Periodic Reporting for period 1 - OMIT (The role of microbial Oxylipins in the MIcrobe-hosT dialogue)
Período documentado: 2021-11-01 hasta 2023-10-31
Background & Significance: In the last decade the gut microbiome has become recognised as a co-evolved super-organ, intimately linked to our own physiology. Comprising trillions of microbes, including bacteria, of different phyla, our gut microbiome performs a range of key functions from aiding in digestion to immune system education. In addition, we now know that certain gut bacteria synthesis membrane associated glycine and sphingolipids which display signalling functions. Problem: However, our knowledge of the types of lipid signals produced by our gut bacteria is limited in particular our knowledge of a subset of lipids known as oxylipins. Oxylipins are generated from the oxidation of unsaturated fatty acids. Human oxylipins (hOXY), are well characterised and are key regulators of inflammation. However, the diversity, functions, and impact of microbially derived oxylipins (mOXY) are not well understood. For instance, what are the types and ranges of mOXY that are produced by residents of our gut microbiome? Are they dietary dependant? What are their roles? How are they differentially influencing health and disease and how can they be exploited for health benefits?
OMIT aims to address some of the key questions related to mOXY following 5 specific research objectives (RO) listed below:
1. RO1: develop and validate an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for the comprehensive extraction and analysis of oxylipins from faeces and bacterial supernatants.
2. RO2: perform bacterial co-incubations (i.e. bacteria + precursor) to determine the oxylipins produced by specific bacteria.
3. RO3: determine the function of mOXY in microbe-microbe interactions.
4. RO4: determine the range and type of mOXY in faeces from healthy and diseased individuals.
5. RO5: determine the function of mOXY in microbe-host interactions.
Why is this important for society? OMIT represents a highly original and innovative approach to significantly improve our understanding of mOXY and their potential importance towards our health / disease status. This will open avenues for microbiome-based approaches to disease risk monitoring and management.
OMIT aims to address some of the key questions related to mOXY following 5 specific research objectives (RO) listed below:
1. RO1: develop and validate an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for the comprehensive extraction and analysis of oxylipins from faeces and bacterial supernatants.
2. RO2: perform bacterial co-incubations (i.e. bacteria + precursor) to determine the oxylipins produced by specific bacteria.
3. RO3: determine the function of mOXY in microbe-microbe interactions.
4. RO4: determine the range and type of mOXY in faeces from healthy and diseased individuals.
5. RO5: determine the function of mOXY in microbe-host interactions.
Why is this important for society? OMIT represents a highly original and innovative approach to significantly improve our understanding of mOXY and their potential importance towards our health / disease status. This will open avenues for microbiome-based approaches to disease risk monitoring and management.
An analytical platform for the extraction, detection and identification of oxylipins in bacterial supernatants and faecal samples utilising a combination of solid-phase extraction, ultra-performance liquid chromatography, high resolution mass spectrometry, and Progenesis software was developed and validated. This platform enables targeted and untargeted analyses of human or microbial (mOXY) oxylipins, and most importantly, facilitates the discovery of novel mOXY, particularly those that may be relevant from a microbe-host-health perspective.
To date, data generated from OMIT suggest that novel mOXY are generated from Pseudomonas aeruginosa, mOXY are detected in faeces from selected healthy volunteers and that a sex-difference may exist in the range and type of oxylipins detected.
Data from OMIT has already been disseminated in two peer-reviewed publications and at national (within Ireland) and International Conferences.
To date, data generated from OMIT suggest that novel mOXY are generated from Pseudomonas aeruginosa, mOXY are detected in faeces from selected healthy volunteers and that a sex-difference may exist in the range and type of oxylipins detected.
Data from OMIT has already been disseminated in two peer-reviewed publications and at national (within Ireland) and International Conferences.
OMIT represents a novel and focused project in the new and rapidly evolving area of bacterial lipids. It has progressed our knowledge of gut associated bacterial lipids and bacterial oxylipins beyond the state of the art including the type and range of lipids form by gut-associated bacteria. In addition, untargeted data generated from OMIT will continue to facilitate and uncover novel bacterial oxylipins.
Long-term, OMIT will have wider societal and socio-economic impacts. HOW? We know the microbiome impacts host physiology and thus health outcomes. We also know that lipids act as signalling molecules and dyslipidaemia is associated with many chronic diseases. We are beginning to understand that the lipids produced by our gut microbiome are also correlated with disease outcomes. OMIT expands, and will continue to expand our current knowledge of the latter and thus open a pandoras box of potential novel lipids that may be utilised for clinicians as biomarkers and in personal medicine, or by the pharmaceutical industry as potential therapeutics to disease. By providing potential biomarkers for chronic disease risk and management, or therapeutics for treatment of chronic disease OMIT will have real societal impact. By aiding the burden of chronic disease OMIT will also have economic impacts by reducing the overall cost of healthcare to government and society.
In addition, open access bacterial lipids databases, results and publications will allow academics to leverage data to progress their specific research question(s) within microbiome or lipidomic research. It will benefit industry, particularly the Mass spectrometry- based industry, who can exploit the results to improve their existing lipidomic software to include bacterial lipid database. Many applications of lipidomic profiling remain confined to the research laboratory; however, this looks set to change and ongoing advances in technology, software, AI means that lipidomics now has significant application within the clinical environment. Thus, in time OMIT will benefit clinicians interested in the emerging subfield of clinical lipidomics as they strive to predict, diagnose, and manage disease based on a individuals lipidome status. OMIT will offer knowledge on how gut microbiome impacts host lipid levels. It will then in turn benefit patients by providing avenues for personalised medicine.
Long-term, OMIT will have wider societal and socio-economic impacts. HOW? We know the microbiome impacts host physiology and thus health outcomes. We also know that lipids act as signalling molecules and dyslipidaemia is associated with many chronic diseases. We are beginning to understand that the lipids produced by our gut microbiome are also correlated with disease outcomes. OMIT expands, and will continue to expand our current knowledge of the latter and thus open a pandoras box of potential novel lipids that may be utilised for clinicians as biomarkers and in personal medicine, or by the pharmaceutical industry as potential therapeutics to disease. By providing potential biomarkers for chronic disease risk and management, or therapeutics for treatment of chronic disease OMIT will have real societal impact. By aiding the burden of chronic disease OMIT will also have economic impacts by reducing the overall cost of healthcare to government and society.
In addition, open access bacterial lipids databases, results and publications will allow academics to leverage data to progress their specific research question(s) within microbiome or lipidomic research. It will benefit industry, particularly the Mass spectrometry- based industry, who can exploit the results to improve their existing lipidomic software to include bacterial lipid database. Many applications of lipidomic profiling remain confined to the research laboratory; however, this looks set to change and ongoing advances in technology, software, AI means that lipidomics now has significant application within the clinical environment. Thus, in time OMIT will benefit clinicians interested in the emerging subfield of clinical lipidomics as they strive to predict, diagnose, and manage disease based on a individuals lipidome status. OMIT will offer knowledge on how gut microbiome impacts host lipid levels. It will then in turn benefit patients by providing avenues for personalised medicine.