Background: Obesity is a global epidemic and is responsible for increasing burdens on public health. Factors like diet and lifestyle have been investigated as modifiable factors that can help prevent the development of obesity, but another possible mediator of obesity development is the gut microbiome. The gut contains a diverse community of microbes that influences several physiological functions in humans and animals. There have been many studies investigating this association between obesity and the microbiota in adults, however, few studies have been done on the establishment of the infant gut microbiota in the context of its association with maternal pre-pregnancy body mass index (BMI), breastfeeding and delivery mode. Hypothesis: We expect maternal pre-pregnancy BMI will be associated with altered microbiota composition of women and their children. However, in children, this association will have less of an effect on the gut microbiota than exposure to human milk in the diet.Methods: Fecal samples and participant information were collected from a subset of dyads enrolled in two related prospective cohorts (ARCHGUT and BABYGUT) in Michigan. Sequencing the V4 region of the 16S gene was used to analyze fecal bacterial samples collected from mothers in their third trimester and infants at 1, 6, 12 and 24 months of age. The microbiota data was analyzed using alpha and beta diversity metrics, negative binomial regression to compare taxa abundances between groups and LonGP, a microbiota analysis tool for longitudinal data sets. Results: We found that fecal bacterial communities from overweight women had lower microbiota diversity than communities from normal weight or obese women and beta diversity of overweight women differed from those of normal and obese women at the genus and phylum levels. Infant alpha diversity at 1 month of age differed in membership (Sorensen index) by maternal pre-pregnancy BMI category and also differed by delivery mode and breastfeeding exclusivity. At 6 months of age, fewer infants born to women with pre-pregnancy obesity were breastfeeding compared to infants born to non-obese women (35.7% and 81.8%, respectively). Maternal pre-pregnancy BMI and human milk exposure were both significantly associated with alpha and beta diversity of the infant microbiota in univariate analyses. However, in multivariate analyses, human milk exposure accounted for 20% of variation in alpha diversity, but pre-pregnancy BMI was not significantly associated with microbiota diversity. The infant diet at six months was the major determinant of alpha and beta diversity of the infant. In our longitudinal analysis of the infant fecal microbiota from 1 month to 2 years of age, we found that age and participant explained most of the changes in abundance in our dataset. In the top 10 most abundant taxa, human milk exposure and antibiotic exposure at the time of sampling were the only variables important besides age and ID, specifically for Lachnospiraceae unclassified and Bacteroides abundances. Lachnospiraceae abundance was much higher as infants aged, in infants receiving 30.Conclusion: Here, we found several associations between the infant gut microbiota and infant exposures during the first two years of life. Exploring the relationship between gut health and early infant exposures could help develop potential preventative treatments for many gut-linked chronic diseases such as obesity.
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