Here are 4 and a bit reasons to pause the probiotic prescription pad.
There certainly are a plethora of probiotic products marketed for infants – but should we give these to the exclusively-breastfed infant? Here are 4 and a bit reasons to pause and reconsider prescribing probiotics directly to the exclusively- or predominantly-breastfed infant under 6 months.
Reason no 1. Breastmilk has it covered.
Breastmilk is the Ultimate Gardener of the Infants Gut Ecosystem
Each mother’s breastmilk contains 100 to 600 different living bacterial species (Hunt, Foster et al. 2011, Boix-Amorós, Collado et al. 2016). This data refers to the species-level richness, if we were to take it to the strain level data, we would find we would be talking about a much bigger number. Breastmilk is a source of primary colonisers including bifidobacteria and lactobacilli species, in addition to a range of butyrate-producing bacteria (Jost, Lacroix et al. 2014, Jost, Lacroix et al. 2015, Milani, Mancabelli et al. 2015, Murphy, Curley et al. 2017).
Alongside bacteria, breastmilk is a source of many prebiotic and prebiotic-like compounds including the human milk oligosaccharides (HMOs). HMOs selectively feed specific bifidobacteria species that play an important role in infant health by supporting healthy gut mucosal immune development along with other important functions (Bode 2015, Wickramasinghe, Pacheco et al. 2015, Arboleya, Stanton et al. 2016). Each mother has a unique set of up to 50 or more HMOs (Niñonuevo, Perkins et al. 2008, Bode 2015). (Note: This may be a conservative estimate of HMO diversity as characterisation of HMOs has been constrained by analytical techniques). Surprisingly, breastmilk has a higher concentration of HMOs than it does protein (Bode 2012). This perhaps exemplifies how evolution has prioritised providing nourishment to the infant gut microbiome. Aside from HMOs there are many other prebiotic and prebiotic-like compounds in breastmilk (Liu and Newburg 2013, Lonnerdal 2013, Pacheco, Barile et al. 2015). Human milk also supplies an array of selective bacteriostatic compounds that are active against potential pathogens and pathobionts (Lonnerdal 2013, Hassiotou and Geddes 2015).
How does microbiota of the breastfed infant cope with rough and tumbles?
The gut microbiome of the breastfed infant has recently been described as resilient in comparison to that of the formula-fed infant (Carvalho-Ramos, Duarte et al. 2018). Studies looking specifically at antibiotic exposure have found that the breastfed infant appears to have a great degree of microbiome resilience or bounce back capacity (Savino, Roana et al. 2011, Azad, Konya et al. 2015, Carvalho-Ramos, Duarte et al. 2018). Given that breastmilk is arguably the perfect synbiotic, it’s not surprising that researchers are finding breastfed infants display microbiome resilience.
Any early antibiotic exposure is of course vastly disruptive to the infant’s ecosystem. Breastmilk is the perfect synbiotic to reduce the disturbance. Breastmilk can be considered the ultimate gardener (and restorer) of the infant gut: seeding, feeding and weeding. Hence, in my opinion, for the most part there is no need for any additional help in this area. One important thing we can do is empower mothers with this knowledge and help them to access good breastfeeding help to support them in attaining their breastfeeding goals. Often a first step to this is linking them in with good peer support organisations like La Leche League and The Australian Breastfeeding Association.
But surely a probiotic supplement will be beneficial to any infant on antibiotics? Or will it? And that’s the question I want us to look at more closely. In this context I assert that it’s important that we consider what that infant is already receiving from breastmilk when we are weighing this up. Furthermore, we need to carefully weigh the evidence for any probiotic treatment but particularly in a young infant – and consider both the potential for harm and benefit based on the evidence on the specific strain in question (more of this below).
Reason No 2. Direct probiotic supplementation may confer some risks to the young infant.
Probiotic supplements contain excipients (and occasionally contaminants) and young infants have a leaky- and immune-naïve gut.
Of course, no probiotic supplement contains only bacteria. They all contain some form of excipients (ranging from simple oil suspensions to complex multi-ingredient powders). Some contain additional sweeteners. Further, post-market surveillance studies indicate that bacteria contamination occurs reasonably commonly, and occasionally with potential pathogens (Drago, Rodighiero et al. 2010, Patro, Ramachandran et al. 2016). Bacterial contamination can also occur in the home.
Why is the infant under 6 months particularly vulnerable to ill effects?
In a nutshell the answer is that their gut is immature and leaky, and they are less able to break down proteins and neutralise pathogens.
More detail on this here
The young infant has greater intestinal mucosal permeability and immature intestinal barrier function. The neonate gut is especially permeable (Le Huërou-Luron, Blat et al. 2010). Breastmilk components assist with the development of the barrier both directly (Turfkruyer and Verhasselt 2015) and via the promotion of a healthy microbiome (Mikami, Kimura et al. 2012, Goldsmith, O’Sullivan et al. 2015). The young infant also has lower gastric acid output. The neonate has a fasting gastric pH of 6-7 contrasting markedly with the adult of pH range of 1-3.5 (Kaye 2011). The infant’s gastric pH gradually decreases each month and matches that of an adult by age 20 to 30 months (Kaye 2011). Furthermore, the infant secretes less gastric and pancreatic proteolytic enzymes and the enzymes have lower activity than that of adults (Blackburn 2007). The combination of reduced proteolytic action (through higher stomach pH, lower enzyme levels and activity) and increased gastrointestinal permeability results in infants absorbing a greater amounts of intact proteins. It also means they are more vulnerable to infection from microbial contaminants should there be any in the probiotic product either at the time of purchase or from contamination in the home.
Add to this that the infant is also immune-naïve, hence more vulnerable to infection. The immature gastrointestinal mucosa is arguably also likely to be more vulnerable to irritation and potential allergic sensitization when exposed to additional ingredients present in supplements.
Exposure to substances other than breastmilk (including food, cows milks, and formula) prior to developmental readiness appears to cause inflammation (Coovadia, Rollins et al.) and in some cases micro-bleeding (Tawai 2012) – both of which dilute the actions of breastmilk (Coovadia, Rollins et al. , Kramer and Kakuma 2012, Quigley, Carson et al. 2016).
Reason No 3. They may not provide any benefit.
Evidence for efficacy in formula-fed infants cannot be generalised to breastfed infants.
When considering evidence for efficacy we need to take into consideration the population characteristics. Exclusively breastfed, partially-breastfed and exclusively formula-fed infants all have different health risks. Many studies assessing the safety and efficacy of probiotics in infants <6 months old have been conducted in formula-fed infants. This population is different to exclusively breastfed infants in numerous ways, including having greater risk of infectious disease (Quigley, Kelly et al. 2007, Duijts, Jaddoe et al. 2010, Quigley, Carson et al. 2016), and a disrupted microbiome (Dogra, Sakwinska et al. 2015, Madan, Hoen et al. 2016). Consequently, probiotics may be more likely to have a beneficial effects in formula-fed infants. Hence these effects cannot be generalized to breastfed infants. Additionally, strain specificity always needs to be considered – evidence relating to one strain cannot be generalized to another strain.
One specific area of probiotic research is the application of probiotics in preterm infants with the intention of reducing the risk of necrotizing enterocolitis (NEC) – a devastating disease for the preterm infant. There appears to be some promising results suggesting that some specific probiotic strains may be able to assist with preventing NEC (Olsen, Greisen et al. 2016, Uberos, Aguilera-Rodríguez et al. 2017). Once again when looking at the evidence it is important to clarify if the evidence of benefit applies to infants being fed their own mothers’ milk, donor breastmilk, and/or formula.
There are some more recent studies assessing specific probiotic strains in breastfed infants. Before we consider prescribing these, I think it’s important that we look at what outcomes were measured and consider whether these are clinically meaningful and relevant to the infants we are working with.
Reason No 4. It may detract from breastfeeding.
When we prescribe probiotics to breastfed babies, what subtle messages are we giving parents? Are we missing an opportunity to empower and educate parents about what their infants are getting from breastfeeding? Are we potentially missing an opportunity to promote breastfeeding?
This is something I ponder.
Something I strive to do is really minimise how often I recommend anything other than a breast going into a young baby’s mouth. This is for all the reasons mentioned above but also because I don’t want parent’s headspace to be taken up with another thing they have to do to their infant.
Treating through the mother – an alternative we would like to promote
Treating through the mother is not a new idea. Certainly, from a more general perspective assuring the mothers physical, mental, and emotional wellbeing has far-reaching flow on effects to the infant’s health.
The entero-mammary pathway hypothesis would suggest that there is a potential for a mother’s intestinal microbial community to continue to interact with their infants’ gut via breastmilk. Animal data (Young, Hine et al. 2015, de Andrés, Jiménez et al. 2018)(reviewed by (Addis, Tanca et al. 2016) and preliminary human studies support this hypothesis (Whitten and Hawrelak 2018).
Based on this premise, nourishing the mothers gut microbiome via dietary modification and prebiotic supplementation may be a tangible way of exposing the infant and potentially seeding the infant with a greater array of beneficial microbes.
Additionally, supplementing mothers with some specific probiotic strains may result in breastmilk transfer of this strain. The following strains have preliminary clinical data suggesting potential for breastmilk transfer L.fermentum CECT5716, L. salivarius CECT5713, L. gasseri CECT5714, L. reuteri DSM 17938, L. salivarius PS2 (Whitten and Hawrelak 2018) and potentially L. rhamnosus GG (based on its appearance in the stool of infants who’s mothers were supplemented, although this may be explained via intra-partum transfer during vaginal birth rather than breastmilk transfer (Dotterud, Avershina et al. 2015, Simpson, Avershina et al. 2018, Whitten and Hawrelak 2018)). Preliminary data does suggest that potential for transfer to breastmilk is a strain specific trait (Whitten and Hawrelak 2018).
Probiotic supplementation to the mother may also influence the immune messages that are transferred through the breastmilk such as increasing breastmilk cytokine TGF-β2 (Rautava, Kalliomäki et al. 2002) and immunoglobulin sIgA (Prescott 2008). These two components may promote mucosal integrity and support reduced tendency to allergic conditions, for example (Brenmoehl, Ohde et al. 2018).
So there you have it, four and a bit things to think about before you bring out your probiotic script pad for the breastfeeding infant.
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