Discovery and Validation of Banana Intake Biomarkers Using Untargeted Metabolomics in Human Intervention and Cross-sectional Studies

Abstract

Background Banana is one of the most widely consumed fruits in the world. However, information regarding its health effects is scarce. Biomarkers of banana intake would allow a more accurate assessment of its consumption in nutrition studies. Objectives Using an untargeted metabolomics approach, we aimed to identify the banana-derived metabolites present in urine after consumption, including new candidate biomarkers of banana intake. Methods A randomized controlled study with a crossover design was performed on 12 healthy subjects (6 men, 6 women, mean ± SD age: 30.0 ± 4.9 y; mean ± SD BMI: 22.5 ± 2.3 kg/m2). Subjects underwent 2 dietary interventions: 1) 250 mL control drink (Fresubin 2 kcal fiber, neutral flavor; Fresenius Kabi), and 2) 240 g banana + 150 mL control drink. Twenty-four-hour urine samples were collected and analyzed with ultra-performance liquid chromatography coupled to a quadrupole time-of-flight MS and 2-dimensional GC-MS. The discovered biomarkers were confirmed in a cross-sectional study [KarMeN (Karlsruhe Metabolomics and Nutrition study)] in which 78 subjects (mean BMI: 22.8; mean age: 47 y) were selected reflecting high intake (126–378 g/d), low intake (47.3–94.5 g/d), and nonconsumption of banana. The confirmed biomarkers were examined singly or in combinations, for established criteria of validation for biomarkers of food intake. Results We identified 33 potentially bioactive banana metabolites, of which 5 metabolites, methoxyeugenol glucuronide (MEUG-GLUC), dopamine sulfate (DOP-S), salsolinol sulfate, xanthurenic acid, and 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline sulfate, were confirmed as candidate intake biomarkers. We demonstrated that the combination of MEUG-GLUC and DOP-S performed best in predicting banana intake in high (AUCtest = 0.92) and low (AUCtest = 0.87) consumers. The new biomarkers met key criteria establishing their current applicability in nutrition and health research for assessing the occurrence of banana intake. Conclusions Our metabolomics study in healthy men and women revealed new putative bioactive metabolites of banana and a combined biomarker of intake. These findings will help to better decipher the health effects of banana in future focused studies. This study was registered at clinicaltrials.gov as NCT03581955 and with the Ethical Committee for the Protection of Human Subjects Sud-Est 6 as CPP AU 1251, IDRCB 2016-A0013–48; the KarMeN study was registered with the German Clinical Trials Register (DRKS00004890). Details about the study can be obtained from https://www.drks.de.

Discovery of Intake Biomarkers of Lentils, Chickpeas, and White Beans by Untargeted LC–MS Metabolomics in Serum and Urine

“…A subgroup of eight participants underwent the fourth intervention with white beans, which was scheduled later. The subjects were on average 28 ± 6 years old (range: [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and had a BMI of 23.8 ± 3.6 kg m −2 (range: 18.6-28.9).…”

“…[20] Very recently, dopamine sulfate was found to be among the BFIs best predicting the intake of banana. [21]…”

Potential of food intake biomarkers in nutrition research

“…Food intake biomarkers can also be combined to achieve or improve classification of dietary intake. A recently published study used five discriminative metabolites to classify high and non-consumers of banana (39) . The predictive ability of these metabolites was tested using ROC curve analysis using partial least squares-discriminant analysis models of biomarker combinations.…”

New Advanced Glycation End Products Observed in Rat Urine by Untargeted Metabolomics after Feeding with Heat‐Treated Skimmed Milk Powder

“…Untargeted metabolomics has been used to discover candidate BFIs for a range of foods and food groups, such as cruciferous vegetables, [ 19,20 ] banana, [ 21 ] citrus, [ 22–24 ] red meat, [ 25 ] and potato products. [ 26 ] Some of the well‐established and validated BFIs include urinary proline‐betaine, the combination of methoxyeugenol glucuronide and dopamine sulfate for intake of citrus [ 27 ] and banana, [ 21 ] respectively. Hence, the discovery and identification of BFIs of HSMP intake may contribute to investigating the nutritional consequences of thermal degradation products from dairy products.…”