TY - JOUR

T1 - Influence of Age, Sex, and Diet on the Human Fecal Metabolome Investigated by 1H NMR Spectroscopy

AU - Cui, Mengni

AU - Trimigno, Alessia

AU - Aru, Violetta

AU - Rasmussen, Morten A.

AU - Khakimov, Bekzod

AU - Engelsen, Søren Balling

N1 - Funding Information: The present study is part of the Ph.D. work of Mengni Cui and was financially supported by China Scholarship Council (CSC) scholarships (CSC201706170084) and University of Copenhagen. The authors also thank the financial support through the CALM project (Clinical Trials NCT02115698), which was approved by the Danish Regional Committees of the Capital Region (H-4-2013-070), and the support from the Danish Strategic Research Council/Innovation Foundation Denmark (COUNTERSTRIKE, Grant no. 4105-00015B). The authors thank the COPSAC research unit for sharing the samples for 40 young participants for this study. Publisher Copyright: ©

PY - 2021

Y1 - 2021

N2 - The human fecal metabolome is increasingly studied to explore the impact of diet and lifestyle on health and the gut microbiome. However, systematic differences and confounding factors related to age, sex, and diet remain largely unknown. In this study, absolute concentrations of fecal metabolites from 205 healthy Danes (105 males and 100 females, 49 ± 31 years old) were quantified using 1H NMR spectroscopy and the newly developed SigMa software. The largest systemic variation was found to be highly related to age. Fecal concentrations of short-chain fatty acids (SCFA) were higher in the 18 years old group, while amino acids (AA) were higher in the elderly. Sex-related metabolic differences were weak but significant and mainly related to changes in SCFA. The concentrations of butyric, valeric, propionic, and isovaleric acids were found to be higher in males compared to females. Sex differences were associated with a stronger, possibly masking, effect from differential intake of macronutrients. Dietary fat intake decreased levels of SCFA and AA of both sexes, while carbohydrate intake showed weak correlations with valeric and isovaleric acids in females. This study highlights some possible demographic confounders linked to diet, disease, lifestyle, and microbiota that have to be taken into account when analyzing fecal metabolome data.

AB - The human fecal metabolome is increasingly studied to explore the impact of diet and lifestyle on health and the gut microbiome. However, systematic differences and confounding factors related to age, sex, and diet remain largely unknown. In this study, absolute concentrations of fecal metabolites from 205 healthy Danes (105 males and 100 females, 49 ± 31 years old) were quantified using 1H NMR spectroscopy and the newly developed SigMa software. The largest systemic variation was found to be highly related to age. Fecal concentrations of short-chain fatty acids (SCFA) were higher in the 18 years old group, while amino acids (AA) were higher in the elderly. Sex-related metabolic differences were weak but significant and mainly related to changes in SCFA. The concentrations of butyric, valeric, propionic, and isovaleric acids were found to be higher in males compared to females. Sex differences were associated with a stronger, possibly masking, effect from differential intake of macronutrients. Dietary fat intake decreased levels of SCFA and AA of both sexes, while carbohydrate intake showed weak correlations with valeric and isovaleric acids in females. This study highlights some possible demographic confounders linked to diet, disease, lifestyle, and microbiota that have to be taken into account when analyzing fecal metabolome data.

KW - H NMR

KW - age

KW - amino acids

KW - carbohydrates

KW - fat

KW - fecal metabolome

KW - sex

KW - short-chain fatty acids

U2 - 10.1021/acs.jproteome.1c00220

DO - 10.1021/acs.jproteome.1c00220

M3 - Journal article

C2 - 34048241

AN - SCOPUS:85108409674

VL - 20

SP - 3642

EP - 3653

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 7

ER -