Gut microbial metabolism of specialized compounds from dietary plants
Abstract/Contents
- Abstract
- Plants are prolific chemists and synthesize a plethora of compounds with diverse bioactivities. We encounter these specialized molecules with every meal through the consumption of plant-based foods. While a diet rich in plants has been shown through epidemiological studies to be protective against chronic diseases like diabetes and cardiovascular disease, the molecular components of plants responsible for these benefits are still unknown. A major challenge in assessing the health impacts of these compounds is identification of the relevant metabolites that result from their digestion. Just as plants are experts at building complex molecules, gut microbiota are specialists in breaking them down. The gut microbiome has enormous capacity for metabolism and has been shown to metabolize a variety of plant compounds. Here, we describe our efforts towards elucidating the metabolic fates of bioactive compounds from dietary plants following consumption, as mediated by the gut microbiome. We began our studies with cruciferous vegetables, such as cabbage and broccoli. Cruciferous plants produce glucosinolates that can be metabolized by gut bacteria to generate cancer-preventive isothiocyanates. We established the genetic and biochemical basis for activation of glucosinolates by a common human symbiont Bacteroides thetaiotaomicron. Using a genome-wide screen, we identified a gene cluster responsible for isothiocyanate production and demonstrated the importance of these genes in determining host exposure to isothiocyanates. We next turned to Solanaceous plants like potato and tomato. We found steroidal alkaloid aglycones, derived from glycosides made in the plant, to be one of the major classes of compounds that accumulate in systemic circulation following tomato and potato consumption. Furthermore, we showed that host exposure to these compounds is gated by gut microbial metabolism, which is responsible for removing sugar side chain from these molecules and modifying the aglycone core. By surveying metabolism of steroidal glycoalkaloids by intestinal bacteria from human donors, we discovered significant inter-individual variation in the products formed, and a screen of human commensals enabled us to identify specific bacterial strains involved. Finally, we performed preliminary in vitro bioactivity assays and metabolomics analyses with human samples to explore the relevance and effects of this metabolism on host physiology. Taken together, we demonstrate two examples of dietarily abundant plant molecules whose bioactivities and bioavailability are mediated by intestinal microbiota. These studies highlight that, from a common dietary plant input, the gut microbiome can impact divergent health outcomes in the host.
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 | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Liou, Catherine San Ru |
|---|---|
| Degree supervisor | Sattely, Elizabeth |
| Thesis advisor | Sattely, Elizabeth |
| Thesis advisor | Dodd, Dylan, 1981- |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Degree committee member | Dodd, Dylan, 1981- |
| Degree committee member | Khosla, Chaitan, 1964- |
| Associated with | Stanford University, Department of Chemical Engineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Catherine Liou. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/ts860ds5913 |
Access conditions
- Copyright
- © 2022 by Catherine San Ru Liou
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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