anxiety and antidepressant medications modulate such as GABA and 5-HT can be produced by bacteria. The implication of this is only slowly being unravelled. The 'mice in the bubble' Most popular: What causes sleep deprivation? Air pollution linked to 60% higher risk of bad sleep If you take away the gut bacteria, the structure and function of the brain changes. One way we and others have been investigating such effects is to study the brains of mice reared in a germ-free environment. You've probably heard of the 'boy in the bubble' – well these are the 'mice in the bubble'. These mice grow up with no exposure to bacteria, and as a result they have alterations in memory and emotional state. When they are stressed they have much greater hormonal responses. These mice also show autistic-like patterns of behaviour, spending as much time focusing on inanimate objects as on other mice and showing increased repetitive behaviours. Most recently we showed that these mice have major changes in the amygdala, an almond-shaped area of the brain that is critical for anxiety and fear responses. The animals have aberrant fear memory responses. Such behavioural and physiological changes are driven by alterations in the underlying brain chemistry. The mice experience dramatic changes in serotonin transmission, as well as changes in key molecules such as brain-derived neurotrophic factor, which plays a fundamental role in forming new connections in the brain. What does all this evidence suggest? That the microbiome in early life is essential for normal brain development – and that changes in the microbiome may be a susceptibility factor for a variety of brain disorders including anxiety disorders. These findings lend credibility to targeting the microbiome for mental health benefits. This can be done by probiotics, prebiotics, diet or even potentially faecal transplant. For such approaches we have coined the term psychobiotics. Although the field of psychobiotics is in its infancy, there are already promising signs, especially from animal models. Can we take psychobiotics instead of Prozac? It's early days and the results of full randomised-controlled-trials are still awaited. But emerging data in the literature is encouraging. A 2013 neuroimaging study in healthy volunteers showed that a fermented milk product containing four different probiotic bacteria was linked to a reduced response in a brain network involved in the processing of emotion and sensation. More recently we have shown that a selective psychobiotic could reduce stress responses and alter brain electrical activity. In the past month studies from McMaster University and the University of California, Los Angeles, have shown that the microbiome can be targeted to affect brain function and behaviour in patients with Irritable Bowel Syndrome. However, we are still a long way from the development of clinically proven psychobiotics. Despite marketing claims to the contrary, most putative probiotics have no psychobiotic activity. Until recently, lax regulation in both the US and the European Union allowed manufacturers to make outlandish claims without supporting data. This situation is changing to protect consumers from fraudulent marketing, but the reality is that only a small percentage of bacteria tested have positive behavioural effects. Some bacteria fail to survive storage in the health food store or are killed by acidity in the stomach. Even if they do survive gut transit, they may be devoid of health benefits. Moreover, there is a need for critical investment in human intervention trials to determine what are the ideal characteristics of a psychobiotic. In the 20th century, the major focus of microbiological research was on finding ways to kill microbes with antibiotics. This century the focus has changed somewhat, with a public recognition that bacteria may have beneficial effects on health. Hopefully soon the psychobiotic revolution will firmly take hold and we will appreciate that a healthy gut microbiome may be essential to happiness as well. John Cryan and Ted Dinan are Principal Investigates at the APC Microbiome Institute in Cork. They are co-authors of the forthcoming book The Psychobiotic Revolution: Mood, Food, and the New Science of the Gut-Brain Connection. Their research is funded by Science Foundation Ireland and a variety of food and pharmaceutical companies. You may be interested in: Exercising in childhood leads to a healthier brain and better metabolism in adulthood How taking care of your gut bacteria could improve your anxiety

Joyce S.A.,APC Microbiome Institute | Gahan C.G.M.,APC Microbiome Institute | Gahan C.G.M.,University College Cork
Digestive Diseases | Year: 2017

The gastrointestinal microbiota plays a central role in the host metabolism of bile acids through deconjugation and dehydroxylation reactions, which generate unconjugated free bile acids and secondary bile acids respectively. These microbially generated bile acids are particularly potent signalling molecules that interact with host bile acid receptors (including the farnesoid X receptor, vitamin D receptor and TGR5 receptor) to trigger cellular responses that play essential roles in host lipid metabolism, electrolyte transport and immune regulation. Perturbations of microbial populations in the gut can therefore profoundly alter bile acid profiles in the host to impact upon the digestive and signalling properties of bile acids in the human superorganism. A number of recent studies have clearly demonstrated the occurrence of microbial disturbances allied to alterations in host bile acid profiles that occur across a range of disease states. Intestinal diseases including irritable bowel syndrome, inflammatory bowel disease (IBD), short bowel syndrome and Clostridium difficile infection all exhibit concurrent alterations in the composition of the gut microbiota and changes to host bile acid profiles. Similarly, extraintestinal diseases and syndromes such as asthma and obesity may be linked to aberrant bile acid profiles in the host. Here, we focus upon recent studies that highlight the links between alterations to gut microbial communities and altered bile acid profiles across a range of diseases from asthma to IBD. © 2017 S. Karger AG, Basel.

Rea K.,APC Microbiome Institute | Dinan T.G.,APC Microbiome Institute | Cryan J.F.,APC Microbiome Institute | Cryan J.F.,University College Cork
Modern Trends in Pharmacopsychiatry | Year: 2017

There is a growing emphasis on the relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and brain health. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the brain, glands, gut, immune cells, and gastrointestinal microbiota that communicate in a complex multidirectional manner to maintain homeostasis. Changes in this environment may contribute to the neuroprogression of stress-related disorders by altering physiological processes including hypothalamic-pituitary-adrenal axis activation, neurotransmitter systems, immune function, and inflammatory responses. While appropriate, coordinated physiological responses, such as immune or stress responses, are necessary for survival, the contribution of repeated or chronic exposure to stress may predispose individuals to a more vulnerable state leaving them more susceptible to stress-related disorders. In this chapter, the involvement of the gastrointestinal microbiota in stress- A nd immune-mediated modulation of neuroendocrine, immune, and neurotransmitter systems and the consequential behavior is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in the effects of the microbiota-gut-brain axis on the neuroprogression of stress-related disorders as a consequence of neuroinflammatory processes. © 2017 S. Karger AG, Basel.

Ryan P.M.,Teagasc | Ross R.P.,APC Microbiome Institute | Fitzgerald G.F.,APC Microbiome Institute | Caplice N.M.,University College Cork | And 2 more authors.
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2015

Purpose of review Health promoting functional food ingredients for cardiovascular health are generally aimed at modulating lipid metabolism in consumers. However, significant advances have furthered our understanding of the mechanisms involved in development, progression, and treatment of cardiovascular disease. In parallel, a central role of the gut microbiota, both in accelerating and attenuating cardiovascular disease, has emerged. Recent findings Modulation of the gut microbiota, by use of prebiotics and probiotics, has recently shown promise in cardiovascular disease prevention. Certain prebiotics can promote a short chain fatty acid profile that alters hormone secretion and attenuates cholesterol synthesis, whereas bile salt hydrolase and exopolysaccharideproducing probiotics have been shown to actively correct hypercholesterolemia. Furthermore, specific microbial genera have been identified as potential cardiovascular disease risk factors. This effect is attributed to the ability of certain members of the gut microbiota to convert dietary quaternary amines to trimethylamine, the primary substrate of the putatively atherosclerosis-promoting compound trimethylamine-N-oxide. In this respect, current research is indicating trimethylamine-depleting Achaea - termed Archeabiotics as a potential novel dietary strategy for promoting heart health. Summary The microbiota offers a modifiable target, which has the potential to progress or prevent cardiovascular disease development. Whereas host-Targeted interventions remain the standard, current research implicates microbiota-mediated therapies as an effective means of modulating cardiovascular health. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Sherwin E.,APC Microbiome Institute | Rea K.,APC Microbiome Institute | Dinan T.G.,APC Microbiome Institute | Cryan J.F.,APC Microbiome Institute | Cryan J.F.,University College Cork
Current Opinion in Gastroenterology | Year: 2016

Purpose of review There is an increasing realization that the microorganisms which reside within our gut form part of a complex multidirectional communication network with the brain known as the microbiome-gut-brain axis. In this review, we focus on recent findings which support a role for this axis in modulating neurodevelopment and behavior. Recent findings A growing body of research is uncovering that under homeostatic conditions and in response to internal and external stressors, the bacterial commensals of our gut can signal to the brain through a variety of mechanisms to influence processes such neurotransmission, neurogenesis, microglia activation, and modulate behavior. Moreover, the mechanisms underlying the ability of stress to modulate the microbiota and also for microbiota to change the set point for stress sensitivity are being unraveled. Dysregulation of the gut microbiota composition has been identified in a number of psychiatric disorders, including depression. This has led to the concept of bacteria that have a beneficial effect upon behavior and mood (psychobiotics) being proposed for potential therapeutic interventions. Summary Understanding the mechanisms by which the bacterial commensals of our gut are involved in brain function may lead to the development of novel microbiome-based therapies for these mood and behavioral disorders. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

PubMed | University College Cork, Teagasc, Cork University Maternity Hospital, APC Microbiome Institute and Mercy University Hospital
Type: Case Reports | Journal: Pediatrics | Year: 2015

Sulfhemoglobinemia is a rare disorder characterized by the presence of sulfhemoglobin in the blood. It is typically drug-induced and may cause hypoxia, end-organ damage, and death through oxygen deprivation. We present here a case of non-drug-induced sulfhemoglobinemia in a 7-day-old preterm infant complicated by hemolytic anemia. Microbiota compositional analysis of fecal samples to investigate the origin of hydrogen sulphide revealed the presence of Morganella morganii at a relative abundance of 38% of the total fecal microbiota at the time of diagnosis. Mmorganii was not detected in the fecal samples of 40 age-matched control preterm infants. Mmorganii is an opportunistic pathogen that can cause serious infection, particularly in immunocompromised hosts such as neonates. Strains of Mmorganii are capable of producing hydrogen sulphide, and virulence factors include the production of a diffusible -hemolysin. The infant in this case survived intact through empirical oral and intravenous antibiotic therapy, probiotic administration, and red blood cell transfusions. This coincided with a reduction in the relative abundance of Mmorganii to 3%. Neonatologists should have a high index of suspicion for intestinal pathogens in cases of non-drug-induced sulfhemoglobinemia and consider empirical treatment of the intestinal microbiota in this potentially lethal condition.

PubMed | University College Cork, APC Microbiome Institute and Karolinska Institutet
Type: Journal Article | Journal: Schizophrenia bulletin | Year: 2016

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n= 1,345,210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) ((2)for heterogeneityP= .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment.

PubMed | University College Cork and APC Microbiome Institute
Type: Journal Article | Journal: Birth defects research. Part C, Embryo today : reviews | Year: 2016

Many childhood diseases such as autism spectrum disorders, allergic disease, and obesity are on the increase. Although environmental factors are thought to play a role in this increase. The mechanisms at play are unclear but increasing evidence points to an interaction with the gastrointestinal microbiota as being potentially important. Recently this community of bacteria and perturbation of its colonization in early life has been linked to a number of diseases. Many factors are capable of influencing this colonization and ultimately leading to an altered gut microbiota which is known to affect key systems within the body. The impact of the microbial composition of our gastrointestinal tract on systems outside the gut is also becoming apparent. Here we highlight the factors that are capable of impacting on microbiota colonization in early-life and the developing systems that are affected and finally how this may be involved in the manifestation of childhood diseases.

News Article | November 11, 2015
Site: www.nature.com

Researchers studying communities of microbes need to up their game. That was the argument made by two articles published on 28 October in Science1 and Nature2, which called for national and international initiatives that would unite microbiome researchers and move the field forward. The initiatives would help researchers to develop better, standardized ways to study microbial communities so that scientists can make meaningful comparisons of data sets across different studies. Some researchers were sceptical. Nick Loman, a bacterial geneticist at the University of Birmingham, UK, tweeted: But the proponents say that the two articles are just starting points for broader discussion in the field. Microbiome studies focus on the bacteria and other microbes living in sites ranging from soil to the human mouth. In the Science piece, US researchers argued that for microbiology to move beyond descriptive studies towards hypothesis- and application-driven science, the field needs to bring in scientists from other disciplines and create tools that manipulate microbial communities and their genes. The authors proposed that a national Unified Microbiome Initiative (UMI) would develop and implement these tools, and called for new funding mechanisms for interdisciplinary research. The Nature article, by authors in the United States, Germany and China, responds to the US researchers’ proposal by calling for an International Microbiome Initiative (IMI). This would coordinate the efforts of a global, interdisciplinary group of scientists, including the UMI, allowing researchers to share data. “By pooling data from scientists from around the world, an IMI would generate much more knowledge than could one country alone,” the authors write. Several scientists greeted the proposals with enthusiasm, including Roman Stilling, a postdoctoral fellow at the APC Microbiome Institute at University College Cork, Ireland. He said in an e-mail to Nature: “Standardization may help ensure reproducibility and may help other researchers with guidelines to follow when they want to start working on the microbiome too.” But Patrick Schloss, a microbiologist at the University of Michigan in Ann Arbor, questioned the need for a global initiative, tweeting: Schloss later tempered his tweets in a blog post, writing that he and others are already developing tools to study microbial data and pursuing hypothesis-driven work. He wrote that funding for interdisciplinary microbiome research would be “awesome”, but added in an interview that a lot of details are missing from the proposals. “In fairness, we don’t really know much about what is being planned,” Schloss says, adding that the proposals seem primarily to be a call for government support, rather than a concrete plan. “There’s no funding mandate, there’s nothing really. Just a bunch of ideas,” he says. These are works in progress, says microbial ecologist Jack Gilbert at the University of Chicago in Illinois, a co-author of the Science article. “To put down immediately at this point that we have a clear funding method, this is what we want to fund, these are the research areas we think are valid, would have been crass,” Gilbert says. Gilbert hopes that the proposals — and the online back-and-forth — will stimulate further discussion and the creation of new research programmes. “No one is saying that we’re going to fundamentally transform the way you do science. We’re saying we’re going to fundamentally transform the way science is funded and the way multidisciplinary science can be implemented,” he says. “This is starting a conversation.” Other scientists expressed concern that standardizing methods and data sharing might stifle creativity in a rapidly evolving field. Loman wrote in an e-mail to Nature that there are often good reasons for methodological differences between microbiologists studying different ecosystems such as the gut or soil. “Should we standardise on one protocol?” he adds. “We don’t even know what the right technique is for many niches.” And as Noah Fierer, a microbial ecologist at the University of Colorado, Boulder, added in a blog post: “Methods are constantly changing (hopefully improving) and many of these improvements come from smaller labs that may not be directly involved in the consortium that decides the consensus methods.” These criticisms of the call for standardization surprised Nicole Dubilier, a co-author of the Nature piece who is a microbiologist at the Max Planck Institute for Marine Microbiology in Bremen, Germany. “If there’s one thing that will help the field, it’s standardization,” she says. “Standardization is the key to comparing results.” Some scientists poked fun at the grand aims of the initiatives. Josh Neufeld, a microbial ecologist at the University of Waterloo in Canada, tweeted:

Bourrie B.C.T.,University of Alberta | Bourrie B.C.T.,Teagasc | Willing B.P.,University of Alberta | Cotter P.D.,Teagasc | Cotter P.D.,APC Microbiome Institute
Frontiers in Microbiology | Year: 2016

Kefir is a complex fermented dairy product created through the symbiotic fermentation of milk by lactic acid bacteria and yeasts contained within an exopolysaccharide and protein complex called a kefir grain. As with other fermented dairy products, kefir has been associated with a range of health benefits such as cholesterol metabolism and angiotensin-converting enzyme (ACE) inhibition, antimicrobial activity, tumor suppression, increased speed of wound healing, and modulation of the immune system including the alleviation of allergy and asthma. These reports have led to increased interest in kefir as a focus of research and as a potential probiotic-containing product. Here, we review those studies with a particular emphasis on the microbial composition and the health benefits of the product, as well as discussing the further development of kefir as an important probiotic product. © 2016 Bourrie, Willing and Cotter.

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