Impact of antibiotics and dietary fibre on gut bacterial diversity: an in vitro approach
File(s)
Author(s)
Johnson, Laura Patricia
Type
Thesis
Abstract
The gut microbiota carries out many roles essential for health. Various factors can affect the structure and function of the gut flora. Antibiotics can perturb the microbial composition, which can negatively affect functioning. Diet can also impact the gut bacterial composition, and can have both positive and negative effects. Therefore, there is a growing interest in therapeutic manipulation of the gut microbiome, and dietary intervention via prebiotics represents an attractive option. However, an important yet often overlooked driver of gut bacterial communities is the impact of ecological and evolutionary dynamics on the whole ecosystem. We require a greater understanding of species interactions and their role within the gut bacterial community. Here, I use in vitro methods to explore the effects of diet and antibiotics on the gut microbiota, whilst considering the impact of ecology and evolution.
I investigated the effects of antibiotics on whole faecal communities, and explored the role of prebiotics in restoration of the bacterial community after antibiotic use. I found that in some cases, prebiotics can counteract the negative effects of antibiotics, both taxonomically and metabolically. I also explored the long-term effects of prebiotic supplementation with inulin on the composition and metabolic profile of whole faecal communities using a chemostat model, and found that prebiotic driven changes resulted in an increase of beneficial genera. Cultures recovered over a period of several weeks from an initial decline in concentrations of key metabolites. I was interested to see whether bacterial communities adapted to the high inulin environment over time, so metagenome sequencing was carried out to assess any genetic changes that occurred after long-term supplementation with inulin. I detected nucleotide changes associated with carbohydrate fermentation, demonstrating potential adaptation to better utilise inulin. Finally, to look at species interactions more closely, I created simplified artificial communities which consisted of a subset of key gut bacterial species. I looked at specific interactions between species in response to long-term inulin supplementation, and found interesting cases of cross-feeding between species species against a background of generally negative species interactions consistent with competition for shared resources.
My research aims to understand more about ecological and evolutionary dynamics of the gut microbiota, in general and in response to prebiotics. Such knowledge can help to optimise dietary intervention strategies to better human health.
I investigated the effects of antibiotics on whole faecal communities, and explored the role of prebiotics in restoration of the bacterial community after antibiotic use. I found that in some cases, prebiotics can counteract the negative effects of antibiotics, both taxonomically and metabolically. I also explored the long-term effects of prebiotic supplementation with inulin on the composition and metabolic profile of whole faecal communities using a chemostat model, and found that prebiotic driven changes resulted in an increase of beneficial genera. Cultures recovered over a period of several weeks from an initial decline in concentrations of key metabolites. I was interested to see whether bacterial communities adapted to the high inulin environment over time, so metagenome sequencing was carried out to assess any genetic changes that occurred after long-term supplementation with inulin. I detected nucleotide changes associated with carbohydrate fermentation, demonstrating potential adaptation to better utilise inulin. Finally, to look at species interactions more closely, I created simplified artificial communities which consisted of a subset of key gut bacterial species. I looked at specific interactions between species in response to long-term inulin supplementation, and found interesting cases of cross-feeding between species species against a background of generally negative species interactions consistent with competition for shared resources.
My research aims to understand more about ecological and evolutionary dynamics of the gut microbiota, in general and in response to prebiotics. Such knowledge can help to optimise dietary intervention strategies to better human health.
Version
Open Access
Date Issued
2017-09
Date Awarded
2018-07
Advisor
Barraclough, Timothy
Sponsor
National Centre for the Replacement, Refinement, and Reduction of Animals in Research (Great Britain)
Grant Number
LATPG.G01500
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)