Longitudinal Multi-Omics Study of a Mother-Infant Dyad from Breastfeeding to Weaning: An Individualized Approach to Understand the Interactions Among Diet, Fecal Metabolome and Microbiota Composition

Giorgia Conta; Federica Del Chierico; Sofia Reddel; Federico Marini; Fabio Sciubba; Giorgio Capuani; Alberta Tomassini; Maria Enrica Di Cocco; Nicola Laforgia; Maria Elisabetta Baldassarre; Lorenza Putignani; Alfredo Miccheli

doi:10.3389/fmolb.2021.688440

Longitudinal Multi-Omics Study of a Mother-Infant Dyad from Breastfeeding to Weaning: An Individualized Approach to Understand the Interactions Among Diet, Fecal Metabolome and Microbiota Composition

Front Mol Biosci. 2021 Oct 4:8:688440. doi: 10.3389/fmolb.2021.688440. eCollection 2021.

Authors

Giorgia Conta^{1

2}, Federica Del Chierico³, Sofia Reddel³, Federico Marini^{1

2}, Fabio Sciubba^{1

2}, Giorgio Capuani^{1

2}, Alberta Tomassini¹, Maria Enrica Di Cocco¹, Nicola Laforgia⁴, Maria Elisabetta Baldassarre⁴, Lorenza Putignani⁵, Alfredo Miccheli^{2

6}

Affiliations

¹ Department of Chemistry, Sapienza University of Rome, Rome, Italy.
² NMR-Based Metabolomics Laboratory of Sapienza (NMLab), Sapienza University of Rome, Rome, Italy.
³ Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁴ Department of Biomedical Science and Human Oncology, University of Bari Aldo Moro, Bari, Italy.
⁵ Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁶ Department of Environmental Biology, Sapienza University of Rome, Rome, Italy.

Abstract

The development of the human gut microbiota is characterized by a dynamic sequence of events from birth to adulthood, which make the gut microbiota unique for everyone. Its composition and metabolism may play a critical role in the intestinal homeostasis and health. We propose a study on a single mother-infant dyad to follow the dynamics of an infant fecal microbiota and metabolome changes in relation to breast milk composition during the lactation period and evaluate the changes induced by introduction of complementary food during the weaning period. Nuclear Magnetic Resonance (NMR)-based metabolomics was performed on breast milk and, together with 16S RNA targeted-metagenomics analysis, also on infant stool samples of a mother-infant dyad collected over a period running from the exclusive breastfeeding diet to weaning. Breast milk samples and neonatal stool samples were collected from the 4th to the 10th month of life. Both specimens were collected from day 103 to day 175, while from day 219-268 only stool samples were examined. An exploratory and a predictive analysis were carried out by means of Common component and specific weight analysis and multi-block partial least squares discriminant analysis, respectively. Stools collected during breastfeeding and during a mixed fruit/breastfeeding diet were characterized by high levels of fucosyl-oligosaccharides and glycolysis intermediates, including succinate and formate. The transition to a semi-solid food diet was characterized by several changes in fecal parameters: increase in short-chain fatty acids (SCFAs) levels, including acetate, propionate and butyrate, dissapearance of HMOs and the shift in the community composition, mainly occurring within the Firmicutes phylum. The variations in the fecal metabolome reflected the infant's diet transition, while the composition of the microbiota followed a more complex and still unstable behavior.

Keywords: HMOs; NMR-based metabolomics; breast milk; gut microbiota; metabolic profiling; omics data integration; targeted metagenomics.