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Pre-, Pro-, Syn- or Postbiotics

Prebiotics, probiotics, synbiotics or postbiotics are terms that have to do with different aspects of fermented foods and their effectiveness. It is quite easy to lose track of what each term means, and sometimes it seems to be a scientific discussion of definitions rather than a useful description. Ultimately, it is about assessment of the expected health effects of a bacterium, a product, a food or even a dead food. So, what is the difference between the different ‘biotics?

Prebiotics are food components, often certain sugars, that are ingested through food. They support the growth of the bacteria already present in the intestine (intestinal microflora), especially those strains of bacteria that have a positive health effect on the host. Oligosaccharides are types of sugar also known as human oligosaccharides (HMO), that mostly consist of three carbon atoms. The infant absorbs large amounts of HMOs through breast milk and the intestinal flora of the babies’ gut develop in a healthy way through the HMO. Finally, the composition of the intestinal microflora is associated with the amount of breast milk, breastfeeding duration, the birth method (vaginal, caesarean section), antibiotics, and many other factors.

Probiotics are living bacteria. However, most living bacteria that you ingest are not probiotics. The definition and effectiveness as a probiotic is attributed to quantities of bacteria, the species of bacteria or even a specific strain of bacteria. A probiotic product, often a drink, contains living bacteria that enter the intestines and there exerts their activity. Known bacteria with a good reputation are Bifidobacteria and various strains of Lactobacillus, e.g. Lactobacillus paracasei strain CBA L74.

Synbiotics are products containing a combination of prebiotics and probiotics. Breast milk is actually a synbiotic. It contains a number of prebiotics as well as all kinds of probiotic bacteria for the baby. Babies get these bacteria from their mother through vaginal birth and the bacteria on the nipples. When mother’s milk is suckled, the baby often ingests, without knowing, ‘contaminated’ milk, bacteria like Lactobacilli, but also maybe Staphylococcus aureus. There is a range of bacteria present in mother’s own milk.

Postbiotics are metabolic products of bacteria, like short-chain fatty acids, and peptides. For example, the company Heinz has multiplied a specific strain of Lactobacillus paracasei, called CBA L74, from skimmed pasteurised milk (15 hours at 37 °C), so that finally about 5.9 x 109 bacteria per gram of product can be found. The fermented product is then pasteurized and freeze-dried to a powder. The powder no longer contains living bacteria, but only the killed bacterial cells and their metabolites, which is consequently characterized as a postbiotic.

When a product is fermented (such as when white cabbage becomes sauerkraut; black tea becomes kombucha, raw milk becomes raw milk kefir), what is then functional in that product? Is it the living bacteria, or is it enough to just take in their remains and metabolic products? Interest in postbiotics arises, among other things, from the same reasoning as when asked whether raw milk should be consumed or not. It is common in our society, that MDs and health officers make a warning for raw milk consumption. They state, that raw milk is potentially dangerous and even are the living bacteria in a probiotic product. Always three risk groups are mentioned: toddlers, the elderly with a weakened immune system and pregnant women. To avoid the risk, therefore the argument is that a (dead) postbiotic is preferred above a (living) probiotic. In their view, postbiotics are of interest of those that are overly concerned about potential risks with raw milk or living bacteria.

Clinical study: Postbiotics in young children

Various studies have been published since 2017 that examine the effects of a postbiotic product. It is a killed and dried fermentation product based on a probiotic fermentation process.

Young children typically get infected and sick by various viruses and bacteria, when they are young, especially in autumn and winter and through day-care centres where they meet lots of other children. An Italian research study investigated the effects of Lactobacillus paracasei strain CBA L74 postbiotic on children who attend one of the day-care centres to determine if infectious diseases can be reduced by a daily dose of CBA L74 (Nocerino et al., 2017). Neither scientists nor children knew what they got, and the children were observed from 3 months of treatment. Every day they received a dose. The study examined CBA L74 made from skimmed pasteurised milk and from rice fermentation (Table 1).

Table 1. Results of the postbiotic treatment study in three groups of children. Milk CBA = postbiotic based on skim milk; Rice CBA = postbiotic based on rice water; control did not receive any postbiotics.

 Milk CBARice CBAControl group
Number of children137118122
Age in month323134
At least one infection52%66%80%
Upper respiratory infection48%59%71%
Ear infection2%4%15%
Acute diarrhoea13%29%31%
Risk of repeated infections10%22%37%
Risk of medical treatment (OR)0.260.551.00

The children were just over 2½ years old and in both groups receiving CBA L74 there was a clear reduction in the number of infections, respiratory problems, ear infections and diarrhoea. The effects were often more pronounced in the milk CBA group, but diseases were also significantly reduced in the rice CBA group. The researchers classify the differences between milk and rice fermentation as insignificant (not statistically significant).

The medical treatments for the postbiotic-treated children were reduced, which is of great importance. Expressed as an odds ratio (OR) and compared to the control group (= 1.00), medical treatments in particular were reduced by 74% in the milk CBA L74 group.

In this study, children only received the bacterial metabolites, not the bacteria themselves. These metabolic products include short-chain fatty acids such as butyrate, propionate and acetate, and products that regulate the immune system. The intestinal flora of children is influenced by the absorption of such metabolic products. Nocerino et al. (2017) found a significant increase in immune peptides in both CBA L74 fermented products. Such peptides are responsible for suppressing the undesirable bacterial growth that can occur in infections or diarrhoea. In This study showed that the presence of living bacteria is therefore not necessary to achieve an effect on the children’s health.

Preclinical study: Postbiotics in mice

A study on mice, examined the impact of a postbiotic product on the fear and behaviour of the mice (Warda et al., 2019). There was one control- and one treatment-group. The treated group received the postbiotic, known as ADR-159, and based on Lactobacillus fermentum and Lactobacillus delbruecki. The fermented product was pasteurized so that no living bacteria were present. After three weeks of diet, both groups of animals were subjected to several stress tests. After 6 weeks the animals were sacrificed, and their blood and organs were examined. Faeces was collected every week to evaluate intestinal flora development in both groups.

ADR-159 supplemented mice had lower corticosterone levels after 6 weeks. This hormone affects, among other things, energy levels, immune responses and stress levels. The ADR-159 had a calming effect on the mice. Interestingly, the change in behaviour in supplemented mice was accompanied by a shift in the intestinal flora, which is an indication of the brain-gut axis. Changes in the gut not only impact allergies, but also outcomes of the brain. Other studies have shown that various gut-living bacteria, different ADR-159 can produce similar effects as seen in this study with lower corticosterone levels, increased social interactions, and less stress.

Further research needs to determine how the value and added value of living bacteria can be compared to the killed bacteria and their metabolites, and the importance of the food matrix in which the bacteria are grown. Most research has been done using sterilized skimmed milk without milk fat. Future research will show whether and what importance raw whole milk has as a starting point.

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