Possibly more personal than a fingerprint is a person’s microbiome, a collection of trillions of microorganisms including bacteria, fungi and viruses that live in a symbiotic relationship with the host, affecting everything from digestion and immunity to mental and skin health.
The best-known is the gut microbiome, which synthesizes vitamins and amino acids, assists in digestion and nutrient absorption, and keeps the gastrointestinal tract health. In addition, the gut contains about 70% of the body’s immune cells, which live in the gut-associated lymphoid tissue (GALT); these immune cells filter external stimuli including pathogens to help the body respond to threats.
There is an interconnection between the GALT and microbiota that impacts the immune response locally and throughout the body.1
“In the past several years, science has found that the microbiome is essential in shaping the development of the innate and adaptive immunity, and in turn the immune system helps to shape the microbiome,” says Vaughn Dubow, Senior Director Product Portfolio Marketing H&W, ADM Nutrition.
Consumers are increasingly aware of the power of the gut microbiome, with more than half (58%) of consumers seeing a connection between the function of bacteria in the gut to wider aspects of wellbeing.2 They are also actively looking for ways to actively support it, whether through diet or supplementation.
In fact, according to Mintel research, nearly three in five US adults say they are trying to eat a diet to encourage a healthy gut and microbiome.3 The market research organization further reports that over two-thirds of Americans would be interested in digestive health products that improve the immune system.4
“Our consumer data has shown that consumers are increasingly looking for products that have multi-functional benefits, with many looking to combine gut/digestive health and other benefits such as immune function,” confirms Dubow.
The cornerstone product of the category has been probiotics, defined as live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. While supplementation with these ingredients has been in play for several decades, their use in the food supply dates back centuries in the production of fermented foods from yogurt and kimchi to pickles and miso.
Among the most common strains used in the food supplement industry are Lactobacillus and Bifidobacterium strains; they are found naturally in the guts of healthy individuals and as part of the natural microflora. Research has confirmed their ability to be metabolically active, but there have been challenges in processing and delivering the fragile organisms into the intestines, where they colonize and exert their positive impacts.
This has led to great interest in so-called “spore formers,” a species of soil-based organisms that form dormant spores as a survival mechanism; when conditions are favorable, the spores can germinate and return to metabolically active bacteria. Perhaps the best-known in this category is the Bacillus subtilis species, a natural inhabitant of the animal and human gut. It was used in Japan to create natto, sticky fermented soybeans, and has since been found to offer not only health benefits, but the ability to address the processing challenges posed in food production.
Different strains of Bacillus subtilis thrive under different conditions, and it is critical to ensure that care is taken to address any potential toxic compounds that could form under germination. For this reason, ADM has taken great care in the development of its DE111™ Bacillus subtilis. Full genome sequencing has been uploaded to GenBank, the genetic sequence database of the National Institutes of Health (NIH).
In addition, the company has confirmed that DE111 grows quickly and most optimally at 37°C (body temperature), with a clinical study showing orally ingested DE111 spores germinate within the small intestine of humans within 3 hours of ingestion.5 Further research confirms the mechanisms involved in germination, as well as the genetic and phenotypic ability of DE111 to survive GI transit and deliver health benefits to the host.6
Health effects of DE111, a unique spore-former
DE111 offers myriad benefits, with some of the most compelling around its ability to support digestive health and the immune system. ADM has invested in clinical trials to ensure companies can deliver highly efficacious products to consumers. “Utilizing clinically backed ingredients enables formulators to guarantee a specific benefit for their active consumer base,” Dubow notes.
“Using a clinically backed ingredient at the proven dose/serving amount enables optimal health benefits as showcased in the clinical trials. Using a non-clinically backed ingredient leaves it up to pure chance whether a product can/will be effective in supporting health in a consumer.”
In the digestive health area, DE111 has been studied for its ability to maximize digestive wellbeing and normalize bowel function. One clinical trial in healthy adults assessed safety and efficacy of daily consumption of DE111 at a dose of 5x10(9) CFU (colony forming units). Researchers found DE111 was able to maintain healthy levels of cholesterol, glucose and triglycerides, indicating its ability to support macronutrient breakdown, while also improving consistency of bowel type, and concluded daily consumption was safe and effective.7
Additional studies have confirmed DE111’s ability to support intestinal regularity. One trial lasting more than three months in healthy adults found DE111 supplementation had a positive impact on healthy bowel index, with the proportion of normal stools increasing from 37% to 43% in the active intervention group.8 Another study, conducted in daycare-attending children aged 2 to 6 years for eight weeks, found a significant reduction in GI discomfort and duration of hard stools.9
Further research connects supplementation with DE111 with a reduction in inflammation, which impacts multiple systems. In a trial in daycare-attending children aged 2 to 6 years, those who received DE111 had an increase in microbiome diversity, with a particular increase in multiple microbial strains involved in reducing inflammation, and decreases in pro-inflammatory species.10
DE111’s ability to positively impact inflammation may play a role in its immunomodulatory properties. In a study involving 44 healthy adults, researchers assessed how four weeks of supplementation with DE111 (1 billion CFU/day) could impact immune response. Daily supplementation yielded a significant decrease from baseline in the basal levels of several immune cell populations, including CD3+ T cells and NKT cells.
In addition, ex vivo stimulation of immune cell populations with inflammatory bacterial lipopolysaccharide (LPS) showed increased immune response. The team concluded DE111 may therefore impact both innate and adaptive immune function.11
“With the innate immune system being our body’s first line of defense, it is always ready to respond to unwanted invaders within the body,” explains Dubow. “This type of immune function is extremely fast-acting, with immune responses being launched within minutes to hours.
“On the other side, we have adaptive immunity, which is far more specialized. It responds slowly, but extremely accurately. This enables it to be able to identify and target specific pathogens, enabling it to learn and ‘remember’ specific germs so it can respond faster the next time it sees them. DE111 is unique in that it can impact both immune systems for both a quick and prolonged response to unwanted invaders within the body.”
Delivering the benefits of DE111
Ultimately, DE111 is delivering synergistic benefits to the body, and doing so quickly. Researchers from Ireland recently concluded “a beneficial role of DE111 in digestion, metabolism, and immune health that appears to begin within hours of consumption”.12 The question then becomes how companies can deliver these benefits to consumers, which is where the benefits of spore-formers come in.
“Spore-formers are highly stable in many ‘harsh’ conditions, including high heat and liquid applications,” Dubow explains. “This provides benefits to the product developer as the ingredient can be added into unique dosage formats including things such as gummies/dietary supplements in addition to food and beverage applications.”
Further, stability tests have revealed virtually no loss of CFU over 24 months when stored at room temperature (25°C) and 40% relative humidity. DE111 has GRAS (generally recognized as safe) status in the United States, with FDA notification, is approved by Health Canada as a natural product and holds non-novel food status in Canada, Australia and New Zealand.
These benefits support its ability to be integrated into multi-ingredient formulations, particularly those with synergistic properties. Dubow comments: “While it is relatively simple to formulate or envision a symbiotic product, one that includes a prebiotic and a probiotic, there are many issues with utilizing traditional LAB bacteria in these formulas as they can be extremely temperamental when combined with other ingredients.
“Spore-based probiotics overcome this formulation hurdle with their stability and ability to be formulated next to nearly any dietary ingredient.”
Given consumers’ interest in increasing dietary fiber for gut and ‘prebiotic’ benefits, as well as the rising awareness of postbiotics for immune and inflammatory health, there are multiple opportunities for innovation that supports the gut and overall health and wellbeing.
References
1. Wiertsema, SP.; et al. (2021). The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients. 13(3):886.
2. ADM. ADM Identifies 2022 Global Consumer Trends and Shares How They’ll Come to Life Next Year.
3. Mintel. US Consumer Approach to Nutrition. 2021.
4. Mintel. US Digestive Health Market Report. 2023.
5. Colom, J.; et al. (2021). Presence and Germination of the Probiotic Bacillus subtilis DE111® in the Human Small Intestinal Tract: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study. Front Microbiol. 12:715863.
6. Mazhar, S.; et al. (2023). In vitro and in silico assessment of probiotic and functional properties of Bacillus subtilis DE111®. Front Microbiol. 13:1101144.
7. Labellarte, G.; et al. (2019). Tolerance and Effect of a Probiotic Supplement Delivered in Capsule Form. Food and Nutrition Sciences. 10(6):626-34.
8. Cuentas, A.M.; et al. (2015). The Effect of Bacillus subtilis DE111 on the Daily Bowel Movement Profile for People with Occasional Gastrointestinal Irregularity. J Prob Health. 5:4.
9. Slivnik, M.; et al. (2020). Effect of Daily Bacillus subtilis DE111® Intake on Gastrointestinal Health and Respiratory Infections in Children Attending Day-care: A Randomised, Parallel, Double-blind, Placebo-controlled Study. J Prob Health. 8(4):225.
10. Paytuví-Gallart, A.; et al (2020). Daily intake of probiotic strain Bacillus subtilis DE111 supports a healthy microbiome in children attending day-care. Benef Microbes. 11(7):611-620.
11. Freedman, KE.; et al. (2021). Examining the Gastrointestinal and Immunomodulatory Effects of the Novel Probiotic Bacillus subtilis DE111. Int J Mol Sci. 22(5):2453.
12. Colom, J.; et al. (2023). Acute physiological effects following Bacillus subtilis DE111 oral ingestion - a randomised, double blinded, placebo-controlled study. Benef Microbes. 14(1):31-44.
