Integrative multiomics analysis of infant gut microbiome and serum metabolome reveals key molecular biomarkers of early onset childhood obesity
Talha Rafiq,
Jennifer C. Stearns,
Meera Shanmuganathan,
Sandi M. Azab,
Sonia S. Anand,
Lehana Thabane,
Joseph Beyene,
Natalie C. Williams,
Katherine M. Morrison,
Koon K. Teo,
Philip Britz-McKibbin,
Russell J. de Souza
Affiliations
Talha Rafiq
Medical Sciences Graduate Program, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada; Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, ON L8L 2X2, Canada
Jennifer C. Stearns
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada
Meera Shanmuganathan
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, Canada
Sandi M. Azab
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Pharmacognosy, Alexandria University, Alexandria 21521, Egypt
Sonia S. Anand
Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, ON L8L 2X2, Canada; Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON L8S 4L8, Canada
Lehana Thabane
Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON L8S 4L8, Canada; Biostatistics Unit, Father Sean O’Sullivan Research Centre, The Research Institute, St Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, Canada; Faculty of Health Sciences, University of Johannesburg, Johannesburg 524, South Africa
Joseph Beyene
Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON L8S 4L8, Canada
Natalie C. Williams
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
Katherine M. Morrison
Department of Pediatrics, McMaster University, Hamilton, ON L8S 4L8, Canada; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4K1, Canada
Koon K. Teo
Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, ON L8L 2X2, Canada; Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON L8S 4L8, Canada
Philip Britz-McKibbin
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, Canada
Russell J. de Souza
Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, ON L8L 2X2, Canada; Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON L8S 4L8, Canada; Corresponding author. Population Genomics Program Department of Health Research Methods, Evidence, and Impact 1200 Main St. West MDCL, Room 3210 Hamilton, Ontario, Canada L8N 3Z5.
Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMIAUC) and skinfold thickness (SSFAUC) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMIAUC and/or SSFAUC >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the Pseudobutyrivibrio and Lactobacillus genera were positively, and Clostridium sensu stricto 1 and Akkermansia were negatively associated with childhood overweight/obesity. Integrative analysis revealed that Akkermansia was positively whereas Lactobacillus was inversely correlated with GABA and SDMA, and Pseudobutyrivibrio was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity.
