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#070 Dr. Eran Elinav On Microbiome Insights Into Personalized Response To Diet, Obesity, And Leaky Gut | Found My Fitness With Dr. Rhonda Patrick

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Key Takeaways

  • The way we respond to a diet is highly individualized – people uniquely respond to diet, even if fed the exact same foods
  • “The dominant factor that determines the diurnal activity of microbes throughout the day is the timing of our feeding.” – Dr. Eran Elinav
  • Our gut microbiome senses when we eat or don’t eat and changes activity accordingly
  • Changes in health status, stress status, medication, the way we live, where we live, etc. reflect on our gut microbes and may impact the risk of developing diseases
  • A leaky gut is related to disease: diverse molecules secreted by the gut microbe are important in creating the normal state of leakiness which allows us to absorb food and block foreign molecules we don’t want in our body – when disrupted, there’s a strong link to disease (cancer, autoimmune & cardiovascular disease)
  • The success of probiotic supplementation depends on whether the exogenous probiotic is welcomed by endogenous microbes in the gut
  • The complexity of taking antibiotics and probiotics: giving probiotics together with antibiotics may protect individuals from adverse effects of antibiotics – but the price may be a chronic disturbance in gut microbiome with probiotics taking over and reducing the diversity of the innate gut microbiome
  • About 80% of overweight people who diet will gain back the weight plus some – the microbiome seems to store a metabolic memory of past obesity which predisposes people to exaggerated weight gain
  • Best practices for a healthy microbiome: (1) maintain a consistent, healthy sleep pattern; (2) stop smoking cigarettes; (3) eat during a regular window during the day (avoid night eating); (4) explore wearing a continuous glucose monitor for personalized data; (5) try a personalized nutrition approach (check out Day Two)

Introduction

Eran Elinav, MD, Ph.D. (@EranElinav), is a professor of immunology and principal investigator at the Weizmann Institute of Science in Tel Aviv, Israel, where he co-directs the Personalized Nutrition Project. His research focuses on understanding the complex interactions between humans and the bacteria that reside in their gut and how these interactions shape human health and disease.

In this episode of Found My Fitness, Rhonda Patrick and Eran Elinav take a deep dive into the microbiome and discuss topics like the circadian rhythm of the microbiome, child development of the microbiome, cholesterol & fats, artificial sweeteners, obesity & much more.

Host: Dr. Rhonda Patrick (@foundmyfitness)

Book: The Personalized Diet by Eran Segal, Eran Elinav, et. al.

Circadian Rhythm Of Gut Microbiome

  • “The dominant factor that determines the diurnal activity of microbes throughout the day is the timing of our feeding.” – Dr. Eran Elinav
  • The finding that our gut has its own circadian clock is a relatively recent discovery
  • Meal timing matters: food intake sends a signal that resets our metabolic response
  • The composition & timing of diet influences our gut composition and function – having surprising outcomes on obesity and diabetes
  • The functions of the microbe change consistently throughout the course of the day
  • When we disrupt the natural circadian rhythm of our diet by changing the pattern or time of our diet, we’re more susceptible to developing obesity and type 2 diabetes
  • Shift workers are at substantial risk of developing obesity and type 2 diabetes
  • Tip: shift workers (and everyone else) can restore the circadian microbiome activity and its effect on the metabolic function of the host by engaging in time-restricted eating 

Composition Of Diet & Microbiome

  • The way we respond to a diet is hugely personal – people uniquely respond to diet, even if fed the same exact foods
  • The composition of our diet is the most dominant factor that impacts gut microbiome – other important factors include stress levels, medication, where we live, access to food  
  • Three ways diet composition can impact microbes: (1) some nutritional input could serve as an energy source to microbes; (2) bacterial communications vary based on the signals we receive from our diet; (3) many dietary components are absorbed by the host (us) – so the changes we make to our diet can impact microbes
  • A healthy adult with a relatively stable lifestyle should have a steady microbiome over time
  • If you abruptly change your diet (e.g., from carnivore to vegetarian) you will change the composition of your gut microbiome to better accommodate the new diet
  • The lack of diversity of the microbiome is correlated to disease in both directions – but we still can’t make causal inferences

Child Development And A Healthy Gut

  • The stability of our microbiome is largely shaped in the first three years of life
  • Emerging data suggest that ages 0-3 is when we shape the microbiome for our adult life
  • Microbiome during childhood is shaped by our environment and parents or caregivers
  • “By subjecting kids to an overly sterile condition, we may be harming them by not allowing their microbiome to be diverse enough to train the immune system and impact healthy metabolism.” – Dr. Eran Elinav  
  • Auto-immune and auto-inflammatory diseases are much less prevalent in lower-income countries where the prevalence of exposure is much higher
  • A child’s microbiome is largely dependent on mothers: infants develop their microbiome from their neonatal surroundings, mostly their mother
  • Microbiome shaping by genetics versus environment: most of the effect of shaping our microbiome comes from the environment – only about 10% is explained by genes
    • There could be important factors coming from genetics, but the weight of the effect is largely environmental
  • It’s encouraging that most of the effect on our microbiome comes from the environment because that means we have some degree of control over configuration

Obesity

  • Recurrent (AKA yoyo) obesity: about 80% of people who are overweight and diet tend to gain the weight back
  • Most diets are efficient at helping people lose weight in the short term because they involve some level of caloric restriction
  • Not only do most people gain back the weight they lost while on a diet, but they also gain back the additional weight
  • In mouse studies: the gut microbiome is persistently disturbed in mice who were obese & dieted versus mice who were obese but never dieted
  • The microbiome seems to store a metabolic memory of past obesity which pre-disposes mice to exaggerated weight gain
  • Treating or ameliorating obesity using grapefruit: a compound found specifically in grapefruit may help avoid or protect against exaggerated weight gain in obese people by preventing degradation of specific microbes (based on mice studies – the human trial is ongoing)
  • Caloric restriction may have a beneficial effect on the microbiome and actually serve as the underlying driver of weight loss

Metabolome

  • The microbiome is like a biochemical factory that modulates thousands of molecules
  • Metabolome: metabolites and compounds churned out by our gut microbiome
  • About 50% of all small molecules found in the blood may originate or be modulated by our gut microbes

Leaky Gut

  • The gut is really designed to withstand a huge amount of foreign molecules in the form of food
  • The gut has developed mechanisms to offer protection from invasion of foreign molecules while allowing intestines to absorb nutrients
  • The healthy leakiness of the gut allows us to absorb food but can lead to an altered ability to withstand food or foreign molecules when disrupted
  • “Leaky gut or altered gut permeability seems to constitute a common denominator factor found in many disease states such as heart disease, cancer, autoimmune disease.” – Dr. Eran Elinav
  • Possible factors contributing to leaky gut: (1) disruption in the connection between tightly regulated cells; (2) disruption in the mucous layer by medication, toxins, food
  • Just like diet, the factors that contribute to leaky gut in one person but not another are hugely individualized
  • Celiac disease (inability to digest gluten): post-genetic risk factor combined with food that leads to clinical manifestation of disease

Prebiotic, Probiotic, Postbiotic

  • Prebiotic, probiotic, and postbiotic all describe interventions to regulate the microbiome and its interactions with the human body
  • Prebiotic intervention: food-related interventions composed of dietary fibers aimed to make the microbiome healthier
  • Probiotic intervention: supplementation of exogenous microbes introduced with the hope of making microbiome more favorable
  • Postbiotic intervention utilizes metabolite supplementation to reintroduce metabolites that may be missing in some disease states
  • Supplementation with probiotics may work in some individuals but not others – around 50% of people experience an inability to colonize exogenous microbes with natural (endogenous) microbes
  • It’s hard to predict who will have favorable outcomes to probiotics – interactions between bacteria in the gut are highly individualized and poorly understood
  • People given probiotics in combination with antibiotics increase colonization by probiotics (because antibiotic empties) but probiotics will inhibit the return of indigenous microbiome after antibiotic use stops
  • Though widely popular, probiotics are not a proven intervention by FDA or other similar bodies
  • Bacteriophage: viruses that do not infect humans or mammals – they only infect bacteria
  • There is research being done with introducing bacteriophages into the gut microbiome to kill bad actors in a targeted way
  • Possible future of precision medicine as it relates to gut health: phage cocktail to eradicate bacteria from the microbiome in combination with probiotics to colonize as replacement  

Cholesterol, Triglycerides, Saturated Fat, Artificial Sweeteners

  • Cholesterol is not just dietary; it’s also produced when our body has an inflammatory response
  • Healthy cholesterol and fatty acid metabolism are modulated by the gut microbiome
  • Data from the microbiome can be used to predict a person’s level of triglycerides – supporting a possible causal association
  • Variability in study results on effects of artificial sweeteners on health could be explained by variability in individual microbiome
  • More studies of the effects of artificial sweeteners have been done on mice than humans but provide a hypothesis

Trimethylamine N-Oxide (TMAO)

  • TMAO is found in red meat and eggs (generated by L-carnitine) and associated with heart disease and atherosclerosis
  • Conflicting data: healthy people (active; no metabolic syndrome) who eat red meat and eggs don’t have a higher rate of mortality than those who eat foods without TMAO precursors
  • One type of food or one risk factor doesn’t explain the entire spectrum of atherosclerosis or heart disease

Best Practices For Microbiome

  • Maintain a healthy sleep pattern and avoid variability in sleep as much as possible
  • Maintain healthy fiber intake but – not all fibers are created equal
  • Stop smoking! Chemicals in cigarettes disturb the composition and function of the microbiome
  • Consider the timing of diet: eat in routine times
  • Explore wearing a continuous glucose monitor to learn how your body responds to certain foods and metabolism under certain conditions (e.g., lack of sleep)
  • Try a personalized nutrition analysis from a company like Day Two
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Notes By Maryann

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