Probiotics have long been recognized as a foundational component of gut health and restoration and even more so since the advent of functional medicine. But as time goes on, research development allows us to understand current scientific and biological phenomena at deeper levels. As the root of many chronic health conditions, the microbiome in the gut continues to be a popular research focus with new development now pointing to prebiotics (alongside probiotics) as another layer of therapy in the restoration of gut health. Prebiotics were first defined in 1995 by Gibson and Roberfroid; however, their focus was limited to studies using bifidobacteria and lactobacilli. By 2004, our understanding of prebiotics was more comprehensive and the definition of prebiotics was appropriately redefined to include three criteria: 1) resistant to gastric acidity and hydrolysis by mammalian enzymes and gastrointestinal absorption; 2) fermented by intestinal microbiota, and 3) selectively stimulate the growth and/or activity of intestinal bacteria associated with health and wellbeing. Finally, in 2010, the definition was modified once more so as not to limit the activity of prebiotics to the intestinal tract, but to expand their benefits to the entire gastrointestinal tract.

Dietary vs. Supplemental Prebiotics

Probiotics help replenish the microbiome with health-promoting bacterial strains, but prebiotics are the substrates that allow the organisms to flourish and persist. Prebiotics are naturally found in many high-fiber carbohydrates including onions, garlic, chicory, Jerusalem artichokes, cabbage, and some legumes. Historically, consumption of these foods was encouraged for probiotic growth and support; however, therapeutic levels of prebiotics via supplementation is now considered a novel and successful approach for restoring gut health. The most commonly used supplemental prebiotics include non-starch polysaccharides (celluloses, hemicelluloses, pectins, gums, and mucilages), inulin, and oligosaccharides such as fructooligosaccharides, galactooligosaccharides, and xylooligosaccharides.

Prebiotic End-products - SCFAs

When prebiotics are metabolized by microbiota through fermentation, they generate short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate, which are able to modulate both the composition and activity of the microbiota. Various bacteria possess differing enzymes that allow them to select the type of prebiotic they are best able to metabolize; therefore, the SCFAs produced can be dependent on the diversity of the microbiota. Butyrate is a common SCFA that is a key energy substrate for colonocytes and enterocytes, regulating cell growth and differentiation. Propionate is a substrate for both intestinal and hepatic gluconeogenesis, inhibits cholesterol synthesis, and regulates lipogenesis. Acetate is often absorbed into peripheral circulation and crosses the blood-brain barrier to promote the health of the gut-brain axis. Collectively, SCFAs produced from prebiotic fermentation support gastrointestinal epithelial cell integrity, glucose homeostasis, lipid metabolism, appetite regulation, immune function, maintains luminal pH, inhibits the growth of pathogens, influences bowel motility, and may stimulate cancer cell apoptosis.

Specific Prebiotic Roles in GI Restoration

In a 2019 review focused on the prebiotic, inulin, and its effect on the management of inflammatory bowel disease (IBD), it was shown that prebiotics modulated the trophic functions of microbiota, enhanced the growth of specific bacterial strains, decreased mucous lesions and inflammation, supported microbiota retention, and strengthened the epithelial barrier in rat IBD models. The health-promoting outcomes of prebiotics were not directly attributed to the prebiotics themselves, but the SCFAs produced by prebiotic fermentation.

Prebiotics are also being utilized to help correct metabolic derangements that are a result of dysbiosis – a common condition that is linked to a variety of chronic health conditions. Metabolic conditions such as obesity and type 2 diabetes (T2D) are associated with dysbiosis. In a 2019 study published in the Journal of Nutritional Biochemistry, when prebiotics isolated and purified from plant-based foods (acorn, quinoa, sunflower, pumpkin seeds, and sago) were fed to high-fat-diet (HFD)-induced obesity/T2D mice, increased SCFA production resulting in significantly reduced gut hyperpermeability and mucosal inflammatory markers. Additionally, hypothalamic energy signaling and the gut-brain axis were positively modulated which resulted in a reversal of the defects in glucose metabolism.

Prebiotic supplementation is quickly growing as a novel therapeutic approach to gut restoration. Future research is treading into the realm of Personalized Microbiome Modulation with Precision (PMMP), which will focus on selecting specific prebiotics with particular structural characteristics for personalized microbiome modulation.