Gut microbiome-derived metabolites characterize a peculiar obese urinary metabotype
Abstract
Obesity is a complex multifactorial disease involving genetic and environmental factors and influencing several different metabolic pathways. In this regard, metabonomics, that is the study of complex metabolite profiles in biological samples, may provide a systems approach to understand the global metabolic regulation of the organism in relation to this peculiar pathology. In this pilot study, we have applied a nuclear magnetic resonance (NMR)-based metabolomic approach on urinary samples of morbidly obese subjects. Urine samples of 15 morbidly obese insulin-resistant (body mass index>40; homeostasis assessment model of insulin resistance>3) male patients and 10 age-matched controls were collected, frozen and analyzed by high-resolution (1)H-NMR spectroscopy combined with partial least squares-discriminant analysis. Furthermore, two obese patients who underwent bariatric surgery (biliopancreatic diversion and gastric bypass, respectively) were monitored during the first 3 months after surgery and their urinary metabolic profiles were characterized. NMR-based metabolomic analysis allowed us to identify an obesity-associated metabolic phenotype (metabotype) that differs from that of lean controls. Gut flora-derived metabolites such as hippuric acid, trigonelline, 2-hydroxyisobutyrate and xanthine contributed most to the classification model and were responsible for the discrimination. These preliminary results confirmed that in humans the gut microflora metabolism is strongly linked to the obesity phenotype. Moreover, the typical obese metabotype is lost after weight loss induced by bariatric surgery.
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Trigonelline is a natural alkaloid found in plants and animals, including humans.
“However, patients with sarcopenia had lower circulating concentrations of trigonelline, a natural alkaloid found in plants4 and animals, including in humans29,30 (Fig. 1a).”
From Trigonelline Is an NAD+ Precursor That Improves Muscle Function during Ageing and Is Reduced in Human Sarcopenia (2024) · cites this paper as [30]
Trigonelline was proposed as a biomarker of metabolic health or physical fitness because urinary trigonelline levels decrease during obesity and increase in professional athletes.
“Trigonelline was proposed as a biomarker of metabolic health or physical fitness because urinary trigonelline levels decrease during obesity and increase in professional athletes29,30.”
From Trigonelline Is an NAD+ Precursor That Improves Muscle Function during Ageing and Is Reduced in Human Sarcopenia (2024) · cites this paper as [30]
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Self-citation
- Authors
- Calvani, R., Miccheli, A., Capuani, G., Tomassini Miccheli, A., Puccetti, C., Delfini, M., Iaconelli, A., Nanni, G., & Mingrone, G.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Sapienza University of Rome (IT)
- Venue
- International Journal of Obesity
- Published
- 2010-03-09
- Volume
- 34
- Issue
- 6
- Pages
- 1095-1098
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2036006402
- Cited by
- 241
- References
- 30
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 14 · 2022: 18 · 2021: 13 · 2020: 21 · 2019: 11 · 2018: 14 · 2017: 16 · 2016: 19 · 2015: 20 · 2014: 15 · 2013: 17 · 2012: 18
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- obesity, gut microbiota, gut microbiota metabolites, insulin resistance, bariatric surgery, biliopancreatic diversion, gastric bypass, hippuric acid, trigonelline, xanthine, weight loss, metabolomics
- MeSH terms
- Blood Glucose, Humans, Insulin Resistance, Intestines, Male, Magnetic Resonance Spectroscopy, Obesity, Pilot Projects, Body Mass Index, Case-Control Studies, Bariatric Surgery, Metagenome, Metabolomics
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