 Echo and Narcissus, I'm in my echo apartment, the apartment with the debris and echoes of a previous life, a life that ended in my mid-thirties surrounded by memories entombed and rarefied in paper. This is my echo apartment and the apartment that you are used to is my Narcissus apartment. Echo and Narcissus, I apologize for the lighting, here it's always very, very sunny and very difficult to get the right mixture of artificial lighting and natural lighting. So today's topic is gut bacteria, the gut microbiome, what goes on in your intestines. Does it somehow interface with your brain? And if it does, what are the outcomes? A hint, borderline personality disorder is intimately connected to your gut bacteria. Yes, I knew it would capture your attention. But before we proceed, I have an address to make, fellow non-countrymen, Germans and Germanites. The German people have been accused of everything imaginable under the sun, but they've never been accused of having a sense of humor. So my apologies for attempting a feeble joke in the previous video that I've made, feeble joke in German. Having made the joke, like the USSR in 1941, I have been besieged by an invading army of gloating and gleeful Schadenfreude nitpickers, Semvaknien, they kept telling me. It's not Guten tag alles, it's Guten tag alle, or Guten tag une alle. Yes, I know, fellow Germans, I know. But this was a joke, alles in German means everything. So when I say Guten tag alles, I'm actually saying a good day, everything, because the narcissist perceives other people as objects, as things, and so the appropriate usage in German would be alles, not alle. Got it? Now, forward march! Okay, Schwanpanim and Schochanim, even Germans. As I said, today we're going to discuss a fascinating topic. We are beginning to realize that the brain is only one element, one component in our mental health, as far as our body is concerned. Every system or every subsystem interacts with every other subsystem to produce an emergent phenomenon, an epiphenomenon known as mental health or mental illness. Now, in the science of epidemiology, the Golden Standard is randomized clinical trial, but these are very rare. The proxy is known as Mendelian randomization. It's a method used to measure variation in genes in order to interrogate their effects on the body. So we approximate what goes on in the body by studying the genetic composition and makeup of people. So when I use Mendelian randomization, you will know what I'm talking about. Let's delve right in. First of all, this is a literature review. I would like to recommend a recent article published in, I think, 2022 in Molecular Psychiatry. It's a publication, the publisher is Springer, and the article is titled The Gut Microbiome in Mental Health, Advances in Research and Emerging Priorities, because authored by Andrew Shubridge, Jocelyn Chu, Alice Martin, and other non-pronounceable names, Vol. 27 Molecular Psychiatry. This is the best overview that I came across. Now, other articles are mentioned in the literature. In the description, the description is under the video, not over the video. In the description, you will find literature. Another article I refer to is Gut Microbiome Brain Axis and Inflammation in Temperament, Personality and Psychopathology. It was published in Current Opinion in Behavioral Sciences, Vol. 44, April 2002, and the authors are Sumich, Heim, Lenzoni, and others. The authors in this article, this second article, postulates the temperament, personality, and even psychopathology are biologically grounded, and the biology of these things exceeds the brain. The brain is only one component, however crucial. In the absence of other components, there are no psychopathologies. So psychopathology, mental illness, is a collaboration, not to say a collusion, between various systems of the body, most notably the neurological system, the brain and neurons in the brain, and the gastrointestinal system. In our gut, in our intestines, there are 4,000 species of microbiota, of bacteria. Not only bacteria, to be very technical, these are not only bacteria, but okay, let's call them bacteria. There are 4,000 species of these things. They inhabit our body, they influence every aspect of human physiological functioning. So why not? Mental health and mental illness. We inherited this delusion or illusion that mental illness and mental health are divorced from the body. This is known as the dualistic problem. It hails back to the car in the 17th century, like mind-body problem. It's as if we have a body and then we have a mind, and the mind is divorced from the body, is not a part of the body, is not even influenced by the body, and of course we know now that it's very wrong. Many trauma-based, many trauma therapies are based on mind-body techniques. The body does affect the mind, and if it affects the mind for the better, it should be able to affect it for the worse. There is a bidirectional relationship between the gut microbiome and brain function that is established beyond doubt. The gut environment, for example, directly influences limbic function via the vagal nerve. It modulates effect and stress responsibility. So when we are stressed, when we are emotional, let alone hyperemotional, our gut bacteria are to blame partly. The effects of this stress and stress affect the ecology of the gut. They affect the ecosystem of the gut. They change the composition and the ratios and the frequencies of the various bacteria. This in turn creates a vicious cycle. This bacteria now affect the brain, which in turn experiences stress, which in turn affects the gut bacteria. Behaviors change, diet, social interaction, introversion, extroversion, agreeableness, numerous other behaviors, defiance, recklessness, all these behaviors involve an intricate feedback loop between our gastrointestinal system and the brain. The gut microbiome modulates the release of inflammatory molecules and hormones. And this indirectly affects brain function, but also amazingly brain structure, the very structure of the brain changes. It's not only neural pathways that are formed, but the entire brain deforms, changes shape. And so the development of gut microbiome starts from gestation, in pregnancy. Even as embryos, we are beginning to absorb bacteria from the maternal environment in the womb and we are beginning to develop our own gut bacteria. Birth, especially birth, natural birth, through the birth canal, infects the emerging newborn with bacteria. Therefore, the newborn, as it sweeps through the birth canal and the mother's vagina, swallows literally bacteria. And this bacteria inhabit the newborn's intestines. During childhood, during adulthood and into old age, this bacteria continue to evolve and to reflect in their composition and interrelationships, the temperament, personality, psychological well-being of the individual involved. Even sexual differentiation and other psychological functions during puberty are the outcomes of gut bacteria. There's a vulnerability to developmental, psychiatric and neurological disorders if the gut microbiome is disturbed, if there is what we call dysbiosis. So what about nutrients? What about food and eating? There is no difference in principle between foods and medications, none. We put something into our gastrointestinal tract and through the gastrointestinal tract, the elements and the components of whatever we have put in are disseminated through the bloodstream everywhere, with the exception of the brain to some extent. So foods are medicines. They are differently packaged medicines. We don't conceive of them as medicines, but they are medicines. They contain, for example, nutrients and micronutrients, which affect gut function, which create or subdue inflammation, fatty acids do this, for example. As we said, gut function and inflammation are intimately connected with temperament and personality. This has been established in clinical and non-clinical groups in multiple studies, but these relationships reflect not only the influence of the microbiome on psychology, but the influence of the psychology on the microbiome. It's a two-way street. It's a never-ending loop. The organism explores the environment, seeks rewards, for example, tasty food, socially interacts. It develops food preferences and so on and so forth, and by interacting and assimilating the environment, because when we eat food, we are putting part of the environment inside our bodies. When we interact with people, we are putting part of the environment inside our bodies. People's smells, the molecules that people emit, HPA molecules and others, they're all digested by us, ingested by us. They all penetrate and invade our bodies. People invade in each other's bodies, and so this internalization, introjection, if you wish, of the physical environment and the social environment, they in turn reconstruct the gut microbiome, which in turn affects the brain. No wonder talk therapy is that effective. So microbiome status is directly linked to psychological function. And here's the thing. Our bodies are gigantic zoos. Only 1% of the combined human and microbial DNA in our bodies is human. Yes, you heard me correctly. Only 1% is human. 99% of the DNA in our bodies is not human, and that includes 100,000 ancient viruses embedded in our cells. We are the world. We are a reflection of the total chain of being internalized, put together to become what we call an individual. Individuals are actually colonies of hundreds of thousands of life forms. And so temperament and personality are fictitious constructs. I've been railing against the constructs of personality itself for many, many years. I don't believe, I believe these are totally counterfactual, they're wrong. Temperament and personality are in flux all the time. They reflect perceived threats, and then we become neurotic. They reflect social interactions, and then we become extroverted or introverted, agreeable or not. They reflect the environment, and then we are open or not open. So interactions, interrelatedness, we are the confluence of numerous processes. We are like Venn diagrams. We are the common area in the two circles or three circles. So the resulting physiological and behavioral changes influence the gut microbiome community, including the genetic components of microbial diversity, biodiversity. And so this way, through these vectors, the gut microbiome functionality is affected. In short, when we imbibe the environment, when we drink it and eat it and smell it, inhale it or whatever, we're affecting our gut microbiome, which in turn interacts with our brains and changes them structurally and functionally. And this may be the explanation for the remarkable individual differences in gut microbiome diversity and composition. And why people have different physical and psychological states of health. The gut microbiota influences temperament and personality via bidirectional communication with the brain, as I said. But the communication is often direct. For example, cranial nerve X is directly linked to the intestines. The immune system, the endocrine system, these pathways go through the gastrointestinal system and are modulated and modified by it. Everything I'm telling you has been substantiated in studies. The gut and the microbial community in the gut and the intestines represent the missing link probably between psychological traits and psychological health and behaviors. The gut contains 10 to the 13th power microorganisms. They are anywhere between 1,000 and 4,000 unique bacterial species. The numerous, there's several major phyla, about four major phyla. So we have firmacutes, we have bacteriodeeds, we have actinobacteria and we have proteobacteria. These are the four families, shall we say. As I said, infants receive most of the microbiome via their mothers. Here's another major contribution of the mother to actually mental health mediated via physiological microbial vector. But the microbiome evolves over life. It's much more complex when you're 40 than when you're four. So how can we explain the emergence of early life temperament, the vestiges of personality and even personality disorders, for example, during early teenage years? If the microbiome is incomplete, how does it have the effects that it does? It seems that psychological developmental growth and evolution, including the evolution and growth and development, the unfortunate development of psychopathology, it seems that these incremental gradual trajectory reflects the fact that the microbiome is evolving. Between the ages of 18 and 27 months, also the ages where there's separation and individuation. The infant temperament is very, very protean, that infant is informed, is half-baked, is a work in progress. And the microbiome phylogenetic diversity in the infant is such that the effects it has on the brain is urgency and extroversion. What I've just told you is an amazing thing because it implies that gut bacteria are the ones that modulate the brain, structure the brain, affect the brain in a way that causes extroversion, urgency. In other words, gut bacteria push us as infants to explore the world, to separate from mommy and to individuate. Gut bacteria make sure through the brain, so they are using the brain. The gut bacteria are using the brain. Gut bacteria make sure using the instrument of the brain that we become extroverted sufficiently to be able to learn about the world and develop a workable internal working model. Now, Richard Dawkins suggested that we are the slaves of our genes. We are nothing but gene containers or gene conveyors. Similarly, one can easily construct a case that we are nothing but slaves to our gut bacteria, that we are nothing but containers, giant warehouses of gut bacteria, an ecosystem with the self-delusion of self-awareness and separateness. In boys, urgency, extroversion has been associated with overall diversity and relative abundance of certain types of femicutes and bacteria deets. So there is a direct correlation between certain types of bacteria, not all gut bacteria, but specific subtypes, families, phyla of gut bacteria, and extroversion and urgency, especially in boys. Here's another argument concerning the difference, the innate differences between boys and girls. It's not true that we are all the same, absolutely not true. And the evolution of these two phylas, these two families of bacteria reflects age, is connected to age, connected to diet. Generally, the relationship between phylogenetic diversity and urgency, extroversion, is unaffected lifelong as long as these two families are dominant and maintained when they become the minority or subdued by other types of bacteria, including very bad bacteria like rostridium. Then there is introversion and withdrawal and avoidance. Interesting, isn't it? Microbiome also affects personality in adults, not only in children. Gamma proteobacteria, for example, including, by the way, pathogens. Escherichia coli, which can kill you, has an effect on your brain and your mind and your traits and your behavior and your qualities and who you are and how you perceive yourself and how others perceive you. Escherichia coli, a pathogenic virulent strain of bacterium, also interacts with your brain and with your mind. So gamma proteobacteria are associated, for example, with neuroticism. And the belief is that they induce inflammation. Inflammation crawls somehow into the brain, affects it somehow. We are not quite sure and this results in neuroticism, but the correlation is extremely high between specific gut bacteria and inflammation and neuroticism. Similarly, major depressive disorder, same vector, same story, same clinical picture. Conscientiousness is characterized, for example, by lower proteobacteria and higher lacno-spiracea, another type of bacteria. Bacterial diversity is associated with openness, agreeableness, you know, these qualities or traits somehow reflect the composition of bacteria in our intestines. The limbic and executive functions are intimately connected to the microbiome. There's a relationship between the gut microbiota and negative emotionality or negative affectivity or even fear. This increases with age and because the limbic region or the limbic networks change, you know, the differential sub-region development of limbic networks, responses to threat, fear responses, fear emotions, they change with age. And similarly, gut microbiota changes with age. So we know that gut bacteria affect the frontal medial temporal connections. They modulate the neuroendocrine system, the hypothalamus pituitary adrenal axis, HPA axis, and so on and so forth. This is established already. What we don't know if this is causation or correlation, we don't know which affects what. We don't know if A affects B or B affects A or there is a C which affects both. We don't know, but there is such a powerful correlation that we can no longer ignore these findings and pretend that there's no connection between our midsection and our blob up here. Development of limbic regions, for example, the amygdala, these regions, development begins soon after conception. There's progressive structural and functional segregation between subregions, even prior to birth. So gut bacteria play a role even then. And again, inflammation is a critical factor. Inflammation somehow negates our physiological defense system. It survives somehow, the attacks by our immune system. Inflammation is persistent, resilient, and systemic. We don't quite know what is the role of inflammation, what is the exact role. We are beginning to realize that inflammation is probably the major process, both physiologically and as far as mental illness is concerned. Adaptive inflammation collaborates with the microbiome in our guts to affect the registration of environmental threats and opportunities. Inflammation biases our perception, promotes harm avoidance, and facilitates recovery from illness. We are beginning to reconceive of inflammation. It's actually a positive process. Gassen and Hill suggested that there is a specific adaptive role for inflammation in social perception, punishment, reward, and associated personality traits. Similarly, the immune system is massively affected. As far as endocrine function, there's a complex relationship between the endocrine, enteric, and immune systems that influence this relationship's influence, physiological and physical health. Hormones act as bidirectional conduits of communication between the microbiome in the gut and the brain. The gut produces hormones, actually. Hormones impact temperament. We've known this for decades. We've known about the connection between hormones, personality, and vulnerability to psychopathology. Nothing new in this. But what is new is the realization that the intestines may be the center of hormonal production, not the brain, not even the kidneys. So for example, serotonin is manufactured 90% in the gut and only 10% in the brain, which explains why antidepressants suck. OK, what about sex? Sex steroid hormone levels in humans are correlated with gut microbial composition and diversity. Their animal studies show a transference of gut microbiota from male to female during intercourse. Section differentiation is literally determined by the bacteria in our guts. With regards to prebiotics and probiotics, meta-analysis suggests that probiotics do affect significantly mood in clinical populations, but not in non-clinical populations. In other words, if you're mentally ill and you take probiotics, it will modulate and regulate your mood. But if you're healthy, mentally healthy, find me one, then the effect will be either muted or non-designable. Some positive findings exist with regards to non-clinical populations, but they are not decisive. Petrochemical workers, for example, when they consume probiotic yogurt or supplement with several species, their levels of depression, anxiety, and stress abate. Prebiotics are more debatable. So there are several associations between gut microbiome, temperament, personality, and psychopathology across the lifespan, even before you're born. Direction of these relationships is not known. We don't know, as I said, what causes what. The correlation is undeniable. There is a role for gut microbes. There is a role in temperament and personality. The diversity and the composition of the microbiome in the gut somehow influences not only mood, affect emotions, depression, anxiety, et cetera, et cetera. They affect social functioning, environmental exploration during separation and individuation phase. They affect vulnerability to physical and psychological clinical observable facts and artifacts. These are very strong statements. I refer you to another article, alterations of the gut microbiota in borderline personality disorder. It was authored by Hannah Rösler. There are Flasbeck and others. And I want to read to you what they have to say. Again, you can find everything in the literature, literature section in the description under the video. This particular article is lifted from Journal of Psycho-Somatic Research, July, 2022. So the authors have this to say. A substantial number of studies has shown that the microbiota are altered in several psychiatric conditions, including major depressive disorder, bipolar disorder, autism spectrum disorder, schizophrenia, and eating disorders. As regards to major depressive disorder, for example, actinobacteria were found to be increased, whereas bacteriodeids were decreased in relation to other phyla, other families. Some studies suggested decreased microbial diversity in major depressive disorder patients. In addition, clinically active major depressive patients seem, active major depression, I'm sorry, seems to be associated with greater alterations of the gut microbiota, in terms of abundance of some bacterial genera compared to patients in remission. As long as there's a flare up of the depression, the gut bacteria composition and diversity is different than when the depression is over. Clearly, when you're depressed, the bacteria in your guts are different than when you're not depressed. This is shocking. A recent meta-analysis continued the authors, reported a relatively inconspicuous alpha diversity as a measure of species diversity of the gut microbiota, but altered beta diversity as a measure of the composition of species relative to one another, particularly less abundance of SCFA-producing bacteria in major mental disorders. In summary, say the authors, studies of the microbiota in psychiatric disorders are promising, as they may offer new insights into the functional connection between the gut and the brain. However, to date, findings are inconclusive, which may reflect the heterogeneity of the clinical population studies and the potential impact of psychotropic medication on the gut microbiota. In the present study, we sought to explore the gut microbiota in females diagnosed with borderline personality disorder. One specific point of interest concerned the potential role of childhood adversity. The gut microbiota begin to develop before birth and continue to mature within the first years of life. Therefore, the impact of early life stress on the gut microbiota may play a role in health outcome. A second objective referred to the confounding effect of psychopharmacology and other medication, a problem which precluded more consistent conclusions in previous studies. Accordingly, say the authors, only unmedicated patients were included in the present study. Our prediction was consistent with the recently published meta-analysis that the gut microbiota composition would differ between BPD borderline patients and healthy controls in terms of better diversity and perhaps SCFA producing bacteria. In addition, we speculated that some taxa would correlate with psychometric dimensions such as disease severity, childhood trauma and experience of chronic stress. In spite of these limitations, the current study is the first to explore the gut microbiota in unmedicated patients with borderline personality disorder. While diversity indices did not differ between the groups, the bacteria-deeds-frimicutes ratio was found to be higher in patients with borderline personality disorder than in controls. So the overall picture was the same, but the ratio between types of bacteria was different in people with borderline personality disorder, especially when controlled for body mass index and depression. Differences in the taxonomic composition of the gut microbiota revealed a potential dysbiosis among SCFA producing bacteria in borderline personality disorder. Another article I would like to refer you to is progress in neuro-psychopharmacology and biological psychiatry. I mean, that's the journal. Progress in neuro-psychopharmacology and biological psychiatry, volume 98. And the article is titled Patho-Ethiology and Pathophysiology of Borderline Personality, Role of Prenatal Factors, Gut Microbiome, Moe and Kappa-Opioid Receptors in Amygdala, PFC, Interactions and so on and so forth. So one of the elements in this study concerned gut bacteria in during gestation, before birth, during pregnancy. What's the role of gut bacteria? During pregnancy, in producing borderline personality disorder, many years later. And the authors say the patho-ethiology and pathophysiology of borderline personality disorder have been relatively underexplored. Consequently, not targeted pharmaceutical treatments or preventative interventions are available. The current article reviews the available data on the biological underpinnings of borderline personality disorder, highlighting a role for early developmental processes, including prenatal stress and maternal dysbiosis, which could lead to borderline personality disorder, patho-ethiology in the newborn. Such factors are proposed to drive alterations in the infant's gut microbiome, in turn modulating amygdala development and the amygdala's two-way interactions with other brain regions. Wow! It means if the gut bacteria of the mother is disturbed, if the mother suffers from dysbiosis, she adversely affects the brain development of her fetus. And the amygdala is damaged and the amygdala's ability to interact and regulate other regions of the brain, which in turn could lead to mental illnesses such as borderline personality disorder, but also psychopathy. Wow! This is wow! The authors continue to say alterations in opioidergic activity, including variations in the ratio of the Mu and Kappa opioid receptors, seem a significant aspect of borderline personality disorder, pathophysiology, contributing to its comorbidities with depression, anxiety, impulsivity and addiction. Stress and dysphoria, say the authors, are commonly experienced in people clustered with borderline personality disorder. The growing body of data, across a host of medical conditions, indicate that stress and mood dysregulation may be intimately associated with gut dysbiosis and increased gut permeability, coupled with heightened levels of oxidative stress and immune inflammatory activity. It urgently requires investigation as to the relevance of such gut changes in the course of borderline personality disorder, symptomatology. Imagine if the problem is in the intestines, we could effectively medicate borderline personality disorder by altering the composition, diversity, genetics and ratio of gut bacteria. We could just give a pill or a series of pills and the borderline will be gone. This is an amazing direction of study. The authors continue accumulating data indicate that borderline personality disorder, symptom exacerbations may be linked to cyclical variations in estrogen, in turn decreasing serotonin and local melatonin synthesis, thereby overlapping with the pathophysiology of migraine and endometriosis, which also have a heightened association with borderline personality disorder. Future research directions and treatment implications are indicated. I couldn't agree more. Okay, I hope you had a fun ride with my gut bacteria and realized that we are a holistic system. It's wrong of medicine and it's wrong of psychology and definitely wrong of psychiatry to isolate a single subsystem and medicate it or treat it or operate on it. Because the body is interconnected. All the systems are interdependent, shape each other, cause each other to function or malfunction, alter everything and above all, our experience of ourselves.