In recent years, the microbiome has moved to the forefront of nutraceutical and food and beverage conversations. With a highlighted presence across all major industry conferences and events as well as exponential growth in patents and scientific publication coverage, it’s easy to see why new startup companies dedicated to mining the microbiome – each in a slightly different manner – are constantly sprouting up.
The microbiome’s rise to prominence has led major industry players to strategically position themselves in the field, from Nestlé Health Science’s investment in clinical stage company Enterome back in early 20161 to DuPont’s recent establishing of its own Microbiome Venture2. But do we really know how to make the most of microbiome science and how it will change the food industry in the future? To answer, we must first explore the microbiome, pre- and probiotics a little further.
The microbiome is the collection of hundreds of species of microorganisms that live on and in the human body. In fact, the number of microbial cells matches that of human cells, with approximately 1013 each for an average adult3. These microbes are chiefly bacteria that live in the gut, which is the reason why attention tends to focus on the gut microbiome.
The widespread industry and media interest around the gut microbiome mainly comes from its impact on human health. It has now been demonstrated that altered microbial compositions and/or activities in the intestine, also known as dysbioses, bear relation to a number of ailments such as inflammatory bowel disease, diabetes, allergies, asthma, autism, obesity, cardiovascular disease and even certain cancers.
Research suggests that some of these medical conditions may be prevented or improved by reverting these dysbioses back to a normal, healthy state, referred to as eubiosis. There is therefore significant interest in understanding the relationship between the microbiome, health and disease in order to design rational microbiome modulating strategies, with food and life sciences companies dedicating considerable resources to the research and development of products which restore the gut’s optimal balance.
The microbiome modulating strategies with which most people are familiar are probiotics and prebiotics, but to understand their impact on the food industry it is crucial rst to understand the difference between the two:
Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host4. While most probiotic strains have previously been developed to support general digestive wellness and immunity, technological advances are now allowing scientists to better characterise the interactions between microbes and their human host in order to develop strains with more specific health advantages.
A strong example here is Lactobacillus plantarum LPLDL® (LPLDL®) from OptiBiotix, a probiotic strain with naturally- occurring metabolic activity which is able to fine-tune the microbiome-liver axis, or the bi-directional communication between our intestinal bacteria and our liver. This cross-talk has profound implications in our cardiovascular health, with the ability to affect blood pressure and cholesterol levels. Suitable for incorporation in functional food applications, LPLDL® enables consumers to take control of their heart health management and has been demonstrated in a human intervention study5 to simultaneously lower blood lipids, LDL (bad) cholesterol and blood pressure.
As live microorganisms with a complex biochemistry, probiotics offer huge promise in all applications that may require an active metabolism for their mechanism of action. However, despite their wide array of potential applications, it should be kept in mind that probiotics also have limitations, among the most consequential of which is that a probiotic approach is currently only viable with a handful of microbial species dominated by, yet not limited to, lactobacilli and bifidobacteria. Knowing that a great deal of our microbiome is composed of non-culturable and strictly anaerobic organisms, the strategy of modulating the microbiome with probiotics may not be the most important one in the long run.
In addition to this, probiotics’ effect is generally transient and restricted to the time in which they are being ingested, so long-term regimes are usually necessary. Most significantly for the nutraceutical and food and beverage industries, probiotics are not suitable for all food applications, with non-sporulated, live microorganisms unsuitable for processes where heat is involved due to temperature sensitivity. This explains why probiotics are normally found in dairy products and food supplements.
Prebiotics, on the other hand, are nondigestible substances, often fibres, that act as food for the gut host micro-organisms and confer health benefits. Most prebiotics available today promote the growth of many different types of gut microbes and this increase in microbial diversity has classically been considered a positive outcome. However, the ultimate goal should be stimulating the growth and activity of only those microbes that can help the human host in order to achieve specific health benefits. This creates the potential for food and pharmaceutical companies to precision engineer the microbiome to improve human health.
Prebiotics are biologically much simpler than probiotics, yet they have the potential to enhance complex biological activities within the microbiome and tend to have more critical and durable effects on the microbiome community than probiotics. Most importantly for the nutraceutical industry, prebiotics are suitable as ingredients in a wide range of food processes and products thanks to their heat resistance.
Pre- and probiotics may be used alone or as a joint strategy, referred to as synbiotics, to harness the unique advantages of each. More recently, with the growing understanding of microbial biochemical pathways, it has become possible to design and develop prebiotics which enhance the growth and activity of a particular probiotic genera or species. The combination of a probiotic with its partner prebiotic is being termed an optibiotic.
For instance, in order to enhance the health benefits of OptiBiotix’s LPLDL® probiotic strain, it has been co-administered with LPGOS®, a galactooligosaccharide (GOS) prebiotic that targets this particular organism. LPGOS® is produced using enzymes extracted from LPLDL®, in essence using the probiotic strain’s biochemical pathways normally used to break down foodstuffs to construct complex oligosaccharides.
Employing gut models, studies have found the use of the optibiotic partnership LPGOS® + LPLDL® to lead to a threefold increase in the strain’s ability to lower cholesterol. In such models, LPGOS® alone promoted the reduction of cholesterol by the members of the microbiome by >20%, proving that either prebiotic or optibiotic strategies may be effective in improving cardiovascular health with this mechanism. By drawing on the unique benefits of probiotics and targeted prebiotics, OptiBiotix’s optibiotic strategy is able to deliver tangible health benefits. This approach has the potential to create targeted prebiotics which can enhance the growth and activity of a wide range of commercial probiotics and indigenous host microbial species.
These developments have substantial potential for the nutraceutical industry, opening up new doors to innovative functional food applications tailored to a wide range of wellbeing concerns from cardiovascular disease to obesity. Leveraging the relationship between our current microbiome and how we process, metabolise and respond to foods, as well as the impact of the foods we eat on our microbiome, the market is making functional foods a viable health management tool.
This next generation of microbiome modulating food and beverage products is better equipped to tackle today’s chronic lifestyle diseases, with food scientists increasingly able to design precision engineering strategies to prevent, manage and treat a wide range of conditions. For example, researchers have been able to accurately predict blood glucose increase after eating by looking at the individual’s microbiome state6. In a different experiment, investigators observed that a weight-loss diet’s degree of success could be predicted upfront by studying the ratio of two genera of bacteria within the patients’ gut microbiome, namely Prevotella and Bacteroides7, whereby the higher the Prevotella-to-Bacteroides ratio, the greater the weight loss was found to be. Nutraceuticals companies can now therefore offer innovative applications that are both natural and backed by science, transforming traditional approached to health management.
By exploring and understanding the capabilities and limitations of pre- and probiotics, the industry can unlock the microbiome as a source of distinctive functional ingredients, such as new probiotic strains, and novel mechanisms to positively impact human health through dietary interventions. In a market where customers are increasingly educated and concerned about wellbeing, there is massive scope for designing science-based approaches to healthier functional foods and this potential is maintaining the microbiome modulation market’s rapid expansion. Pre-, pro- and optibiotics are one of the most dynamic and exciting fields in food science and technology and it is a momentous time to be involved.
For more information about Optibiotix, please visit www.optibiotix.com
- Nestlé Health Science. Nestlé Health Science invests existing investors as Enterome raises €14.5 million in Series C financing round. (2016).
- DuPont. DuPont establishes microbiome venture to lead development of new microbiome science-based solutions. (2017).
- Sender, R., Fuchs, S. & Milo, R. Are we really vastly Outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164, 337–340 (2016).
- World Health Organization. Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food. (2002).
- Costabile, A. et al. An in vivo assessment of the cholesterol- lowering ef cacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults. PLoS One 12, e0187964 (2017).
- Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).
- Hjorth, M. F. et al. Pre-treatment microbial Prevotella-to- Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention. Int. J. Obes. (2017).