Self Help

The Mind-Gut Connection - Emeran Mayer

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Matheus Puppe

· 49 min read

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  • The prevalence of dementia has increased in Japan over recent decades, which some propose is linked to a dietary shift away from traditional fish and plant-based diets towards higher meat and animal product consumption.

  • Data suggests increased consumption of animal fat is most strongly associated with rising Alzheimer’s disease rates in Japan.

  • Other populations, like Native Americans and indigenous Central Americans, have also experienced health declines when shifting from traditional plant-based diets to the North American diet.

  • These dietary shifts may negatively impact metabolic and brain health by influencing the composition and diversity of the gut microbiome. Traditionally plant-based diets are associated with a healthier microbiome and reduced inflammation.

  • The health benefits of diets like the traditional Japanese and Okinawan diets are likely in part due to their positive effect on regulating interactions between diet, the gut microbiome, and the gut.

  • Understanding these complex communications between the brain, gut and microbiome is important for making informed dietary decisions to maintain health and potentially understanding disease.

  • The traditional machine model view of the body sees diseases as broken parts that can be fixed with surgery or medications. This has led to skyrocketing healthcare costs in the US without corresponding improvements in health outcomes.

  • Chronic diseases like IBS, chronic pain, depression have proven difficult to treat with this model. Rates of obesity, autoimmune disorders, brain diseases have also risen significantly in recent decades.

  • The gut (digestive system) and brain are intricately connected through the gut-brain axis, not independent as traditionally thought. The gut has its own nervous system and more immune cells than any other organ. It produces various hormones and stores 95% of the body’s serotonin.

  • The gut senses information in food and communicates bidirectionally with the brain. This shows it is a much more complex and important organ than viewed as just a mechanical digestion device. The outdated machine model is insufficient to understand modern health challenges, and a new integrated view is needed.

  • The gut and brain communicate bidirectionally through neural, hormonal, and inflammatory signaling pathways. Signals from the gut generate sensations like fullness or nausea, and the brain can trigger gut reactions in return.

  • Gut feelings are stored in the brain and can influence decisions related to food, social relationships, and work.

  • Recent advances in understanding the gut microbiome have shifted attention to the trillions of microbes living symbiotically in our guts. Technological improvements enabled their discovery and characterization.

  • The human microbiome project studied these microbes and their role in health and disease. Disturbances to the gut microbiome are linked to various disorders.

  • The gut contains the largest populations of microbes, over 100 trillion from about 1000 bacterial species containing many more genes than human cells. These microbes evolved with humans for billions of years.

  • Our individual microbiome profiles depend on genetics, environment, diet and lifestyle. Microbes play a vital role in human physiology through functions like digestion and immune system regulation.

  • Further research is unraveling complex interactions between the gut, brain and microbiome with potential implications for understanding human nature and evolution.

Here are the key points:

  • New science shows that humans are “supraorganisms” composed of both human and microbial components that are interdependent. The microbial components vastly outweigh the human components.

  • The human microbiome is closely interconnected with microbiomes in the environment through a shared biological communication system. This means humans are intimately tied into the web of life on Earth.

  • Understanding our role as supraorganisms has important implications for concepts of health, disease, and our place in the natural world.

  • Imbalances in the gut microbiome (dysbiosis) are linked to various gut and brain disorders like IBS, ulcerative colitis, autism, Alzheimer’s, Parkinson’s, and depression.

  • Restoring a healthy gut microbiome diversity through probiotics, prebiotics, dietary changes, or fecal transplants can help treat some of these conditions.

  • Changes in lifestyle, diet, and widespread antibiotic use may be contributing factors to rising rates of disorders linked to gut dysbiosis, like autism and neurodegenerative diseases.

  • The gut-brain axis and microbiome-brain connections are important areas of research that could lead to new treatment approaches for numerous health conditions.

Here is a summary of key points regarding ic dietary interventions:

  • The gut microbiome plays an important role in mediating how food affects mental well-being and brain function. Gut microbes produce metabolites that can influence the brain and have impacts on things like inflammation, obesity, and disease.

  • Early life diet and environment programs gut microbial composition and food preferences. However, the gut microbiome can adjust to different diets, digesting a wide range of foods regardless of an individual’s diet type (omnivore, pescatarian, etc.).

  • Microbe-produced metabolites from digestion can impact the gastrointestinal tract, including its nerves and immune cells. Some metabolites reach the bloodstream and influence distant organs like the brain. This gut-brain communication is implicated in various diseases.

  • Dietary interventions like probiotics have shown potential benefits in some studies by modifying the gut microbiome composition and its effects. Special diets, probiotics, or supplements are sometimes recommended when patients have unexplained gut symptoms to try and “normalize” gut function.

So in summary, the gut microbiome mediates how diet impacts mental health and brain function via metabolites, and dietary interventions aim to modulate the gut microbiome and its effects on the brain-gut axis.

  • Many people suffer from abnormal bowel habits and conditions related to altered brain-gut interactions, such as irritable bowel syndrome, chronic constipation, indigestion, and heartburn. These issues affect nearly 15% of the US population.

  • The gut is closely linked to the brain and emotions. Stress and other psychological factors can trigger gut reactions and symptoms through pathways involving the hypothalamus and corticotropin-releasing factor (CRF).

  • Cyclical vomiting syndrome is one example where stress triggers attacks of severe vomiting and pain through exaggerated CRF and gut responses. Diagnosis was difficult for one patient until his mother correctly identified it based on his symptoms and triggers.

  • Correctly understanding the brain-gut connection is important for diagnosing and treating functional gastrointestinal disorders that arise from altered interactions rather than identifiable diseases. However, this connection is often overlooked by both doctors and patients.

  • Normal digestion is a highly coordinated process involving stomach acid, enzymes, peristalsis, nutrient absorption, and more that breaks down and moves food through the gut. The enteric nervous system and gut microbiota also play key roles in this process and its connection to the brain.

  • The enteric nervous system (ENS), sometimes called the “second brain”, is a network of over 50 million neurons in the gut wall that controls digestion without input from the brain or spinal cord.

  • The ENS coordinates peristaltic movements to move food through the esophagus, stomach, and intestines. It also generates waves to flush microbes out of the small intestine into the colon every 90 minutes when the GI tract is empty.

  • Experiments have shown sections of intestine can propel objects independently without any brain or spinal cord input, demonstrating the autonomous control of the ENS.

  • However, the brain can disrupt these digestive functions through the neural and hormonal pathways that connect the brain and gut. Negative emotions like stress, anger, or anxiety can inhibit or reverse normal movements.

  • Early experiments in the 1800s first observed that emotions directly impact stomach function. For example, anger slowed one man’s digestion whose stomach could be directly observed through an abdominal wound.

  • It’s now understood that both the sympathetic and parasympathetic nervous systems connect the brain to the ENS to coordinate emotional states with gut sensations and movements.

  • Both positive and negative emotions are believed to alter the activities and communication of cells, microbes and nerves in the gut, though positive impacts are less understood. The brain acts as an “override” to the ENS during emotionally arousing situations.

  • The gut and brain are strongly connected via the enteric nervous system and bidirectional communication via nerves, hormones and immune factors.

  • Emotions are processed in the limbic system of the brain, which activates emotional response programs that coordinate bodily changes. These programs can alter gut function and reactivity rapidly.

  • Stress activates the hypothalamic-pituitary-adrenal axis, increasing levels of corticotropin-releasing factor and cortisol. This triggers anxiety responses and influences gut function.

  • Chronic stress or trauma can cause long-term changes in these stress response systems and how the gut responds to triggers. Genetics and early life experiences also influence emotional programming.

  • Recalling stressful past events via places, people or thoughts can reactivate emotional programs and trigger gut symptoms, even without a clear food trigger. Understanding this brain-gut connection is important for managing functional GI disorders.

  • Ongoing research is exploring if mind-based interventions like meditation can positively influence gut responses by modifying emotional processing in the brain.

This passage discusses how the gut and brain communicate with each other through sensory signals and sensations. It profiles one patient, Bill, who was diagnosed with cyclical vomiting syndrome, a condition caused by excessive release of the stress hormone CRF in the brain.

The doctor explained to Bill and his mother that excess CRF was prompting his symptoms of anxiety, palpitations, sweating, and abnormal gut contractions. This provided a scientific explanation for his condition and relieved their uncertainty about the diagnosis. Understanding the biological mechanism also helped tailor an effective treatment.

Bill’s symptoms typically occurred in the early morning due to the brain’s normal peak in CRF secretion at that time. The doctor further explained how CRF shifts the body into “fight or flight” mode and disrupts normal gut function. Bill was given several medications to calm hyperactive stress circuits and reduce CRF release.

This treatment was successful - Bill only had one vomiting episode in the following three months. By understanding the cause of his condition, Bill was able to self-treat episodes and gradually reduce medications over time. He was then able to resume his normal activities and rebuild his life.

  • Frank is a 75-year-old retired schoolteacher who has been experiencing gastrointestinal issues for 5 years, including IBS-like symptoms of bloating, discomfort, and irregular bowel movements.

  • He also experiences sensations of something being stuck in his esophagus, frequent belching, discomfort behind his sternum that sometimes feels menthol-like and makes him cough, and feeling short of breath.

  • These symptoms started suddenly 5 years ago coinciding with the loss of his wife. He had mild IBS symptoms since childhood.

  • Extensive medical tests have not revealed a cause. It seems he has a functional gastrointestinal disorder causing hypersensitivity in his GI tract.

  • His partner noted his symptoms get worse when eating unhealthy, high-fat foods like chocolate cake, pizza, fries and rich cheeses.

  • It’s possible these high-fat foods played a role in sensitizing his gut-brain communication. Patients like Frank can be hypersensitive to normal gut functions and external stimuli.

  • Given the gut’s complex sensory system, it’s not surprising disturbances can cause overreactions to normal foods or sensitivities to additives. Frank may be sensitive to changing food supplies in a way most are not.

  • Our gut contains many taste and smell receptors that detect chemicals in our food and signals from gut microbes. These receptors located throughout the GI tract, not just in the mouth and nose.

  • Sweet receptors help regulate glucose absorption and satiety. Bitter receptors may respond to microbial metabolites and play a role in obesity. They can also stimulate ghrelin release and increase appetite.

  • Olfactory receptors found in the gut pick up similar cues. All these chemical sensors likely communicate with gut microbes.

  • The nervous system relies on specialized gut lining cells to sense events in the gut without direct contact with contents. These endocrine cells signal to nerves like the vagus nerve.

  • The gut is the body’s largest endocrine organ. Cells release hormones that signal fullness, hunger, and other states to the brain.

  • Immune cells in gut patches also signal to the brain via inflammatory molecules called cytokines.

  • The gut provides constant information to both the enteric and central nervous systems about food contents, responses, and potential threats. This allows for optimal digestion and elimination of toxins when needed.

So in summary, the gut contains many sensory systems that detect cues from food and microbes and communicate bidirectional signals between the gut and brain. This total gut awareness is vital for health, well-being, and coordinating an appropriate response.

The gut has an elaborate sensory system that communicates extensively with the brain through interoceptive signals. The gut’s sensory network covers an area 200 times larger than the skin’s surface area. This sensory network detects movement, pressure, chemical and nutritional information in a manner analogous to a basketball court covered in millions of tiny movement sensors.

The vagus nerve plays a major role in transmitting gut sensations to the brain. It carries signals both from the gut to the brain and vice versa. Cutting the vagus nerve, as was once commonly done to treat ulcers, deprives the brain of important interoceptive information from the gut. As illustrated by patient George Miller, this can cause a variety of unpleasant and hard to explain gut and whole body symptoms.

Serotonin is a key signaling molecule that links gut events like food poisoning to digestive and emotional responses. When certain toxins or chemotherapy drugs activate serotonin-releasing cells in the gut, it triggers vomiting and diarrhea as a survival mechanism to expel toxins. Serotonin levels also influence brain arousal systems and mood. The elaborate two-way communication between gut, brain and microbiota via the vagus nerve and signaling molecules like serotonin is important for overall health and well-being.

The passage discusses research on gut-brain communication conducted in the 1970s-80s at the Center for Ulcer Research and Education (CURE). A key focus was gut peptides or hormones, which were initially thought to function as simple on/off switches for processes like stomach acid secretion.

Researcher John Walsh had an interest in these gut peptides. Around this time, it was discovered that exotic frogs produced peptides in their skin to deter predators. When ingested by birds, these peptides triggered bad gut reactions. This showed frogs and birds shared a chemical communication system.

Scientists then searched for similar peptides in mammals. They extracted and purified peptides from pig intestines on a large scale. When injected in animals, specific peptides like gastrin increased stomach acid secretion, while secretin increased pancreatic secretions.

This revealed gut peptides function as a complex universal biological language used by gut microbes to communicate with the digestive system and even the brain. This shifted understanding of gut peptides from simple switches to a more sophisticated signaling system. This research laid important groundwork for understanding gut-brain communication.

  • Scientists Jesse Roth and Derek LeRoith discovered that gut peptides similar to insulin and other mammalian hormones were produced by microorganisms in bacterial cultures. This suggested these hormones originated in primitive single-celled organisms over a billion years ago, not animals as previously thought.

  • Further studies found ancient microbial versions of many other gut peptides and neurotransmitters like noradrenaline, endorphins, serotonin and their receptors. This indicated signaling molecules used in the gut, nervous system and immune system originated in microbes.

  • In 1991, the author published a speculative review article with Pierre Baldi proposing these signaling molecules represent a “universal biological language” used not just in the gut but between cells, organs and systems in many organisms including humans, frogs and plants. They suggested applying information theory to understand how much information different signaling molecules can transmit.

  • However, the scientific community was not yet ready to accept the idea of microbes influencing brain and behavior. It took nearly 30 more years of research on brain-gut interactions for gut microbes to gain prominence in this area, validating some of the early predictions from Roth, LeRoith and the author’s speculative paper.

  • Ancient civilizations like Egyptians, Mesopotamians, Indians, Chinese practiced enemas and intestinal cleansing to treat disease, believing toxins formed in the intestines caused illness. The Ebers Papyrus outlines using enemas to treat various GI issues.

  • Hippocrates and Greeks also saw the gut as origin of disease and used enemas. They adopted the Egyptian view that rotting food causes toxins leading to imbalance of the four humors.

  • Through history, many believed in concepts like intestinal toxins, yeast, leaks causing illness and pursued cleansing diets, supplements to fix the gut. However, digestive issues often remained, questioning effectiveness.

  • Humans use non-scientific rituals to reduce health threats they can’t control. Cleansing diets aim for a “clean gut” but this contradicts science. Popular authors whip up gut fears.

  • Some microbes like parasites and viruses can hijack the brain through the gut-brain axis to manipulate host behavior for their own survival and reproduction, as seen in toxoplasma and rabies virus. Others like gut bacteria also profoundly influence the brain-gut connection.

Here’s a summary of the key points:

  • Scientists previously thought they understood bidirectional communication between the brain, gut, and enteric nervous system via hormones, immune signals, and the vagus nerve.

  • However, it’s now clear that the gut microbiota plays an integral role as well, communicating with the brain through metabolites, hormones, neurotransmitters, and other compounds produced from digesting food.

  • Over billions of years, gut microbes developed sophisticated biochemical signaling (“microbe-speak”) to communicate with each other and primitive marine hosts like hydra.

  • Early hosts received benefits like digestion abilities and toxin expulsion from their microbiota, while microbes gained a nurturing environment.

  • This symbiosis led to gut nervous systems and secretory cells that regulate digestion via microbiota-derived compounds like neurotransmitters.

  • As animals evolved, gut nervous systems remained in charge of basic digestion while central nervous systems took over other behaviors via emotions and separate yet connected networks.

So in summary, the passage describes how gut-brain communication evolved from primordial microbial signaling to today’s complex interplay involving the brain, gut, enteric nervous system, and microbiota.

This passage discusses the communication or “microbe-speak” between gut microbes and the brain. It has evolved over hundreds of millions of years into a cooperative relationship where the microbes and host benefit each other. The microbes live in the gut and communicate with the enteric nervous system and immune system through various channels.

One key channel is the immune system. Dendritic cells in the gut wall detect signals from microbes and communicate with the immune system. Under normal conditions, they recognize peaceful signals and no response is needed. But harmful bacteria trigger an inflammatory response.

The gut is lined by a protective mucus layer in two layers. Microbes live in the outer layer while the dense inner layer keeps them away from the epithelial cells. If microbes breach this barrier, immune cells beneath the lining are activated and tailor the immune response depending on the microbes detected.

This microbe-immune-brain dialogue is dynamic and complex. Disturbances can be implicated in diseases like IBD, obesity, and brain disorders like depression and Alzheimer’s. The gut microbiota act like an internet connection, communicating information to the brain in varying amounts through different channels.

The microbe poses a potential danger through molecules like lipopolysaccharide (LPS) that is a component of gram-negative bacteria cell walls. LPS can increase gut permeability, allowing microbes to interact more with the immune system.

A high-fat, low-fiber diet leads to changes in gut bacteria composition and reduces protective factors like mucus layer thickness. This allows more microbes and molecules to cross the gut and engage the immune system, triggering systemic inflammation.

The gut immune response produces cytokines that can cause local or systemic inflammation. Cytokines also affect the brain through the vagus nerve or by crossing the blood-brain barrier to activate microglia. This gut-brain communication is implicated in various diseases.

Microbial metabolites produced from diet are neuroactive and make up 40% of circulating molecules. They signal the brain directly and via serotonin-producing enterochromaffin cells in the gut wall. This influences various mental and behavioral processes.

The gut, immune system, nervous system, and microbiome constantly communicate through signaling molecules and adapt to each other’s changes. Together they form an integrated brain-gut-microbiome axis of communication that science is continuing to uncover. Early life experiences and stress can impact this axis and gene expression patterns long-term.

  • The author was fascinated by psychosomatic medicine pioneer Dr. John Romano’s book exploring connections between early life experiences and adult health when training in the early 1980s, but it took over 20 years to apply those insights to patients.

  • Now the author always asks patients about their childhood experiences, finding it reveals important clues about illnesses, without needing specialized training. Over half of patients report family troubles like parental illness, divorce, abuse, addiction.

  • A 35-year-old patient Jennifer described lifelong stomach pains and recent worsening. Tests found nothing physically wrong. She was prescribed antidepressants and acid suppressants but told nothing more could be done.

  • Studies show adverse childhood experiences increase risks of poor adult health, heart disease, mental health issues. Biological mechanisms connecting early stress to later health are now better understood.

  • The author’s question about Jennifer’s childhood unlocked a story of prenatal and family stresses, matching traits in her mother and grandmother. This historical insight gave confidence to help Jennifer by addressing brain-gut interactions programmed by early life stressors.

  • Basic animal studies in the 1980s showed that stress affects animals like rats and monkeys in similar ways as humans. A major focus was on the interactions between mothers and offspring.

  • Experiments found that nurturing rat mothers led to less stressed adult offspring, while negligent mothers led to more anxious, depressive, and addictive adult offspring. Similar results were found in monkeys.

  • Further studies identified biological mechanisms underlying these behaviors. Neglected animals had altered brain development and neurotransmitter systems related to stress response.

  • Researchers then studied how early life stress in rats affects the brain-gut axis. Pups of stressed mothers showed IBS-like hypersensitivity, pain, anxiety, and stress-induced diarrhea as adults. Blocking the brain stress chemical CRF reduced symptoms.

  • However, efforts to develop CRF-targeting drugs for IBS failed, suggesting the human brain-gut system is more complex. Neuroimaging was then used to study how early adversity affects the adult human brain directly.

  • Stress experienced early in life, such as childhood adversity or trauma, can alter brain structures and neural activity even in otherwise healthy adults. These changes are mediated by the brain’s salience network, which processes threat and bodily signals.

  • Such alterations are not necessarily accompanied by mental health issues but may confer higher risk. They put individuals at greater risk of developing stress-sensitive disorders like anxiety, depression, or IBS later in life.

  • Studies have shown that the effects of early life stress can be transmitted intergenerationally, increasing risk of psychiatric disorders in offspring. Epigenetics provides a potential mechanism - adversity can chemically tag genes in a way that persists throughout life and is passed on.

  • Poor parenting in rats leads to epigenetic changes that alter brain development and stress responses in offspring. This cycle can propagate for generations through altered maternal behavior. Similar inheritance of stress susceptibility is likely in humans.

  • Epigenetics overturned the idea that acquired traits cannot be genetically inherited. It also challenged Freudian theories, showing how early adversity can directly wire the brain to confer lifelong stress sensitivity. Appropriate nurturing is important for developing a healthy stress response system.

  • While many factors can buffer humans from early stress, certain mind-based therapies may help reverse some of its brain and behavioral effects by strengthening prefrontal cortex control over emotional circuits.

  • Our interactions with the trillions of microbes in our gut are very important for our health and development. Early life stress like separation from parents can profoundly impact the gut microbiome.

  • Stress causes changes in gut function like contractions and secretion of juices that alter the living conditions for gut microbes. Stress hormones like norepinephrine also make pathogens more aggressive.

  • Studies in rhesus monkeys found that separation stress temporarily reduced protective gut bacteria like lactobacilli and increased pathogens. However, the effects were short-lived as monkeys adapted.

  • Further research found that alterations in the gut microbiome from poor maternal care led to long-lasting changes in brain development and behavior in offspring like anxiety and depression. This suggests the gut microbiome plays a role in stress-related psychiatric disorders.

  • Maternal stress during pregnancy can also impact the baby’s gut microbiome and brain development through several pathways. Stress reduces beneficial vaginal and gut bacteria in mothers and offspring. Changes to the metabolites produced by the baby’s microbiome may affect developing brain circuits.

  • Having a diverse gut microbiome early in life during pregnancy and birth seems important for healthy neurodevelopment. Modern births disrupting the natural transmission of microbes could impact this. Modulating the gut microbiome may help treat stress-related disorders involving the brain-gut axis.

  • A newborn’s gut microbiome is initially seeded by microbes from the mother’s vaginal microbiota during a vaginal birth. This provides the infant with beneficial bacteria like Lactobacillus to colonize the gut.

  • The mother’s vaginal microbes also give the baby enzymes to digest breast milk sugars.

  • C-section birth disrupts this process, as the baby’s gut is instead populated by microbes from the mother’s skin, doctors/nurses, and other infants. Important beneficial bacteria take longer to establish and harmful bacteria like Clostridium difficile are more common.

  • Disruptions to the early gut microbiome from C-sections or antibiotics may negatively impact brain development and increase risks of obesity, autism, and other disorders later in life.

  • Early life stress experienced by the mother, such as from cancer diagnoses or difficult births, can program the baby’s stress response system and alter gut and brain development through epigenetic changes and effects on the gut microbiome. This increases risks for anxiety, depression, IBS, and other stress-related disorders.

  • Therapies like CBT, hypnosis, mindfulness can help override adverse early life programming by changing brain wiring and stress responses. Medications may also help by modifying neurotransmitter systems impacted by early life stress. The goal is to provide new learning experiences that can offset dysfunctional brain-gut circuits programmed in early development.

  • Studies suggest our gut microbiota play a role in regulating emotions and mental state. Antibiotics that disrupt the gut microbiota can potentially induce anxiety and mood changes.

  • Lucy experienced severe panic attacks and increased anxiety months after taking two courses of antibiotics for sinus infections. Her gut microbiota may have been altered by the antibiotics, leading to digestive issues and later anxiety symptoms.

  • Animal studies show that treating mice with antibiotics changed their gut microbiota composition and made them less anxious in behavioral tests. Once the antibiotics stopped, their microbiota and behavior returned to normal.

  • Gut microbes are thought to produce neurotransmitters that influence brain signaling and emotion centers. Disrupting the microbiota via antibiotics may impact neurotransmitter production and mental well-being.

  • Maintaining a diverse, healthy gut microbiota through probiotic intake and fermented foods may help support mental health and reduce susceptibility to conditions like anxiety after antibiotic use. The microbiota plays an important regulatory role in the brain-gut connection and emotion regulation.

  • Studies in mice found that antibiotics that altered gut microbiota also reduced anxiety-like behavior. This effect was dependent on the vagus nerve, suggesting gut microbes communicate with the brain via this route.

  • Some gut microbes can produce GABA, a neurotransmitter that regulates emotional responses. Changes in gut microbes from conditions like liver disease can increase GABA levels in the brain, dampening cognitive and emotional functions.

  • Probiotics like Lactobacillus have been shown to reduce anxiety-like behavior in mice. This suggested probiotics containing GABA-producing bacteria could potentially treat anxiety in humans.

  • A clinical trial gave women a probiotic yogurt containing Bifidobacterium lactis or a non-fermented milk product. Brain scans found those eating the probiotic showed less reactivity in emotional brain regions during an emotion recognition task.

  • The probiotic did not significantly alter overall gut microbiota composition. It is hypothesized probiotic metabolites, or stimulation of gut serotonin by microbes, reached the brain through the blood or vagus nerve to influence emotional responses.

  • This was one of the first demonstrations that manipulating gut microbiota through probiotics can measurably change human brain function related to emotions. It opens up new possibilities for treating brain-gut disorders through nutrition and probiotics.

  • Depression and anxiety disorders often share similar symptoms like feeling nervous, irritable, having difficulty sleeping or concentrating. Around half of depressed patients also have symptoms of anxiety.

  • Studies in mice have shown that manipulating the gut microbiome through probiotics or other means can influence anxiety-like behaviors. This led to the hypothesis that gut microbes, termed “melancholic microbes”, may play a role in depression.

  • More recent human studies provide evidence supporting this hypothesis. The composition of depressed patients’ gut microbiomes can classify them as depressed. When fecal matter from depressed patients was transferred to mice, it altered the mice’s behaviors in depression-like ways.

  • Probiotic supplementation studies in humans have found preliminary evidence that certain probiotic strains may help improve mood, anxiety and psychological distress in depressed individuals. Larger clinical trials are still needed.

  • Stress can significantly alter the gut microbiome in ways correlated with depression-like behaviors in mice. Chronic stress is a risk factor for depression in humans, which may involve changes in the gut microbiota. Germ-free mice also show altered stress responses compared to normal mice.

So in summary, research is increasingly showing connections between the gut microbiome, stress responses, and depression/anxiety behaviors, though more human studies are still needed to fully understand these relationships. Manipulating the microbiome through diet or probiotics may eventually provide novel treatment approaches.

  • Chronic stress can harm gut health by promoting growth of pathogens and making gut more permeable. It can lead to prolonged GI symptoms after infection.

  • Mrs. Stone, a patient, developed long-lasting IBS symptoms after contracting traveler’s diarrhea during a period of chronic stress from her divorce and job.

  • Acute stress has protective effects on gut by strengthening defenses against infection, but too much chronic stress negates these benefits.

  • Positive emotions like happiness may also impact gut microbes through chemical signals from brain to gut. These signals could benefit gut health and protect against infection.

  • Our emotions and their impact on gut reactions can significantly alter the metabolites produced by gut microbes and the signals they send to our bodies, influencing thinking and feelings.

  • Abnormal gut microbes in people with conditions like autism could potentially impact behavior. Replacing abnormal microbes with healthy ones may help improve both GI and behavioral symptoms.

  • Jonathan, an autistic patient, saw his GI and behavioral symptoms worsen after antibiotics, suggesting a role for altered gut microbes. He was hoping a microbiome-focused treatment could provide relief.

  • The patient, Jonathan, suffered from gastrointestinal symptoms as well as obsessive thoughts and anxiety. He believed his symptoms were caused by parasites in his gut.

  • Testing of Jonathan’s gut microbiome revealed an altered microbiome composition similar to what is seen in autism and IBS. However, multiple factors like his restricted diet, stress, and IBS could have contributed to this.

  • Jonathan and his mother asked if he should try fecal transplantation or probiotics to alter his microbiome and help his symptoms.

  • The doctor explained that studies on these treatments for autism symptoms are ongoing, but several things could help Jonathan now. He recommended a more balanced diet including probiotic foods, herbal laxatives, and continuing CBT to help manage anxiety.

  • After two months following this treatment plan, Jonathan’s gastrointestinal symptoms improved significantly. He was less obsessed with parasites and more interested in understanding the link between diet, microbiome and health.

  • Antonio Damasio introduced the somatic marker hypothesis, which suggests emotions are linked to bodily states like rapid heartbeat or muscle tension. When we experience emotions, the brain stores memories of these bodily reactions.

  • The insular cortex can retrieve these “somatic markers” to recreate emotional feelings from memory without the actual bodily sensations. This creates a library of emotional experiences stored as gut feelings.

  • Recent research shows the gut microbiome plays a critical role in emotion processing. The bidirectional communication between the brain, gut and microbes forms a feedback loop where signals can be triggered from any part of the system.

  • Diet, stress and other factors can influence the gut microbiome and thereby modulate emotional development and responsiveness over a lifetime. While basic emotions are genetically determined, interactions with the gut microbiome help determine the intensity and uniqueness of individual emotional experiences.

  • Intuitive decision making, or gut feelings, have significantly influenced the author’s life path, from leaving his family business to pursue science to relocating his career internationally. While low-risk for him, intuitive decisions can be life or death for others.

  • Stanislav Petrov incorrectly received a warning in 1983 of an incoming nuclear strike from the US, but dismissed it as a false alarm. If he had confirmed it, it likely would have triggered a retaliatory strike and massive loss of life.

  • Initially, Petrov gave rational explanations for doubting the alarm, like the small number of missiles detected and issues with the new detection system. However, he later admitted he followed a “funny feeling in his gut” that it was erroneous.

  • Gut feelings and intuitions involve quickly processing vast personal wisdom and experiences outside of rational thought. The biological basis involves the brain’s salience system, which detects what demands attention.

  • Signals from the gut are encoded by receptors and sent to the brain, especially the insular cortex which processes interoceptive information. This results in consciously perceived gut feelings that inform our behaviors and sense of self. The insular cortex plays a key role in transforming raw sensations into refined, salient emotional gut feelings.

  • Our accumulated lifetime of gut feelings amount to a rich library of personal information that influences our decisions, emotions, and identity in important ways beyond rational thought alone. Petrov’s gut feeling likely saved the world from catastrophe.

  • Our brains store a vast amount of data collected every day related to personal experiences, emotions, motivations, gut feelings, etc. from birth onward. This database informs gut-feeling based decision making.

  • Early emotional memories associated with outcomes of decisions can reinforce certain gut feelings. Pleasant or unpleasant physical sensations like hunger, fullness, pain, pleasure get associated with these memories.

  • An experiment linking interoception (ability to perceive internal body sensations) and emotional intelligence found those best at tracking their own heartbeats scored highest on empathy. Greater interoceptive awareness predicts better emotional skills.

  • Early in life, gut feelings of hunger versus fullness lay the foundation for distinguishing good versus bad experiences. Proper feeding alleviates bad hunger feelings and promotes good feelings of satisfaction, influencing how infants perceive the world.

  • Gut microbes in breastfed infants may help calm emotions by metabolizing compounds like GABA, making infants feel good and relieving hunger pangs. Their role in early gut feelings and development is an area of emerging research.

  • The frontal insula and prefrontal cortex regions related to gut feelings are unusually large in humans compared to other species, likely enhancing our emotional and social abilities. Rare von Economo neurons in these areas may further differentiate human intuitive decision making.

Here is a summary of key points about fast, intuitive judgments based on the passages:

  • Intuitive judgments are made quickly through a system involving “intuition cells” or VENs (visceromotor effectors neurons) located in the brain’s insular cortex and cingulate cortex.

  • VENs allow for rapid communication between the brain’s salience network and other areas to adjust quickly to social situations based on gut feelings.

  • When meeting someone new, the brain quickly creates a mental model of them drawing on stereotypes, perceptions, and gut feelings before slower, reasoned judgments.

  • Humor and laughter help recalibrate intuitive judgments in changing situations by resolving uncertainty.

  • VENs may have evolved in mammals for complex social behaviors, intuition, and empathy. Abnormalities could contribute to autism spectrum disorders.

  • Animals lack the brain wiring for self-aware emotions like humans have, so their emotions are not truly equivalent despite appearances.

  • Gut feelings guide decisions away from negative past experiences and toward positive ones quickly, sparing us reliving all details.

  • Women may have more sensitive brain arousal systems attuned to physical and emotional feelings from experiences like childbirth.

  • While intuition evolves adaptively, it can be corrupted today by trauma, mood disorders, and targeted advertising exploiting basic gut feelings.

  • Frank experienced high anxiety and gastrointestinal symptoms at the thought of an upcoming meeting at a restaurant, due to catastrophizing - negatively predicting the worst possible outcome.

  • Catastrophizing prevents people from rationally assessing situations and is common in depression and chronic pain, where attention is narrowed to only negatives.

  • When deciding on wine, people use different decision-making strategies - rational/linear types base it on knowledge, sensory types on aroma/flavor detection, intuitive types on emotional memories of wine experiences.

  • Dreams may provide a glimpse of our internal “gut feeling videos” as brain regions processing emotion and memory are active during REM sleep while movement areas are turned off.

  • The author underwent Jungian psychoanalysis and dream analysis, which helped integrate emotional memories and connect with inner wisdom, leading to trusting gut feelings over external advice in decisions.

  • Dreams are one way to access gut feelings, hypnosis is another, less intensive approach than psychoanalysis.

  • Hunter-gatherer populations like the Yanomami of the Amazon potentially provide insights into our ancestral diet and microbiome, as their lifestyle and diet have changed little from our evolutionary past.

  • The author had a personal experience observing the Yanomami in the 1970s during a film expedition, renewing his interest in their lifestyle when later learning about studies comparing their microbiome to Western populations.

  • Some key dietary aspects of the Yanomami include a reliance on foraged foods like tubers, fruits, and game meat according to the local environment. They also consume virtually no added salt.

  • Studying traditional diets like the Yanomami can help inform debates around optimal modern diets and shed light on how our co-evolved gut microbiome may have functioned under an ancestral diet. Returning to such diets may help restore gut and brain health altered by today’s processed Western diets.

  • The author lived with the Yanomami people in the Amazon rainforest for 2 months to observe and study their lifestyle and diet.

  • The Yanomami diet consists mainly of plants like bananas, tubers, and greens. They also eat small amounts of lean meat from wild animals hunted in the forest, like monkeys, pigs and deer. Their food is prepared simply by roasting or baking, with no added fats.

  • This diet, rich in diverse plant foods and lean meat, is similar to the traditional diets of other indigenous groups like the Guahibos and Malawians that have been studied.

  • Research has found these groups have distinct gut microbiomes compared to Westernized populations, associated with their traditional plant-based diets low in processed foods and animal products.

  • Seasonal studies of the Hazda people also found their gut microbiomes varied according to seasonal changes in their traditional diet of fruits, tubers and meat.

  • While not advocating a Paleo diet, the author argues observing these groups provides insights into how diet impacts gut health and the co-evolution of humans and gut microbes.

  • Researchers analyzed gut microbiome data from 18 populations across 16 countries with varying lifestyles. They found gut microbial communities were closely related to modernization, with traditional populations having more diverse microbiomes.

  • Studies show people on typical Western diets have lost up to 1/3 of gut microbial diversity compared to traditional hunter-gatherer populations. This loss is comparable to the estimated 30% decline in global biodiversity since 1970.

  • Reduced gut microbiome diversity from Western diets could impact resilience against infections and disease, analogous to effects of reduced biodiversity in natural ecosystems.

  • Differences in gut microbiomes between traditional and Westernized populations were found in infants before dietary exposures, suggesting early life factors like breastfeeding play an important role in shaping lifelong microbiome development.

  • A longitudinal study tracked microbiome development in a breastfed infant from birth to age 2.5. It shifted from milk-digesting microbes to plant-fiber digesters even before solid foods, demonstrating influence of breastmilk.

  • Composition of breastmilk, particularly prebiotic human milk oligosaccharides, is driven by maternal diet and important for selectively feeding beneficial microbiota in infants’ developing guts. This early microbiome programming influences later health outcomes.

Here is a summary of the key points about how a new diet can alter the gut microbiota:

  • When your diet changes, it creates new living conditions for the microbes in your gut. This allows natural selection to act on the microbes, favoring those best adapted to the new diet. Microbes can also adapt their gene expression to new diets.

  • Studies have shown that switching to an animal-based high-fat diet or plant-based diet causes changes in gut microbiota composition within days, with animal-based diets inducing larger changes.

  • Microbes involved in processing plant fibers/carbohydrates decrease on animal-based diets, while bile acid-tolerant microbes increase. Fermentation metabolites also change accordingly.

  • The gut microbiota has an ability to rapidly shift composition and function in response to dietary changes, allowing humans to adapt to varying food availability throughout history.

  • However, one study found no clear differences between urban omnivores vs vegetarians/vegans, suggesting other environmental factors also shape microbiota composition over the long term.

So in summary, the gut microbiota can change significantly within days of a new diet through natural selection and microbial adaptation, but other lifestyle factors also play a role over the longer term.

  • The study compared the gut microbiota and metabolites of omnivores and individuals who had been on a vegan diet for at least 6 months.

  • They found only modest differences in gut microbiota composition between the two groups. However, metabolite profiles in blood and urine differed, reflecting the vegans’ lower protein/fat intake and higher carbohydrate intake.

  • The vegan diet led to increased metabolism of plant sugars by gut microbes and higher production of related metabolites. The omnivore diet led to higher levels of animal-sourced amino acids and lipids.

  • This shows that diet can change microbial metabolite production without largely altering microbiota composition.

  • Significant microbiota differences between global populations may require generations or early life exposures to develop.

  • Rural/traditional populations have a “permissive” microbiota that produces beneficial metabolites like short-chain fatty acids more efficiently from plant foods.

  • Western populations have a less efficient “restrictive” microbiota, even on plant-rich diets, possibly due to loss of key species like Ruminococcus bromii that break down resistant starches.

  • One’s microbiota composition is influenced by the environment they are born into, and changing diet later in life may not fully reshape it to more traditional configurations. However, metabolite profiles do change with dietary changes.

  • Plant-based diets have important health benefits for the gut-brain axis. Butyrate produced by gut microbes from fiber feeds the colon lining and prevents leakage. It also creates feelings of satiety to regulate food intake.

  • The gut microbiome produces over 500,000 metabolites that can influence the nervous system. Metabolites are produced via 7 million microbial genes, far more than the human genome.

  • An estimated 40% of circulating metabolites are produced by gut microbes, not human cells. The gut microbiome plays a key role in signaling between all bodily systems, including the brain.

  • A Western diet high in animal fat and refined sugars disrupts this microbial signaling and promotes chronic low-grade inflammation, impacting brain regions that control appetite. This reprograms the gut-brain-microbiome axis in an unhealthy way.

  • Our modern diet departs dramatically from what humans evolved with and is overwhelming our defense systems. Livestock are also altered through confinement and unnatural feed, changing the composition of animal products. Evolution has not caught up to these rapid dietary changes.

  • A diet high in animal fat can harm the brain by triggering chronic low-grade inflammation even before a person becomes obese. A single high-fat meal is enough to switch on the immune system in the gut.

  • Regular consumption of high-fat animal foods can cause persistent low-grade inflammation and impair the gut-brain axis that regulates appetite. This reduces the brain’s sensitivity to satiety signals.

  • Gut microbes play a key role. A high-fat diet alters the gut microbiome in a way that increases inflammation-causing molecules like LPS that breach the gut barrier and activate the immune system. This systemic inflammation impacts appetite regulation in the brain.

  • Studies in animals show that altered gut microbes can transfer metabolic effects like obesity and impaired appetite control to germ-free recipients. The gut microbiome influences the inflammatory response to diet that affects the brain.

  • A high-fat diet can also impair appetite-regulating receptors and sensitivity in the gut wall itself, reducing the gut’s communication with the brain about satiety. This contributes to overeating and weight gain.

  • Several studies in animals and humans have found that eating fatty and sugary “comfort foods” can help reduce stress and anxiety by down-regulating the stress response system. Stressed rats and rats that experienced early adversity ate more of these foods and had reduced stress levels.

  • A study at UCLA found that women who regularly ate comfort foods when stressed had lower stress responses and cortisol levels when exposed to an acute stressor in the lab. However, these women also tended to be more obese.

  • Another study had subjects ingest fat while listening to sad music. They reported improved mood and showed reduced emotional brain responses, suggesting fat can have a comforting effect by stimulating gut signals.

  • Modern high-fat, high-sugar diets can overwhelm the brain’s reward and appetite control systems, which evolved for limited food availability. This remodeling of brain systems, coupled with easy access to highly palatable foods, can lead to food addiction in vulnerable individuals.

  • About 20% of obese people show signs of food addiction, craving certain foods that strongly activate the brain’s reward system through conditioning. Viewing food ads can trigger cravings by stimulating this reward system.

  • Modern industrial agriculture and food production negatively impact the gut microbiome and brain-gut connection in both humans and farm animals.

  • Animals raised on factory farms live in deplorable conditions, are fed unnatural diets like corn instead of grass, and must be treated continuously with antibiotics due to disease. This chronic stress and inflammation likely affects their gut microbiomes and the health of the foods produced.

  • Industrial crop farming relies on monocultures and heavy use of fertilizers and pesticides that disrupt natural soil and environmental diversity. This could impact microbiomes in bees, soil, and humans through the food system.

  • The collateral damage of widespread chemical use like glyphosate on weed resistance is largely unknown but could contribute to increases in diseases like obesity, autism, Alzheimer’s through impacts on gut microbiomes.

  • Americans have also consumed increasing amounts of food additives like salt, sugar and fat without proper long-term safety testing, which did not consider impacts on the gut microbiome and brain health. More research is needed on these effects.

The passage discusses several common food additives and their potential negative health effects:

  • Artificial sweeteners like saccharin, sucralose and aspartame may increase risk of metabolic diseases like diabetes. Studies in mice showed they altered gut microbiota and caused glucose intolerance. Human studies also linked them to higher weight and blood sugar.

  • Food emulsifiers like polysorbate 80 and carboxymethylcellulose disrupted the gut mucus layer in mice studies, allowing bacteria access to the gut lining and promoting inflammation, obesity and metabolic syndrome. They also changed gut microbiota composition.

  • “Vital gluten,” a purified gluten additive, is added widely to processed foods. While its dangers are clear for the 1% with celiac disease, excessive gluten consumption may also negatively impact gut health and immunity.

  • None of these short term toxicity tests can inform about long term effects on brain health. Overall, many common additives may promote low-grade inflammation and metabolic changes by altering gut microbiota in ways that endanger the body and brain. More research is still needed.

  • Some people have a sensitivity or allergy to gluten, a protein found in wheat, barley and rye. This can cause digestive issues and other symptoms. A gluten-free diet helps alleviate these issues.

  • However, recent claims that gluten is broadly harmful even without sensitivity or celiac disease lack strong scientific evidence. French and Italian diets, which include breads and pastas, do not seem to cause issues.

  • Linda Schmidt experienced digestive issues like IBS that improved on a gluten-free diet, even though she did not have celiac disease. This may indicate non-celiac gluten sensitivity, a poorly understood condition.

  • Factors like a high-fat diet, artificial sweeteners, and food emulsifiers may alter gut sensors and the gut-brain axis, causing new sensitivities in sensitive individuals.

  • Constipation is a common early symptom of Parkinson’s disease, which may begin in the gut years before neurological symptoms. The disease may spread from the gut to the brain through the vagus nerve.

  • Gut microbiota changes are found in Parkinson’s patients and linked to diet. Shifting to a plant-rich diet through foods like the Mediterranean diet may help prevent or slow the disease’s progression by maintaining a healthy microbiome.

The passage describes a visit to the Adriatic coast region of Italy. It discusses the rolling hills dotted with sunflowers, vineyards, olive trees and wheat fields that slope down to the sea. The scenery reflects the diverse local agriculture.

While dining with friends at a restaurant near the Piazza del Popolo, the group is served a variety of small dishes made from local ingredients, including lasagna, brisket, vegetables, octopus and cheeses. Wine is produced from organically grown grapes in the area.

Marco explains that most foods come from within 50 miles, including fish, cheeses, olives, fruit and game meats. Meals have strong seasonal components based on availability. Wines also vary based on soil composition and proximity to the sea.

The town of Fermo has a long history of agriculture dating back to Benedictine monks in the 9th century. Their farming practices and writings still influence the region today.

The passage discusses the health benefits of the traditional Mediterranean diet as confirmed by research studies. It attributes benefits to antioxidants, polyphenols and anti-inflammatory effects from foods like olive oil. Finally, it describes observing the annual olive harvest from centuries-old trees that produce higher polyphenol oil.

  • traditional Mediterranean, Japanese, Korean, and other diets promote gut and overall health due to high levels of polyphenols and fiber from plants like nuts, berries, olive oil. These support gut microbiome balance.

  • gut microbiome plays a key role in translating these diets into health benefits by interacting with the brain via the gut-brain axis. Factors like social connectedness around mealtimes also likely contribute.

  • optimal health involves physical, mental, emotional and social well-being as well as peak performance. Fewer than 5% of Americans experience this.

  • traits of optimally healthy superagers include resilience, curiosity, positivity, ability to bounce back from adversity, and maintaining productivity into old age.

  • most people experience “suboptimal health” with mild symptoms like fatigue, weight gain, digestion issues but no clear disease diagnosis. Lifestyle factors like diet can help optimize gut microbiome and move such individuals toward a healthier state.

  • Individuals may experience frequent digestive issues, fatigue, pain, and limited energy for social activities due to chronic stress and wear and tear on the body (allostatic load).

  • This “predisease state” can increase systemic inflammation, even if diagnostic criteria for specific illnesses are not met. Biomarkers of inflammation may be elevated.

  • Factors like chronic stress, high-fat diets, and leaky gut can combine to further exacerbate inflammation through impacts on gut microbes and the brain-gut axis.

  • Over time, this inflammatory state from diet, stress, and gut dysfunction could potentially push individuals from a predisease state into serious health issues like metabolic syndrome, heart disease, cancer, or neurological diseases.

  • Maintaining a healthy gut microbiome through diet, stress management, and resilience can help minimize inflammatory risks and support optimal health long-term. Diversity in gut microbes supports stability against disruptions.

  • Exposure to antibiotics can reduce gut microbial diversity and be difficult to recover from. Antibiotics are easy to decrease diversity with but hard to increase diversity above established early life levels through probiotics or diets later in life.

  • Early life, especially the first 3 years, is crucial for establishing a person’s long-term gut microbiome composition and diversity. Factors like stress, antibiotics, and diet during this period can permanently impact the microbiome.

  • Maintaining a diverse and resilient gut microbiome protects against disease by making the ecosystem stable and able to recover from perturbations. Those with less diverse or resilient microbiomes may be more vulnerable to health issues.

  • Interventions to optimize the microbiome like probiotics or diets are generally not effective when done in isolation. A comprehensive lifestyle approach is needed that addresses diet, stress, and other contributing factors.

  • The gut-microbiome-brain connection is most sensitive during early life development, adulthood, and old age. Early life shaping of this connection can impact later life health and disease risk.

  • Understanding the gut microbiome could lead to personalized treatments and disease screening tools. But more research is still needed to determine how to restore or maintain a healthy microbiome.

Here are the key points about manipulating the gut microbiome from a health perspective:

  • Practice organic farming of your gut microbiome by choosing high-quality, nutritious foods and limiting unhealthy additives.

  • Cut down on animal fat, as it promotes obesity, disease risk, and negatively impacts brain health.

  • Maximize gut microbial diversity by eating a variety of plant fibers and prebiotics from plant foods.

  • Eat fermented foods and probiotics to support gut microbial diversity, especially during times of stress or antibiotic use.

  • Avoid mass-produced, processed foods and maximize organically grown options to limit exposure to harmful additives.

  • Be mindful of prenatal nutrition and stress, as it can impact fetal and child brain development via the gut-brain axis.

  • Eat smaller portions and consider periodic fasting to manage calories/fat intake and potentially starve bad gut microbes.

The overall approach is to manage diet, lifestyle and food choices in a way that cultivates a diverse, healthy gut microbiome through nutrition and limiting exposure to harmful substances.

  • Fasting may have positive effects on brain function and well-being by resetting the gut microbiome and communication between the gut and brain.

  • When the stomach is empty, contractions sweep microbes from the small intestine to the colon. This ‘migrating motor complex’ helps regulate microbes.

  • Fasting may also reset appetite control mechanisms and sensitivity to hunger/fullness hormones.

  • Negative emotions like stress can harm the gut microbiome and increase intestinal permeability. They affect microbial composition and metabolites produced.

  • It’s best to avoid eating when stressed, angry or sad as it worsens gut reactions and imbalances the gut-brain axis.

  • Positive emotions like happiness may benefit the gut microbiome by producing different metabolites that influence the brain.

  • Social interactions around meals likely provide gut benefits through promoting connectedness and well-being.

  • Mindfulness can help regulate emotions and tune into gut feelings to understand bodily states.

  • Exercise has clear brain and likely gut microbiome benefits through various pathways like reducing stress.

The passage advocates moving from a passive approach to medication to taking responsibility for optimally functioning of our brain-gut axis. It suggests becoming “ecological systems engineers” with knowledge of how gut microbiota interact with the brain. The goal is to understand these interactions and maximize our health by getting the gut-microbiota-brain connections working at peak effectiveness. This proactive approach would involve gaining knowledge and motivation to influence our internal systems for better health outcomes.

Here is a summary of the references provided:

The references discuss various connections between the gut microbiome and human health and behavior. Key topics covered include:

  • How the gut microbiome is established early in life and can be influenced by factors like birth method and breastfeeding.

  • Associations between gut microbes and conditions like obesity, depression, inflammation, and brain development/behavior. Altering the microbiome through diet or other means can impact these.

  • The gut as having its own nervous system (enteric nervous system) that communicates bidirectionally with the brain. Microbes influence neurological and neuroendocrine pathways.

  • Potential psychobiotic effects of certain microbes on mental health conditions. Probiotics can change brain activity and behavior.

  • Mechanisms like gut permeability, neurotransmitter production, and immune responses through which microbes interface with host physiology.

  • Differences in microbiome composition linked to diets like Mediterranean, high-fat Western, vegetarian, etc. Diet influences microbe-mediated disease risk.

  • Applications for microbiome research, like developing microbiota-based diagnostics/therapies or probing complex host-microbe interactions in health and disease.

In summary, the references cover research establishing the gut microbiome as a critical interface between environmental, dietary, and psychosocial factors and physiological/mental health outcomes in humans.

Here is a summary of the key points from the cited papers:

  • Mayer et al. papers from 2000-2015 discuss the neurobiology of stress and gastrointestinal disease, the gut-brain axis, the role of gut microbes in brain function and disorders, and how probiotic consumption can modulate brain activity.

  • Sender et al. 2016 re-evaluate the ratio of bacterial to host cells in humans.

  • Schnorr et al. 2014 characterize the gut microbiome of Hadza hunter-gatherers.

  • Smits et al. 2017 find seasonal variations in the gut microbiota of Hadza foragers.

  • Pelletier et al. 2015 show the Mediterranean diet is linked to preserved brain structural connectivity in older adults.

  • Psaltopoulou et al. 2013 find a meta-analysis association between the Mediterranean diet and reduced risk of stroke, cognitive impairment, and depression.

  • Vals-Pedret et al. 2015 find a randomized clinical trial linking the Mediterranean diet to reduced age-related cognitive decline.

  • Moss 2013 summarizes links between diet, namely salt, sugar and fat, and health outcomes like heart disease.

  • Relman 2015 discusses the future of personalized medicine with human microbiome characterization.

Here are summaries of the papers:

Van Oudenhove et al. (2011) found that fatty acids can help attenuate negative emotional and neural responses to sadness in humans by stimulating gut-brain signaling.

Volkow et al. (2013) proposed that obesity has addictive properties and suggested the addictive dimension of obesity should be considered when developing treatment strategies.

Walsh (1975, 1998) discussed gastrin, a peptide hormone that stimulates stomach acid secretion and investigated peptides as regulators of gastric acid secretion.

Weltens et al. (2014) examined the link between fat signaling, reward, and emotion and proposed mechanisms by which fat signaling and reward systems are connected to emotions.

Wu et al. (2011, 2016) studied the link between long-term dietary patterns and gut microbial communities (enterotypes) and compared metabolomics of vegans and omnivores, finding constraints on diet-dependent gut microbiota metabolite production.

Yano et al. (2015) found that gut bacteria can regulate host serotonin production in mice.

Yatsunenko et al. (2012) investigated the human gut microbiome across age and geography, finding microbiome variation with age and geography.

Zeevi et al. (2015) developed a model to personalize nutrition by predicting glycemic responses to foods for individuals.

Zheng et al. (2016) found that gut microbiome remodeling in mice induced depressive-like behaviors through pathways mediated by the host’s metabolism.

Here is a summary of the key points about diet and the gut microbiome from the passage:

  • The diets of hunter-gatherers, Mediterranean diet, and North American diet are discussed in terms of their impact on the gut microbiome.

  • Industrial agriculture, pesticides/chemicals, processed foods, and high animal fat are said to negatively impact the gut microbiome.

  • Plant-based diets, natural/organic foods, fiber, and targeting the gut microbiome through diet are proposed to have beneficial effects.

  • Specific aspects of diet discussed include portion size, artificial sweeteners, emulsifiers, gluten, and wheat allergy.

  • The role of emotions, stress, antibiotics, breast milk, exercise, fertility, and lifespan/aging are mentioned in relation to shaping the gut microbiome.

  • Maintaining a diverse and healthy gut microbiome is emphasized through diet, lifestyle modifications, and novel therapies.

  • The gut microbiome is linked to digestive health, immunity, metabolism, brain function, social behavior, depression, anxiety, appetite, obesity, and general physical and mental well-being.

In summary, the passage covers the control and impact of different dietary patterns on the gut microbiome and its connections to overall health and disease. Maintaining a diverse microbiome through diet is highlighted as important.

  • The gut microbiome influences neurotransmitters, mood, energy levels, hunger signals, immune function and inflammatory responses. Microbes communicate with the brain via hormones, neurotransmitters and the vagus nerve.

  • Stress impacts the gut through corticotropin-releasing factor which can increase permeability and susceptibility to infections. Early life stress can alter the gut microbiome long-term. Managing stress is important for gut and brain health.

  • Diet greatly shapes the gut microbiome. A traditional Mediterranean diet with plant fibers promotes diversity while a high-fat Western diet allows opportunistic pathogens to thrive and increase inflammation. Prebiotic and probiotic supplements can benefit the microbiome.

  • Conditions like IBS, anxiety, depression, Parkinson’s and Alzheimer’s are linked to alterations in the gut microbiome. Therapies aiming to optimize the microbiome like dietary changes, probiotics and stress management techniques may help treat or prevent these issues.

  • An integrated approach considering diet, lifestyle, environment and mind-body therapies offers the best strategy for long-term gut and brain health optimization. Early investments are most impactful for long-term resilience and disease prevention.

Here is a summary of the reviews and background provided:

The book “The Mind-Gut Connection” by Dr. Emeran Mayer details the intricate connections between the brain, gut, and gut microbiome. It explains how the enteric nervous system functions as a “second brain” that communicates biochemically with trillions of bacteria in the gut. This interaction, termed “microbe-speak”, likely influences behaviors, emotions, decisions, and possibly mental health.

The reviews praise Mayer as an expert in this field and call the book the best layperson guide to the subject so far. It synthesizes recent microbiome research with patient stories and recommendations for improving communication between the two brains through diet, lifestyle, and mind-body techniques. The goal is to attain optimal health and wellness through a holistic understanding of this mind-gut relationship.

The reviewers believe the book will interest those seeking to better understand how their body works and how to train the minds and gut for better health. It provides authoritative yet accessible information on this emerging area linking brain, gut and microbes.

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