Beyond Nutrition: Human Milk Metals and Metalloids Shape Infant Microbiota

Authors: FLORES-VENTURA, EDUARD - Institute Of Agrochemistry And Food Technology; BERNABEU-LORENZO, MANUEL - Institute Of Agrochemistry And Food Technology; CALLEJÓN-LEBLIC, BELÉN - Universidad De Huelva; CABRERA-RUBIO, RAÚL - Institute Of Agrochemistry And Food Technology; Yeruva, Laxmi; ESTAÑ-CAPELL, JAVIER - University Of Valencia; MARTÍNEZ-COSTA, CECILIA - University Of Valencia; GARCÍA-BARRERA, TAMARA - Universidad De Huelva; CARMEN COLLADO, MARÍA - Institute Of Agrochemistry And Food Technology

Submitted to: Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/8/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Metals (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Tl, and Pb) and gut microbes (i.e., microbiota) have historically co-evolved. Early in life human milk metals may influence infant gut microbiota composition and health outcomes. To investigate the metals content within human milk and its influence on the infant's gut microbiota within the first 2 months after birth, milk samples from 69 mother-infant dyads from a clinical study were leveraged. In independent cross-sectional analyses of mother-infant pairs from two separate time-points, significant variations in metals concentrations and microbial abundances were observed. In mature lactation stage, seven significant correlations between metals and microbiota were identified. Notably, correlation analyses indicated a higher abundance of the Streptococcus genus when Mn and V concentrations were lower. This study highlights the significance of metal-microbiota interactions in early infant development. Mn may be the most potential metal to influence microbiota, and Streptococcus to potentially be the most influenced genus by metals with the infant gut microbiota.

Technical Abstract: Background: Metal (loid)s and microbiota have historically co-evolved, thus interactions may shape microbial ecology, and initial infant gut seeding influencing infant health in the short and long term. Aim: Our objective was to investigate the metal (loid) content within human milk and its influence on the infant's gut microbiota within the first 2 months after birth. Methods: Human milk samples from 69 mother-infant dyads from the MAMI cohort collected at two time points were included. Maternal-infant clinical records and infant growth during the first year of age were also available. Human milk metallomic profiling was obtained by inductively coupled plasma–mass spectrometry, and profiles were analysed via unsupervised machine learning K-means clustering, permutational multivariate analysis of variance, and post-hoc tests. Infant gut microbiota was analysed by 16S rRNA gene sequencing. Additionally, Spearman’s rank correlation coefficients, along with an integration of metallomic profiles with microbiota data, provided insights into metal (loid)-microbiota relationships. Results: In independent cross-sectional analyses of mother-infant pairs from two separate time-points, significant variations in metal (loid) concentrations and microbial abundances were observed. During early lactation stage, no significant correlations were observed. However, in mature lactation stage, seven significant correlations between metal (loid)s and microbiota were identified. Notably, correlation analyses indicated a higher abundance of the Streptococcus genus when Mn and V concentrations were lower. Furthermore, alpha-diversity indexes, including Chao1 and ACE, exhibited negative correlations with Fe and Mn (r ˜ -0.7, p-values < 0.05 for all aforementioned). Conclusion: Our study highlights the significance of metal (loid)-microbiota interactions in early infant development. Showing that Mn may be the most potential metal to influence microbiota, and Streptococcus to potentially be the most influenced genus by metals in the infant gut microbiota. Future research should explore these interactions at a strain level and the implications on infant health and development.