Microorganisms colonize the infants’ guts when they are born: do they come from their mothers, who pass them on during delivery?
The question has long been debated by scientists, because the answer might lead to new therapeutic scenarios. If strong evidence is found that the mother before or during childbirth is likely to transmit a particular microbe that can be detrimental to the future infant health, it could be possible to test the mother while she is pregnant and offer some treatment-preventing treatment for the child.
The same principle occurs with the microorganisms that help the physiological development of the child (for example, by “training” its immune system): if the mother could not pass them to on the child, we might give them to the child in another way.
However so far, the process of “vertical transmission”, has been difficult to observe due to technical restraints.
But now a group of researchers from the University of Trento, with the department of Obstetrics and Neonatology of the hospital of Trento, is breaking new ground: in a pilot study, the researchers have found that vertical transmission does indeed occur at least for some species of bacteria and it can also be systematically studied. To achieve this, the researchers have combined laboratory and novel computational techniques.
The study - which has been funded by Fondazione Caritro and, in part, by the Ministry of Education, Universities and Research, and the European Commission – was published this week in mSystems, an open access journal of the American Society for Microbiology.
The study found several identical bacterial strains present in fecal samples from both infants and their mothers that were distinct from those found in other infants or mothers, a sign of vertical transmission. In addition, transmitted strains from the Bacteroides and Bifidobacterium species were found to be active in both the mother and infant gut microbial communities (called microbiomes), an indication that the vertical transmission did occur and can occur over time.
«Early infant exposure is important in the acquisition and ultimate development of a healthy microbiome», said senior study author Nicola Segata, PhD, an assistant professor at the Centre for Integrative Biology (Cibio) at the University of Trento, Italy. «We developed methods to identify the vertical flow of microorganisms from mothers to infants and showed that mothers are sources of microbes that might be important in the development of the infant gut microbiome. This revolution, explains Segata, is called metagenomics: it is a methodology based on biotechnologies to detect a person’s microorganisms from stools or saliva samples through the sequencing of genetic material and the computational analysis of data. The classic approach would require the cultivation of microorganisms in laboratory: this practice has other advantages but is slow, expensive and very difficult for most bacteria that constitute the microbiota».
Previous studies have observed the same microbial species within mothers and infants and therefore suggested that transmission occurred.
«But in reality, unless you can see the same strain or genetic variant, it’s very hard to conclude that», said study co-senior author Adrian Tett, PhD, a senior research associate with the Centre. «We demonstrated that vertical transmission of microorganisms from mother to child can be inferred without using in vitro cultivation methods and therefore the study will follow up on a larger scale without using time-consuming cultivation approaches».
The studies on the microbiota
Every human being has a genetic heritage, which is passed to us from our parents, and a unique microbiota, a set of bacteria, viruses and fungi that inhabit our body and outnumber our own cells. Unlike our genome, the composition of the microbiota depends on a series of non-hereditary factors (age, diet, use of antibiotics, just to name a few) and, as in the case at issue, on the exposure to the mother’s microbiota at birth. While scientific research on human genome has been going on for a long time, studies on the microbiota are more recent. Through the analysis of a person’s microbiota it is possible to identify the microorganisms that characterize his or her personal set and, potentially, to establish his or her risk to develop certain diseases.
«Almost all the microbial strains in healthy people have functional properties that are indispensable for the human body; for example, they help in digestion. However, the presence of certain variants of non-pathogenic microorganisms, explains Nicola Segata, head of the Laboratory of Computational Metagenomics at the Centre for Integrative Biology (CIBIO) of the University of Trento, may involve a higher risk to contract complex and/or autoimmune diseases like diabetes, Crohn disease and ulcerative colitis».
Scientific evidence
In the study that has just been published, Segata and colleagues collected fecal and breast milk samples from five mother-infant pairs identified by the department of Obstetrics and Neonatology of Trento Hospital when the infants were three months old. They collected additional samples from two of the mother-infant pairs again when the infants were 10 months old, and from another mother-infant pair when the baby was 16 months old. They applied a laboratory technique called shotgun metagenomic sequencing to 24 microbiome samples (eight mother fecal samples, eight infant fecal samples and eight breast milk samples) to see which microbes were present. They used an additional tool called metatranscriptomics in fecal samples from two of the pairs to see which microbes were active.
«Initially, as expected, the mothers’ intestines had greater microbial diversity than those of the infants. However, the gut microbiome of the 16-month-old child had shifted toward a more mother-like composition with an increase in microbial diversity. Breast milk samples had limited diversity shortly after birth; skin microbes were observed in only low numbers in the infants’ gut microbiomes, suggesting that skin microbes do not colonize the human gut».
To analyze microbial transmission from mother to infant, the team further analyzed the metagenomic samples at a finer level to assess specific bacterial strains. One infant harbored a strain of the common infant bacterium Bifidobacterium bifidum that was 99.96% identical to his mother’s but clearly distinct from B. bifidum strains seen in the other infants, offering strong evidence for vertical microbial transmission. Another infant had strains of two other bacteria, Coprococcus comes and Ruminococcus bromii, that were over 99% identical to his mother’s.
«While it is still too early for results on all the fifty pairs, Segata concluded, there is probably a substantial fraction of bacteria in the infants that come from the mothers». The work goes on for Cibio researchers and staff from the department of Obstetrics and Neonatology of Trento Hospital and the University of Parma, as they are examining other mother-infant pairs from the birth of the children until their first year of age. «Our study will continue, and we will compare microbe transmission routes during vaginal and Cesarean section deliveries, breastfeeding, and skin-to-skin contact shortly after birth».
The American Society for Microbiology, the publisher of the new journal, is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to promote and advance the microbial sciences. ASM advances the microbial sciences through conferences, publications, certifications and educational opportunities. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.