Colleen Cutcliffe (on the microbiome)

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• Antibiotic use in early life, particularly in infants, is strongly linked to later development of conditions like obesity, diabetes, allergies, depression, asthma, ADHD, and Crohn's disease because it severely damages the developing microbiome.  Copied to clipboard!
• The human microbiome is a vast ecosystem, representing 1-3% of body mass and possessing hundreds of times more genes than the human genome, and its study is a relatively new science, gaining significant traction only in the last 25 years due to DNA sequencing technology.  Copied to clipboard!
• A healthy gut is defined as a resilient gut, and key strains like *Akkermansia mucinophila* are crucial for maintaining the gut lining structure, being one of the key strains lost with age, and are primarily found in breast milk during early life.  Copied to clipboard!
• The beauty of the microbiome is that it is constantly changing and everything within it is recoverable, offering hope where genetics might suggest predisposition.  Copied to clipboard!
• The gut and brain are intimately connected via the vagus nerve, and gut neurons produce key neurotransmitters like serotonin, dopamine, and GABA, suggesting the gut can be targeted for neurological conditions like Parkinson's and Alzheimer's.  Copied to clipboard!
• Animal studies suggest that supplementing with *Akkermansia* can resolve stress and anxiety behaviors, sometimes performing better than Prozac by increasing GABA production.  Copied to clipboard!
• The hosts debate the ethical obligation to inform others when content, particularly visual media, is suspected to be AI-generated, contrasting this with respecting personal beliefs like religion where truth may be secondary to peace or contentment.  Copied to clipboard!
• The value of truth versus peace in life depends on the established goal, suggesting that one should pursue their goal (whether knowledge, peace, or connection) in a way that allows them to meet it.  Copied to clipboard!
• The conversation concludes with personal anecdotes about the effects of the microbiome product discussed with Colleen Cutcliffe and a lengthy tangent on the subjective value and authenticity of collectibles like Beanie Babies.  Copied to clipboard!

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Introduction of Guest Colleen Cutcliffe

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(00:00:23)

• Key Takeaway: Colleen Cutcliffe is a microbiome scientist and health advisory board member for Johns Hopkins Bloomberg School of Public Health, co-founder of Pendulum Therapeutics.
• Summary: Dr. Colleen Cutcliffe is introduced as a microbiome scientist and CEO/co-founder of Pendulum Therapeutics. The hosts note their long-standing interest in the microbiome space, specifically mentioning fecal transplants. Pendulum Therapeutics creates probiotics and prebiotics with a high degree of oversight.

Microbiome Importance and Future

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(00:01:50)

• Key Takeaway: The microbiome is fascinating, with increasing links being established between gut microbes and various ailments.
• Summary: The discussion highlights the incredible nature of the microbes in the digestive system and their role in bodily functions. There is an exciting future ahead as researchers link more ailments directly to microbiome health. The guest’s company, Pendulum, is focused on developing microbiome supplements.

Personal Background and COVID Impact

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(00:04:41)

• Key Takeaway: The guest’s husband is an ER physician, providing a firsthand perspective on the initial chaos and exposure during the COVID-19 pandemic.
• Summary: The conversation briefly shifts to the guest’s background, noting her husband is an ER physician who considered isolating himself during early COVID-19. The guest shared that her company almost failed during the pandemic due to the stress and uncertainty.

Guest’s Academic and Career Path

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(00:07:07)

• Key Takeaway: Dr. Cutcliffe’s PhD is in biochemistry and molecular biology, with prior research focusing on skin cancer and Wilm’s tumors.
• Summary: Dr. Cutcliffe grew up in Atlanta and attended Westminster High School before earning her PhD in biochemistry and molecular biology. Her postdoctoral work involved searching for markers for children’s kidney tumors, and she later worked in pharma developing Parkinson’s drugs.

Inspiration for Microbiome Company

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(00:16:19)

• Key Takeaway: A study linking early-life antibiotic use to later obesity and diabetes, combined with her premature daughter’s health issues, prompted Dr. Cutcliffe to start Pendulum Therapeutics.
• Summary: The catalyst for starting the company was a paper showing that infants on many antibiotics later developed obesity and diabetes. A Mayo Clinic study expanded this link to include allergies, depression, asthma, and ADHD. Dr. Cutcliffe realized she could use her technical knowledge to help millions, including her daughter.

Microbiome Basics and Sterilization

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(00:17:20)

• Key Takeaway: The human microbiome is an ancient, co-evolved ecosystem of bacteria, viruses, and fungi, and modern society’s obsession with sterilization inadvertently harms this beneficial system.
• Summary: The science of the microbiome is relatively young, exploding in publications since 2000 due to sequencing technology. Humans have as many microbes as cells in the digestive tract, representing 2-6 pounds of body mass. Over-sanitizing with antibacterial products throws out beneficial microbes along with the harmful ones.

Hyena Microbiome Research Example

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(00:20:32)

• Key Takeaway: Hyenas possess an oral microbiome with antibiotic-like properties that allow them to safely consume rotting meat, a trait scientists are researching for new antibiotics.
• Summary: Many animals rely entirely on their gut microbes for digestion, but hyenas offer a unique example in their oral microbiome. A scientist studying hyena mouths was bitten, refused antibiotics based on his knowledge of their ‘clean’ mouth flora, and healed without infection. This highlights the powerful, protective capabilities of certain microbial communities.

Human Repulsion to Feces

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(00:22:50)

• Key Takeaway: Humans are uniquely repulsed by feces compared to other primates, a trait hypothesized to have evolved when humans began living in dense, settled civilizations.
• Summary: The hosts question why humans are uniquely repulsed by feces when many animals (like dogs sniffing butts or horses rolling in mud) benefit from exposure. This repulsion likely developed as a protective mechanism when humans started living in close quarters, concentrating waste in one area.

C. diff and Fecal Transplants

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(00:23:53)

• Key Takeaway: Fecal Microbiome Transplants (FMTs) are the most successful treatment for recurrent C. difficile infection, achieving success rates over 90% by flooding the gut with competing microbes.
• Summary: C. difficile overgrowth occurs when antibiotics wipe out competing microbes, allowing C. diff to reproduce unchecked, which can be fatal. Standard antibiotic treatment for recurring C. diff is ineffective as it trains the bacteria to be more resilient. FMTs work by reintroducing the necessary competitors, making it an incredibly effective intervention.

Microbiome Link to Obesity and GLP-1

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(00:25:21)

• Key Takeaway: Obesity and diabetes are strongly linked to the absence of specific gut microbes that naturally stimulate the body’s GLP-1 production for insulin regulation and satiety signaling.
• Summary: Two specific microbial strains stimulate the body’s natural GLP-1, which signals the brain to feel full and aids in insulin release. Individuals with obesity or Type 2 diabetes are often missing these strains. Depletion can be caused by antibiotics, poor diet (lack of fiber/polyphenols), stress, aging, travel, and hormonal changes like menopause.

Gut Resilience and Akkermansia

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(00:28:27)

• Key Takeaway: Gut resilience allows the system to withstand assaults, and Akkermansia mucinophila is the only known strain that maintains the gut lining structure, which resembles a wooden fence with weakening glue over time.
• Summary: A resilient gut can handle assaults, but depletion leads to issues like food sensitivities often associated with ’leaky gut syndrome.’ Akkermansia mucinophila is vital for repairing the gut lining by replacing the ‘glue’ (tight junctions) between epithelial cells. This strain is one of the key ones lost during aging.

Supplementation and Delivery Challenges

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(00:35:04)

• Key Takeaway: Effective probiotic supplementation requires both the correct, viable strain (like Akkermansia) and specialized enteric-coated, time-delayed release capsules to survive stomach acid and reach the distal colon.
• Summary: Many supplements on the market claiming to contain specific strains like Akkermansia do not actually contain them upon sequencing. Furthermore, probiotics must be protected from stomach acid to reach the lower intestine where they function. Taking probiotics with food can help decrease stomach acidity and aid survival.

Engine and Fuel Analogy

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(00:36:34)

• Key Takeaway: Optimizing the microbiome requires a ‘one-two punch’: the right microbial engine (strains like Akkermansia) and the right high-octane fuel (fibers and polyphenols).
• Summary: The microbiome needs both the correct bacterial strains and the specific nutrients to feed them for peak performance. Fibers and polyphenols found in foods like berries and olive oil serve as this essential fuel. Supplementing fiber is often necessary because achieving adequate intake through diet alone is difficult.

Shame, Environment, and Cravings

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(00:37:46)

• Key Takeaway: External environmental factors, including internal microbial environments, are statistically more successful levers for change than relying solely on willpower, which is often accompanied by misplaced shame.
• Summary: The shame associated with shortcomings, like sugar addiction, often prevents people from recognizing the environmental factors at play. Products that stimulate natural GLP-1 can reduce cravings by correcting the microbial signaling to the brain, leading to epiphanies about identity versus environment.

Initial Microbiome Seeding

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(00:39:45)

• Key Takeaway: The initial seeding of a baby’s microbiome primarily occurs through vaginal delivery and subsequent feeding via breast milk, which contains both the necessary strains and the prebiotics (food) to feed them.
• Summary: Babies are mostly sterile in the womb, receiving their first major microbial seeding during vaginal delivery, followed by breast milk. C-section delivery bypasses the vaginal seeding, which is a known depletion event, though modern formulas attempt to compensate with prebiotics. Heating breast milk too high can destroy beneficial microbes like Akkermansia.

Breast Milk Handling Caution

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(00:45:33)

• Key Takeaway: Heating frozen breast milk on high heat degrades proteins and kills beneficial microbes like Akkermansia.
• Summary: Heating frozen breast milk too quickly or at high temperatures degrades essential proteins. This high heat also kills the beneficial microbes, such as Akkermansia, present in the milk. This was identified as a significant learning lesson for the speaker.

Microbiome Recoverability and Guilt

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(00:46:12)

• Key Takeaway: Early life events like C-sections or formula feeding are recoverable through microbiome optimization, as the gut ecosystem is constantly changeable for the better.
• Summary: No one should feel guilty about early life decisions like C-sections versus vaginal birth or formula versus breastfeeding. These are early-life events where optimization is possible. The microbiome is beautiful because it is constantly changing, meaning there is always hope for improvement.

Gut-Brain Axis Communication

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(00:46:40)

• Key Takeaway: The gut-brain connection is facilitated by the vagus nerve, through which the gut sends neurotransmitters like serotonin, dopamine, and GABA directly to the brain.
• Summary: The brain and gut are part of one complex, communicating system, connected by the vagus nerve. The gut produces significant amounts of neurotransmitters, including serotonin, dopamine, and GABA, which can signal the brain via this nerve highway. Furthermore, gut neurons constantly regenerate, unlike brain neurons.

Gut Link to Neurodegenerative Disease

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(00:47:48)

• Key Takeaway: Plaques associated with Parkinson’s and Alzheimer’s disease appear first in gut neurons before migrating to the brain, suggesting gut targeting as a preventative measure.
• Summary: The speaker’s early research focused on Parkinson’s disease, noting that the characteristic brain plaques also show up in gut neurons first. This suggests a theory where misfiring gut neurons send signals that lead to brain pathology. Targeting the gut could potentially prevent the onset of conditions like Parkinson’s and Alzheimer’s.

Akkermansia vs. Prozac in Mice

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(00:49:21)

• Key Takeaway: In a mouse model, Akkermansia supplementation reversed stress and anxiety behaviors (immobility in water, lack of curiosity, low activity) as effectively as, and sometimes better than, Prozac.
• Summary: A study compared the effects of Akkermansia and Prozac on stress-induced mice across three behaviors: swimming immobility, object exploration, and general activity levels. Both Akkermansia and Prozac restored these behaviors to levels seen in healthy, unstressed mice. The theory is that Akkermansia helps by producing large amounts of the stress-reducing neurotransmitter GABA.

Microbiome Intervention and Medication

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(00:51:40)

• Key Takeaway: Customers, with physician guidance, have successfully reduced their reliance on prescription drugs by improving their microbiome through supplementation.
• Summary: While Pendulum Therapeutics has not conducted clinical trials specifically on drug reduction, customers have reported lowering their medication dosages under physician supervision by improving their gut health. This suggests that optimizing the microbiome can complement or potentially reduce the need for certain pharmaceuticals.

GLP-1 Drugs and Homeostasis

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(00:52:14)

• Key Takeaway: The body’s natural tendency toward homeostasis means that long-term use of drugs like GLP-1s may lead to the body becoming ‘deaf’ to the signal, requiring increased dosage over time.
• Summary: The speaker is not anti-GLP-1 drugs but is cautious about using them for decades, preferring to use all available tools, including microbiome support. The body is designed for homeostasis, often adjusting back to a baseline, which is why external signals like opiates or insulin can eventually require higher doses. Long-term repercussions for healthy individuals using GLP-1s are currently being determined through ongoing experimentation.

Microbiome as Public Health Tool

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(00:54:51)

• Key Takeaway: Since 88% of people are metabolically unhealthy, optimizing the microbiome offers a crucial tool to combat chronic conditions like diabetes and heart disease, independent of diet and exercise.
• Summary: The global problem of metabolic unhealthiness, affecting 88% of people, persists despite current interventions like diet and exercise, which are not always simple to maintain. The microbiome unlock suggests that even those who eat well and exercise may benefit from intervention due to lost microbes. A 90-day microbiome trial often results in reduced food cravings and sustained energy as the primary positive outcomes.

Artificial Sweeteners and Microbiome

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(00:58:40)

• Key Takeaway: While studies show artificial sweeteners change the microbiome, the long-term clinical meaning of those changes for individual health outcomes is not yet established.
• Summary: There is evidence that artificial sweeteners alter the composition of the microbiome. However, the long-term consequences of these changes—whether they are better or worse for an individual—remain unknown. The data needed to draw definitive conclusions about the impact of these sweeteners is still emerging.

Halle Berry’s Investment and Packaging

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(00:59:13)

• Key Takeaway: Halle Berry became an investor in Pendulum Therapeutics after experiencing a significant, sustained drop in her A1C levels from using their product.
• Summary: Halle Berry, who manages diabetes, saw her A1C drop by one to two points after using the product, which is a substantial clinical change. She joined the company to help build the brand, emphasizing that packaging and brand experience are critical for consumer adoption, even when the science inside is superior. The initial Petri dish-inspired packaging failed due to usability issues, leading to a successful redesign based on customer feedback.

Probiotic Science vs. Marketing

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(01:04:27)

• Key Takeaway: Pendulum Therapeutics differentiates itself by investing heavily in science, being the only probiotic company invested in by the Mayo Clinic and the number one GI doctor-recommended Akkermansia brand.
• Summary: Many competing probiotics have similar ingredients despite having better packaging and marketing. Pendulum’s strength lies in its scientific rigor, evidenced by multiple investments from the Mayo Clinic. They are unique in bringing deep scientific discovery to consumers rather than pursuing only a drug pathway, making them the first probiotic shown to help with diabetes.

AI Video Detection and Ethics

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(01:23:08)

• Key Takeaway: The primary giveaway for AI-generated videos is often the unnatural dialogue patterns and rapid-fire, overly coherent reactions of bystanders, rather than just the visuals.
• Summary: The speaker suspects many shared videos, like the moose fighting the bear or the 3D street murals, are AI-generated due to unnatural dialogue and reaction speeds. The ethics of pointing out AI fakery are debated, but the speaker generally prefers not to let people believe untruths, except perhaps in areas like religion. The physics of 3D murals also suggest they only appear real from a specific camera vantage point.

AI Video Authenticity Debate

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(01:33:17)

• Key Takeaway: The potential for AI-generated videos to influence life choices necessitates a clear standard for disclosing their artificial origin.
• Summary: The fear surrounding AI-generated content stems from its potential to guide significant life decisions based on fabricated information. A consensus is sought on whether one should always reveal suspected AI content, even if it brings temporary happiness to the recipient. The importance of tracing content back to its source to verify reputation is highlighted as a defense against deception.

Truth vs. Peace in Beliefs

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(01:36:47)

• Key Takeaway: The ultimate goal—whether full knowledge or peace—should dictate the imperative to challenge another person’s beliefs.
• Summary: The value of truth must be weighed against the value of peace, contentment, and connection when evaluating information. One should only advocate against a perceived lie if that lie negatively impacts the self, otherwise, humility suggests accepting different realities. The inherent subjectivity of reality means no single perspective is entirely objective.

Microbiome Product Follow-up

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(01:39:40)

• Key Takeaway: Early personal experience suggests the microbiome supplement may reduce chronic pain, such as severe arthritis discomfort.
• Summary: The host reports cautiously optimistic personal results after consuming the probiotics, noting no adverse effects when reintroducing bread. His mother experienced a significant reduction in hip arthritis pain, dropping from an 80 to a 15 level of discomfort within eight days. The host also mentions having the GLP1 product but has not yet administered it due to refrigeration requirements.

Bizarre Food Combinations Anecdote

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(01:41:35)

• Key Takeaway: Extreme layering of disparate food items, like putting wings and salsa on a frozen pizza, suggests a lack of palate refinement rather than creativity.
• Summary: The host describes his father’s habit of topping a frozen pizza base with numerous unrelated items like chicken wings, salsa, and chow mein noodles. This practice is contrasted with the culinary principle of layering complementary flavors (salt, fat, acid). Such extreme combinations might result in a flavor profile that tastes like nothing, similar to mixing too many colors to create black.

Palos Verdes Research Fact Check

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(01:44:54)

• Key Takeaway: The longevity research study known as the 90-Plus Study is conducted in Laguna Woods, formerly Leisure World, not Rancho Palos Verdes.
• Summary: The 90-Plus Study, originating from UC Irvine, tracks residents in Laguna Woods who live into their 90s to determine longevity factors. The community was originally named Leisure World before being renamed Laguna Woods. These two locations are geographically distinct, separated by 28 miles, clarifying the location of the research.

First Generation Immigrant Definition

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(01:48:34)

• Key Takeaway: The U.S. Census Bureau defines the first generation as foreign-born individuals who permanently resettle, contrasting with the common understanding that the first generation are children born in the new country.
• Summary: Sociologically, the term ‘generation’ refers to a collective group born and living at the same time, suggesting the first generation born in the U.S. are the true first generation. The Census Bureau uses ‘generational status’ specifically for immigration, labeling the immigrant parent as first generation. Logically, one cannot join an age-based cohort midway through its existence in a new country.

Coprophagy in Animals

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(01:56:41)

• Key Takeaway: Coprophagy, or the eating of feces, is a common survival strategy for many species, including baby birds, elephants, and rabbits, to acquire essential gut bacteria or nutrients.
• Summary: Animals engage in coprophagy to gain necessary gut bacteria for digestion, re-ingest lost nutrients, or due to instinctual hunger. While tigers typically avoid it, tigresses may consume their cubs’ feces to eliminate scent trails and protect them from predators. Rare documented cases show tigers consuming elephant dung, likely for specific nutrient absorption.

Beanie Baby Value and Nostalgia

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(02:01:33)

• Key Takeaway: The monetary value of Beanie Babies like ‘Valentino’ is highly speculative and often inflated, rendering the sentimental value of a damaged collectible more significant.
• Summary: The host received a ‘Valentino’ Beanie Baby, which is distinguished from ‘Le Shitty’ by having a heart patch instead of an American flag. The host admitted to writing his name on the toy and removing its tag, actions that severely diminish its potential resale value. Online listings show a wide price variance, suggesting that authenticated, mint-condition items command higher prices than damaged ones.