The scene opens up to a birds-eye view of the African savannah. From afar, all seems calm: the tall grass sways in the wind as sunlight bathes the sparse trees and bushes in gold. But as you zoom in closer there’s something else: a cluster of dark shapes in motion on the horizon. Sounds of a feeding frenzy hit you before you can distinguish one animal from another in the mass: the yapping of hyenas and screeching of vultures as they descend on an fresh antelope carcass. A pride of lions pads away, licking their jowls and letting the scavengers finish the rest.
This is our classic idea of an ecosystem. It is also one of the more easily understood models of the human gut microbiome – something Dr. Lawrence David allude to during his talk this week. A complex and dynamic community of different species all fighting to survive on scraps, grow, and reproduce. Bacteria don’t quite get the David-Attenborough-narrated nature-channel-treatment, but the dynamics of this microecosystem is incredibly important to human health. Just like real ecosystems provide services like air and water filtration, the gut microbiome provides services like immune defense, fiber degradation, and provisioning of important biomolecules. In return, we provide a home in our gut and nutrients from our food for the microorganisms. Aside: this 2018 paper from the Yoder lab has an interesting take on viewing the microbiome as an ecosystem with classic ecosystem services- http://yoderlab.org/cms/wp-content/uploads/2018/03/McKenney-et-alMolEcol.2018.pdf
Lawrence’s presentation primarily focused on the food actually getting to the microbiome. But what if people aren’t eating, at least not the traditional way? In our savannah, what if the grass has dried up, depleting antelopes of their food source? Or the lions decided to go vegetarian to reduce their carbon footprints, leaving minimal antelope carcasses to feed on? We would expect the communities involved to change drastically because of a lack of food availability. Do the hyenas die out and leave space for wild dogs to proliferate?
This is the question (well… analogous to the question) that my mentor, graduate student Jun Zeng, has set out to answer. In our project, the patients in question are hematopoietic stem cell transplant (HSCT) patients. In other words, patients who have received bone marrow transplants to treat various cancers. This usually involves chemotherapy to kill off cancerous cells. Oftentimes, nausea and inflammation leave patients undergoing this process unable to eat food enterally (through the intestine) without extreme discomfort. Doctors will resort to total parenteral nutrition (TPN). Under TPN, nutrients are delivered directly into the bloodstream.
Jun has set out to answer the question: how does TPN alter the composition and function of the microbiome in HSCT patients? He’s already analyzed the compositional part of this project, utilizing 16S sequence sequencing from stool samples to determine that TPN radically alters the diversity and makeup of bacteria in the gut. I will be working on a subset of this larger project, mainly focusing on the “function” aspect. More specifically I am looking at bacteria’s ability to break down insoluble fibers in the gut and product short chain fatty acids (SCFA) in the process. SCFAs are beneficial to gut health and indicators of functioning microbiomes.
My two main questions are: do TPN patients have less dietary fiber available to their gut microbiomes? And, subsequently, do the microbiomes of patients on TPN have reduced capacity to break down dietary fiber? This first question will be helpful in confirming our assumption that less food and actual dietary fiber is able to get to the gut microbiota during TPN. If that checks out, we can then perform an experiment in which a fiber is added to the samples and then left to be degraded by the bacteria present. After some time, comparing the amount of fiber left between normal diet and TPN patient samples should help us understand if TPN promotes species less able to break down fiber. This has implications for the treatment of stem cell transplant patients and any other patient under consideration for TPN. We’ll be able to better understand the risks associated with TPN or, potentially, inform efforts to return microbiome function with probiotics or prebiotics following treatment.
