Longitudinal intestinal microbiome collection and cultivation reveals site-specific compositions and functions
Abstract/Contents
- Abstract
- The spatiotemporal structure of the human microbiome, proteome, and metabolome reflects and determines regional intestinal physiology and may have implications for disease. Yet, we know little about the distribution of microbes, their environment, and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals. To address these deficiencies, my thesis work aimed to profile the composition and function of the microbiome along the spatial gradient of the intestinal tract using a variety of different techniques and model systems. In CHAPTER 2, I work with the Tabula Sapiens consortium to collect immune cells and microbial contents from matched regions of the human intestinal tract of organ donors. We found spatially distinct microbial communities and immune transcriptomic profiles. In CHAPTER 3, I work with the Tabula Microcebus consortium to elucidate the composition of the microbiota along the mouse lemur intestinal tract in two lemurs: one with recent antibiotic history and one without recent antibiotics. Similar to human organ donors, we found incredibly diverse and spatially distinct microbial communities in a mouse lemur that did not recently take antibiotics. However, we found profoundly lower diversity all throughout the intestinal tract of the mouse lemur that had recently taken antibiotics, highlighting how perturbances to the microbiota can influence both small intestine and large intestine communities. In CHAPTER 4, I attempt to address many of the limitations of using organ donors by studying the human intestinal microbiota using an ingestible sampling device that allows for noninvasive collection of human intestinal contents during physiological conditions. We were able to profile spatially distinct microbiotas, bile acids, and secreted human proteomes along the intestinal tract of 15 healthy human subjects. Further, we were able to integrate this multi-omics dataset to provide important biological insight into microbial interactions with bile acids and the human proteome that have important implications for human health. In CHAPTER 5, I use cultivation techniques to acquire small intestine and stool-derived in vitro communities, along with a comprehensive library of isolates (> 400), from the human small intestine and stool of a single subject. Mouse colonization of these communities and isolates reveals how taxa maintain a preferential spatial niche, as well as highlight the importance isolate ancestry in undergoing spatially distinct dynamics in response to a diet switch. Ultimately, I was able to annotate compositional and functional differences in the microbiome along the intestinal tract using a variety of different methods, highlighting the need for investigation beyond the stool microbiota to be able to further harness and tune the effects of the microbiota on human health.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Culver, Rebecca Neal |
|---|---|
| Degree supervisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Bhatt, Ami (Ami Siddharth) |
| Thesis advisor | Fordyce, Polly |
| Thesis advisor | Sherlock, Gavin |
| Degree committee member | Bhatt, Ami (Ami Siddharth) |
| Degree committee member | Fordyce, Polly |
| Degree committee member | Sherlock, Gavin |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Rebecca N. Culver. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/yf746qw8258 |
Access conditions
- Copyright
- © 2023 by Rebecca Neal Culver
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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