Ep. 37: “Co-Evolution of the Human Microbiome” Featuring Drs. Ruth Ley and Sara Clasen
Sep 13, 2022
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Dr. Ruth Ley, a microbiome science expert, and Dr. Sara Clasen, a postdoctoral fellow, dive into the fascinating co-evolution of humans with their gut microbiomes. They discuss how gut microbes adapt to human biology and the silent recognition of flagellins by TLR5, crucial for immune regulation. The conversation also explores the interplay between intestinal IgA and circadian rhythms, as well as innovative CAR T-cell therapies using CRISPR. Together, they illuminate the mutual adaptations that impact health and the future of microbiome research.
The co-evolution of humans and their gut microbiomes reveals significant adaptations and associations shaped by genetic history and environmental migrations.
Dietary patterns greatly influence gut microbiome composition and immune response, highlighting the importance of nutritional choices in sustaining health.
Circadian rhythms play a crucial role in modulating immune functions like IgA secretion, emphasizing the benefit of synchronizing meal timing with natural body rhythms.
Deep dives
Co-evolution of the Microbiome and Humans
The discussion highlights the concept of co-evolution between the human microbiome and its host, emphasizing the long-term association shared over generations. Research indicates that specific strains of gut bacteria coincide with the genetic history of populations, suggesting that these microbes have adapted alongside humans as they migrated across different regions. Evidence shows that as human populations diversified, their microbiomes changed correspondingly, indicating reciprocal adaptations that underscore co-evolution. The implications of this research extend to understanding how the human microbiome may influence various health conditions and responses to treatments.
Impact of Diet on Gut Microbiome Composition
The podcast delves into how dietary patterns significantly influence gut microbiome composition, and consequently, the immune system's response. Researchers discovered that specific dietary inputs resulted in variations in IgA production, which in turn affected the composition of beneficial bacteria in the microbiome. These findings suggest a dynamic feedback loop where diet influences microbiome diversity, which then interacts with immune responses. Such insights underscore the importance of dietary choices in fostering a healthy gut microbiome and maintaining overall health.
Circadian Rhythms and Immunological Responses
The relationship between circadian rhythms and immune responses is explored, focusing on how the timing of nutrient intake can modulate immune functions like IgA secretion. Research findings show that the production of IgA demonstrates a diurnal pattern, which is affected by the body’s internal clock. This means that when dietary habits are synchronized with natural physiological rhythms, immune responses may be optimized. This connection highlights the need for understanding how lifestyle factors, such as meal timing, can enhance immune system performance.
Advancements in CAR T-Cell Therapy
The advancements in CAR T-cell therapies are examined, particularly emphasizing breakthroughs in engineering methods using CRISPR to enhance lymphoid cancer treatments. A recent clinical trial showcased the successful application of CRISPR technology to produce CAR T cells without viral vectors, resulting in promising safety and efficacy data. Early results indicated durable responses in a significant number of patients, showcasing the potential of this novel approach. This development could pave the way for more effective cancer treatments, as research continues to focus on optimizing T-cell engineering for broader applications.
Role of Immune Cells in Skin Health
The role of innate immune cells, specifically ILC2s, in controlling skin commensals like Demodex mites is discussed, emphasizing their importance in maintaining skin health and preventing conditions such as rosacea. Changes in the function of ILC2s lead to enhanced overgrowth of these mites, resulting in inflammation and skin lesions. This research illustrates how immune responses are not solely defensive but also involved in regulating the population of beneficial commensals on the skin. Additionally, findings demonstrate that a balanced immune response is essential for preventing colonization and maintaining skin integrity.
Dr. Ruth Ley is Managing Director of the Max Planck Institute for Biology Tübingen and Director of the Department of Microbiome Science. Dr. Sara Clasen is a postdoctoral fellow in the same lab. Together, they’re interested in the co-evolution of humans with their microbiomes. They use basic science to investigate the evolutionary history of gut microbes, how they have adapted to life inside humans, and how they affect human biology and health. More recently, they published a pre-print on the silent recognition of flagellins from human gut commensal bacteria by TLR5.
Hair Follicles and Mites – Scientists show that innate type 2 immunity controls hair follicle commensalism by Domedex mites.
The Search for a Shared Neoantigen – Using quantitative immunopeptidomics, researchers have identified a tumor stroma-specific target for T cell therapy.
Gut Microbes Surf the IgA Cycle – New research suggests that circadian networks comprising intestinal IgA, diet, and microbiota converge to align circadian biology in the intestine and to ensure host-microbial mutualism.
A New Way to Make CAR-T Cells – Researchers have successfully generated non-viral, gene-specific targeted CAR-T cells through CRISPR-Cas9.
