TY - JOUR
T1 - Association of Body Mass Index with Fecal Microbial Diversity and Metabolites in the Northern Finland Birth Cohort
AU - Loftfield, Erikka
AU - Herzig, Karl Heinz
AU - Caporaso, J. Gregory
AU - Derkach, Andriy
AU - Wan, Yunhu
AU - Byrd, Doratha A.
AU - Vogtmann, Emily
AU - Männikkö, Minna
AU - Karhunen, Ville
AU - Knight, Rob
AU - Gunter, Marc J.
AU - Järvelin, Marjo Riitta
AU - Sinha, Rashmi
N1 - Publisher Copyright:
©2020 American Association for Cancer Research.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Background: Obesity is an established risk factor for multiple cancer types. Lower microbial richness has been linked to obesity, but human studies are inconsistent, and associations of early-life body mass index (BMI) with the fecal microbiome and metabolome are unknown. Methods: We characterized the fecal microbiome (n ¼ 563) and metabolome (n ¼ 340) in the Northern Finland Birth Cohort 1966 using 16S rRNA gene sequencing and untargeted metabolomics. We estimated associations of adult BMI and BMI history with microbial features and metabolites using linear regression and Spearman correlations (rs) and computed correlations between bacterial sequence variants and metabolites overall and by BMI category. Results: Microbial richness, including the number of sequence variants (rs ¼ -0.21, P < 0.0001), decreased with increasing adult BMI but was not independently associated with BMI history. Adult BMI was associated with 56 metabolites but no bacterial genera. Significant correlations were observed between microbes in 5 bacterial phyla, including 18 bacterial genera, and metabolites in 49 of the 62 metabolic pathways evaluated. The genera with the strongest correlations with relative metabolite levels (positively and negatively) were Blautia, Oscillospira, and Ruminococcus in the Firmicutes phylum, but associations varied by adult BMI category. Conclusions: BMI is strongly related to fecal metabolite levels, and numerous associations between fecal microbial features and metabolite levels underscore the dynamic role of the gut microbiota in metabolism. Impact: Characterizing the associations between the fecal microbiome, the fecal metabolome, and BMI, both recent and early-life exposures, provides critical background information for future research on cancer prevention and etiology.
AB - Background: Obesity is an established risk factor for multiple cancer types. Lower microbial richness has been linked to obesity, but human studies are inconsistent, and associations of early-life body mass index (BMI) with the fecal microbiome and metabolome are unknown. Methods: We characterized the fecal microbiome (n ¼ 563) and metabolome (n ¼ 340) in the Northern Finland Birth Cohort 1966 using 16S rRNA gene sequencing and untargeted metabolomics. We estimated associations of adult BMI and BMI history with microbial features and metabolites using linear regression and Spearman correlations (rs) and computed correlations between bacterial sequence variants and metabolites overall and by BMI category. Results: Microbial richness, including the number of sequence variants (rs ¼ -0.21, P < 0.0001), decreased with increasing adult BMI but was not independently associated with BMI history. Adult BMI was associated with 56 metabolites but no bacterial genera. Significant correlations were observed between microbes in 5 bacterial phyla, including 18 bacterial genera, and metabolites in 49 of the 62 metabolic pathways evaluated. The genera with the strongest correlations with relative metabolite levels (positively and negatively) were Blautia, Oscillospira, and Ruminococcus in the Firmicutes phylum, but associations varied by adult BMI category. Conclusions: BMI is strongly related to fecal metabolite levels, and numerous associations between fecal microbial features and metabolite levels underscore the dynamic role of the gut microbiota in metabolism. Impact: Characterizing the associations between the fecal microbiome, the fecal metabolome, and BMI, both recent and early-life exposures, provides critical background information for future research on cancer prevention and etiology.
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U2 - 10.1158/1055-9965.EPI-20-0824
DO - 10.1158/1055-9965.EPI-20-0824
M3 - Article
C2 - 32855266
AN - SCOPUS:85097413905
SN - 1055-9965
VL - 29
SP - 2289
EP - 2299
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 11
ER -