Dr. Justin Sonnenburg: How to Build, Maintain & Repair Gut Health

Dr. Justin Sonnenberg on Gut Microbiome

• Gut microbiome: trillions of microorganisms throughout the digestive tract 
  • Also found in the nose, mouth, and skin
  • Most microbes are in the distal gut and colon
• Microbiome supports hormonal health, brain health, and immune system function 
  • Manufactures neurotransmitters that impact mood and brain function
• Spatial organization of microbiota in the gut 
  • Crypts and niches: little caves within the digestive tract where certain microbiota reside
• Factors that support a healthy gut microbiome 
  • Fermented foods
  • Fiber
• Impact of behaviors on microbiome 
  • Who you touch, kiss, hug
  • Interaction with animals
• Microbiome constantly modified by behavioral and nutritional interactions, as well as mood and internal reactions to the outside world
  Microbiota in the Human Body
• Dense bacterial community in the gut 
  • 30% to 50% of fecal matter is microbes
  • Hundreds to 1000 species of microbes in the gut
• Other life forms in the gut 
  • Archaea, eukaryotes, fungi, viruses, bacteriophages
• Different microbiota along the digestive tract 
  • Oral microbiota in the mouth, adapted to oxygen exposure
  • Esophagus and stomach have less dense microbial communities
  • Small intestine is less studied due to difficulty in accessing
  • Colon has the densest and most studied microbial community

Microbiota Development in Newborns

• Fetus in the womb is in a sterile environment
• Microbiota assembly occurs during the first days, weeks, months, and years of life
• Factors affecting microbiota development 
  • C‑section vs. vaginal birth
  • Breastfed vs. formula fed
  • Presence of pets in the household
  • Exposure to antibiotics

Healthy vs. Unhealthy Microbiome

• Defining a healthy microbiome is a complex question
• Dysbiosis refers to an unhealthy microbiome
• Many factors contribute to a healthy or unhealthy microbiome
• Current research is focused on understanding and defining a healthy microbiome
  Healthy Microbiota and the Human Microbiome Project
• Complex topic, context matters 
• Healthy microbiota varies between individuals and populations
• Human Microbiome Project (2008–2009) aimed to define healthy vs. diseased microbiomes 
  • Documented vast number of genes in gut microbes
  • Found tremendous individuality in gut microbiomes
  • Traditional populations had different microbiomes than industrialized societies

Traditional vs. Industrialized Microbiomes

• Traditional populations’ microbiomes more representative of early human evolution
• Industrialized microbiomes may be adapted to current lifestyles or deteriorated due to antibiotics and Western diets
• Microbiomes can exist in stable states, resistant to change

Reprogramming the Gut Microbiome

• Emerging field focused on changing gut microbes for health benefits
• Gut microbiomes have resilience and resistance to change
• Achieving a new stable state requires restructuring communities and resisting pull back to original state

Multigenerational Study on Mice

• Mice on low fiber, high fat diet lost microbiome diversity over generations
• Returning to high fiber diet did not recover diversity in later generations
• Fecal transplant from high fiber diet mice restored diversity
• Establishing new stable states requires access to right microbes and proper diet

Microbiota and pH Sensitivity

• pH varies along the digestive tract, more or less fixed for a given location
• Certain microbiota thrive at specific locations due to pH sensitivity
• Changes in food can robustly change the microbiome
  Microbiome and Diet
• Food plays a significant role in the quality of the microbiome 
• Regional differences in the gut affect the microbiome 
  • pH gradient along the length of the gut
  • Nutrient gradient: simple sugars in the small intestine, depleted in the colon
  • Immune system is active in the small intestine
• Mucus lining in the gut helps retain microbes and resist being washed out 
  • Some microbes attach to and eat the mucus lining
  • Microbial communities can form in crypts, invaginations in the intestine

Cleanses and Fasting

• Limited high-​​quality science on the effects of cleanses and fasting on the microbiome
• Potential benefits for those with metabolic syndrome or poor diets
• Adherence to strict diets may be easier for some people due to neurobiological and psychological factors

Healthy Diet Recommendations

• Mediterranean or plant-​​based diet is widely accepted as healthy 
  • High fiber, whole grains, legumes, vegetables, and fruits
• Simple rules for a healthy diet: 
  • Eat food, not too much, mostly plants (Michael Pollan’s mantra)
  • Focus on a high-​​fiber, plant-​​based diet
• Gastroenterology fellows find it difficult to get people to change their diets unless it involves simple elimination or strict rules
  Fasting, Dietary Regimes, and Gut Microbiota
• Fasting and dietary regimes can affect gut microbiota 
  • Extended fasting can lead to bacteria that specialize in eating mucus
  • This can cause inflammation if mucus is consumed in excess
• Short-​​term fasting may have metabolic benefits, but long-​​term effects on gut microbiota are unknown
• Cleanses and flushes can disrupt the gut microbiota, leaving rebuilding to chance

Carbohydrates and Gut Microbiota

• People may feel better cutting out carbohydrates due to the quality of carbs in industrialized countries 
  • Processed carbs contribute to glycemic index and can lead to diabetes
• Complex carbohydrates (microbiota accessible carbohydrates) are beneficial for gut microbiota 
  • These carbs are fermented by gut microbiota and are important for health

Human Genetic Adaptation to Diet and Gut Microbiota

• Human genetic adaptation to diet can occur over short periods of time 
  • Example: lactase persistence allowing some populations to consume dairy throughout life
• Gut microbiome can also adapt to cultural differences in diet 
  • Example: degradation of seaweed in Southeast Asian populations
• Most human ancestors were hunter-​​gatherers, consuming large amounts of plant material 
  • Example: Hadza hunter-​​gatherers in Africa consume 100–150 grams of dietary fiber per day, compared to 15 grams in a typical American diet
  • Plant-​​based diets were more reliable and consistent for hunter-​​gatherers
    High Fiber Diet and Brain Development
• High fiber diet is not a preference, but a result of availability and consistency for survival 
• Brains are wired for caloric density, craving sugar, fat, and calories
• Protein and fat are essential for brain development

Hazda Diet

• Prefer to eat meat and honey, but consume a lot of plant fiber due to availability
• Avoiding processed foods is beneficial for the microbiome

Processed Foods and Microbiome

• Processed foods have negative impact on gut biology and microbiota
• Artificial sweeteners can have a massive negative impact on the gut microbiome and lead to metabolic syndrome
• Emulsifiers in processed foods can disrupt the mucus layer, leading to inflammation and metabolic syndrome

Artificial Sweeteners vs. Plant-​​Based Sweeteners

• Artificial sweeteners: detrimental or signaling different events in the gut
• Plant-​​based sweeteners: less negative or more healthy due to evolutionary exposure and smaller amounts needed for sweetness
• Studies still need to be done on plant-​​based sweeteners

Personal Dietary Choices

• Avoiding artificial sweeteners and sweet foods in general
• Gradually migrating diet away from sweet foods to less sweet options
• Retraining palate to enjoy less sweet foods
  Microbiome and Nutrition
• Importance of fiber in maintaining a healthy microbiome 
• Fasting and cleansing not necessary before repopulating the microbiome 
  • Studies on this topic are limited
  • Flushing the gut could be part of future treatments, but currently seems “half-​​baked”

Fiber and Fermented Foods Study

• Collaboration between multiple labs and researchers
• Aim: understand how high fiber and high fermented food diets affect the microbiome and immune system
• Challenges in changing people’s diets and maintaining control in food studies
• Some studies focus on supplements, probiotics, and prebiotics, which can be more controlled

Future of Microbiome Research

• Potential for personalized microbiome treatments in precision health
• Reprogramming the gut microbiome to improve health and reduce inflammation
• Importance of studying the microbiome in humans to ensure relevance and applicability
  High Fiber and Fermented Food Diets
• High fiber diet: 
  • Increase plant-​​based fiber intake (whole grains, legumes, vegetables, nuts)
  • Aim for over 40 grams of fiber per day
  • Results in less saturated fat, less animal-​​based protein, more plant-​​based protein
• High fermented food diet: 
  • Consume naturally fermented foods with live microbes (yogurt, kefir, sauerkraut, kimchi, fermented vegetables, pickles)
  • Avoid canned fermented foods, as they often do not contain live microbes
  • Choose unsweetened yogurts to avoid added sugar
  • Beer not included in the study, kombucha was
• Study results:
  • High fiber diet hypothesis: more short-​​chain fatty acids, more diverse microbiota, less inflammation in the immune system
  • Individualized responses to dietary fiber, no clear pattern across the cohort
  • High fermented food group showed increased microbiota diversity and reduced inflammation
  • Stepwise reduction in inflammatory markers (e.g., interleukin six and interleukin twelve) during the study

• Note: The notes above summarize the diets and the results of the study.
  Fermented Foods, Fiber, and Gut Microbiome Study
• Study duration: 14–17 weeks 
  • Intervention phase: 4‑week ramp, 6‑week maintenance period
• Participants reported more energy, clearer thinking, better sleep, improved complexion, and reduced allergies
• No significant findings in cognition and mood
• Improved bowel habits observed

Fiber Group Findings

• Three different immune response groups observed 
  • One group with overall less inflammation
  • Two groups with mixed results (partly more inflammatory, partly less inflammatory)
• People with the highest diversity gut microbiomes at the start of the study were most likely to have decreases in inflammation 
  • Suggests that a diverse microbiota may be better equipped to degrade a wide variety of dietary fiber, leading to a more positive response
    Gut Microbiome and Health
• Depleted gut microbiome may not respond well to high fiber diet 
• Industrialized world may have lost fiber-​​degrading microbes
• Immigrants to the US lose gut microbiome diversity and fiber-​​degrading capacity

Sanitization and Microbe Exposure

• Over-​​sanitization may have negative effects on gut microbiome
• Exposure to environmental microbes may be important for immune system education
• Balancing exposure to microbes and maintaining hygiene is crucial

Gut Microbiome Communication with the Body

• Immune system plays a role in monitoring gut microbes
• Pyres patches and dendritic cells sample microbes to educate immune system
• Cells in the gut perceive metabolites produced by microbiota
• Enteric nervous system sends signals to the brain
• Immune cells can travel to other mucosal surfaces to educate them
• Microbial metabolites can enter the bloodstream and affect various receptors in the body
• Some microbial metabolites can cross the blood-​​brain barrier, potentially affecting mood and neurological disorders
  Kidney Disease and Mental Fog
• Kidney disease can lead to mental fog due to the buildup of metabolites in the bloodstream 
• The impaired filtering process in the kidneys allows more molecules to cross the blood-​​brain barrier
• Mental fog is a common symptom of kidney disease

Probiotics

• Many probiotics on the market lack proper quality control and regulation
• Look for independent validation and reputable brands when choosing probiotics
• Probiotics may help with certain conditions, but results vary greatly between individuals
• It’s best to find a study that supports the specific probiotic for the desired effect

Prebiotics

• Consuming a variety of plants and diverse fiber is better for fostering gut microbiota diversity than purified fibers
• Purified fibers can cause rapid fermentation in the gut, which may have negative effects on liver metabolism
• Combining high fiber and fermented foods may have a synergistic effect on gut health

General Recommendations

• Avoid processed and highly palatable foods with hidden sugars and emulsifiers
• Consume fiber and fermented foods for a healthy gut microbiome
• Experiment with probiotics and prebiotics to find what works best for your individual needs

Sonnenberg Lab and The Good Gut Book

• Justin Sonnenberg and his wife, Erica, co-​​run the Sonnenberg Lab and have written a book called “The Good Gut”
• The book aims to make gut microbiome information accessible to non-scientists
• The Sonnenberg Lab is currently planning a study on the effects of high fiber, high fermented food, and a combination of both on gut health
  Personal Journey and Research on Gut Microbiome
• Center for Human Microbiome Studies at Stanford 
  • Home base for dietary intervention studies
  • Provides information on ongoing research
• Lab website for more information on research 
  • Always looking for study participants

Importance of Gut Microbiome

• Vital cargo that needs to be taken care of for overall health
• Previously associated with infectious diseases and negative aspects
• Growing understanding of its importance in overall health

Resources and Further Information

• Sonnenberg Lab website: sonnenberglab​.stanford​.edu
  • Recruitment for studies on nutrition and gut microbiome
• Book: “The Good Gut” by Dr. Justin Sonnenberg and Dr. Erica Sonnenberg 
  • Available on Amazon and other platforms