What happens if you give c-section babies a vaginal microbiome?

Babies born by cesarian section have greater likelihoods of autoimmune diseases during childhood and later in life.  They also have a gut microbiome that resembles their mother’s skin right after birth. On the other hand, babies that are born vaginally have a gut microbiome that resembles their mothers’ vaginas, and are at lower risk for asthma and allergies.  Given the importance of the microbiome on immune development, many scientists believe that there may be a link between mode of delivery, the initial infant gut microbiome, and normal immune development.

One possible method to ensure a baby that is born by c-section is initially colonized by his or her mother’s vaginal microbiome is to swab the mother’s vagina and transfer her microbiome to the baby immediately after birth.  Researchers from New York University performed this exact experiment, and measured the changes that occurred in the gut after this intervention.  They published their results in the journal Nature Medicine.

In the study, 18 women were split into 3 groups: 7 women gave birth naturally, 7 women gave birth by c-section, and 4 women gave birth by c-section but had their vaginal flora transferred to the babies.  This last group of women had their vaginas screened for pathogens shortly before birth.  After the c-section, and within 2 minutes after, gauze was rubbed in the new mothers’ vaginas and then rubbed all over babies’ mouths, faces, and bodies.  The babies’ skin and gut microbiomes were measured and compared to the other two groups.  As expected, the babies born vaginally had microbiomes that resembled their mothers’ vaginas, and the babies born by c-section had microbiomes that resembled their mothers’ skin.  Interestingly, the c-section babies that were inoculated with their mothers’ vaginal microbiomes, had a microbiome that closely resembled their mothers’ vaginas, even after 1 month.  In addition, there were no adverse consequences to the microbiome transfer.

This was a small proof of concept study that successfully showed a vaginal microbiome transfer to c-section babies could properly colonize a newly born infant.  Further studies still need to confirm that the skin microbiome is unhealthy for a c-section baby, but if it is, then these vaginal flora inoculations may become a critical procedure to ensure a healthy immune system for all newborn infants.

Helicobacter pylori genome found in the stomach of a 5300-year-old Ice man

Oetzi the Iceman

Oetzi the Iceman was found in 1991 in the high Oetzal Alps that span Italy and Austria.  He is a mummy who gained popularity in the scientific community because of how well he was preserved and thus the potential to provide a glimpse into Europe’s past (he is thought to be around 5,300 years old, alive in the European Copper Age).  Many studies have examined his diet, health, and genetics, but recently researchers were able to discover identify and examine his stomach and intestines.  Biopsy samples were collected and PCR analysis determined the presence of the gram-negative bacteria Helicobacter pylori. 

H. pylori can be found in about half of the world’s population, and while research has pointed to the harmful effects of this bacterial strain, recent work has supported that the bacteria can in fact protect against some illness such as acid reflux and asthma.  However, extensive characterizing Oetzi Iceman’s H. pylori could also shed light on ancient human migration patterns.  Specifically, modern strains of H. pylori are assigned to distinct populations based on their geographical heritage, originating from either ancestral Asian populations (AE1) or hybrids between North Africa and Europe (AE2). 

Comparative whole genome analysis showed that Oetzi Iceman’s H. pylori genome has highest similarity to three apAsia2 H. pylori genomes from India, and further high-resolution analysis of ancestral motifs revealed a co-ancestral matrix, showing that H. pylori shares ancestry with Indian strains but also with most European strains.  Low levels of H. pylori ancestry was shared with the AE2 ancestry, which was interesting to scientists as it suggests AE2 introgression into Europe after the Copper Age.  This was later than what has been proposed previously by the scientific community.  Ultimately, these findings showed that Oetzi Iceman had H. pylori with strong AE1 genetic Asian origins, suggesting that the AE2 bacteria from African heritage began arriving after the Copper Age of European civilization.  

How many bacteria vs human cells are in the body?

When people ask me what the microbiome is, part of my answer usually includes the fact that there are 10 times as many bacteria in the body as human cells in the body. Unfortunately, I may no longer be able to use that statistic. A recent study out of the Weizmann Institute in Israel states that the number of bacteria may actually be very similar to the number of human cells in the body.

The authors of the study found that the 10:1 ratio of bacterial to human cells goes back to a 1977 study by Dwayne Savage and an earlier 1972 paper estimating the number of bacterial cells in the human body. The Weizmann scientists redid the estimate and found that there were about 39 trillion bacterial cells in the body. They also estimated the number of human cells in the body, about 84% of which are red blood cells, finding there to be about 30 trillion human cells in the body.

While this results in about 1.3 bacterial cell per human cell, the numbers may vary significantly from person to person and could change significantly with each defecation. They estimate that the range of bacterial cells goes from about 30 to 50 trillion in each individual. Women may also have a higher ratio of bacterial cells than human cells because they have fewer human cells, specifically red blood cells.

While this study does not take into account fungi, viruses, and archaea which all make up the human microbiome and would increase the ratio of microbes to human cells, the often stated ratio of 10:1 for bacterial cells to human cells is most likely not accurate. While I will no longer be able to use this fun fact in my description of the microbiome, it does not take away from the importance of bacterial cells in human health. 

Starch rich diets can influence the gut-microbiome and subsequently behavior

The microbiome’s role in modulating the gut-brain axis has been well-supported by a large body of evidence.  Many experiments in the past have demonstrated this in preclinical models by administering probiotics with specific bacterial strains or by fecal microbiome transplant in rodent models, which were then associated with changes in behavior.  Diet has also been implicated in these modulations, as food intake can influence species diversity and composition.  Low-digestible carbohydrates, or resistant starch, have received attention as being beneficial toward health, as these components are not digested but rather fermented by resident microbiota to produce an array of beneficial metabolites.  In a recent study, researchers from Texas Tech University investigated whether a diet rich in resistant starches were also associated with changes in behavior.

48 mice were randomly assigned to 3 different treatment groups, with each group either fed normal corn starch diet, a resistance starch rich diet, or an octenyl-succinate diet for 6 weeks.  The animals were monitored for weight, were subject to robust behavioral tests, and fecal samples were examined for microbiota composition.  The animals on the resistant starch diet exhibited similar weight gains as compared to the normal corn starch diet, and the octenyl-succinate group demonstrated lower weight gain.  Fecal microbiota analysis revealed diet correspondence to specific diet, and that resistant starch diet groups displayed increases in Verrucomicrobia and Actinobacteria as compared to octenyl-succinate and normal corn starch group, respectively.  In all groups, mice displayed significant anxiety-like-behavior in an elevated plus maze, and in open-field tests the mice fed resistance starch rich and octenyl-succinate diet mice exhibited high-anxiety-like behaviors. 

This data again supports that diet manipulation can have marked influence on behavior, and that starch rich diets could perhaps induce undesirable behavioral effect via modulation of the gut-brain axis.  This could be an important drawback to the beneficial components provided for microbial fermentation.  

Breastmilk contains many prebiotics to support the growth of beneficial bacteria in the infant’s gut.  It also contains bacteria that seed the infant’s gut.  Previous research has shown that the bacteria in breast milk do indeed take hold and colonize the gut, and so it is imperative to infant microbiome development.  An article published last week sought to discover if the breastmilk microbiome changes depending on mode of delivery, especially since we have seen that C-section infant’s have much different microbiomes than their vaginally delivered counterparts.  The scientists published their results in the journal Microbiome.

The scientists tested the breastmilk of 39 Canadian women.  Despite various backgrounds, each woman’s milk was dominated by Staphylococcus, Enterobacteriaceae, and Pseudomonas.  Moreover, there were not major differences in the breast milk microbiomes between modes of delivery, showing that it is not effected by C-section of vaginal birth.  In addition, the gender of the baby did not change the microbiome either.  Interestingly, the microbiomes were very different between mothers, meaning that babies are being exposed to highly diverse bacteria from milk.  In one case 80% of the bacteria were staphylococci, and in another case more than 50% was Pseudomonas.

There is little evidence that shows how differences in breast milk microbiomes are affecting children.  That said, we know the microbiome is critical to immune system development, and therefore it reasons that these differences may be important.  In any event, it is useful to see that mode of delivery itself is unlikely to change the breastmilk microbiome.

Malassezia spp. microorganisms also inhabit skin during acne

Most people experience acne at some point in their life, and the AMI has discussed the microbiome’s role in this skin condition many times in our blog and podcasts.  Cutaneous inflammation is observed in people with acne, as well as increased amounts of the Propionibacterium acnes (P. acnes) bacteria.  However, a recent study conducted by dermatologists in Japan quantitatively examined microbiota in follicular skin contents, and providing more evidence that Malassezia spp. fungi may also be present during facial acne episodes in addition to P. acnes. 

15 untreated acne patients were selected for the study, all of whom had not received previous treatments with topical and/or steroid/antibiotic regiments.  A comedo extractor was used to collect follicular contents from inflammatory acne lesions from the cheek and foreheads of patients, and these samples were subject to DNA extraction and subsequent PCR analysis to characterize microbiota species.  Staphylococcus and Propionibacterium were found in follicular contents, but interestingly Malassezia spp. fungi were also observed.  Furthermore, Malassezia spp. fungi in follicular contents were correlated with inflammatory acne and with content on the skin surface, while Staphylococcus and Propionibacterium were not. 

These findings suggest that Propionibacterium acnes may not be the only microbiota skin residents related to acne.  While this was not the first paper to point to Malassezia spp. fungi as implicated in acne, these researchers addressed prior experimental method concerns and utilized advanced quantitation methods such as PCR rather than culture-methods.