The Prophylactic Use of Probiotics (to Combat Microbiome Alterations Due to C-section and Early Life Antibiotic Use)

The article I read yesterday was a natural follow-on from my last post, about autism and its relationship to perturbations in the gut microbiome. This one was about a double-blind, placebo-controlled study using probiotics to restore normal gut microbiota in infants who were either born via c-section or given antibiotics early in life.[i]

Before I describe the study and its results, I want to list a few of the critical points the paper makes in its opening paragraphs:

1. I’ve written before about the timing of early-life exposure to bacteria.  These authors state:  “It is likely that infants are adapted to receiving specific microbial signals at critical time windows during their early development.  The gut microbiota…critically influence the development of the immune system, with potentially irreversible effects on disease susceptibility.”
2. “Overall, gut microbiota development in early life likely contributes significantly to the long-term health of the host.”
3. C-sections and antibiotics both disrupt the normal development of the bacterial microbiome. These have both “…been found to be associated with later metabolic and immunological diseases, such as overweight, allergic disease, type 1 diabetes and inflammatory bowel disease.”
4. Previously, a double-blind, placebo-controlled study of over 1000 infants at risk for developing allergies showed, “…the risk of allergic disease among caesarean-born infants could be reduced by pre- and postnatal supplementation of a multispecies probiotic…” The probiotic was a mix of Bifidobacterium breve, Proprionibacterium freunderreichii, Lactobacillus rhamnosus (2 strains).

This particular study was really very interesting in that these researchers tested the efficacy of this same probiotic mix in a variety of birth situations and their results are pretty incredible.

First, they looked at babies born vaginally who received no antibiotics.  The levels of Bifidobacterium breve and Lactobacillus rhamnosus were significantly higher in the supplemented group (up to 10X more in the babies who were breast-fed, less though in the formula fed ones).  In the control group (so not supplemented with the probiotic), breast-fed babies still had higher levels of B.breve but not even vaguely as high as those given the supplement, while the un-supplemented formula-fed babies did not have B.breve as a dominant group, “…suggesting that B.breve is a natural colonizer of breastfed infants.”

In fact, they discovered – looking further at the bacteria of these babies – that breast-fed babies had specific differences to the formula-fed ones: “…most of the supplement-induced changes observed in the breast-fed infants were not present in the formula-fed infants.  In the breast-fed group, the abundance of lactobacilli was 100% increased and that of bificobacteira 29% increased in response to the supplement.”  So breast milk has a huge effect on the colonization of good flora.  More on this later.

The scientists went on to test whether or not, using the probiotic, they could ameliorate the alterations in gut flora in babies who were either born via c-section or given antibiotics.

The c-section babies’ microbiota was “…clearly different from the vaginally born infants.”  However:  “Remarkably, in the supplemented group, birth mode did not have a significant impact on microbiota composition.” Wow.

Next, they tested the effects of antibiotics on the microbiota and whether or not the probiotic could ameliorate any changes.  In the probiotic-untreated control group, “…infants who had been treated with one or more antibiotic courses showed a clearly different microbiota composition compared to those that had received no antibiotics.”  However, in the experimental (probiotic treated) group, “…antibiotic use did not have significant overall impact.”  Double wow.

The results therefore demonstrated that “…most of the antibiotic- and caesarean-associated changes in the faecal microbiota of infants could be corrected or reduced by a probiotic supplementation to mother and infant.”  Furthermore, “….breastfeeding together with the probiotic supplementation offer optimal results in terms of supporting the microbiota development in these infants.”

A couple of other items of note:

1. While the probiotic supplement was actually a symbiotic one and contained the prebiotic oligosaccharides, there were still differences in the gut flora of formula-fed versus breast-fed babies, leading the researchers to conclude that, “…the amount of oligosaccharides in the supplement was insufficient to promote bacterial strains.” In fact, in the formula-fed babies who were given the probiotic, the decrease in certain strains of bacteria indicated that most certainly, the amount of prebiotic was too low to maintain the growth of certain beneficial species.
2. “The results indicate that formula-fed infants may require additional supplementation of prebiotics that mimic the natural abundance of HMOs [human milk oligosaccharides] in breast milk to achieve the benefits of probiotics.”
3. I thought this was really interesting too. Even though L.rhamnosus does not utilize HMOs, it benefited from breast milk.  The reason likely is that the increase in species that do use HMOs created a more favorable environment for the L.rhamnosus to thrive.
4. L.rhamnosus and B.breve are both anti-inflammatory and the former has been shown to reduce milk allergy in infants.

The article’s conclusion:  “Early-life antibiotic treatments and caesarean birth influence a large fraction of the global population and are associated with global epidemic health problems…Therefore, treatments achieving even modest improvements at the level of individuals have the potential to induce great health benefits at the population level.”

As the parent of a son with autism, and a history of inflammatory bowel disease and immune deficiency, who was given antibiotics intravenously for 5 days starting at 36 hours old (and told to stop breast feeding), this kind of research has become tremendously personal to me.  Believe me – were I pregnant now, I’d do things very differently than I did 25 years ago…

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[i] Korpela, K, et. al. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants.  Microbiome. 2018:6(182). DOI: 10.1186/s40168-018-0567-4}