The benefits of prebiotics and latest research

The influence of the gut microbiome on health has gained great interest and evidence in recent years. Much research has focused on the use of live bacteria supplements or probiotics for influencing and supporting the growth and diversity of the microbiome. However, an important adjuvant to probiotic use is the practice of including prebiotics in the diet and supplementation. This blog looks at the benefits of prebiotics and latest research for their influence on the microbiome and wider physiology.

The function of fibre for gastrointestinal health has long been understood, prebiotics are specific types of fibre which can be degraded by the gut microbiota. Humans lack the enzymes to degrade the bulk of prebiotic dietary fibres. Therefore, these nondigestible carbohydrates pass the upper gastrointestinal tract unaffected and are fermented in the caecum and the large intestine by the anaerobic caecal and colonic microbiota.

The prebiotics concept was introduced for the first time in 1995 by Glenn Gibson and Marcel Roberfroid. Prebiotic was described as “a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health”. In 2008, the 6th Meeting of the International Scientific Association of Probiotics and Prebiotics (ISAPP) defined “dietary prebiotics” as “a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health”.¹

By the provision of energy sources for gut microbiota, prebiotics can modulate the composition and the function of these microorganisms. When prebiotics are degraded by gut bacteria the final products produced are mostly short chain fatty acids, SCFAs, namely: acetic acid, butyric acid, and propionic acid, which are subsequently used by the host as a source of energy.  Sometimes, a by-product of the fermentation of a complex prebiotic  is a substrate for another microorganism, called cross-feeding. The species Ruminococcus bromii degrades resistant starches, and several species can utilise the fermentation products of this reaction, in addition, some products may have antagonistic effects on other species.

The following criteria are used to classify a compound as a prebiotic:¹

• Resistant to acidic pH of stomach, cannot be hydrolyzed by mammalian enzymes, and also should not be absorbed in the gastrointestinal tract
• Fermented by intestinal microbiota,
• The growth and/or activity of the intestinal bacteria can be selectively stimulated by this compound and this process improves host’s health

Functions of Prebiotics

Short Chain Fatty Acid (SCFA) production;

Short chain fatty acids are produced in the lumen of the gut by fermentation of prebiotics. They are then absorbed across the gut lining into the blood stream and transported to other organs of the body, where they act as substrates or signal molecule.^2-4

SCFAs have been shown to;

• Promote growth and differentiation of colonocytes (cells that line the colon) by providing fuel thereby supporting the integrity of the digestive lining.
• SCFAs in the gut perform various physiological functions including dictating colonic mobility, colonic blood flow, and gastrointestinal pH, which can influence uptake and absorption of electrolytes and nutrients.
• SCFAs are well known for their anti-inflammatory functions by modulating immune cell chemotaxis, reactive oxygen species (ROS) release as well as cytokine release.
• Butyrate has been associated with anticancer activity on a variety of human cancer cell lines.
• SCFAs might directly influence the brain by reinforcing Blood Brain Barrier (BBB) integrity, modulating neurotransmission, influencing levels of neurotrophic factors and promoting memory consolidation. They are also speculated to have a mediational role in the microbiota–gut–brain axis crosstalk.
• Dietary intervention studies indirectly implicate a mediational role for SCFAs in cognition and emotion.
• Animal studies provide direct evidence of the effects of SCFAs on neuropsychiatric disorders and psychological functioning, whereas human studies are sparse, suffer from methodological limitations and offer inconsistent conclusions.

Supporting gut function and motility

Prebiotics cause a reduction of intestinal pH and maintain the osmotic retention of water in the bowel. Thereby supporting a supportive environment for the growth of commensal bacteria as well as healthy bowel movements but preventing dryness of stool which can contribute to constipation.

Supporting diversity and growth of the microbiome

Different prebiotics as they have different chain lengths and structures, these are fermented by different strains of bacteria and therefore support a more diverse microbiome. Additionally, shorter chain length prebiotics have a greater osmotic capacity therefore draw more water into the gut which can aid bowel movement but also can contribute to diarrhoea, therefore a variety can help support normal bowel movement but attenuate loose stools.

Research

Studies have looked at the effects of prebiotics on specific conditions, as they have multiple influences on the microbiome and physiology, they can have an effect on many conditions. Below are some studies that have looked at individual conditions and systems.¹

Digestive health:

Leaky gut – as SCFAs provide fuel to enterocytes as well as eliciting anti-inflammatory  effects

Crohn’s Disease  –A group study in 2006 reported that supplementation with 15 g/day FOS for 3 weeks elevated Bifidobacteria population in the faeces and improved Crohn’s disease

Colo-Rectal Cancer – Butyrate has been demonstrated to have protective effects against the risk of colorectal cancer, as well as its progression, via inducing apoptosis. A clinical trial demonstrated that symbiotic therapy (Lactobacillus rhamnosus and Bifidobacterium Lactis plus inulin) could reduce the risk of colorectal cancer by reducing the proliferation rate in colorectal, inducing colonic cells necrosis, which leads to improving the integrity and function of epithelial barrier. Additional studies showed that the disease occurs less commonly in people who often eat vegetables and fruit. This effect is attributed mostly to inulin and oligofructose (common prebiotics).

Immune function – Consuming prebiotics can improve immunity functions by increasing the population of protective microorganisms. Animal and human studies have shown that prebiotics can decrease the population of harmful bacteria by Lactobacilli and Bifidobacteria.

The mechanism of a beneficial effect of prebiotics on immunological functions remains unclear. Several possible models have been proposed:

• Prebiotics are able to regulate the action of hepatic lipogenic enzymes by influencing the increased production of short-chain fatty acids (SCFAs), such as propionic acid.
• The production of SCFAs (especially of butyric acid) as a result of fermentation was identified as a modulator of histone acetylation, thus increasing the availability of numerous genes for transcription factors.
• The modulation of mucin production.
• It was demonstrated that FOS and several other prebiotics cause an increased count of lymphocytes and/or leukocytes in gut-associated lymphoid tissues (GALTs) and in peripheral blood.
• The increased secretion of IgA by GALTs may stimulate the phagocytic function of intra-inflammatory macrophages

Nervous/cognitive

The effect of prebiotics and nervous and cognitive function seem to be multi-factorial. SCFAs, in particular butyrate, have been shown to be able to cross and also support the stability of the blood brain barrier and elicit influences on cognition. They additionally communicate with the brain via the vagus nerve and elicit benefits via this pathway. In addition, Neurotrophic factors, such as nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), and BDNF that regulate the growth, survival and differentiation of neurons and synapses in the CNS also play important parts in learning and memory and in a range of brain disorders have been also shown to be modulated by SCFAs.⁴ Mice fed with prebiotics showed diminished stressor-induced anxiety-like behaviour.

They have additionally shown to be important in child brain development as the mother-to-child transfer of commensal bacteria in the uterus has been shown to influence an infant’s immune system development.

Prebiotic structure

As mentioned above different gut bacteria produce different enzymes which are able to ferment prebiotics, therefore different structures and chain lengths of the carbohydrate, will support the growth of different bacteria. Gut diversity is an important factor in the health benefits elicited on the host, therefore different sizes and structures of prebiotics are important as they can support the diversity of the gut. It is useful to use a variety of different prebiotic especially when considering supplementation.

• PHGG (Partially Hydrolised Guar Gum) – Consumption of partially hydrolysed guar gum stimulates Bifidobacteria and butyrate-producing bacteria in the human large intestine and has bene shown to ameliorate intestinal inflammation via modulation of gut microbiota and SFAs.^7,8
• FOS (Fructo-oligosaccharides) – intake favours the growth of health-promoting bacteria while reducing pathogenic bacteria populations. Moreover, the end products of FOS fermentation by the intestinal microbiota, short chain fatty acids (SCFA), act as substrates or signaling molecules in the regulation of the immune response, glucose homeostasis and lipid metabolism⁹
• GOS (Galacto-ologosaccharides) – have been shown to stimulate Bifidobacteria and Lactobacilli. Bifidobacteria in infants have shown high incorporation with GOS. Enterobacteria, Bacteroidetes, and Firmicutes are also stimulated by GOS.¹
• Inulin – shown to have influences on immune function, cardiovascular health and lipid homoeostasis.¹
• Acacia gum – shown to produce an increase in bifidobacteria and lactobacilli, research support benefits to blood sugar and appetite regulation^1,9-11
• Larch Arabionogalactan – formula containing Lactobacillus strains, arabinogalactan, and colostrum towards increasing the number of activated NK cells in the peripheral blood as well as decreasing IL-6 and IFN-γ levels in the faecal samples, both in healthy individuals and patients with IBS.⁹ larch arabinogalactan can possibly act indirectly through microbiota-dependent mechanisms and/or have a direct effect on the immune system via the gut-associated lymphoid tissue (GALT).¹³
• Marshmallow root – possess mucilage properties with potential to reduce inflammation, protect digestive lining and aid repair¹⁴
• Pectin – modulates the microbiota and elicits multiple influences on health. May play a protective role with prebiotic properties in the prevention of obesity and associated metabolic and inflammatory disorders¹⁵

It can be seen from the above that prebiotics have the potential to support health not only of the digestive system but of multiple systems within the body, therefore they are an important consideration for supplementation but also to include in the diet.

Dietary sources of prebiotics include; onions, chicory, pomegranate, olives, baked apples and Jerusalem artichoke. The most important thing for supporting diversity and providing prebiotics is to consume a highly diverse diet of wholefoods (try and aim for 50 different wholefood per week).

Key takeaways

• Prebiotics are specific carbohydrate fibres which cannot be digested by humans but are able to be fermented by gut bacteria and provide them with fuel.
• The end products of prebiotic fermentation by bacteria are short chain fatty acids (SCFAs), such as butyrate, acetate and propionate, which elicit multiple effects on the physiology of the body, particularly on digestive, immune and cognitive health.
• SCFAs Promote growth and differentiation of colonocytes (cells that line the colon) by providing fuel thereby supporting the integrity of the digestive lining. They perform various physiological functions including dictating colonic mobility, colonic blood flow, and gastrointestinal pH, which can influence uptake and absorption of electrolytes and nutrients.
• SCFAs might directly influence the brain by reinforcing BBB integrity, modulating neurotransmission, influencing levels of neurotrophic factors and promoting memory consolidation. They are also speculated to have a mediational role in the microbiota–gut–brain axis crosstalk.
• A variety of different structure and chain lengths of prebiotics is important for supporting different gut bacteria as they possess different enzymes, so can ferment different fibres. Therefore, a diversity of prebiotics supports a diversity of gut bacteria.

References

1. Davani-Davari D, Negahdaripour M, Karimzadeh I, et al (2019) ‘Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications’, Foods 8(3):92
2. Tan, Jian & Mckenzie, Craig & Potamitis, Maria & Thorburn, Alison & Mackay, Charles & Macia, Laurence. (2014). The Role of Short-Chain Fatty Acids in Health and Disease. Advances in immunology. 121. 91-119.
3. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325-2340.
4. Dalile, B., Van Oudenhove, L., Vervliet, B. et al. The role of short-chain fatty acids in microbiota–gut–brain communication. Nat Rev Gastroenterol Hepatol 16, 461–478 (2019).
5. Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG (2014) ‘Minireview: Gut microbiota: the neglected endocrine organ’, Mol Endocrinol, Aug;28(8) pp1221-38.
6. Ohashi Y, Sumitani K, Tokunaga M, Ishihara N, Okubo T, Fujisawa T (2015) ‘Consumption of partially hydrolysed guar gum stimulates Bifidobacteria and butyrate-producing bacteria in the human large intestine’, Benef Microbes, 6(4):451-5.
7. Akagi T, Naito Y, Higashimura Y, Ushiroda C, Mizushima K, Ohashi Y, Yasukawa Z, Ozeki M, Tokunaga M, Okubo T, Katada K, Kamada K, Uchiyama K, Handa O, Itoh Y, Yoshikawa T (2016) ‘Partially hydrolysed guar gum ameliorates murine intestinal inflammation in association with modulating luminal microbiota and SCFA’, Br J Nutr, Oct;116(7) pp1199-1205.
8. Caetano BF, de Moura NA, Almeida AP, Dias MC, Sivieri K, Barbisan LF (2016) ‘Yacon (Smallanthus sonchifolius) as a Food Supplement: Health-Promoting Benefits of Fructo oligosaccharides’, Nutrients, 8(7) pp436.
9. Jangra S, Pothuraju R (2020) ‘Functional Significance of Gum acacia in the Management of Obesity’, Curr Pharm Des, 26(3) pp.293-295.
10. Al-Asmakh M, Sohail MU, Al-Jamal O, Shoair BM, Al-Baniali AY, Bouabidi S, Nasr S, Bawadi H (2020) ‘The Effects of Gum Acacia on the Composition of the Gut Microbiome and Plasma Levels of Short-Chain Fatty Acids in a Rat Model of Chronic Kidney Disease’, Front Pharmacol, Dec 22;11 pp569402
11. Slavin J (2013) ‘Fiber and prebiotics: mechanisms and health benefits’, Nutrients, 5(4) pp1417-1435.
12. Velikova T, Tumangelova-Yuzeir K, Georgieva R, Ivanova-Todorova E, Karaivanova E, Nakov V, Nakov R, Kyurkchiev D (2020) ‘Lactobacilli Supplemented with Larch Arabinogalactan and Colostrum Stimulates an Immune Response towards Peripheral NK Activation and Gut Tolerance’, Nutrients, Jun 7;12(6) pp1706.
13. Dion C, Chappuis E, Ripoll C (2016) ‘Does larch arabinogalactan enhance immune function? A review of mechanistic and clinical trials’, Nutr Metab (Lond), 13:28.
14. Zaghlool SS, Abo-Seif AA, Rabeh MA, Abdelmohsen UR, Messiha BAS (2019) ‘Gastro-Protective and Anti-Oxidant Potential of Althaea officinalis and Solanum nigrum on Pyloric Ligation/Indomethacin-Induced Ulceration in Rats’, Antioxidants (Basel), 8(11) pp.512.
15. Jiang T, Gao X, Wu C, et al (2016) ‘Apple-Derived Pectin Modulates Gut Microbiota, Improves Gut Barrier Function, and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity’, Nutrients, 8(3) pp126.

Last updated on 2nd February 2022 by cytoffice