Prebiotics in human breast milk are associated with infant weight

Human breast milk contains nutrients and compounds that are beneficial for infants. Human milk oligosaccharides (HMOs) are a group of important complex carbohydrates that are found in breast milk. These HMOs are important in the developing infant because they serve as a prebiotic, helping to shape the infant’s gut microbiome by facilitating the selection of beneficial bacteria. The link between gut microbiota composition and infant obesity has led to speculation that HMOs might affect certain bacteria that in turn lead to decreased body fat. Because HMO composition of female breast milk varies over the course of lactation, researchers in Oklahoma and California tested to see whether differences in milk HMO content are associated with infant body weight. The results of their study were published in The American Journal of Clinical Nutrition.

Twenty-five mother-infant pairs participated in this study. On average, the mothers were 29.5 years of age and overweight before conception. When the infants were 1 month and 6 months old, the mothers supplied breast milk samples to test for HMO composition. Concurrently, the infants’ body fat composition, weight, and length were measured.

The findings suggest that HMOs are associated with infant body weight, fat mass, and lean mass at both 1 month and 6 months. A diversity of HMOs, such as LNFFPI (lacto-N-fucopentaose I, a sugar), DSLNT (difucosyl-LNT, a sugar), and FDSLNH (fucosyl-disialyl-lacto-N-hexaose, a sugar) accounted for 33% of the fat mass, which was more than other variables such as gender, and mothers’ pregnancy BMI. infant fat mass than did sex, pregnancy BMI.  LNFPI was inversely associated with 1 month old infant weight, while at 6 months it was inversely associated with weight, lean mass, and fat mass. Overall, the presence of a diverse group of HMOs decreased infant body mass.  While this study has its limitations because it does not specifically test the bacterial composition of the gut, it is a first step to identifying an association between HMOs and infant BMI. As obesity remains an epidemic in the United States, perhaps the microbiome is the first place to look towards to prevent the disease. 

New research shows that Bifidobacteria transfer from mother to child

Both natural birth (as opposed to birth by C-section) and breastfeeding are topics that stir up a lot of conversation among mothers and the scientific community. For example, there is the question of whether breastfeeding rather than formula feeding has some specific benefit to an infant’s health. Well, what about the infant’s gut microbial health? A new article published by Applied and Environmental Microbiology takes a look at whether natural birth and breastfeeding coincides with an exchange of bacteria from mother to child.

Four mother and infant pairs were included in the study that was meant to discover whether the mother transfers any bacterial strains to the infant during vaginal birth and breastfeeding. In particular, the scientists were looking at the genus Bifidobacterium because this group has been known to be early colonizers of the infant gut. In addition, this genus has specific ways of digesting a human mother’s milk. Mother-infant pairs 2 and 4 exclusively breastfed, while pairs 1 and 3 supplemented with formula. Milk samples were collected from the mothers and fecal samples were collected from the mothers and children.

After sequencing the bacteria, B. adolescentis, B. angulatum, B. breve, B. dentitum, B. pseudolongum and B. thermacidophilum were found to be common between all of the mother and the infant fecal samples. The scientists then looked to see which bacteria were in both the mother’s milk and the infant’s fecal sample. The results suggest that the milk may be responsible for transferring B. adolescentis, B. angulatum, B. breve, B. longum and B. pseudolongum to the infant. Interestingly, there were also some bifidobacteria strains that were unique to the infant, suggesting that either they went undetected in the mother or that the infant was exposed to this bacteria from somewhere else.

After six months, samples were collected again in order to see how/if the sample compositions change. The scientists found that, especially in the infants, the abundance of bifidobacteria decreases. This is most likely due to changes in diet – less breastfeeding and more formula feeding – and perhaps environmental exposure. All in all, the results of this experiment shows that the infant microbiome might indeed be influenced by a vertical transfer of bacteria from mother to child. With more evidence of this as a possibility, science may begin looking into more complete analyses with larger study sizes.  

Randomized clinical trial shows probiotic may not be an effective treatment for colic

Many families have experienced colicky infants who have excessive and inconsolable crying.  The cause of this behavior is largely unknown, however it is beginning to be linked to a variety of diseases, including allergies and gastrointestinal disorders.  Many remedies have been suggested to help assuage these infants, including probiotic therapies, but thus far the evidence of their efficacy is unknown.  Researchers in Finland put one of the probiotic therapies, using Lactobacillus rhamnosus GG (LGG), to the test and conducted a double blind randomized clinical trial to discover whether it decreased colic.  They published their results last week in Nature Pediatric Research. 

The scientists studied 30 colicky infants in the study, who were split evenly into a probiotic group and a control group.  The mothers of the probiotic group orally administered LGG to their children once a day for 28 days, while the mothers of the control group orally administered a placebo.  During this time the mothers kept diaries of how long the child cried, as well as collected stool samples for microbiome testing.  The results showed that the probiotics did not alter the amount of crying for each infant when compared to the placebo group.  In addition there was no statistical difference in the microbiome’s of both groups.

Unfortunately for the families of colicky infants, this study did not show that LGG was an effective colic therapy.  There are other studies that conflict with this one though, so perhaps different types of bacteria, or larger doses could improve efficacy.  The relationship between the microbiome and colic is unclear, however, given the recent advances in gut-brain axis research, we would not be surprised if the two are connected.

The maturation of the microbiome during the first year of life

Dr. Jeffrey Gordon recently published a review article describing the importance of the proper development of the microbiome in the early stages of life.  One paper that certainly would have made it into the review if it was published in time is a new paper published last week out of Sweden and China that studied the developing microbiome of children over the course of their first year of life.

The team of scientists studied 98 women and their newborn babies. They sequenced the mother’s stool, the newborns stool, and again the child’s stool at 4 and 12 months. Throughout the study, because they used a technique called shotgun sequencing, they identified 4,000 new microbial genomes.

The infants in the study were breastfed for varying amounts of time with some never being breastfed at all. The researchers found that breastfeeding and the timeline of cessation of breastfeeding was critical to driving microbiome development. Many had previously hypothesized that it was the time at which solid foods were introduced was most important for microbiome development, however this study found that it was the time at which breastfeeding was stopped. Children that stopped breastfeeding earlier had microbiomes more similar to adults at 12 months while children who were breastfed for the duration of the study continued to have microbiomes dominated by Bifidobacterium and Lactobacillus.

The scientists also found that the 15 babies born via C-section had different microbiomes than the other 83 babies studied.  The infants born via C-section had microbiomes that more closely resembled skin and mouth microbial communities while the babies born vaginally had microbiomes more closely resembling the bacteria in their mother’s stool.

We still don’t know exactly what a “healthy” microbiome looks like and which microbial profile is best for the child. This study provides a very solid experimental design to study the development of the microbiome and allows for the continued monitoring of these children’s microbial development over the course of their lives. 

Multiple studies show connection between early life antibiotics and obesity

Childhood obesity is a growing problem not just in the United States, but around the globe. While diet and exercise are basic ways to reduce weight, there can be many complex causes of weight gain. Stress, caloric intake and genetics have all been seen to have a correlation with weight gain. Recent studies, however, have suggested a possible microbiome connection, through a correlation between obesity and the antibiotic exposure. A recent review published in Advances in Obesity, weight management & control described various studies on this subject.

 The researchers discussed five studies that were related to childhood obesity and antibiotic intake. In a Canadian study of 616 children participating in a Study of Asthma, Genes and the Environment survey, a significant relationship was found, particularly for boys, between obesity at ages 9 and 12 and first antibiotic exposure at 3-12 months. In the UK, the Avon Longitudinal Study of Parents and Children found that antibiotic prescription before 6 months of age led to higher Body Mass Index during 10 to 38 months, while later antibiotic intake did not lead to this association. In a study done by Bailey with 65,480 children, 69% of children had infant or preadolescent obesity if they had taken antibiotics during the first 23 months of their life.

 In a fourth study discussed by the article, a large cross sectional study ISSAC was performed in New Zealand on 74,946 male children between the ages of 5 and 8. The study found that boys who had taken antibiotics during their first year of life had higher BMIs later in life. Finally, in a Danish study by Ajslev, 28,364 children were administered antibiotics before 6 months of age and were followed up for the next 7 years. A significant association between antibiotics and obesity was found only for boys.

 Based on these studies, it seems apparent that altering the microbiome through antibiotic use early in life is associated with an increase in BMI.  As many people have recognized in recent years, farmers give antibiotics to their livestock to help them gain weight, and a similar phenomenon may be occurring in humans.  Scientists like the AMI’s advisory board member Martin Blaser have taken up this cause, and he has lectured about this connection many times in recent years.  We know that the microbiome impacts weight gain through diet and nutrition, so it should come as no surprise that decreasing the abundance of many bacterial species through antibiotics may cause obesity.

The nasal microbiome of infants may impact risk of developing asthma

Many lower respiratory illnesses have been shown to associate with specific lung, throat and nasal bacteria, but the role of the microbiome is still unclear, and mechanisms for the connection have yet to be proven.  Of particular interest is asthma, which affects around 7% of people in the US, and increases a person’s risk for many other conditions.  While it is normally diagnosed in toddlers, scientists believe that the groundwork for the disease is actually laid during infancy.  With that in mind, researchers in Australia performed the first longitudinal study of infants’ nasopharyngeal (nose and throat) during the first year of their lives, and tracked episodes of respiratory illness during that time.  They discovered a strong connection between the microbiome and respiratory illness, including asthma, and last month published their results in Cell Host and Microbe.

The researchers collected nasopharyngeal microbiome samples from 234 infants at different time points during their first year of life.  Most infants’ microbiomes were dominated by the following species: Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Alloiococcus otitidis.  Interestingly, this was true for infants regardless of birth delivery mode (i.e. cesarean or vaginal) as well as length of breast feeding.  In contrast, having a furry animal in the house tended to increase the abundance of Streptococcus, but having older siblings tended to decrease it.  In addition, there were strong seasonal effects on the microbiome, with Haemophilus being associated with the summer, and Moraxella the winter.  In children with respiratory illness, Haemophilus, Moraxella, and Streptococcus were most frequently measured, and Staphylococcus, Alloiococcus, and Corynebacterium least frequently measured.

When the scientists compared their results with the asthma outcomes of the children at 5 years old they noticed one significant trend.  Colonization by Streptococcus at around 2 months old, which was asymptomatic at the time and occurred in 14% of infants tested, was strongly connected to chronic wheezing (itself an indication of asthma) at 5 years old.  They suggest that the developing airways in infants may be especially vulnerable to Streptococcus.

This long term study does a really nice job of defining how the microbiome grows and develops in the airways of infants – something which previously hadn’t been performed at such a large scale.  While this study alone does not figure out exactly what the microbiome’s role is in childhood respiratory illnesses, it does provide a baseline for future studies to work off of.