U.S. Department of Health and Human Services

Early-life exposures affect infant health

Three recent studies have shown how dietary and other environmental exposures, including those that shape the internal environment created by gut microbes, are critically important during the first few years of life, with implications for a lifetime of good health.  These exposures include not only the diet of the mother and child, but also other experiences that have a large impact on the bacterial populations of a child’s gut, such as antibiotic treatment and delivery by vaginal or cesarean modes.  More and more, the gut microbial community is being appreciated for its effects on human health, and the first 3 years of life is an important period for maturation of this gut microbial community.  For example, by training the developing immune system, gut microbes are thought to play a possible role in guarding against autoimmune diseases such as type 1 diabetes and inflammatory bowel disease, as well as other immune-related diseases, including asthma and allergies.  Early disturbances in the gut microbial community from such factors as antibiotics or cesarean delivery have also been linked to an increased risk for metabolic disorders, such as obesity.  Studies by three research groups have delved into how great an impact these early exposures can have on infants, potentially affecting their future health.

As part of the Healthy Start Study, researchers studied over 1,000 pairs of mothers and infants from multiple ethnic backgrounds to see how different types of foods eaten during pregnancy might affect infant body fat.  The mothers were recruited during pregnancy.  The researchers collected blood samples and information from the mothers on such subjects as physical activity and diet.  Throughout pregnancy, participating mothers also completed several 24-hour dietary recalls online to provide a more complete picture of their diets.  After delivery, information was collected in the hospital on the mothers and babies, including measurements of the infants’ length, weight, and skin-fold thickness.  The researchers also estimated the infants’ body composition, including fat mass and fat-free mass.  The mothers’ diet quality was measured using a scoring system based on the 2010 Dietary Guidelines for Americans.  The researchers found that consuming a lower-quality diet (e.g., more fat and sodium, and fewer fruits and vegetables) during pregnancy was associated with a higher percent of fat mass in the newborns, regardless of how much the women had weighed before pregnancy.  The researchers plan to continue studying these infants to figure out what effect a larger fat mass at birth has on the risk of developing obesity in childhood and later in life.  This study highlights a potential way to improve the health of newborns—eating more healthfully during pregnancy.

Another research group followed the gut microbial development of 43 U.S. children during their first 2 years using genetic techniques to characterize the evolving community of bacterial species present in their stool samples during this dynamic period of development.  They collected vaginal swabs, rectal swabs, and stool samples from mothers, both before and after delivery, and stool samples from the infants.  Typically, infants’ gut microbes follow a developmental program of maturation with some species dominating the mix at certain stages, which continues from birth until around age 3, after which point the microbial mix resembles that of adults.  The researchers identified three major phases in the development of the gut microbiome in early life, with a type of bacteria called Enterobacteriaceae dominating in the first month, a more dynamic period from 1 to 24 months of life, then a more adult-like gut bacterial community resembling their mothers’ around age 2 years.  However, they observed that the predominant species in the mix were affected in early life by delivery mode (vaginal versus cesarean section), infant diet (breastfeeding versus formula feeding), and antibiotic treatment, particularly during the dynamic middle phase.  After the first few months of life, infants delivered by cesarean section had less diverse and less mature gut microbial communities than those in vaginally delivered infants.  With antibiotic treatment, the diversity of species in the gut also diminished, and the developmental maturation of the gut microbial community as a whole was delayed; however, the effect was less than that of delivery mode.  Gut microbiota diversity and maturity was also reduced between ages 1 to 2 years in infants fed with formula compared to breastmilk.

A similar study focused on the gut microbial changes in 39 children living in Finland during their first 3 years of life, using some more in-depth DNA sequencing of the children’s stool samples.  In these children, all of whom were breastfed for some amount of time, the gut microbial community development was most rapid during the first 6 months of life.  As with the study of the gut microbiota in American children, the researchers found the Finnish children who were born by cesarean section or who received antibiotic treatment had a less diverse set of bacterial species in their gut.  However, unlike the American study, they found that a proportion (20 percent) of vaginally born children also showed reduced numbers of some key bacterial species, called Bacteroides, that were lacking in all of those born by cesarean.  Also unique to this analysis was their ability to probe deeper into the specific strains of bacteria present within the species.  Through this analysis, they could see that antibiotic treatment had an even greater impact on reducing gut microbial community diversity at the level of specific bacterial strains than it did at the species level.  Antibiotic treatment was also associated with a less stable gut microbial community and an increase in antibiotic resistance genes.

More research will be needed to understand fully the long-term effects of these early exposures—from the quality of the mothers’ diet during pregnancy to disruptions within the infant gut microbiome due to delivery mode, antibiotic treatment, or feeding method—on the health and disease risk of children as they grow.  For example, future studies could determine, at the level of bacterial genes and their gene products, the implications of these disruptions for gut microbial community function and, by extension, human health.

Shapiro ALB, Kaar JL, Crume TL, Starling AP, Siega-Riz AM, Ringham BM, Glueck DH, Norris JM, Barbour LA, Friedman JE, and Dabelea D. Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study. Int J Obes (Lond) 40:1056-1062, 2016.

Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H, Lieber AD, Wu F, Perez-Perez GI, Chen Y, Schweizer W, Zheng X, Contreras M, Dominguez-Bello MG, and Blaser MJ. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med 8:343ra82, 2016.

Yassour M, Vatanen T, Siljander H, Hämäläinen AM, Härkönen T, Ryhänen SJ, Franzosa EA, Vlamakis H, Huttenhower C, Gevers D, Lander ES, Knip M, on behalf of the DIABIMMUNE Study Group, and Xavier RJ. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 8:343ra81, 2016.