Prebiotics: Is fiber specificity the key to increasing the consistency of prebiotic benefits?

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Prebiotics sales are expected to grow 15% annually and reach approximately $20 billion globally by 2030.¹ Despite this commercial success, for the general population the benefits of prebiotics largely depend on the host microbiota composition, which differs between healthy individuals.

The gap between prebiotic demand and benefit predictability represents a tremendous opportunity for natural product manufacturers that wish to offer consumers consistent benefits. Science reveals a promising path forward for both, ensuring more-consistent effects and capturing a greater share of sales. Over the past decade, researchers have suggested the importance of classifying prebiotic fibers hierarchically by the specificity of their impact on the gut microbiota, which seems driven by their molecular complexity. In short, fiber structure matters.

Prebiotics are fibers and oligosaccharides that nourish and promote the growth of specific beneficial microorganisms already present in the gastrointestinal tract. Several steps are involved in the metabolic process of breaking down complex carbohydrates that the human enzymes cannot digest. Certain gut bacteria have specific enzymes that degrade fibers into smaller units that in turn are further hydrolyzed by other bacteria called secondary fermenters. This conversion process creates short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. These SCFAs and other metabolites feed gut microorganisms, provide energy for intestinal epithelial cells, regulate various physiological functions, and thus support overall host well-being.

The composition and structure of a prebiotic fiber determines which gut bacteria/microbial species can ferment and thus grow on it, increasing their abundance in the gut microbiota and providing them with a competitive advantage. As each individual has his or her own characteristic microbiota, a given fiber may lead to different effects in distinct individuals. Consequently, consistent microbial shifts can best be achieved with fibers that act as “specific” stimulants of bacteria commonly present in the gut of healthy people.

We believe fiber specificity is a game-changer for prebiotic product formulation. As scientific understanding of the microbiome and prebiotics advances, a growing number of researchers envision a new class of precision prebiotics that can deliver specific and consistent health benefits to consumers.

The Challenge of Gut Microbiota Modulation

The microbiome is considered the new frontier in human health research. While medical and scientific journals are filled with exciting discoveries, we are only beginning to understand this astonishingly complex ecosystem that many researchers consider to be a “second brain.” The digestive tract involves multiple bodily systems and about 30 ft of tubular organs—the esophagus, stomach, and intestines. The adult GI tract is home to an interrelated community of thousands of microbial species, trillions of microbial cells, and genes that influence virtually every aspect of human health and wellness.

The composition of gut microbiota is unique to every individual, and there is no definition yet of “healthy human gut microbiome.” Newborns acquire their initial intestinal bacteria from the mother and the environment. Their gut microbiota becomes progressively more complex until the age of 3–4 years and is then continually influenced by diet, lifestyle, environmental, and genetic factors. Scientists have discovered many far-reaching associations between health and disease on the one hand and microbiota composition and, more importantly, microbiota function on the other. Specific gut microbial strains have been proposed to influence metabolism, immune function, cardiovascular health, and—through the gut-brain axis—even mood and cognitive health.

Modulation of the gut microbiota to improve human health is a challenging proposition. In the fiercely competitive gut environment, trillions of microbial cells fight or cooperate for nutrition and persistence. The type, size, and interactions of microbe populations present in the gut can vary greatly and determine a prebiotic fiber’s impact. Achieving meaningful shifts in microbiota composition depends on baseline composition and requires precision targeting of specific bacterial strains or consortia.

Fiber specificity is key. For example, low-specificity fibers with a simple structure can be utilized by numerous different microorganisms, and their effect is thus highly dependent on one’s preexisting microbiota. Some fibers, meanwhile, have extreme specificity and can only be utilized in those subjects that have the rare microorganisms that can ferment it. The sweet spot—fibers of medium to high complexity—can be used to target specific beneficial microorganisms commonly present in humans with precision, thus consistently supporting different aspects of human physiology.

Research Supports Fiber Specificity Theory

The notion that fibers with “discrete structures” could be used to favor bacteria in the competitive intestinal environment was first proposed in 2014 by Professor Bruce Hamaker, director of Whistler Center for Carbohydrate Research, and his team at Purdue University.² Subsequent research by Professor Hamaker provided further evidence that fiber specificity could play a significant role in modulating microbiota composition and function.³ To wit:

• Low-specificity fibers (e.g., fructooligosaccharides, inulin) are easily consumed by many different microorganisms, making their positive impact on health highly dependent on the baseline microbiome composition of an individual.
• High-specificity fibers (e.g., xanthan, insoluble beta-glucans) are fermentable by only a relatively small number of gut bacteria that may only be present in a subpopulation of humans. Therefore, their positive impact may be limited.
• Medium-specificity fibers (e.g., soluble beta-glucans, type II resistant starches) that precisely stimulate bacterial strains that are believed to support significant health benefits may be the best strategy for developing innovative dietary interventions that benefit most, if not all, consumers.

Researchers in Canada, Ireland, Australia, and other countries have published data supporting the need for classifying prebiotic fibers by specificity.^4,5

Figure 1: Multiple studies demonstrate that prebiotic fiber specificity could play a significant role in modulating microbiota composition and function. Medium-specificity fibers deliver consistent benefits, including production of short-chain fatty acids (SCFAs), with minimal gas production.

Latest Research: Fiber Specificity Matters

The latest research demonstrating that structural complexity of prebiotic fibers is critical for optimal gut microbiota benefits is a recently published ex vivo study comparing the prebiotic effects of three dietary fibers of varying specificity—inulin, carrot rhamnogalacturonan-I (cRG-I), and xanthan—on the intestinal microbiota of 24 healthy adults in parallel.⁶ (Disclosure: This study was sponsored by our company, NutriLeads BV.)

Fecal samples of each subject were incubated for 48 hours. The donor samples reflected the variability of the human gut microbiota and represented the three main human “enterotypes.” High-throughput ex vivo SIFR technology simulating digestion and fermentation was used to measure changes in gut microbiota composition and function. Both inulin and xanthan resulted in changes in microbiota composition that maintained or increased interpersonal differences. For inulin, this followed from its low specificity, whereas for xanthan its excessive specificity resulted in responders and non-responders.

In contrast, cRG-I, a medium- to high-specificity fiber, selectively stimulated taxa or species of bacteria that are commonly present in the microbiome of healthy human adults. This resulted in robust stimulation of beneficial microorganisms across all subjects despite preexisting variation in overall gut microbiota composition. cRG-I consistently increased the abundance of beneficial bacterial species, including Bifidobacterium spp. (B. longum and B. adolescentis) as well as anti-inflammatory species (e.g., F. prausnitzii, A. hallii, R. hominis) independent of starting microbiota composition.

While all three prebiotics significantly increased production of short-chain fatty acids (acetate, propionate, and butyrate), cRG-I led to more consistent individual levels of total SCFAs than inulin, with lower gas production at an equivalent daily dose of 1.5 g/day. Importantly, the prebiotic effects of cRG-I were already observed at an equivalent daily dose as low as 300 mg/day.

Figure 2: A Systemic Intestinal Fermentation Research (SIFR) study compared the prebiotic effects of three dietary fibers of varying specificity—low, medium, and high—on the intestinal microbiota of 24 healthy adults in parallel. RG-I resulted in robust stimulation of beneficial microorganisms across all subjects despite preexisting variation in overall gut microbiota composition.

Implications for Product Innovation

Precision prebiotics are the future. They enable specific targeting of beneficial consortia of gut commensal bacteria that may produce robust and consistent health benefits, such as immune health, gut barrier integrity, overall gut health, and mental health.

Precision prebiotics can be developed into products with predictable benefits for mass consumer populations. They also can be utilized in personalized-nutrition gut-health recommendations and may be combined with probiotics or polyphenols or other health-promoting ingredients to develop synergistic combinations.

About the Authors

Ruud Albers, PhD, is founder and chief scientific officer of NutriLeads, a Netherlands-based supplier of plant-derived ingredients clinically proven to strengthen human health. He previously held several leadership positions during 14 years at Unilever, where he built and led the global expertise group on nutrition, immunity, and gut health. Albers received a MSc in medical biology and a PhD in immunomodulation from Utrecht University and studied intestinal metabolism at Rockefeller University in New York.

Annick Mercenier, PhD, is NutriLeads’s senior director of R&D. After receiving a PhD at the Free University of Brussels and a postdoctorate at the ETH Zurich, she held leadership positions at Transgène SA, Institut Pasteur of Lille, and Nestlé Research Center, gaining expertise in microbiology, microbiota, functional ingredients, and immune-related disorders. Mercenier is the co-inventor of more than 50 patents and the author of more than 120 peer-reviewed scientific publications and book chapters.

References

1. Grand View Research. Global prebiotics market size, share & trends analysis report by ingredients (FOS, inulin, GOS, MOS), by application (food & beverages, dietary supplements, animal feed), by region, and segment forecasts, 2022–2030. https://www.grandviewresearch.com/industry-analysis/prebiotics-market
2. Hamaker, B.R.; Tuncil, Y.E. A perspective on the complexity of dietary fiber structures and their potential effect on gut microbiota. J Mol Biol. 2014, 426 (23), 3838-3850. DOI: 10.1016/j.jmb.2014.07.028
3. Cantu-Jungles, T.M.; Hamaker, B.R. New view on dietary fiber selection for predictable shifts in gut microbiota. mBio. 2020, 11 (1), e02179-19. DOI: 10.1128/mBio.02179-19
4. Deehan, E.C.; Yang, C.; Perez-Muñoz, M.E.; et al. Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production. Cell Host Microbe. 2020, 27 (3), 389-404. DOI: 10.1016/j.chom.2020.01.006
5. Warren, F.J.; Fukuma, N.M.; Mikkelsen, D.; et al. Food starch structure impacts gut microbiome composition. Msphere. 2018, 3 (3), e00086-18. DOI: 10.1128/mSphere.00086-18
6. Van den Abbeele, P.; Deyaert, S.; Albers, R.; Baudot, A.; Mercenier, A. Carrot RG-I reduces interindividual differences between 24 adults through consistent effects on gut microbiota composition and function ex vivo. Nutrients. 2023, 15 (19), 2090. DOI: 10.3390/nu15092090