Why prebiotics are vital to efforts to modulate the gut microbiome and improve health

The importance of the gut microbiome to human health is undisputed. A large body of evidence now shows that the composition of microbial communities in the gut modulates human and animal health from the bowel to the brain, driving a surge in interest in modulating the balance of gut microorganisms. Early efforts in the field focused on the delivery of the microorganisms themselves but it is now clear this is only one piece of the puzzle. To promote a healthy gut microbiome, people need to factor in prebiotics, a source of food for good gut microbes.

In recent years, researchers have agreed to visualise the gut microbiome as another organ of the human body.^1​​ This virtual organ ferments dietary fibers and other non-digestible substrates, resulting in the production of short chain fatty acids (SCFAs) such as acetate, propionate and butyrate, as well as several small metabolite molecules.

Research has linked SCFAs to key processes in and outside the gut, including cholesterol metabolism, glucose generation and building immunity against diseases. Through these and other associated mechanisms, researchers have tied the imbalances of the gut microbiota to the risk of developing Type 2 diabetes, obesity, inflammatory bowel disease, fatty liver disease and a multitude of other chronic inflammatory conditions. As per the latest WHO reports, noncommunicable chronic and lifestyle diseases kill 40m people every year worldwide, equivalent to 70% of deaths annually.^2​​ And shockingly, as per the Lancet​’s recent report, 11m deaths in 2017 — one in five of all deaths — was attributable to unhealthy diet.^3​​

Recognition that the gut matters in human health has driven the proliferation of probiotic products designed to boost the presence of microorganisms with positive properties. Yet, while studies have linked these products to health improvements and the probiotic supplement sector has grown into a $2bn a year business, there remain concerns that orally-administered microorganisms are unable to take hold in the gut and may not be the complete solution to change the makeup of its microbial community. ^{4​, 5​}​

The search for ways to modulate microbial communities is fuelling research into the provision of food products that encourage the growth of certain microorganisms. These ingredients are indigestible by humans but are fermentable by microbes, enabling them to serve as food for friendly microbes. Such ingredients, called prebiotics, can improve bowel movement and enhance the growth of probiotics and existing friendly bacteria, thereby driving increased production of health-promoting SCFAs.

Multiple studies have validated the use of dietary fiber — or mostly prebiotics such as fructooligosaccharide and galactooligosaccharide — in the modulation of the microbiota and achievement of various health benefits.^6,7​​ These studies have linked the consumption of dietary fibers to rises in the relative abundance of bacteria associated with specific health benefits, such as Bifidobacterium and Lactobacilli​, and the production of SCFAs thought to drive these positive effects.^8,9​​

Supplement manufacturers have begun to seize the opportunity, resulting in the triple-digit growth of the prebiotic sector and the ongoing rise of the larger, more established market for products that combine prebiotics and probiotics. Yet, functional foods may be a better platform to help people consume substances that are good for gut health.

Meeting the needs of formulators​

Any fermentable dietary fiber can serve as a growth substrate for gut microbes that have enzymes capable of breaking these fibers but some are more attractive to product developers than others. The best ingredients are easy to formulate into a wide range of functional foods, simple to handle, support a number of claims and packaging descriptors, lead to products with desirable sensory properties and deliver health benefits to the consumer.

Tata Chemicals developed Fossence to provide manufacturers with such a prebiotic ingredient. The ingredient is a short-chain fructo-oligosaccharide (FOS) that is found naturally in fruits and vegetables. The in-house process developed by Tata uses nature-inspired fermentation technology to make FOS from cane sugar. The resulting prebiotic is a naturally-sweet, 100% soluble dietary fiber with a low glycemic index and low calories. Fossence is generally recognized as safe (GRAS) by the US Food and Drug Administration.

Those characteristics set Fossence apart from other dietary fibers. Notably, it is very rare for a dietary fiber to be fully soluble and sweet to taste. Fossence in contrast, is available in sweetness-to-sucrose grades ranging from 40% to 70%, enabling formulators to use it to create foods with less added or no added sugar. As Fossence pairs well with polyols and other natural sweeteners, such as maltitol and stevia, it can even help to eliminate sugar from products altogether.

These features open up new formulation opportunities and product benefits, including many that fit with the rising concept of healthy indulgence — adding goodness for the gut and reducing sucrose load — that recognizes consumers’ desire for tasty, convenient foods and drinks that can be incorporated into healthy lifestyles.

Fossence enables formulators to meet this desire by creating gut friendly and at the same time reduced sugar products in a variety of formats like breakfast milk drinks, breads, muffins, cookies, nutribars, beverages and even functional chocolates and coffee drinks.

Fossence, as a good humectant and binding agent, also contributes to other properties as sugar does to product textures. The sensory properties of products are enhanced by Fossence, which helps to make foods and beverages more consumer friendly.

The breadth of products into which Fossence can be incorporated reflects its other characteristics. The ingredient in isolation is stable at high temperature, particularly when it is incorporated into a food matrix, and it acts as a binder to hold other ingredients together as well as being a humectant, meaning it retains moisture.

Validating the effects of Fossence​

To succeed, Fossence needs to do more than meet the formulation requirements of food and drink producers and sensory demands of consumers; it also needs to deliver the health benefits associated with prebiotics.

Studies suggest Fossence is well placed to deliver those benefits. Fossence’s short chains mean it is more readily fermentable than longer-chain dietary fibers, resulting in a higher digestive tolerance and faster increases in health-promoting SCFAs.

To further validate Fossence, Tata is embarking on multiple preclinical and clinical assessments of the prebiotic. Working with Yale University, one of its academic partners in the US, Tata is evaluating the effect of Fossence on germ-free mice with human gut microbiomes that mimic people with certain health conditions. The use of mice is giving Tata a better idea of the impact of Fossence on the gut without using a complicated human model. This also supports the deciphering of the mode of action at a micro level.

Tata plans to publish data from the animal models soon and use it to inform its clinical development efforts. Those efforts are already underway, with Tata embarking on a program designed to show the effect of Fossence on endpoints including fasting blood glucose and resistance to infections.

Across these studies, Tata investigated the effect of Fossence on the composition of the human gut microbiome and carried out a large-scale, 1,000-cohort mapping of the Indian human gut microbiome and compared it with western gut.^10​​ This holistic approach to the assessment of Fossence will help to understand both the effects of Fossence and the mechanisms that drive them, enabling Tata to draw a line between the consumption of the probiotic, shifts in the microbiome and changes to health-related biomarkers.

Through these studies, Tata is set to cement the status of prebiotics as a cornerstone of efforts to improve human health by modulating the gut microbiome. And, in doing so, provide food and drink manufacturers with a scientifically-validated ingredient that supports novel products and compelling marketing messages. It is time we rethink how we use platforms like regular foods and beverages to deliver healthy indulgence.

References​

1.      Valdes, A. M., Walter, J., Segal, E. & Spector, T. D. Role of the gut microbiota in nutrition and health. BMJ​ 361​, k2179 (2018).

2.      Noncommunicable diseases. WHO Available at: https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases&sa=D&ust=1556530722861000&usg=AFQjCNHxB_HNhtOMGskSLzU78G3pbmL59A​. (Accessed: 29th April 2019)

3.      Afshin, A. et al. Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet​ (2019). doi:10.1016/S0140-6736(19)30041-8

4.      Kristensen, N. B. et al. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med. ​8​, 52 (2016).

5.      2018 NBJ Supplement Business Report. Nutrition Business Journal: Data insights for the health industry Available at: https://www.nutritionbusinessjournal.com/reports/2018-nbj-supplement-business-report/​. (Accessed: 23rd April 2019)

6.      Veronese, N. et al. Dietary fiber and health outcomes: an umbrella review of systematic reviews and meta-analyses. Am. J. Clin. Nutr. ​107​, 436–444 (2018).

7.      Thompson, S. V., Hannon, B. A., An, R. & Holscher, H. D. Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. ​106​, 1514–1528 (2017).

8.      Venkataraman, A. et al. Variable responses of human microbiomes to dietary supplementation with resistant starch. Microbiome​ 4​, 33 (2016).

9.      Martínez, I., Kim, J., Duffy, P. R., Schlegel, V. L. & Walter, J. Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS One​ 5​, e15046 (2010).

10.    Tandon, D. et al. A prospective randomized, double-blind, placebo-controlled, dose-response relationship study to investigate efficacy of fructo-oligosaccharides (FOS) on human gut microflora. Sci. Rep.​ 9​, 5473 (2019).