Short-chain fructo-oligosaccharides and their effect on the immune system
Digestion | Ingredients
In the last decade, mainly owing to increasing demand for sugar reduction and fibre enrichment in the food and beverage industry, the global dietary fibre market has witnessed significant growth. Many of these ingredients are also recognised as prebiotics, which offer a wide range of gut and immune health benefits
The role played by the human microbiota in immune development and its responses is increasingly well understood, reports Dr Fernando Schved, Vice President R&D and CSO, Galam.
Likewise, the contribution played by probiotics, prebiotics and synbiotics and their effects on the microbiota have gained much attention.1
Short-chain fructo-oligosaccharides (sc-FOS) are among the most researched non-digestible soluble prebiotic dietary fibres consumed by humans.
A myriad of beneficial attributes has been documented for prebiotics; for example, the ability of prebiotics such as sc-FOS to affect our immune system is of great importance and may play a key role in sustaining the body’s immune system.2–15
The immunomodulating action of prebiotics such as sc-FOS is primarily mediated (but not only) via effects on the “innate immune system” by both direct and indirect mechanisms.
How prebiotics such sc-FOS act on the immune system
A commensal microflora provides intrinsic protection against potentially pathogenic bacteria by competing for both nutrients and controlling the colonisation of prospective pathogens (by lowering the pH of the colon, for example).
The human colon plays a central role in our immunity via mechanisms including mucosal barriers and the GALT system (gut-associated lymphoid tissue), which is the largest human immune tissue.
In mammals, intestinal immunity is largely maintained by interactions between gut microbiota and the GALT.16 GALT stimulation may be mediated by the bifidogenic effect of prebiotics such as sc-FOS; as such, its role is crucial to the digestive tract of newborns and infants by promoting the maturation of B-type immune cells.17,18
In animal models, dietary sc-FOS increased the intestinal immunoglobulin A (IgA) response in the small intestine as well as in the colon.19,20
Most of the knowledge related to the understanding of mechanisms by which prebiotics such as sc-FOS affect the immune system has been derived from animal models and GALT-associated responses.19–23
Short oligosaccharide components of sc-FOS (namely kestose and nystose) have been reported to be rapidly and preferably used by Bifidobacteria and certain Lactobacillus species because of the unique enzymatic abilities that are innate to these bacteria.
Indeed, sc-FOS is characterised by a relatively low threshold bifidogenic dose of only 2.5 g/day. The stimulatory action of prebiotics (such as sc-FOS) on the immune system may occur via two mechanisms:
- the bifidogenic effect; the ability of sc-FOS to induce the proliferation of Bifidobacteria and certain Lactobacillus species, which results in inhibitory growth effects on potentially pathogenic bacteria (competition for nutrients, acidification of the colon lumen and increased release of short-chain fatty acids [SCFAs] in the lumen)
- the direct or indirect activation of components of the immune system.24
Activation pathways by which sc-FOS positively affects components of the colonic immune system may include
- activation by contact with gut dendritic cells (DC), which are responsible for sampling immune active components from the gut content, and intraepithelial lymphocytes (IEL), which can react while activated by ingested food components
- modulation of the innate immune barrier by improving the integrity of “tight junctions” (the paracellular space between epithelial cells) or by sending signals from epithelial cells to the underlying immune cell layer and preventing “leaky gut” phenomena (which induces inflammation)
- SCFA such as butyrate and propionate have been reported to induce the differentiation of T-regulatory cells, assisting the control of intestinal inflammation and reducing both inflammation and the risk of bowel diseases/colorectal cancer.1
Moreover, the mucosal barrier (local immune system) separates and protects colonocytes facing the colon lumen and serves as a first line of defence by reducing full systemic immunity.
SCFAs (mainly butyric acid) have been reported to induce mucin secretion and enhancing physiological protection.8
SCFAs (such as acetate) may also provide benefits to colon health by improving both the blood flow and oxygenation of the colonic mucosa, resulting in increased barrier integrity.24
Butyrate may increase mucosal depth by enhancing cell differentiation at the bottom level, reducing apoptosis at the apex of the villi as demonstrated in a piglet study.25
Immunoprotection against viral infections and diarrhoea
Prebiotics such as sc-FOS may also contribute immunoprotective activity in cases of respiratory infections such as common flu, which are often a result of viral agents such as Influenza.26
For example, in a human study, fructo-oligosaccharides were included as a constituent of a nutritional formula (9%) for seniors (183-day follow-up, age >65).
This study demonstrated a positive enhancement of the immune function as measured by antibody and lymphocyte proliferation (day count reduction) with symptoms of upper respiratory tract infection following an influenza vaccination.27
In an animal trial, the addition of sc-FOS has been shown to bind “toxin A” alongside changes in the composition of mucosal immune cells (an increased number of macrophages in the lamina propia).
An important aspect of immunity enhancement by sc-FOS is the prevention of infectious diarrhoea and/or alleviation of its symptoms.
In children (1–14 years of age) suffering from acute diarrhoea, Juffrie showed that sc-FOS — dosed at 2.5–5 g/day — was able to reduce the duration of diarrhoea events compared with the control group.28
Immunoprotection against carcinogenesis and oxidative stress
sc-FOS has been reported to reduce the concentrations of potential procarcinogens produced in the colon.
A 42-day human clinical study (12 healthy subjects, both genders, age 20–34) explored the effects of sc-FOS supplementation at 4 g/day (as chewable tablets and a drink) on faecal flora and certain activities of reductive enzymes associated with the conversion of procarcinogens to carcinogens (β-glucuronidase and glycocholic acid hydroxylase).
Moreover, sc-FOS has been shown to neutralise the activity of ROS (reactive oxygen species) such as hydroxyl radicals. Pejin and colleagues demonstrated the capacity of sc-FOS components (1-kestose and nystose) to scavenge hydroxyl radicals (•OH), suggesting their potential immunoprotective role.29
Therefore, sc-FOS may help to reduce the damage derived from oxidative stress and inflammation caused by improper nutrition.30
- D. Zheng, et al., “Interaction Between Microbiota and Immunity in Health and Disease,” Cell Research 30, 492–506 (2020).
- F. Bornet and F. Brouns, “Immune-Stimulating and Gut Health-Promoting Properties of Short-Chain Fructo-Oligosaccharides,” Nutrition Reviews 60(11), 326–334 (2002).
- J.L. Carlson, et al., “Health Effects and Sources of Prebiotic Dietary Fiber,” Curr. Develop. Nutr. 2(3): https://doi.org/10.1093/cdn/nzy005 (2018).
- D. Davani-Davari, et al., “Prebiotics: Definition, Types, Sources, Mechanism, and Clinical Applications,” Foods 8(3), 92: doi: 10.3390/foods8030092 (2019).
- G.T.C. Delgado, et al., “The Putative Effects of Prebiotics as Immunomodulatory Agents,” Food Research International 44, 3167–3173 (2011).
- E. Franco-Robles and M.G. López, “Implication of Fructans in Health: Immunomodulatory and Antioxidant Mechanisms,” The Scientific World Journal 2015 (2015): doi: 10.1155/2015/289267.
- R. Frei, et al., “Prebiotics, Probiotics, Synbiotics and the Immune System: Experimental Data and Clinical Evidence,” Current Opinion in Gastroenterology 31(2), 153–158 (2015).
- K.R. Panday, et al., “Probiotics, Prebiotics and Synbiotics: A Review,” J. Food Sci. Technol. 52, 7577–7587 (2015).
- S. Patel and A. Goyal, “The Current Trends and Future Perspectives of Prebiotics Research: A Review,” 3 Biotech 2, 115–125 (2012).
- D. Peshev and W. Van den Ende, “Fructans: Prebiotics and Immunomodulators,” Journal of Functional Foods 8, 348–357 (2014).
- P.D. Schley and C.J. Field, “The Immune-Enhancing Effects of Dietary Fibers and Prebiotics,” Br. J. Nutr. 87, S221–S230 (2002).
- A.T. Vieira, et al., “The Role of Probiotics and Prebiotics in Inducing Gut Immunity,” Frontiers in Immunology 4, 1–11 (2013).
- M. Vinolo, et al., “Regulation of Inflammation by Short Chain Fatty Acids,” Nutrients 3(10), 858–876 (2011).
- L. Vogt, et al., “Immunological Properties of Inulin-Type Fructans,” Critical Reviews in Food Science and Nutrition 55, 414–436 (2015).
- N. Yahfoufi, et al., “Role of Probiotics and Prebiotics in Immunomodulation,” Current Opinion in Food Science 20, 82–91 (2018).
- W.S. Garrett, et al., “Homeostasis and Inflammation in the Intestine,” Cell 140(6), 859– 870 (2010).
- A-C. Lundell, et al., “Infant B Cell Memory Differentiation and Early Gut Bacterial Colonization,” The Journal of Immunology 188, 4315–4322 (2012).
- D. Paineau, et al., “Effects of Short-Chain Fructooligosaccharides on Faecal Bifidobacteria and Specific Immune Response in Formula-Fed Term Infants: A Randomized, Double-Blind, Placebo-Controlled Trial,” J. Nutr. Sci. Vitaminol. 60, 167–175 (2014).
- A. Hosono, et al., “Dietary Fructo-Oligosaccharides Induce Immuno-Regulation of Intestinal IgA Secretion by Murine Peyer’s Patch Cells,” Biosci. Biotechnol. Biochem. 67(4), 758–764 (2003).
- Y. Nakamura, et al., “Dietary Fructooligosaccharides Upregulate Immunoglobulin A Response and Polymeric Immunoglobulin Receptor Expression in Intestines of Infant Mice,” Clinical Experimental Immunology 137(1), 52–58 (2004).
- N. Manhart, et al., “Influence of Fructo-Oligosaccharides on Peyers’ Patch Lymphocyte Numbers in Healthy and Endotoxemic Mice,” Nutrition 19(7–8), 657–660 (2003).
- F. Pierre, et al., “Short-Chain Fructoligosaccharides Reduce the Occurrence of Colon Tumors and Develop Gut-Associated Lymphoid Tissue in Min Mice,” Cancer Research 57, 225–228 (1997).
- F. Pierre, et al., “T Cell Status Influences Colon Tumor Occurrence in Min Mice Fed Short Chain Fructo-Oligosaccharides as a Diet Supplement,” Carcinogenesis 20(10), 1953–1956 (1999).
- M.D. Howard, et al., “Blood Flow and Epithelial Cell Proliferation of the Canine Colon are Altered by Source of Dietary Fiber,” Veterinary Clinical Nutrition 6(2), 8–15 (1999).
- T. Tsukahara, et al., “Stimulation of Butyrate Production in the Large Intestine of Weaning Piglets by Dietary Fructooligosaccharides and Its Influence on the Histological Variables of the Large Intestinal Mucosa,” Journal of Nutritional Science and Vitaminology 49, 414–421 (2003).
- A. Trompette, et al., “Dietary Fiber Confers Protection Against Flu by Shaping Ly6c– Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism,” Immunity 48, 992–1005 (2018).
- B. Langkamp-Henken, et al., “Nutritional Formula Enhanced Immune Function and Reduced Days of Symptoms of Upper Respiratory Tract Infection in Seniors,” JAGS 52, 3–12 (2004).
- M. Juffrie, “Fructooligosaccharides and Diarrhea,” Bioscience and Microflora 21(1), 31–34 (2002).
- B. Pejin, et al., “In Vitro Anti-Hydroxyl Radical Activity of the Fructooligosaccharides 1-Kestose and Nystose Using Spectroscopic and Computational Approaches,” International Journal of Food Science and Technology 49, 1500–1505 (2014).
- H. Yan, et al., “Short-Chain Fructo-Oligosaccharides Alleviates Oxidized Oil-Induced Intestinal Dysfunction in Piglets Associated with the Modulation of Gut Microbiota,” Journal of Functional Foods 64, 103661 (2020).