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Baby gut microbiota and bacterial milkshakes

Atrandi Biosciences

Microfluidics, Single-Cell Analysis, & High-Throughput Screening

发布日期: 2024年11月6日

A little while ago we wrote about the development of gut microbiome in newborn babies. We discussed research by Aargaard et al. (2014) pointing to the placenta as a possible source of microbes which colonize the gut before the baby is even born; subsequently, a baby is exposed to microbes during birth and, afterwards, through diet and from the environment. However, since then, we have found more research on this topic, including studies contradicting research cited in our first post and an unorthodox method to artificially supplement the baby gut microbiome after delivery via C-section.

A reader pointed out that the study by Aargaard et al. (2014) which appeared to find a placental microbiome has been disputed and contradicted by subsequent research (Goffau et al. 2019, Turunen et al. 2021). The number of bacteria found in placenta samples by Aargaard et al. was small and most likely stemmed from contamination. Goffau et al. (2019) searched for bacterial DNA in placenta samples, carefully eliminating possible contamination sources and validating the results using different methods and suitable controls. They concluded that the placenta does not have a microbiome. However, in some of the samples they found a type of pathogenic bacteria, Streptococcus agalactiae, which is more commonly encountered in the genital tract of the mother and can lead to a potentially fatal sepsis in the newborn. This indicates that, while placenta does not have a microbiome, it can be inhabited by pathogenic bacteria.

At this point the evidence points to the fact that babies are first exposed to gut colonizing microbes during birth. In fact, a study by Kennedy et al. (2021) showed this by collecting rectal swab samples from neonates during C-section deliveries after sectioning but before the baby was removed from the uterus. 16S rRNA sequencing yielded no microbial signal distinct from negative control and bacteria detected by culture-based methods were attributed to contamination from skin.

Baby gut microbiota and bacterial milkshakes – Atrandi Pulse

Baby’s first exposure to gut-colonizing microbes during birth has a great impact to the development of its gut microbiome. Compared to vaginal delivery, during C-section the baby is significantly less exposed to microbes of the mother’s genital tract and fecal matter – two important sources of bacteria for the baby’s microbiota. This is associated with increased risk of immune diseases later in life. Thus, it might be beneficial to somehow supplement the gut microbiome of these babies.

However, the bacterial community, to which babies are exposed during birth, is complex and not well defined and we do not know which strains from the maternal microbiome end up colonizing the baby’s gut. Therefore, it is not as simple as giving babies a lab-made probiotic drink. Instead, a group of scientists in Finland (Korpela et al. 2020, Carpen et al. 2022), after carefully screening the mothers for diseases and pathogens, gave their babies (born via C-section) a very small amount of the mother’s fecal matter in her own milk with the first feeding. At 3-month follow-up, the microbiome of these babies resembled that of vaginally born infants and no adverse effects were observed.

This pilot study was small (only seven babies), but currently a larger, placebo-controlled trial is underway, and the early data aligns with previous observations (Lenharo 2024). However, Otto Helve, the primary investigator of the ongoing trial, talking to Nature News, emphasized that this treatment should not be undertaken lightly – careful screening must be performed to avoid transmitting any disease or pathogens from the mother to the baby. Additionally, not all C-section babies may require such treatment: even though over large populations negative C-section effects have been observed, on an individual level the C-section-associated risk of disease may be small, depending on other risk factors. Therefore, the Finnish scientists are also investigating whether certain high-risk groups would benefit most from the “poo milkshake”.

A lot of the research on infant gut microbiome so far has been performed using bulk methods of bacterial 16S rRNA and shotgun metagenomic sequencing, which might allow to identify the species, but certainly not the strain of bacteria. Developing single-cell sequencing methods could be beneficial to deepen the knowledge in this field, especially when searching for specific strains that pass from mother to child to possibly develop a lab-made supplement for gut microbiomes of babies.

Atrandi Biosciences has developed the semi-permeable capsule (SPC) technology which enables microbial DNA sequencing at single-cell level, allowing to identify strains and quantify species in the sample.