A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants

• Main Authors: Christophe Lay, Collins Wenhan Chu, Rikky Wenang Purbojati, Enzo Acerbi, Daniela I. Drautz-Moses, Paola Florez de Sessions, Song Jie, Eliza Ho, Yee Jiun Kok, Xuezhi Bi, Shuwen Chen, Shi Ya Mak, Mei Chien Chua, Anne E. N. Goh, Wen Chin Chiang, Rajeshwar Rao, Surasith Chaithongwongwatthana, Nipon Khemapech, Voranush Chongsrisawat, Rocio Martin, the JULIUS Study Group, Guus Roeselers, Ying Swan Ho, Martin L. Hibberd, Stephan C. Schuster, Jan Knol
• Format: Article
• Language: English
• Published: BMC 2021-06-01
• Series: BMC Microbiology
• Subjects: Microbiome; Infant; C-section; Synbiotics
• Online Access: https://doi.org/10.1186/s12866-021-02230-1

Abstract Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.