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The Potential of Probiotics for Human Health

The potential of probiotics for human health

This article was originally published in Health Europa Quarterly on 3 May 2018, and is published here with permission.

Johan van Hylckama Vlieg is the vice-president for microbiome and human health innovation at Chr. Hansen A/S, a global leading bioscience company that develops and produces cultures, enzymes, probiotics and natural colours for the food, nutritional, pharmaceutical and agricultural industries.

Speaking at the 5th Microbiome R&D & Business Collaboration Forum: Europe, van Hylckama Vlieg provided a valuable insight into some of the exciting potential application areas of probiotics.

The history of probiotics

“Developing live bacteria for health beneficial purposes is not new in itself,” van Hylckama Vlieg began. “In fact, we’re standing on the shoulders of giants.” He pointed as evidence to Russian zoologist Élie Metchnikoff, who, more than a century ago, alluded to the concept of probiotics, which are defined by the World Health Organization as ‘live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host’.

Metchnikoff saw that “people that used consumed fermented food in the area of Eastern Europe where he was originally from actually lived longer, and he even postulated that people [who] may not be able to take a fermented food should take the bacteria as a product” – i.e. as a probiotic supplement – van Hylckama Vlieg said.

In his 1907 work The prolongation of life, Optimistic Studies, Metchnikoff asserted that the ‘dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes’.

This idea has since given rise “to a whole industry and a broad range of products,” van Hylckama Vlieg continued, both in fermented milks, e.g. Yakult and Activia, and in dietary supplements. In both instances, the active bacteria are commonly lactic acid bacteria, or Lactobacillales, and Bifidobacteria.

Lactobacillus rhamnosus and peanut allergy

One such probiotic strain is Lactobacillus rhamnosus, which is owned and produced by Chr. Hansen and, according to van Hylckama Vlieg, is “probably the best-documented bacterium” and “the paradigm of probiotic research”. Not only is it the subject of much academic research, it has also been under investigation in a large number of clinical trials, where it has been tested in a range of populations, including preterm infants, pregnant women and the elderly.

“More than 300 clinical studies [have been] published – of varying quality, but I think many of them very, very good – and show evidence” that L. rhamnosus can prevent or alleviate infections, as well as allergy, van Hylckama Vlieg said.

Highlighting one specific example, he turned his attention to the interaction of the gut microbiome and peanut allergy, which affects a growing number of people around the globe and can in some instances be life-threatening. He pointed to a trial by researchers at the Australian-based Murdoch Children’s Research Institute which found the strongest evidence yet that a probiotic-based cure may be possible for peanut allergy.

In the study, which was first published in The Lancet, Child & Adolescent Health, 48 children were given either an experimental immunotherapy treatment containing L. rhamnosus and peanut protein in increasing amounts or a placebo once daily over a period of 18 months. By the end of the study, 82% of the children on immunotherapy were able to eat peanuts without experiencing a reaction.

Followed up four years later, 80% of the newly tolerant children were still eating peanuts as part of their normal diet and 70% of them were found to have developed long-term tolerance.

If confirmed in a phase III trial, the study’s authors believe the findings could have implications for other food allergies, as well.

“It shows the drug potential of this viable material,” van Hylckama Vlieg said.

Lactobacillus plantarum has been shown to reduce the incidence of neonatal sepsis

Lactobacillus plantarum has been shown to reduce the incidence of neonatal sepsis

Lactobacillus plantarum and neonatal sespsis

He moved on to also highlight a 2017 study by an international team of researchers at the University of Nebraska Medical Center (UNMC) College of Public Health (US) which demonstrated that a particular combination of good bacteria in the body has a significant effect on the incidence of sepsis in infants.

Sepsis is defined by the World Health Organization as a ‘life-threatening condition that arises when the body’s response to infection causes injury to its own tissues and organs’ and is responsible for more than one million newborn deaths every year, the majority of them in developing countries.

The Nature-published trial, which was led by Dr Pinaki Panigrahi, a professor of epidemiology and paediatrics at UNMC, enrolled 4,556 newborns from 149 villages in Odisha, India, and monitored them for 60 days. In their first days of life, some of the infants were given a placebo while others were given an oral synbiotic preparation consisting of Lactobacillus plantarum ATCC-202195 and fructooligosaccharide, which occurs naturally in fruits and vegetables such as onions, bananas and asparagus, as well as breast milk.

The results were remarkable: in the first two months following birth, sepsis and deaths were reduced by 40%. The oral synbiotic preparation also resulted in fewer lower respiratory tract infections. According to the study’s authors, the findings ‘suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195’.

“I think this is a really important publication for the probiotic field because it shows the power and potential of bacteria in this area,” van Hylckama Vlieg said.

Probiotics and cancer

Lactobacillales and Bifidobacteria “are also associated to indication areas that I probably five or ten years ago would never have thought would be possible,” he then added, pointing as evidence to two studies in the area of immune blockades and cancer, both of which suggest that microbes could be effectively used – alone or in combination with existing immunotherapies – to treat a wide range of cancers. One shows that Lactobacillus johnsonii improves the efficacy of an anticancer drug called cyclophosphamide, while the other, originally published in Science, demonstrates that commensal Bifidobacterium promotes anti-tumour immunity and facilitates the efficacy of programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy. Biotechnology company Evelo Biosciences is now working to take this discovery further.

“This is no longer the exotic bacteria but the ones that we sort of knew so well but have completely new indication areas, so [it’s] very exciting,” van Hylckama Vlieg told the forum.

Lactobacillus murinus and high blood pressure

He then went on to highlight yet another study, published by Nature in 2017 and led by a team of scientists in Germany and the USA, which implies that a type of beneficial bacteria called

Lactobacillus murinus could protect against the damaging effects of a high-salt diet.

The researchers arrived at this finding by feeding mice an increased amount of table salt for two weeks. This had the effect of depleting the number of L. murinus in their gut and boosting the levels of pro-inflammatory immune cells, or Th-17 cells, which in turn saw their blood pressure go up.

After being given a probiotic containing L. murinus, the mice experiencing hypertension saw both their blood pressure and Th-17 populations go down.

Repeating the experiment in 12 humans – this time adding 6,000 milligrams of table salt a day to the subject’s diet over two weeks – delivered the same result: L. murinus decreased, Th-17 increased, and blood pressure rose. Similarly, when subjects were given a commercially available probiotic for a week before consuming the high-salt diet, both their blood pressure and the level of L. murinusin their gut remained normal.

Given that hypertension is a key risk factor for cardiovascular disease, the leading cause of death worldwide, these findings have significant implications for human health.

Again, said van Hylckama Vlieg, this is “something that I would not have easily imagined, but through interaction with the immune system you can also potentially address this” crucial health area.

Most exciting of all is that the above studies represent just a snapshot of the work going on in the field of probiotics, with much of their potential still to be discovered. As van Hylckama Vlieg highlighted at the beginning of his presentation, it is certainly an exciting time to be in microbiome research.

There will be a dedicated track on probiotics, prebiotics and nutrition at the 3rd Probiotics Congress: USA. Download the agenda here to find out more.

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