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Our bodies are home to a vast ecosystem of microbes – the microbiome – that has a powerful effect on the brain. OUR RELATIONSHIP WITH MICROBES is usually described as an arms race, with humans and bacteria on opposing sides.
Our microbes, especially those living in the gut, have a powerful influence on the brain, influencing our emotions, our thoughts and even our memory. In fact, evidence accumulated in the last five to 10 years shows that these microbes, which predominantly live in the gastrointestinal tract, shape the development and function of the brain.
Three researchers at the forefront of research on the microbiome-brain connection recently spoke with The Kavli Foundation about how microbes communicate with the brain and whether we can modify the gut microbiome to treat disorders of the brain and mind.
TRACY BALE, PhD - is a professor of neuroscience at the School of Veterinary Medicine and Perelman School of Medicine at the University of Pennsylvania. CHRISTOPHER LOWRY, PhD - is an associate professor in the Department of Integrative Physiology and Center for Neuroscience at the University of Colorado Boulder and director of the Behavioral Neuroendocrinology Laboratory. SARKIS MAZMANIAN, PhD - is the Louis & Nelly Soux Professor of Microbiology at the California Institute of Technology and a 2012 MacArthur Fellow. The following is an edited transcript of a roundtable discussion, which took place via teleconference on December 1, 2014.
THE KAVLI FOUNDATION: The idea that the microbes living in our gut have an effect on the brain is a relatively new one. SARKIS MAZMANIAN: For more than a decade, my laboratory has been studying the interaction between microbes and the immune system.
CHRISTOPHER LOWRY: My lab has been studying interactions between bacteria, the nervous system and emotional behavior for about 15 years.
The turning point for looking at gut-microbiome-brain interactions in my lab really came with our first collaboration with Rob Knight, who leads the American Gut Project here at CU-Boulder. TRACY BALE: My lab works on the impact of stress during pregnancy on the developing brain using a mouse model of early maternal stress.
TKF: What are the big questions about the gut-microbiome-brain connection that researchers are trying to answer right now? BALE: Now that we know the microbiome changes in response to stress, I think the field is trying to understand the processes by which the gut microbiome alters the brain.
MAZMANIAN: Another big question is whether we can treat brain disorders, such as autism, by aiming therapies at the gut. BALE: Sarkis covered most of what people currently understand about what’s happening in the gut.
MAZMANIAN: Emeran Mayer and his colleagues at the University of California, Los Angeles, used functional magnetic resonance imaging, or fMRI, to look at the effects of specific microorganisms on brain activity. BALE: Developmentally, that’s a harder question, because you can’t do controlled experiments in newborns. TKF: Tracy, you’ve talked about the close connection between a mother’s vaginal microbiome, which a baby encounters as it passes through the birth canal, and her newborn baby’s. Tracy Bale studies the effects of early prenatal stress on the fetal brain and the microbiome.
BALE: There are key developmental windows when the brain is more vulnerable because it’s setting itself up to respond to the world around it.
What’s interesting, from our experiments on the effects of exposure to early maternal stress in mice, is that if you look at those babies in adulthood, their microbiome may be completely normalized, but if you then stress them or give them an immune challenge, you see big differences again in the way their bodies respond. TKF: Christopher, you’ve suggested that a lack of exposure to the many bacteria we evolved with may be contributing to our ills, including psychiatric disorders such as depression and anxiety. Christopher Lowry has studied the effects of treatment with a common soil bacterium called Mycobacterium vaccae (pictured) in mice.
LOWRY: There are certain psychiatric disorders like post-traumatic stress disorder, or PTSD, and depression that seem to be associated with increased inflammation, a ramped-up immune response in the body and in the brain.
LOWRY: Our current studies use heat-killed bacteria rather than probiotics, which the World Health Organization defines as live microorganisms that confer a health benefit to the host when administered in adequate amounts. TKF: Have you changed your behavior as a result of your research into the connection between the microbiome and a healthy body and brain?
MAZMANIAN: As we all know, it’s still the very early days in terms of trying to understand the effects of the microbiome, even for inflammatory bowel disease or obesity, which have been studied much more than any neurological condition. BALE: As a parent, I would also say I’ve spent a lot more time thinking before allowing my child to take antibiotics. In a mouse model of autism, Sarkis Mazmanian and his team of researchers at Caltech corrected the leaky gut that is often associated with the disorder by treating the mice with Bacteriodes fragilis.
TKF: Sarkis, you’ve called recent discoveries “harbingers of extensive, currently undescribed, links between gut bacteria and the nervous system.” Can you speculate on what other links between the gut microbiome and the brain might emerge?
MAZMANIAN: It’s already been shown that cognition in germ-free mice is reduced in comparison to normal mice. There are other anecdotal reasons to believe that neurodegeneration may have some connection to the microbiome, or vice versa, because the three major neurodegenerative disorders – Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis, or ALS – all have a GI component to them. Each part of the human body is home to a different community of microbes, according to research conducted by the American Gut Project and the NIH Human Microbiome Project.
LOWRY: There are regulatory issues related to giving live or dead bacteria for treatment of psychiatric and neurological disorders, and those are significant issues that will have to be dealt with. Although they look intimidating they are almost completely harmless such as gas and bloating.Side effects of probiotics may include mild.

Probiotics are largely unregulated but they can’t make claims to cure or prevent a disease.
Overall it wouldn’t hurt to take these but they are kind of hard to swallow for me at least (and I take huge softgel prenatals). Can Probiotics Prevent Candida How to evaluate probiotic supplements: must contain prebiotics (its own natural food source) in a symbiotic broad spectrum of soil based organisms (SBOs). You dog may have a food allergy or an intolerance or they may be suffering from a chronic illness. In severe cases your veterinarian will recommend a prescription dog food or a raw foods diet on a very strict schedule. If this is the case, you can then compare dog food brands and find the food right for your dog. Limited ingredient dog foods have simple recipes using very few ingredients making them much easier to digest.
These foods are great for dogs with severe digestive issues but can help any dog with poor digestion.
So talk to your veterinarian, compare some of these different options, and transition them carefully, and soon your dog and their stomach will be healthier and happier!
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Being an entrepreneur specializes in blogging, social media, internet marketing I have worthy knowledge and experience in different fields. Three researchers discuss the emerging gut-microbiome-brain connection and whether microbes may help treat brain disorders. But, as new research is showing, a better metaphor is “brothers-in-arms.” The 10,000 or so different types of microbes, including bacteria, viruses and fungi, that inhabit our bodies form a balanced ecosystem called the microbiome.
On January 15, a microbiologist and a neuroscientist will discuss the emerging science of the human microbiome, which is more intimately linked to human health than ever imagined. They influence a range of complex human behaviors, including learning and memory, mood and emotion, and appetite and satiety. She is studying the effects of early prenatal stress on fetal brain development and has shown that they are partly mediated by the microbiome.
Lowry is developing new strategies to prevent and treat anxiety and depression, including the use of beneficial microbes that live in the gut.
A microbiologist and immunologist by training, Mazmanian studies how the brain, the immune system and the microbiome interact in health and disease, including autism spectrum disorder.
I took this path in the last five years because, through conversations with neuroscientists here at Caltech, I realized there are many parallels between the immune and nervous systems. But the data we’ve generated so far have shown that microbes interact with the brain by producing molecules that impact behavior without altering the immune system. We’ve found, for example, that mice exposed to an inactivated soil bacterium called Mycobacterium vaccae increase production of the neurotransmitter serotonin in the brain, which has antidepressant-like effects. Together, we’ve been investigating ways of modulating the immune system to prevent stress-related psychiatric disorders, such as anxiety and mood disorders. There was a Radiolab episode on NPR that provoked a conversation in the lab about the vaginal microbiome, which is the main source of the bacteria that first populate a newborn baby’s gut.
One of the barriers to treating psychiatric and neurological disorders is that we often don’t understand the underlying disease mechanisms; in other words not only what to target but where those targets are in the body.
Sarkis, how do you think the microbes in the gut are communicating with the brain and driving behavior?
We’ve shown, for example, that a metabolite produced by gut bacteria is sufficient to cause behavioral abnormalities associated with autism and with anxiety when it is injected into otherwise healthy mice.
He showed that treating healthy people with fermented milk products containing probiotics, or healthy bacteria, altered brain activity in regions linked to emotion. But there are plenty of studies ongoing in Europe and in Canada where researchers are giving vaginal lavages to the newborns delivered by C-section to ensure that they are getting a nice dose of their mother’s microbiome.
Can you expand on how this natural form of inoculation helps lay the foundation for brain development?
At the same time, as Sarkis pointed out, the gut microbiome is helping to prepare the baby’s immune system.
So even acute exposure to prenatal stress seems to alter how an organism responds to changes in its environment in the long term. Just the very concept that microbes can have profound effects on the brain may be hard for a lot of people to believe. So microbes that can modulate the immune system and limit inflammation may have some benefit, either by alleviating the symptoms of certain types of psychiatric disorders or, in the best possible scenario, preventing them. We have a series of studies that we’re getting ready to publish that suggest that certain types of heat-killed microbes can prevent syndromes that you would expect following chronic stress. That being said, as Chris mentioned, diet is a major driver of microbiome configuration and so I think that there is enough reason to believe that specific foods “are better” for the microbiome than others: eating a high fiber diet with lots of fruits and vegetables, resistant starches such as those from seeds and nuts, and, in general, a diet that is closer to the one we evolved to eat, including foods that were available before agriculture and fast food restaurants came along. There’s no disputing their utility or efficacy but we shouldn’t just throw antibiotics at every illness.
Mice that received treatment also exhibited fewer behaviors associated with autism, such as anxiety. Are we going to find that the microbiome also plays a role in cognition or neurodegenerative diseases, for example? While the microbiome has not yet been implicated in neurodegeneration, there’s a lot of speculation about this issue because there are data showing that a Mediterranean diet protects against Alzheimer’s, a neurodegenerative disease.
In fact, many patients who are ultimately diagnosed with Parkinson’s are known to have had GI disturbances decades before they develop motor symptoms. We had a session on the microbiome at the annual meeting of the Society for Neuroscience this year but it was our third year submitting it.
I think the field is now at the point where we’ve established the validity of our models and are beginning to show how the microbiome affects the brain.
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Dogs with digestion issues have special dietary considerations and it is important that we compare dog food brands to find the best possible food for their particular issues. This is extremely important because many times poor digestion is a sign of a larger health problem. Your vet may also recommend a specific exercise routine to help move their digestion along.
Typically you will look for dog foods that are fiber rich, contain pre and probiotics, digestive enzymes like glucosamines and glutamines, digestion enhancing ingredients like beet pulp, grain sorghum, and barley, and phytonutrients.
Often times limited ingredient dog foods are also made with novelty proteins like vegetable protein or game meats, which may be easier for dogs with food intolerances to livestock meat to digest.
Dogs lack the enzyme amylase in their saliva, which is essential to help break down starches.

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I love to put ideas and conclusions on different topics, news and articles on the basis of my researching and analyzing abilities. They are mostly beneficial – as integral to our survival as we are to theirs – helping us to digest food, make vitamins, combat infection and much more.
They have also been linked to disorders of the central nervous system including anxiety, depression, autism and multiple sclerosis, which may be a consequence of an ecosystem that has fallen out of balance. Though we haven’t ruled out an immune link, we have discovered mechanisms by which microbial molecules may directly interact with the nervous system. Although this work is still in progress, it’s clear that the microbiota plays an important role in stress-induced chronic anxiety, at least in animal models.
We started thinking about the environmental factors, such as stress, that could change the vaginal microbiome and wondering if that would have an impact on our model of brain development.
Some questions we’re all still trying to answer include the composition of the gut microbiota, its effects on the permeability of the lining of the gastrointestinal tract, its effects on whole-body inflammation, and its effects on neuronal signaling from the gut to the brain. If the therapeutic targets are in the brain then it becomes particularly challenging because of the blood-brain barrier, a network of blood vessels that protects the brain from harmful substances. This suggests that microbial molecules may connect the gut to the brain via the circulatory system. We’ve shown in our mouse model of early maternal stress, for example, that short-term changes to the microbiome during a critical period of development can result in brain changes.
So, if mom’s microbial ecosystem changes – due to infection, stress or diet, for example – her newborn’s gut microbiome will change too, and that can have a lifetime effect. But I tend to think that by understanding these effects, one can do something about the epidemics of anxiety, autism and attention deficit and hyperactivity disorder, also known as ADHD, that we’re seeing in today’s society.
So yes, I think taking or being exposed to these types of bacteria during adulthood can be beneficial, although clearly their major influences are during development, as Tracy and Sarkis have pointed out. It’s becoming clear from the American Gut Project that an important source of gut microbial diversity is the number of different plants we eat.
And because we know diet helps shape the microbiome, one can imagine that eating a Mediterranean diet could affect the microbiome in a way that protects against neurodegeneration.
And a recent study showed that patients with Parkinson’s disease have different microbiomes than matched controls.
But I can tell you that there are still vast numbers of people, especially in psychiatry, who don’t believe this is real.
At the same time, I’ve been surprised and gratified by the fact that our work hasn’t received widespread rejection by the neuroscience community. If you have bad breath, gingivitis or periodontitis A probiotic lozenge or mouthwash might be your best bet. Senior dogs and puppies have sensitive digestive systems and the wrong food can exacerbate these issues. Once the problem is diagnosed, your veterinarian will make recommendations on dietary changes to help your dog overcome these issues. Many dog owners have found success with limited ingredient foods, so it is a great place to start when looking for a new food.
So if the grains in their dog food have not been properly processed, many dogs will have difficulty digesting them. Since microbes were having such a profound effect on the immune system, I wondered whether they were having an effect on the brain, too. It blossomed from there because the relationship between a newborn’s gut microbiome and his or her mother’s vaginal microbiome is almost one-to-one, with a newborn’s microbiome changing in direct response to its mother’s.
But if a neurological condition actually originates in the gut, which we believe is the case for some individuals with autism, then delivering therapeutics is much easier. It could alter how the gut, and the immune system within the gut, develops and how the brain develops. We’re learning that society may be doing things that are not in the best interest of a child’s health and by understanding those things we can change practices and prevent, for a lack of a better term, mistakes during critical periods of development. We have a program in the lab that’s very, very early looking at Alzheimer’s and Parkinson’s diseases in mouse models, but there’s nothing solid to report yet.
While this is an exciting finding, this kind of study needs to be interpreted with caution as it is an association and does not prove a causative link. With that being said, if you talk to most neuroscientists, they have a hard time finding any credibility in the link between the microbiome and neurobiology. It certainly hasn’t received widespread acceptance either, but when I discuss my research with card-carrying neuroscientists they seem to be quite open-minded about the possibility.
Monitor their progress and see if there are any negative changes in their appetite, behavior, or health. We wondered, how does this interaction alter the way a baby’s brain develops in our mouse model of early prenatal stress?
In my lab, we’ve been able to alter some of the symptoms associated with autism, such as repetitive behaviors, in mice by feeding them specific bacterial species. For example, the leaves of a spinach plant are estimated to harbor more than 800 different species of microbes.
So there are flash bulbs going off in the dark, suggesting that very complex neurodegenerative disorders may be linked to the microbiome. It’s still a very, very new concept with much more experimental validation necessary, and honestly I have no issue with that. I even scrolled all the way to the bottom to see if there was an explanation for this or even a box with all the missing quotation marks stacked up inside. If You're Currently Taking Or Are Considering Taking Probiotics, I Recommend That You Make Sure It Has These Directions: Mix one packet with one glass (8 oz) of water or juice.
Finally, certain breeds and purebreds tend to have more sensitive digestion than other dogs.
So it is recommended if your dog has food intolerances, you try to introduce a grain-free food. It turns out that stress changes the levels of Lactobacillus, a gut-dwelling lactic acid-producing bacteria that affects the brain’s chemistry, in both mothers and their offspring. These bacteria modulate molecules in the gut and in the blood that affect the nervous system. These are microbes that you can’t sterilize from the plant because they’re actually inside of it. Cycles of Life manufacturers and distributes safe and effective nutritional supplements - for humans and animals - which focus on strengthening the immune system and promoting digestive health with an emphasis of using naturally heat stable probiotics which help to Water kefir is a source of beneficial bacteria. After another week, increase the amount to three-quarters, and then ultimately, after one more week, you will feed them 100% of their new food.
And so having access to this kind of microbial diversity through the things that we eat is probably very important. These seminal findings, the flash bulbs, are only just beginning to illuminate our vision of the gut-microbiome-brain connection. Abstract: The preoperative management of locally advanced rectal cancer has evolved over the years to establish fluoropyrimidine-based chemoradiation as the usual standard of care.
During this process watch for any changes and make sure you report back to your veterinarian your progress. I’ve also added sand from ocean beaches to my children’s sandbox, I let my kids swim in lakes, and we take probiotics.

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