Human Infant Gut Microbiota. The impact of cesarean delivery and antibiotics on gut microbiota and its association to child growth/obesity

The importance of the microbiome in human health, especially in early life, is now being acknowledged. However, microbial data bear more resemblance to ecological survey data and bring with them a new level of complexity compared to, for instance, genome data. For example, data are usually given as relative abundances and not absolute amounts. A method to deal with this has been published and is now in common use and highly cited(Mandal S et al. Microb Ecol Health Dis 2015). Knowledge about which factors affect intestinal flora was limited when we began this project. We studied mother's intake of 28 macro and micronutrients during pregnancy, and observed that fat and fat-soluble vitamins, especially Vitamin D, are among the most potent modulators of intestinal flora, and not enough fiber as we expected (Mandal et al., Microbiome . 2016). Others have confirmed that the Vitamin D metabolism seems to play a crucial role in the intestinal flora composition. We also studied whether early birth influences gut microbiome composition and function in early life (Dahl et al., In review). We also explored how caesarean section influences the composition of the intestinal flora in early in life (Eggesbø M et al. In revision). Preterm birth is the major cause of deaths among newborns worldwide, and surviving babies are at higher risk of serious infections and other negative health effects, thus important to prevent. We have found that the intestinal flora of the mother can be a risk factor for preterm birth (Dahl et al., Plos One 2018), showing that it is not only the flora of the vagina that is important. Among 121 spontaneous births, we found that mothers of preterm babies have a lower variety of bacteria in the intestine than mothers who gave birth to term babies, and a lower rate of "good bacteria" such as Bifidobacterium. We have also studied whether why overweight mothers are likely to get overweight children may be due to the transmission of bacteria that are potentially obesity-causing. We confirmed this; that there were certain bacteria that were common in obese mothers and that these bacterial species were transferred to their babies (Stanislawski M et al., Microbiome 2017). We also studied whether the composition of the intestinal flora in the first two years of life had a bearing on BMI at the age of 12 and found that there was a strong connection (Stanislawski M et al. In revision). We have also previously found correlation between early intestinal flora and rapid growth in infant age, which is a risk factor for later obesity (White R et al., Plos Comp Science). In that early paper we only studied the first four months and used specific probes, so the studies complement each other. Confirming these findings, the results of the project may help provide dietary recommendations for pregnant women who are at risk of premature birth, or help to develop probiotics that can change the intestinal flora of pregnant women. This can also be used the future treatment of pregnant obese, to reduce the chance that the children will become overweight as a result of the transfer of obesity-creating bacteria.

The crucial role of gut microbiota in human health is now being acknowledged. Early infancy is a period of special interest due to the presence of developmental windows that rely on microbial stimulus from the gut, involving development of tolerance and s tress responses. Furthermore, early gut microbiota is of interest as a determinant of the final adult microbiota. Factors disturbing early evolvement of gut microbiota, such as caesarean delivery, may have long term effects on health. Gut microbiota may a lso play a role in the development of obesity. By combining expertise in epidemiology, statistics, molecular genetics, microbiology and microbial ecology, we will explore this arena. A collaboration has been set up with some of the top frontier researcher s within this field and will expand on an already wide net work of national and international researchers. The NoMic cohort was established for the specific purpose of studying gut microbiota and its association to health and consists of 525 newborns in w hom fecal samples have been collected at six age points up to two years of life. Microbial DNA has been extracted from all samples and will be analyzed by Rob Knight's team. The project is expected to lead to cutting edge knowledge on microbiota compositi on, the long term influences of caesarean delivery and perinatal antibiotic use, and its association to growth and obesity. We will further study the association between caesarean delivery and later weight/overweight in the MoBa cohort which includes 1060 00 mother child pairs. This research could be of potential importance for policy makers with regard to caesarean delivery and prophylactic antibiotics. Furthermore, it will increase our knowledge on the etiology of obesity, and may provide a basis for pro phylactic interventions in the long term. Obesity is now one of the major risk factors for disease and a better understanding of the reasons for the exponential increase is desperately needed.