The potential of using blood and urine samples in gut health research

Gut health research has been typically focused on analysing faecal samples to identify microbial species in the gut and to study the metabolites produced by these species. However, recent advancements in metabolic analysis of blood and urine now enable researchers to explore the function of gut microbiota even in large cohorts: how the microbiota affects health, how it responds to environmental exposures, and how it influences the development and maintenance of chronic diseases.

Gut microbiota leave traces in numerous ways

The gut microbiota can be considered as an organ that produces compounds that are distributed to various tissues, regulating numerous processes in the human body. Many of these compounds are absorbed by circulation, therefore in addition to faeces, they also can be traced in blood and urine.

Perhaps the best studied compounds produced by bacterial metabolism are short chain fatty acids, of which the most abundant molecule is acetate, which is associated with cardiovascular disease risk (Kurilshikov 2019). Acetate is absorbed by the bloodstream and excreted in urine, and can be detected in both fluids. It was recently established that the level of acetate in blood, rather than in faeces, is relevant for estimation of this molecule’s health associations, presumably because short chain fatty acids are quickly absorbed rather than secreted into faeces (Kurilshikov 2019). Another example is TMAO which also can be traced in both blood and urine. This compound has been identified as the previously unrecognised link between specific dietary nutrients, gut microbes and cardiometabolic diseases. Therefore, measuring TMAO holds huge potential in developing different intervention strategies for prevention of cardiovascular diseases.

However, bacterial metabolites, such as short-chain fatty acids, can provide only a fraction of the full picture of how bacteria affect human health. Gut health has an indirect, yet, powerful effect on the body via leakage of fragments of dead bacteria into circulation. These pieces of bacterial cell walls feed low-grade chronic inflammation, and their increased levels in circulation are reflected in changes in the blood levels of lipoproteins, lipids and glucose. Eventually, the bacterial material contributes to metabolic disorders such as obesity, type 2 diabetes and cardiovascular diseases (Cani et al. 2012). Importantly, gut microbiota composition can be modified by exogenous and endogenous events, which is why researchers have high expectations for the gut microbiota being a modifiable causative factor for cardio-metabolic diseases.

 

Metabolomics can help to connect the dots 

As the health effects of gut microbiota may develop over several years, showing causality is difficult to achieve in human studies. Blood and urine metabolomics open new doors by enabling researchers to study the impact of gut microbiome on different areas of health. Gut microbiota are associated with a plethora of health conditions, including not only cardiovascular diseases, but type 2 diabetes and obesity, autoimmune diseases and mental disorders such as depression. Many of these associated diseases, such as type 2 diabetes, have signature metabolite levels that can be detected in blood and urine, thus metabolomics can help researchers to identify these complex associations. A well-known example is the observation of altered glucose levels in the blood and urine of type 2 diabetes patients.

Detailed metabolic profiling can provide a comprehensive overview of metabolic health which can help reveal connections between gut condition, gut microbes, nutrition, numerous disease areas and overall health condition. It grants a quantifiable overview of host health status while giving indications of future disease risks, making it a helpful tool for tracking intervention outcomes and identifying new therapeutic targets. In addition to the scientific benefits, patients often prefer giving blood or urine samples over faecal sampling, thus using blood or urine can help with recruiting and patient retention.

 

What can NMR provide to gut health research?

Recent evidence has shown that NMR metabolomics can provide novel biomarkers for gut diseases. As NMR provides a meaningful overview of host health, it’s particularly suitable for identifying connections between different areas of health and disease.

For instance, a low-grade inflammation marker in blood, glycoprotein acetyls (GlycA), has shown promising evidence as a viable biomarker for inflammatory bowel disease, increased intestinal permeability and microbiota richness (Dierckx et al. 2019; Mokkala et al. 2017; Kurilshikov et al. 2019).

Another example is low density lipoprotein (LDL). LDL carries lipids in the blood and is a risk factor for atherosclerosis. It was recently shown that in obese people certain gut microbes are associated with LDL lipids, whereas this association was absent in general population (Kurilshikov 2019). Such findings can help to explain how certain gut microbes may contribute to body weight and to disease risk. Kurilshikov and colleagues also used blood metabolomics to identify bacterial metabolic pathways and bacterial species associated with a higher cardiovascular disease risk phenotype.

 

Key points

  • Comprehensive metabolic profiling in blood and urine can be a powerful tool to explore the function of the gut and track the impact of gut microbiota composition on certain disease outcomes.
  • Using blood and urine samples can improve recruiting and patient retention, as patients often prefer providing these samples over faecal sampling.
  • NMR metabolomics can provide novel biomarkers for gut research and is a particularly suitable method to reveal connections between different areas of health, such as the impact of the gut on cardiovascular diseases.

Extra reading:

Interested how Nightingale's metabolomics platform can support gut microbiome research? Read more here.

References:

Cani et al. “Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity,” Gut Microbes 2012;3(4):279–288.

Kurilshikov et al. “Gut Microbial Associations to Plasma Metabolites Linked to Cardiovascular Phenotypes and Risk: A Cross-Sectional Study” Circulation Research. 2019;0.

Dierckx et al. “GlycA, a nuclear magnetic resonance spectroscopy measure for protein glycosylation, is a viable biomarker for disease activity in IBD” JCC 2019;13(3):389–394.

Mokkala et al. “Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women“ Metabolism - Clinical and Experimental 2017;69:43–50.

 

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