Author: Dario

A new diagnostic frontier: metabolomics

THE’otorhinolaryngology It is the medical discipline that studies the pathologies of ear, nose and throat, and includes inflammatory, infectious, immunological and tumor conditions. In recent years, an innovative technology, the metabolomics, is revolutionizing this field. It allows to analyze the metabolites, i.e. the products of cellular metabolism, in biological fluids such as blood, saliva or urine. Metabolomics represents the final phase of the so-called “-omics” sciences (genomics, proteomics, etc.) and is able to offer a detailed view of the patient’s health status. Thanks to this technology, it is possible to identify useful biomarkers for the early diagnosis, the prognosis and the therapy monitoring, contributing to the development of the precision medicine.

Clinical applications: from sleep apnea to cancer

Numerous studies have applied metabolomics to common diseases in otolaryngology. For example, in head and neck cancers, specific altered metabolites have been identified in saliva or blood, such as glutathione or the amino acids, which could indicate the presence of a tumor even in its early stages. In patients with allergic rhinitis,an involvement of the fatty acid metabolism and of the inflammatory processes, while in the obstructive sleep apnea metabolomics has revealed alterations in lipid and sugar levels, helping to better understand the mechanisms underlying this pathology. Even in conditions such as hearing loss or the Meniere’s disease, metabolite analysis provided important clues about the inflammation and oxidative stress affecting the inner ear.

Current challenges and future prospects

Experts believe that metabolomics is destined to become a key technology in clinical laboratories. This will require developing shared guidelines and conducting large-scale studies. The ability to understand ear, nose, and throat diseases and disorders at the molecular level represents a turning point for modern medicine, with concrete benefits for early diagnosis, personalized care, and therapeutic efficacy.

For further information: 

Noto A, Piras C, Atzori L, Mussap M, Albera A, Albera R, Casani AP, Capobianco S, Fanos V. Metabolomics in Otorhinolaryngology. Front Mol Biosci. 2022 Sep 8;9:934311. doi: 10.3389/fmolb.2022.934311.

New insights into the metabolomic profiles of benign prostatic hyperplasia

In recent years, the metabolomics It has proven to be an innovative tool to better understand thebenign prostatic hyperplasia (BPH). Several recent studies have shown that patients affected by BPH present significant alterations in metabolomic profiles, particularly in compounds involved in the metabolism of amino acids, of the lipids and of the sugars. These metabolic changes reflect the chronic inflammatory state and hormonal changes associated with prostate enlargement. Analyzing samples of urine, blood And seminal fluid, researchers have managed to identify biomarkers that could help in the early diagnosis and in monitoring disease progression.

Metabolomics as a diagnostic tool

One of the most promising developments is the use of metabolomics to distinguish thebenign prostatic hypertrophy from pathologies that can have similar symptoms, such as prostate cancer. Studies conducted with mass spectrometry techniques have highlighted specific metabolomic signatures which allow for greater diagnostic accuracy. This approach could reduce the use of invasive tests, such as biopsy, while improving theaccuracy in differential diagnosis. Furthermore, thanks to the identification of specific metabolites, it is possible to monitor the effectiveness of drug treatments and personalize therapies based on the patient’s metabolomic response.

Towards personalized therapies

Metabolomics is not only useful in diagnosis, but also in the development of new therapeutic strategies. Some studies have shown that drug administration can modify the metabolomic profiles in patients with benign prostatic hypertrophy, suggesting a potential for the creation of targeted therapies. In the future, thanks to the detailed understanding of the metabolomic pathways involved in thebenign prostatic hypertrophy, it will be possible to intervene more specifically, reducing side effects and increasing the effectiveness of the treatment. This represents an important step towards a precision medicine, even in areas that have been considered little explored so far, such asbenign prostatic hypertrophy.

For further information: 

• Zniber M, Lamminen T, Taimen P, Boström PJ, Huynh TP. 1H-NMR-based urine metabolomics of prostate cancer and benign prostatic hyperplasia. Heliyon. 2024 Mar 31;10(7):e28949.
• Pérez-Rambla C, Puchades-Carrasco L, García-Flores M, Rubio-Briones J, López-Guerrero JA, Pineda-Lucena A. Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia. Metabolomics. 2017;13(5):52.

A diagnosis still too subjective

There schizophrenia It is a serious and debilitating mental disorder that affects between 0.3% and 0.7% of the population. Symptoms are divided into positives (delusions, hallucinations, disorganized behavior) and negatives (apathy, emotional isolation) and often appear at a young age. Currently, the diagnosis is based exclusively onclinical interpretation of symptoms, a method that may be imprecise, especially in the presence of symptoms that overlap with other disorders such as bipolar disorder or theautism. It is therefore essential to identify more objective tools to recognize the disease early and improve treatment options.

The potential of metabolic biomarkers

In recent years there has been a growing interest in identifying biomarkers, i.e. measurable biological indicators that can support the diagnosis of psychiatric disorders. Among the emerging techniques, the metabolomics, which analyses the metabolites —small molecules present in body fluids such as blood, urine, or cerebrospinal fluid. This discipline allows us to obtain a snapshot of the physiological state of the organism. In schizophrenia, recent studies have observed alterations in the levels of essential polyunsaturated fatty acids (PUFA), vitamin E, creatinine, glutamate and other compounds. These variations could constitute a metabolic signature of the disease, useful both for early diagnosis and for monitoring the response to treatments.

Towards more precise medicine

From the analysis of hundreds of metabolites, for which advanced techniques such as mass spectrometry and the nuclear magnetic resonance, recurring patterns emerge. If confirmed by further research, the metabolomic biomarkers could revolutionize the diagnosis and the clinical management of schizophrenia, making psychiatry a more objective and personalized.

For further information: 

Davison J, OGorman A, Brennan L, Cotter DR. A systematic review of metabolite biomarkers of schizophrenia. Schizophr Res. 2018 May;195:32-50.

Metabolomics applied to depression

There metabolomics it is a science that studies the metabolites, or small molecules present in our body that reflect our state of health. These metabolites change in response to disease, stress, or diet. In depressionMetabolomics allows us to analyze how the body reacts at a chemical level, opening new avenues to better understand the disease. Recent studies have identified specific alterations in the metabolites of depressed people, suggesting that depression is not just a problem of the mind, but also involves the metabolism of the body.

Biomarkers of depression

Thanks to metabolomics, researchers are looking for biomarkers, that is, signals in the blood or urine that may indicate the presence of depression. For example, it has been seen that some substances linked tocellular energy or to the regulation of thehumor They are often unbalanced in depressed subjects. This approach can help make more precise diagnoses and choose more targeted treatments. Furthermore, we study how these molecules change with treatments, so as to predict which therapies will be most effective for each patient.

Towards a more personalized care

Metabolomics opens the door to personalized medicine, where treatments are tailored to each person’s chemical profile. This is particularly useful in depression, which can present itself in many different ways. Some studies have found that there are distinct metabolic profiles for different types of depression, such as that related to lack of energy or the one with more symptoms anxious. Knowing these differences can improve the effectiveness of treatments and reduce side effects.

For further information:

• Bot M et al. Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls. Biol Psychiatry. 2020;87(5):409-418. doi: 10.1016/j.biopsych.2019.08.016.
• Czysz AH et al. Can targeted metabolomics predict depression recovery? Results from the CO-MED trial. Transl Psychiatry. 2019;9(1):11. doi: 10.1038/s41398-018-0349-6.
• de Kluiver H et al. Metabolomics signatures of depression: the role of symptom profiles. Transl Psychiatry. 2023;13(1):198. doi: 10.1038/s41398-023-02484-5.
• Wang Y et al. Metabolomics on depression: A comparison of clinical and animal research. J Affect Disord. 2024;349:559-568. doi: 10.1016/j.jad.2024.01.053.

What is Parkinson’s disease and why is it difficult to diagnose?

The Parkinson’s disease It is a brain disease that affects mainly, but not only, older people and causes problems with movement, such as tremors, slowness and muscle stiffness, but also non-motor disorders such as depression and digestive difficulties. Currently, the diagnosis is mainly based on theclinical observation, but it can often be wrong, because the symptoms are similar to those of other diseases. Even brain imaging, such as MRI, does not always help decisively. For this reason, many researchers are looking for new, more reliable methods, such as the use of biomarkers in the blood or urine, which are chemicals that can more accurately indicate whether a person has Parkinson’s.

A new approach: metabolomics to study Parkinson’s disease

In a recent study from 2024, researchers used the metabolomics, which analyses the metabolites, that is, the small molecules produced by our body. This technique has allowed us to compare the blood of healthy people with that of Parkinson’s patients. They have been identified 15 altered metabolites, And 11 of these were reported for the first time as possible signs of the disease. The alterations concern in particular the caffeine metabolism, of the bile acids and of thearachidonic acid, all substances involved in important functions of the body. In addition, a model was created with artificial intelligence able to distinguish sick people from healthy people with a94% accuracy, much higher than the diagnosis made by the doctor alone.

What does this discovery mean for early diagnosis?

The results show that some metabolites present in body fluids (like blood, but also other fluids like urine) can become useful tools for a more precise and earlier diagnosis of Parkinson’s disease. The use of automatic models like the decision trees It also allows you to make the analysis easy to interpret, helping doctors make better decisions. These discoveries can lead not only to more effective diagnosis, but also to new personalized care, improving the quality of life of people affected by this complex disease.

For further information: 

Santos WT, Katchborian-Neto A, Viana GS, Ferreira MS, Martins LC, Vale TC, Murgu M, Dias DF, Soares MG, Chagas-Paula DA, Paula ACC. Metabolomics Unveils Disrupted Pathways in Parkinsons Disease: Toward Biomarker-Based Diagnosis. ACS Chem Neurosci. 2024 Sep 4;15(17):3168-3180. 

What is metabolomics and why is it important?

There metabolomics is the study of chemicals in our bodily fluids (such as urine or blood), calls metabolites, which arise from the functioning of the body. A recent study has analyzed 1,400 metabolites to understand if some of them are connected to the depression. Researchers have found that various metabolites they can increase or reduce the risk of depression. For example, substances such as N6-acetyl-lysine they seem protect us from disease, while others, such as the LysoPE(18:0/0:0), they can favor its onset. These findings suggest that analyzing metabolites could help better understand what causes depression.

The body’s pathways involved in depression

The metabolites found are linked to important pathways of the body, like the fat digestion, the energy production, the defense against oxidative stress and the brain function. Some metabolites also influence the immune system and the intestinal microbiota, elements that more and more research links to mental health. These findings show that depression is not only dependent on emotional or brain chemical factors, but also on how the body works at a metabolic level.

New possibilities for diagnosis and treatment

Thanks to the metabolomics, we could diagnose depression before it occurs, simply by analyzing urine or blood. Furthermore, we could personalize care based on the metabolites present in each person. The study also opens new avenues for developing drugs that act on specific metabolic processes, improving outcomes and reducing side effects. In summary, metabolomics is a new and promising tool for understand, prevent and better treat depression.

For further information: 

Dong T, Wang X, Jia Z, Yang J, Liu Y. Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study. Front Psychiatry. 2024 Jun 6;15:1391535. doi: 10.3389/fpsyt.2024.1391535. eCollection 2024.

An alliance between brain and gut

Autism, or autism spectrum disorder (ASD), is a complex condition that affects neurological development and manifests itself with difficulties in communication, behavior, and social interactions. In addition to the genetic basis already identified, an increasingly relevant element is the role of the so-called gut-brain axis (GBA), a two-way communication system between the gastrointestinal tract and the brain. In particular, the intestinal microbiome, or the set of microorganisms that live in the intestine, appears to influence the immune, neurological and metabolic balance, potentially contributing to the development of autism. 

The Microbial Signatures of Autism 

A recent study used an advanced approach based on data from multiple sources (microbiome, diet, gene expression, immunology) to identify common signals among individuals with ASD. The study, which involved numerous researchers from widely varying geographic locations, analyzed 25 omics datasets, comparing children with ASD to their non-ASD peers, matched for age and sex to reduce statistical bias. The following were identified: 591 microorganisms more present in children with autism and another 169 overlapping with those of non-ASD children. Among the most relevant microbial genera are Prevotella, Bifidobacterium, Bacteroides and Desulfovibrio. Furthermore, these bacteria are linked to alterations in brain gene profiles, to selective diets often poor in amino acids essential for the synthesis of neurotransmitters, and changes in inflammatory cytokine levels such as IL-6 and TGF-β. These relationships suggest afunctional architecture common that connects the intestine and the brain. Other studies highlight the important role of Clostridia and a lack of Lactobacilli and Bifidobacteria. Some differences may be related to diet (selective or not). Not all children with autism spectrum disorder are the same. In any case, the gut microbiota appears to play a key role.

Therapeutic implications and future prospects 

A particularly interesting aspect of these studies is the observation of changes in the microbiome after fecal microbiota transplant (FMT) treatments, which led to improvements in behavioral symptoms in autistic children. It should be noted, however, that this is not a routine procedure. Furthermore, it has been found that microbes associated with ASD tend to decrease over time after the intervention. Although it is not yet possible to state a definitive direct causal relationship, these findings lay the foundation for therapeutic strategies that aim to modulate the microbiome to improve autism symptoms. 

For further information: 

Morton JT, Jin DM, Mills RH, Shao Y, Rahman G, McDonald D, Zhu Q, Balaban M, Jiang Y, Cantrell K, Gonzalez A, Carmel J, Frankiensztajn LM, Martin-Brevet S, Berding K, Needham BD, Zurita MF, David M, Averina OV, Kovtun AS, Noto A, Mussap M, Wang M, Frank DN, Li E, Zhou W, Fanos V, Danilenko VN, Wall DP, Cárdenas P, Baldeón ME, Jacquemont S, Koren O, Elliott E, Xavier RJ, Mazmanian SK, Knight R, Gilbert JA, Donovan SM, Lawley TD, Carpenter B, Bonneau R, Taroncher-Oldenburg G. Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles. Nat Neurosci. 2023 Jul;26(7):1208-1217. doi: 10.1038/s41593-023-01361-0.

Altered metabolic pathways in disease

Although the Parkinson’s disease Although Parkinson’s disease is not the result of a metabolic disorder, cellular energy disruption and metabolic changes play an important role in the development of the disease. Parkinson’s disease is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Parkinson’s disease is the most common neurodegenerative movement disorder. As life expectancy increases, the prevalence and incidence of Parkinson’s disease is expected to increase. In 1990, 2.5 million people worldwide were affected by Parkinson’s disease. This number increased to 6.1 million in 2016, with a further doubling expected by 2040. Understanding how changes in metabolites lead to the progression of Parkinson’s disease may allow the identification of individuals in the earliest stages of the disease and the development of new therapeutic strategies. 

Towards new therapies and early diagnoses

The diagnosis of the Parkinson’s disease up to now it has been based on clinical symptoms, on medical history and response to dopaminergic therapy. DATscan (dopamine transporter scan) helps differentiate Parkinson’s disease from other movement disorders, such as essential tremor. However, does not distinguish between the different types of atypical parkinsonism. Accumulating evidence suggests that a series of subtle clinical changes may precede motor manifestation by years or even decades. The pathogenic mechanisms involved in Parkinson’s disease are only partially understood. The lack of reliable and objective measures for the detection, diagnosis and progression of Parkinson’s disease This constitutes a significant obstacle. It is also necessary to identify individuals in the early stages of the disease process, before symptoms develop, in order to optimize therapeutic intervention.

Why Metabolomics is Useful in Parkinson’s Disease 

Several research groups are using metabolomics to differentiate the metabolic profiles that characterize the motor progression of Parkinson’s disease and dyskinesia, gait, and balance, as well as non-motor symptoms such as depression and cognitive decline. Metabolomics allows for the comprehensive identification and quantification of metabolic products (the metabolome) and is considered an important tool for identifying metabolic biomarkers of disease status. Many factors, including age, sex, diet, drug exposure, and the presence of the disease, influence the metabolome. Recent technological advances have allowed the characterization of hundreds of metabolites. metabolic profile complete biological fluids (serum/plasma, liquor, urine, saliva) is one non-invasive tool which can be used to help predict the incidence, severity and progression of the disease. The advantage of metabolomic analysis, based on 1H nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), lies in its ability to discriminate more than 6500 metabolites and small molecules which define the chemical signature of biological activity and identify qualitative and quantitative changes. THEanalysis of the identity and concentration variations of metabolites can be used to better understand the biological changes during the development and progression of Parkinson’s disease pathological conditions. 

For further information: 

Ostrakhovitch EA, Ono K, Yamasaki TR. Metabolomics in Parkinsons Disease and Correlation with Disease State. Metabolites. 2025 Mar 18;15(3):208. doi: 10.3390/metabo15030208.

Depression and altered metabolism

The major depressive disorder (MDD, from the English Major Depressive Disorder) is a condition, often chronic, characterized by molecular alterations And dysregulation of metabolic pathways. Single metabolites and targeted metabolomic platforms have revealed several metabolic alterations in depression, including the energy metabolism, the neurotransmission and the lipid metabolism. In one study, 820 metabolites were identified using the Metabolon metabolomics platform in 2770 subjects from a Dutch cohort, with extensive clinical characteristics (1101 subjects with current MDD, 868 with MDD in remission, 801 healthy controls).

The revealing metabolites

The diagnosis of MDD was based on psychiatric interviews according to the DSM-IV. Depression severity was measured with the Self-Report Depressive Symptom Inventory.. The association between metabolites, MDD status, and depression severity was assessed at baseline and at 6-year follow-up. At diagnosis, 139 metabolites were associated with current MDD status and 126 with depression severity, with 79 metabolites overlapping.. 

The metabolomic signature of depression 

The metabolomic profile of depression identified indicated a altered lipid metabolism with downregulation of long-chain fatty acids And upregulation of lysophospholipids. This metabolomic signature offers a window into the pathophysiology of depression and a potential entry point for the development of novel therapeutic approaches through a more comprehensive coverage of the metabolome, to further specify the metabolic dysregulations in the depression and reveal mechanisms that have not yet been identified.

For further information: 

Jansen R, Milaneschi Y, Schranner D, Kastenmuller G, Arnold M, Han X, Dunlop BW; Mood Disorder Precision Medicine Consortium; Rush AJ, Kaddurah-Daouk R, Penninx BWJH. The metabolome-wide signature of major depressive disorder. Mol Psychiatry. 2024 Dec;29(12):3722-3733. doi: 10.1038/s41380-024-02613-6.

The contribution of metabolomics to the early diagnosis of autism

THE’autism It is a neurodevelopmental disorder characterized by difficulties in social communication and repetitive behaviors. Due to the large clinical heterogeneity of the disorder, early diagnosis remains complex. metabolomics, or the study of metabolites in body fluids, is emerging as a promising tool for identifying biomarkers useful for the early diagnosis of autism, especially in subjects at risk such as siblings of autistic children or carriers of genetic syndromes. Recent studies have highlighted alterations in amino acid metabolism, oxidative stress, mitochondrial dysfunctions And metabolites derived from the intestinal microbiota in subjects with autism spectrum disorder (ASD). 

Metabolites and severity of the clinical profile

Metabolomics can also help understand the variability of symptoms of autism. Some metabolites, such as p-cresol and theHPHPA, are associated with the severity of symptoms and are produced by intestinal bacteria (such as Clostridia spp.). High levels of these compounds appear to correlate with repetitive behaviors and cognitive impairments. Alterations in the levels of neurotransmitters (such as serotonin and GABA) are linked to more marked symptoms. Furthermore, in children with developmental regression, distinctive metabolic profiles have emerged, suggesting that certain metabolites may reflect different clinical trajectories. In this perspective, metabolomics could contribute to the phenotypic stratification and to the personalization of interventions.

Metabolomics and comorbidity in autism

People with autism spectrum disorder often present associated medical conditions, in particular gastrointestinal disorders And of sleep. The difficulty in communication makes these issues difficult to identify. Metabolites produced by the intestinal microbiota, detected through metabolomic analyses, can offer biological clues on these disorders. For example, abnormal levels of serotonin, melatonin or specific organic acids have been linked to sleep or intestinal disorders. In this sense, metabolomics can become a valuable ally for the integrated clinical management of the patient with autism, improving the quality of life and the effectiveness of treatments.

For further information: 

Siracusano M, Arturi L, Riccioni A, Noto A, Mussap M, Mazzone L. Metabolomics: Perspectives on Clinical Employment in Autism Spectrum Disorder. Int J Mol Sci. 2023 Aug 29;24(17):13404. doi: 10.3390/ijms241713404.