April 15, 2025 Leah Guthrie

Science Talks
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Science Talks: Dr Leah Guthrie

Tuesday April 15, 2025 at 10:30am EST

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Join Dr Leah Guthrie [Website][LinkedIn] as she tells us about her latest research investigating how gut bacterial metabolites contribute to differences in disease outcomes by modulating host cellular processes!

Leah received her BA in Biology from Swarthmore College, PhD in Biomedical Sciences from Albert Einstein College of Medicine, was a HHMI Hanna Gray postdoctoral fellow at Stanford University, and is currently an Assistant Professor at UC Berkeley Bioengineering. Ask her anything!

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  1. How do you distinguish between correlative and causative effects when studying the microbiome and their impact on kidney cell signaling in general?
  2. Could you speak more upon how chemoinformatics with mass spectrometry to identify novel microbial metabolites?
  3. What resources did you look into to help find the reserach environment you wanted early and how did you know it was the right fit for you?
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  1. How was the “American Diet” defined and validated for homogeity across individuals?
  2. What were the biggest limitations of the study, and how do you plan to address them in future research?
  3. What techniques did you use to quantify inter-individual variability in irinotecan metabolism—was it purely metabolomics, or did it include functional assays as well?
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Science - Are the harmful metabolites mentioned in your study only produced by certain bacteria? For potential clinical interventions down the road, do you suspect that you would be attempting to eliminate the bacteria that produce those metabolites, or instead introduce a genetically edited version of them?
Method - How do you account for/sort through the vast diversity of microbiomes of people and animals you study? Especially considering diet seems to account for very little of the diversity.
Career - What made you want to study the microbiome?

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  1. Given your lab’s focus on host-microbiome communication, what are your thoughts on the relative influence of host genetics versus microbiota-derived factors in shaping immune development across individuals?
  2. Could you share insights on how you control for high inter-individual variability in these datasets when trying to draw functional conclusions, especially in small or moderate-sized human cohorts?
  3. how would you recommend finding the “right” lab or research question and what should one look for in a mentor?
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  1. Could changing the gut microbiome help prevent kidney disease, not just treat it?
  2. How do you figure out which gut chemicals come from food and which from bacteria?
  3. What strategies helped you find mentors and research opportunities early in your career, especially in interdisciplinary areas like microbiome-host interactions and computational biology?
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  1. What parameters were used to define a “healthy” person for the 21 individuals?

  2. Were only the phylum and family taxa profiled for the specific bacteria found? If so, what was the reason; if not, why were those the only ones pointed out in the article?

  3. How did you know lab research was what you wanted to do long term?

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  1. With so many diets like keto, carnivore, etc., what made you decide to go with a relatively normal diet as the homogenous diet. Do you think that more extreme diets listed above can have more of an impact on metabolites?
  2. Would researching on model organisms be easier than humans when trying to identify how metabolites contribute to disease outcomes?
  3. When did you get started on your first independent project and how did you work through it?
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  1. What do you see as the most unanswered question in the role of the microbiome in preventative health care? What do you want to do to try and answer it?
  2. What technologies are you most excited about right now in microbial research?
  3. If you were selecting students to take into your lab, what would you look for?
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  1. Since publishing the paper on the effect of diet on the human gut microbiome and concluding that a mix of dietary modification and microbial therapies is necessary to control MDM profiles, have you identified possible microbial therapies that might be effective?
  2. Could you test the impact of personal microbial diversity in animals in renal failure? It seems like someone in renal failure might have lost some interpersonal variation, and thus diet variation might have a different effect?
  3. What skills do you look for a student to have if they are interested in joining your lab?
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  1. What possible next steps would you take to assess how the microbiome influences variability in the efficiency of the conversion of glycuronidated substrates?
  2. Can you elaborate more on LC-MS/MS analysis and what it is helpful for in general?
  3. You mentioned in your advice to trainees hoping to start labs that they should consistently set time aside to think creatively and generate new ideas. What does this process look like to you and how has this helped you throughout your career?
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  1. Dr. Guthrie talks about using the gut microbiome to help prevent or treat kidney disease. I’m wondering, what might be some challenges or limitations to actually using microbiome manipulation in real medical treatments?

  2. In the 7-day homogeneous diet study, even when everyone ate the same thing, their microbiome-related metabolites were still super different. Does this mean diet alone isn’t enough to change our microbiomes? And if that’s the case, what else would we need to actually shift those harmful metabolite levels?

  3. The second paper shows that gut microbes can actually reactivate a chemotherapy drug and cause serious side effects. Should we start considering a patient’s microbiome before prescribing treatments like this? Could adjusting treatment plans based on someone’s gut bacteria make chemo safer or more effective?

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  1. Would the decrease in phylodiversity be a clue into the impact of the microbiome with respect to kidney disease?
  2. How would you address the huge variability observed in humans? There’s a bunch of studies that show each section of a human would have vastly different taxonomic distribution due to different environmental factors in play.
  3. How would you go about creating a method to study more about a topic and was there any moments where you had to be creative to find out more about a certain phenomenon due to limitations?
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  1. Science – Your study showed that even when people ate the exact same diet for a week, their gut chemicals (metabolites) stayed unique. What do you think keeps this personal “microbiome fingerprint” intact? For example, could it be gut viruses (phages) controlling bacteria? Or is it more towards how the gut lining interacts with microbes or even bacteria sharing food with each other (cross-feeding)?Understanding this could explain why some people’s microbiomes change easily with diet while others don’t.

  2. Method – In your work on how gut microbes reactivate a chemo drug (irinotecan), how did you figure out whether the bacteria were responsible versus the liver? Did you use tools like animals to test bacteria’s role or even lab experiments in growing bacteria in dishes (in vitro) to see what they produce? What challenges did you face translating these findings to real patients, who have complex diets and lifestyles?

  3. Career – Microbiome research mixes biology, computing, and medicine. For students diving into this field, how do you stay deeply skilled in one area while learning just enough about others? What mistakes should they avoid?

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  1. Science–how have you been able to establish a direct tie with the microbiome and kidney cell signaling?
  2. Methods–How do you feel about probiotics and their potential in the medical field for “restoration” of microbiomes?
  3. Career–how did you decide you wanted to pursue a PhD? How difficult was it to achieve assistant professor status?