Quantify the impact of the microbiome
Quantify the impact of the microbiome
Metabolomics | The functional readout of the microbiome’s impact
Metabolites are the easiest message to quantify in microbiome-host communication. Standardized metabolomics provides a precise functional readout of the impact of microbial communities, anchoring the interpretation of gene-derived functions to the actual effectors that are metabolites.
Metabolomics also measures host metabolites that are modulated in response to microbial communities. Thus, the use of standardized and quantitative metabolomics provides the functional readout that bolsters our understanding of the microbiome’s impact in health and disease.
Here are a few examples:
Circulating tryptophan derivatives and SCFAs play an essential role in host immune training | Belkaid and Harrison 2017
Indole derivatives associate with osteoarthritis pain | Mehta et al. 2023
The interplay between indoxyl sulfate, TMAO and SCFAs link the microbiome to kidney damage in a mouse model of hypertension | Avery et al. 2023
Fecal levels of bile acids associate with microbial community structures in pediatric patients with Crohn’s disease | Connors et al. 2020
p-cresol sulfate and other microbiota-derived metabolites are present in the brains of patients with Parkinson’s disease | Kalecký et al. 2023
SCFAs protect blood-brain barrier function | Knox et al. 2022
High-soluble-fiber diet modulates gut microbial communities and plasma levels of corresponding microbial metabolites (SCFAs, p-cresol sulfate) and influences pulmonary vascular remodelling | Pakhomov et al. 2023
3-indole acetic acid could modulate response to chemotherapy in pancreatic cancer | Tintelnot et al. 2023
Read the blog: Does metabolomics have a place in microbiome research?
Quantify the impact of the microbiome with standardized metabolomics
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Short-chain fatty acid PLUS (SCFA+) assay
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Metabolomics supports microbiome-related innovation
Quantifying microbial metabolites and their effects on the host provides a wealth of new therapeutic targets and approaches, supporting preventive, predictive, personalized and even participatory (4P) medicine:
Fecal microbiota transplant (FMT)
Metabolomics provides predictive markers of patient response to FMT | Routy et al. 2023.
Prebiotics
Diet impacts the immune system via fiber-derived microbial metabolites | Pakhomov et al. 2023.
Postbiotics
Supplementation with microbial metabolites impacts the course of complex diseases such as multiple sclerosis | Duscha et al. 2020
Fecal microbiota transplant is the transfer of living gut microbiome from healthy individuals with promising results for gastrointestinal ailments, but also for neurological, autoimmune and metabolic disorders. However, for FMT as for drug-based therapies, not all patients are responsive.
Patient responses vary both for FMT and drug-based therapies, and metabolomics has provided clues to:
- Understand differences in response
- Improve care with significant stratification
- Provide personalized treatments
- Improve response to treatment, e.g. with dietary changes (prebiotics) or supplementation (postbiotics)
Drive therapeutic innovation with metabolomics
Microbial metabolites prime the body for complex diseases
The origin of complex or multi-factorial diseases cannot be explained by genetics alone. Metabolomics helps fill in the blanks. Growing evidence implicates the Western-style diet (WSD), obesity and metabolic disease as risk factors, underlining the need for a metabolic perspective when studying these conditions.
In our whitepaper on the common origin of complex chronic diseases, we used metabolomics to illustrate the link between the WSD, health and disease. We created metabolic models of cancer, neuropsychological and autoimmune diseases, tracing the impact of metabolites from the WSD on gut microbiome composition, function and signaling in patients.
Microbial metabolites such as deoxycholic acid and other secondary bile acids, branched-chain amino acids, short-chain fatty acids, and tryptophan derivatives associate with multiple complex diseases and can be linked to many pathophysiological hallmarks.
The whitepaper proposes models of priming for complex chronic diseases that show how metabolomics can:
- Mechanistically Explain the relevance of the gut microbiome in these conditions
- Support the design of future studies to uncover new prodromal biomarkers of complex diseases
- Reveal new potential drug targets
- Understand and exploit the effects of diet and supplementation on drug efficacy and patient response
Learn more about the role of the microbiome in complex diseases
The microbiome and the immune system
While each autoimmune disease has its own unique set of susceptibility genes, conditions such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and type 1 diabetes (T1D) share susceptibility loci that affect antigen presentation to T and B cells.
In autoimmune diseases, affinity maturation wrongly selects B cells that target the body’s own tissues instead of pathogens. These cells may persist for years until another trigger activates them, prompting an immune attack against the body.
The metabolic models for the autoimmune diseases described in our whitepaper begin with the same three steps:
- Innate immune system suppression
- Shift to pro-inflammatory T helper cells
- Hyperinflammatory environment
These steps prime the immune system for autoimmunity, often years before symptoms occur. Deficiencies or changes in microbial metabolites can trigger numerous mechanisms involved in these three steps, as shown on the figure.
SCFAs, polyunsaturated fatty acids, and indole derivatives have all been shown to affect the host’s immune system. Altered metabolite ratios, such as secondary to primary bile acids, are also a common trait in complex diseases, especially at early stages.
More resources on the microbiome’s impact
Gut microbiome | Myths and metabolites
How does the microbiome affect host metabolism and health and wellbeing? How does dysbiosis contribute to disease? Professor Hannelore Daniel discusses these questions and debunks a few myths about the microbiome.
Phenomics & Microbiome
In this episode, Alice Limonciel and Marc-Emmanuel Dumas discuss metabolites as the messengers of the microbiome towards the host, the added value of investigating multiple measures of the phenotype in the context of liver disease, and how machine learning and AI will impact the field in the near future.
Whitepaper – Complex diseases
Complex chronic diseases continue to rise, while efficient therapies and preventive actions remain elusive. This whitepaper provides a new perspective through the prism of metabolomics.