THE HUMAN MICROBIOME: A New Frontier in Health

University of California Television (UCTV)54 minutes read

Human microbiome research focuses on studying diverse microbial communities and their impact on health, using various tools like biomarker gene sequencing and metagenomics. Factors like diet, medications, and environmental exposures significantly influence the microbiome's composition and function, impacting various diseases and immune responses.

Insights

  • DNA-based methods like biomarker gene sequencing and shotgun metagenomics help identify and understand the microbial communities in the human body, aiding in comparing health and disease samples.
  • The human microbiome is greatly influenced by early life exposures, diet, medications, infections, and environmental toxins, shaping its diversity and composition throughout life.
  • Variations in gut microbiomes across populations, with differences in microbial profiles and metabolic pathways influenced by diet, highlight the impact of environments on the microbiome and its implications for health and disease.

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Recent questions

  • How does the human microbiome impact health?

    The human microbiome, consisting of diverse bacteria, fungi, and viruses in and on the body, influences digestion, drug metabolism, and immune responses. Factors like diet, medications, infections, and environmental toxins shape the microbiome throughout life, with early exposures like birth method and nutrition strongly affecting gut microbiome development. Imbalances in the microbiome are linked to diseases like obesity, depression, and autism spectrum disorder, highlighting the crucial role of these microbial communities in overall health.

  • What methods are used to study the human microbiome?

    Researchers use DNA-based tools like biomarker gene sequencing, shotgun metagenomics, and meta transcriptomics to identify and understand the microbial communities in the human body. These methods allow for the sequencing of microbial genes, RNA expression, and all DNA in a sample to reveal the composition, functions, and capabilities of the microbiome. Mass spectrometry and metabolomics further aid in identifying small molecules and proteins produced by the microbiome, providing insights into microbial-host interactions.

  • How do different populations' gut microbiomes compare?

    Studies comparing gut microbiomes in developing and developed nations show significant variations in microbial profiles, influenced by environmental factors. Less developed nations exhibit greater diversity and types of bacteria in their gut microbiomes compared to developed nations like the U.S. Visualization of distance calculation reveals similarities in gut microbiomes between individuals, while populations like the Marindian and Malawian show enrichment for specific metabolic pathways due to their plant-based diets.

  • What role does diet play in shaping the gut microbiome?

    Plant-based diets maintain gut microbiome stability, while animal-based diets cause significant changes, impacting the production of short-chain fatty acids like acetate and butyrate. These dietary differences affect gut health and microbial composition, with studies showing that diets rich in processed foods lead to metabolic pathway enrichment for processing simple sugars. Understanding the impact of diet on the gut microbiome is crucial for maintaining overall health and preventing diseases linked to microbiome imbalances.

  • How are early-life microbiome exposures linked to disease development?

    Early-life exposures like birth method, nutrition, and microbial encounters shape the gut microbiome, influencing immune responses and disease development trajectories. High-risk babies for asthma have distinct gut microbiomes from healthy babies, leading to delayed diversification and increased disease risk. Studies have identified specific neonatal gut microbiomes associated with allergies and asthma later in life, highlighting the critical role of early-life microbiome composition in shaping immune maturation and disease outcomes.

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Summary

00:00

Understanding Human Microbiome: Impact on Health and Diversity

  • Human microbiome research focuses on studying diverse communities of bacteria, fungi, and viruses in and on the human body to understand their impact on health.
  • Tools like DNA-based methods are used to identify microbes without needing to culture them, such as targeting the 16S ribosomal RNA gene for bacteria and interspacer region two for fungi.
  • Biomarker gene sequencing reveals the presence and relative abundance of different microbes, aiding in comparing health and disease samples.
  • Shotgun metagenomics goes further by sequencing all DNA in a sample to understand the genes and capabilities of the microbial community.
  • Meta transcriptomics involves sequencing RNA to see what genes are being expressed by the microbes at the time of sampling.
  • Mass spectrometry and metabolomics allow for the identification of small molecules and proteins produced by the microbiome, crucial for understanding microbial-host interactions.
  • The human microbiome is incredibly diverse, with millions of microbial genes found in just over 1,200 fecal samples, influencing digestion, drug metabolism, and immune responses.
  • Early life exposures, like birth method and nutrition, strongly shape the gut microbiome, with diversity increasing until around age three.
  • Throughout life, factors like diet, medications, infections, and environmental toxins continue to influence and shape the microbiome.
  • Microbiomes vary significantly between populations, as shown in studies comparing gut microbiomes in developing and developed nations, highlighting the impact of different environments on microbial profiles.

16:36

"Gut Microbiome Diversity and Health Implications"

  • Visualization of distance calculation shows similarity in gut microbiomes between individuals.
  • U.S. gut microbiomes differ significantly from those of the Marindian and Malawian populations.
  • Less developed nations exhibit greater diversity and types of bacteria in their gut microbiomes compared to the U.S.
  • Amerindian and Malawian populations show enrichment for alpha-amylases due to plant-based diets.
  • U.S. population displays enrichment in metabolic pathways for processing simple sugars from processed foods.
  • Plant-based diets maintain gut microbiome stability, while animal-based diets cause significant changes.
  • Short chain fatty acids acetate and butyrate decrease in animal-based diets, affecting gut health.
  • Various diseases like obesity, depression, and autism spectrum disorder are linked to gut microbiome imbalances.
  • Fecal microbial transplant, transferring healthy gut microbiomes, shows high efficacy in treating Clostridium difficile infection and autism spectrum disorder.
  • Fecal microbial transplant's effectiveness varies, with 40% response rate in ulcerative colitis patients and caution needed in its application.

33:10

Early-life gut microbiomes impact allergy and asthma.

  • Many studies have explored the origins of allergy and asthma, with birth cohort studies revealing factors like formula-feeding, antimicrobial use, and cesarean section increasing disease risk.
  • Conversely, reduced allergy and asthma risk in children is linked to breastfeeding, exposure to animals, and inner-city environments with cats, mice, and cockroaches, enhancing microbial diversity.
  • A study on mice showed that feeding lactobacillus species reduced allergic inflammation in airways, with significant decreases in IL-4, IL-5, and IL-13, key molecules promoting inflammation.
  • Further research indicated that live lactobacillus supplementation protected against respiratory syncytial virus (RSV) infection, reducing reactive airways and inflammatory markers.
  • Metabolic changes induced by altered gut microbiomes, particularly an increase in anti-inflammatory lipids, were found to protect airways against viral infections.
  • Immune cells exposed to plasma from mice with lactobacillus supplementation showed reduced inflammation and antigen presentation, suggesting gut microbiome alterations can impact immune responses.
  • High-risk babies for asthma had different meconium microbiomes from healthy babies, leading to delayed diversification and distinct gut microbiome development trajectories.
  • A large birth cohort study identified three distinct neonatal gut microbiomes, with babies having NGM3 at one month old being three times more likely to develop allergies and asthma later in life.
  • NGM3 babies showed a loss of bacteria and an increase in allergenic fungi like rodatorola and Candida, indicating a complex microbial composition influencing disease development.
  • Metabolomic analysis revealed a potential link between gut microbiome composition, microbial metabolites, and immune maturation, suggesting early-life microbiomes play a crucial role in shaping immune responses and disease outcomes.

48:42

"Gut Microbiome Shapes Allergies and Asthma"

  • Babies who develop allergies and asthma have reduced polyunsaturated fatty acids and increased 12,13 DiHOME lipid.
  • NGM1 and NGM2 microbiomes are tolerogenic, educating the immune response differently from NGM3.
  • Immune cells from healthy adults were co-incubated with gut microbiome products from high-risk NGM3 and low-risk NGM1 babies.
  • Co-incubation with NGM3 fecal water increased allergic T-cells and reduced regulatory T-cells.
  • 12,13 DiHOME lipid skews immune response, reducing regulatory T-cells and IL-10 production.
  • Injection of 12,13 DiHOME lipid in mice exacerbated allergic response in airways.
  • Babies at high risk of asthma had gut microbiomes enriched for 12,13 DiHOME-producing bacterial genes.
  • Increased epoxide hydrolase genes in gut microbiome correlated with higher risk of allergies and asthma.
  • Synthetic cocktail of microbes designed to prevent asthma by shaping immune response and altering microbiome development.
  • Gut microbiome composition in early life influences obesity, skin health, upper airway microbiome, and disease development trajectories.

01:04:55

"Microbiome Research: Health, Disease, and Therapeutics"

  • Research is focused on understanding the microbiome's role in health and disease development.
  • Trials are being conducted on fecal microbial transplants to create tailored synthetic microbial communities for specific patient subsets.
  • Microbes are being used to combat other microbes, with a focus on phage therapy targeting key pathogenic organisms.
  • Studies are targeting specific organisms like Moraxella catarrhalis in the upper airway for phage therapy interventions.
  • Efforts are being made to use microbes to express specific molecules like IL-10 to reduce inflammation.
  • Research is being conducted on the impact of diet on the microbiome, with a pilot study in ulcerative colitis patients.
  • Development of bespoke synthetic microbial cocktails is underway to enhance treatment efficacy.
  • The focus is on early life microbiome interventions to prevent disease and develop novel therapeutics.
  • Probiotics in food and over-the-counter products vary in microbial types and quantities, impacting their efficacy.
  • Studies on the fetal microbiome show microbial presence in meconium, suggesting early microbial encounters in utero.

01:21:03

Microbes' Role in Allergy and Asthma

  • Increased allergy and asthma development in western worlds
  • Need to focus on understanding microbial functions rather than just the organisms themselves
  • Helicalbacter Pylori is common but controlled in healthy conditions by stomach conditions and surrounding organisms
  • Deeper understanding of how specific microbes drive disease processes leads to more precise targeting of those processes
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