Associations between maternal microbiome, metabolome and incidence of low-birth weight in Guatemalan participants from Women First Trial

Authors: Ruebel, Meghan; GILLIE, STEPHANIE - University Of Colorado; Yeruva, Laxmi; TANG, MINGHUA - University Of Colorado; FRANK, DANIEL - University Of Colorado; GARCÉS, ANA - Instituto De Nutrición De Centroamérica Y Panamá (INCAP); FIGUEROA, LESTER - Instituto De Nutrición De Centroamérica Y Panamá (INCAP); LAN, RENNY - Arkansas Children'S Nutrition Research Center (ACNC); ASSRESS, HAILEMARIAM - Arkansas Children'S Nutrition Research Center (ACNC); KEMP, JENNIFER - University Of Colorado; WESTCOTT, JAMIE - University Of Colorado; HAMBIDGE, K. MICHAEL - University Of Colorado; SHANKAR, KARTIK - University Of Colorado; KREBS, NANCY - University Of Colorado

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Low birth weight (babies born at less than 2,500 grams) affects approximately 15 to 20 percent of global births annually and is associated with poor child development. We leveraged stool samples from pregnant women from Guatemala that are part of the Women First Clinical Trial to better understand how the maternal gut microbiome and circulating metabolites may predict risk of low birth weight infants. Results indicated that less beneficial gut microbes and circulating metabolites of the mother are associated with low birth weight infants compared to normal weight. Future research should target more specific functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight.

Technical Abstract: Background: Low birth weight (LBW; < 2,500g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings. Methods: This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 wk were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk only). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine. Results: No differences in ß-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 wk was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers (p< 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance. Conclusions: Collectively, the findings indicate that alterations in the maternal microbiome and metabolome were associated with LBW. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight.