DescriptionWestern common cultural and medical practices such as Cesarean sections (C-sections), use of antibiotics, or formula feeding, can alter the early life gut microbiome and the host normal developmental trajectory. When perturbations of the gut microbiome occur early in life, it increases the risk of metabolic diseases and obesity later in life. Thus, the increasing rates of childhood obesity worldwide, and the increasing use of C-sections and antibiotics are of great concern. Animal studies have also shown increased body weight gain driven by antibiotics and C-sections. To address the contribution of microbes to host metabolic phenotypes, we transferred feces from 3-months-old human babies discordant to birth mode [vaginal delivery (VD) or C-section (CS)] into 3 days old germ-free mice via their mother gavage. Mice were fed normal chow until week 11, and then were challenged with a high fat diet for 4 weeks.
Mice in the litters engrafted human gut microbiota differently in each inoculum group: CS mice had lower alpha diversity (Shannon index Kruskal Wallis p<0.002), lacked Bacteroides, and had higher Hungatella and Bifidobacterium, in relation to the animals receiving VD inoculum. The two mouse groups had significant differences in beta diversity (Bray Curtis and Jaccard, Permanova pairwise nonparametric test p=0.001 and p=0.001).
On the host side, male mice receiving CS inoculum grew smaller than those in the VD group (Wilcoxon p=0.041 for week 7 and week 11). At week 15, animals who consumed HFD for 4 weeks had significantly gained weight (between week 11 and 15), with only VD males showing significantly higher body weight than conventional C57BL/6J mice from Jackson’s Labs. Both fat and lean mass were significantly impacted in both groups by HFD, without differences between the VD and CS groups. Additionally, there were no significant inoculum group differences in serum leptin, insulin, or ghrelin.
This study demonstrates that the fecal microbiota from human babies born by Cesarean section is functionally different than that from vaginally born babies, with implications in metabolic development, that will need further explorations.