Main Text
Metabolomics is the science focused on the study of the metabolism in
living organisms1. Their aim is to measure the
metabolites that are the intermediate and final molecules of the
biological processes. The entire collection of the metabolites is called
the metabolome. Changes in the biological system would be reflected in
the metabolome, since metabolites are involved in the biological
functions. The metabolome is affected by the interaction of different
factors such as the host, diet, lifestyle, pharmacological treatment and
gut microbiota among others. Being the latter one of the most important
factors as the gut hosts the largest number of microorganisms in the
body (e.g. up to 109 bacteria per gram of
luminal content2).
Currently, there is not a single technique that detects the entire
metabolome. Metabolomics uses high-throughput techniques that allow
structural elucidation, such as mass spectrometry (MS), which in
combination with a separation technique such as liquid chromatography
(LC) provides broad detection of metabolites.
Recently, Bar, N. et.al. analysed 491 serum samples from healthy
individuals using LC-MS, for whom they have collected extensive clinical
lifestyle dietary, genetics, and gut microbiota data3.
The serum metabolic profile consisted of 1,251 metabolites encompassing
mainly lipids, amino acids, xenobiotics, carbohydrates, peptides, and
nucleotides, and 30% of unidentified compounds. The reproducibility,
accuracy, and long-term stability of the metabolomic data was validated
by two tests. First, authors compared the levels of creatinine and
cholesterol from metabolomics to those obtained using standardized
laboratory tests, obtaining good correlation results (Pearson’sr> 0.75). Second, significant correlation (Spearmanp = 0.68 ±0.06) was obtained between metabolic profiles before and
after one week in a small cohort. These results confirm that the
metabolic profile is unique and specific for each
individual3.
From the factors that affect the metabolome, diet and the gut microbiota
had the largest predictive power with 48.9% and 30.8%, respectively
(Figure 1). This highlights and confirms the importance of diet and gut
microbiota in the levels of serum metabolites. Robustness and
reproducibility of the gut microbiota results were validated in two
independent cohorts revealing strong associations between serum
metabolites and gut microbiota3. Interestingly, this
relationship between the gut microbiota and serum in pediatric allergy
and asthma has been recently described4. Children with
food allergy with or without asthma compared to those with asthma alone
showed significant alterations in the metabolism of secondary biliary
acids as well as aromatic amino acids. These are products of
microbiota-dependent enzymatic conversion in the gut. This study
suggests that the observed modulation in amino acid and lipid
metabolites may be strongly dependent on immune cells interplay with the
gut microbiota4. Other metabolites related with gut
microbiota are the short chain fatty acids (SCFA). In a recent review,
it was described that SCFAs acetate, propionate, butyrate, and
pentanoate promote both regulatory T and B cells differentiation and
their potential beneficial effects on the prevention of food
allergy5.
Another review associates the gut microbiota with asthma and allergy and
suggest that the mechanisms by which gut microbiota influence local
immune responses include the altered differentiation of immune cell
populations and the local production of metabolites that affect distal
sites in asthma6.
Recently, Bar, N. et.al. pointed that the gut microbiota may modulate
the production of many circulating metabolites independent of
diet3. Among the taxa, Firmicutes andBacteriodetes were the main bacterial predictors of serum
metabolites3. For instance, the ratio of theFirmicutes and Bacteroidetes phylum levels could be a
significant indicator for certain diseases such as obesity.
Additionally, the modulation between diet and microbiota, and their
impact on serum metabolome were tested. As a proof of concept Bar, N.
et.al. analysed a week-long intervention with sourdough bread or
industrial white bread3. Indeed, changes in diet, and
the intervention with prebiotics, probiotics, and symbiotics are
different approaches to modulate the gut microbiota with the aim of
treating diseases. These strategies, which are being increasingly
studied, are promising for the development of a preventive therapy by
restoring altered microbiome functionality or as an adjuvant in specific
immunotherapy7.
Although the study of Bar, N. et.al. is compelling, it has some
limitations3. One of the main limitations is based on
the use of samples from healthy individuals, as the disease and the
pharmacological treatment are two of the main factors that modify the
serum metabolome. As examples, current evidence has shown that severe
allergic phenotypes displayed a characteristic plasma
signature8. In addition, grass-pollen sublingual
immunotherapy response is different in serum of active and placebo
allergic patients9.
To sum up, metabolomics is a useful resource for studies either for
understanding the molecular mechanisms in health and disease, or in
interventional studies with systemic metabolic alterations.
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