Title: Probiotics and Prebiotics
Key words: colonic microflora, colonic mucosa, lumen, breast milk, substrates, proteins, pathogens, immune compromised, dietary intake, supplementation, immune tolerance, bifodobacteria, FOS, normal microflora, antibiotics, dysbiosis, chemotherapy, bowel dysfunction
Date: June 2001
Category: The Gut
Author: Dr M Draper
'Death sits in the bowels; a bad digestion is the root of all evil'Hippocrates, c. 400 BC
Introduction The human colonic microflora is a complex microbial ecosystem and the most heavily colonised region of the digestive tract (1012 bacteria/gram content). The colonic mucosa is unable to nourish itself from the blood (1), its nutritive demands must be met from the lumen, initially from breast milk (2). Different nutrients, e.g. short-chain fatty acids, amino acids, polyamines, growth factors, vitamins, and antioxidants are produced by non-pathogenic, commensal, protective probiotic flora (3,4). In the first weeks of life, these are originally derived from the birthcanal and bowels of the mother. The substrates for the production of nutrients are prebiotics, which consist mainly of ingested fibres and complex proteins (colon food), however it also includes necrotic mucosal cells, mucous, gastro-intestinal secretions including bile acids, bacteria and yeasts.
Why modulate microflora?
Ruminants derive considerable benefit from their bowel microflora and there is accumulating evidence that they play an important role in human health (5). Studies have shown that Bifidobacteria including Lactobacillus species (6) preserve and synthesise key nutrients (7,8), eliminate toxic components from food (9), protect food from decay, and eradicate pathogens including pathogenic E.coli (10), Helicobacter pylori (11) and other species. Lactobacillus species rarely become pathogenic and only in an immune compromised host (12). Immune tolerance can break down in inflammatory bowel disease (13). Colorectal carcinoma has been associated with low counts of Bifidobacteria and low dietary intakes of Fructo-oligosaccharides (FOS) and Inulin. Supplementation of prebiotics in rats have been shown to inhibit colonic preneoplastic crypt foci (14).
Probiotics are viable, live microbial food supplements which bypass digestion and become active in the colon (15). Various types of probiotic exist:
(a) single species
Thermophillic (eg Lactobacillus in Buttermilk)
Bio-cultures (eg Bifidobacterium in Bio-Yoghurt)
Mesophilic (eg Streptococcus in cottage cheese)
(b) Multiple species (eg ' Bifidophilus Xtra '(Cytoplan) containing L. acidophallus, L. bifidus, Rhamnosus sp. and Strep. feacalis.) The obvious indications for use would be to restore normal microflora after antibiotics or gastroenteritis and to correct dysbiosis that maybe part of other conditions eg IBS. The multiple species approach on theoretical grounds is the most appealing, however detection of probiotic species in the faeces can be short lived and they can disappear on cessation of supplementation (16). This can be overcome clinically by rotating or repeating courses if benefit likewise was only temporary. Some patients appear to be upset by them and complain about abdominal discomfort or other symptoms which discontinue on cessation and perhaps indicate that this type of treatment needs refinement. Different types of probiotics may be required in different conditions or in certain patients.
Prebiotics are naturally occurring, non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and /or activity of one or more species of Bidobacteria and thus improve health (17).Examples are xylose, lactulose, mannose, fructo-oligosaccharides (FOS), polymers such as oligofructose (18) and inulin (19).A review of production, properties and applications (20) shows how importantly the food industry views the development of prebiotics in functional foods. Prebiotic and micronutrient enrichment in processed foods and supplements is occupying a niche in the market previously enjoyed by nutraceutical and supplement companies. The addition of prebiotics is also being viewed as a safeguard in that taking too much would result in diarrhoea. An Infant formula feed (Omneo Comfort by Cow & Gate) encourages the growth of Bifidobacteria towards the levels found in breast fed babies. I have used a preparation with FOS and other ingredients including glutamine, soya isoflavones, micronutrients and conjugated linoleic acid (Natures Own -Breakthrough) in a variety of patients with bowel dysfunction including those undergoing chemotherapy.
Synbiotics include pre and probiotics eg Yakult (single species) and FOS-A-DOPHILUS (6 species with FOS 600mg per capsule - Cytoplan) with the idea of improving survival and implantation. Further research will yield new products to stimulate growth and development of beneficial flora.
References (1) Bengmark, S. (2000) ' Colonic food: pre- and probiotics.' Am J Gastroenterol, 200001, 95: 1 suppl , S5-7.
(2) Yoshita, M. et al (1991) ' Development of the normal intestinal flora and its clinical significance in infants and children.' Bifidobacteria Microflora 10: 11-17.
(3) Bengmark, S. (2000) ' Prospects for new and rediscovered therapies: probiotics and phage.' in Andrew, PW et al.(ed) ' Fighting infection in the 21st cenentury' Blackwell Science, London.
(4) Cummings, J.H. & Macfarlane, G.T. (1991) ' A review : the control and consequences of bacterial fermentation in the human colon.' J Appl Bacteriol 70: 443-459.
(5) Zeimer, C.J. & Gibson, G.R. (1998) ' An overview of Probiotics, Prebiotics and Synbiotics in the Functional Food Concept; Perspectives and Future Strategies. Int Dairy J 8: 473-9.
(6) Ahrne, S. et al. (1998) ' The normal Lactobacillus flora of healthy human rectal and oral mucosa.' J Appl Microbiol 85: 88-94. (7) Yoriko, D. et al. (1985) ' Comparative Studies on synthesis of Water-soluble Vitamins among Human Species of Bifidobacteria.' Agric Biol Chem 49 (1):13-19.
(8) Cummings, J.H. & Macfarlane, G.T. (1997) ' Role of intestinal bacteria in nutrient metabolism.' Clin Nutr 16: 3-11.
(9) Hayatsu,H & Hayatsu, T. (1993) 'Suppressing effect of Lactobacillus casei administration on the urinary mutagenicity arising from ingestion of fried ground beef in the human.' Cancer Letters 73: 173-9.
(10) Mack, D.R. et al. (1999) ' Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression.' American Physiological Society G 941-950.
(11) Coconnier, M-H. et al. (1998) ' Antagonistic Activity against Helicobacter infection in Vitro and in Vivo by the Human Lactobacillus acidophilus Strain LB.'
Appl Environ Microbiol 64,no 11: 4573-80.
(12) Husni, R.N. et al. (1997) ' Lactobacillus Bacteremia and Endocarditis: Review of 45 cases.' CID 25: 1048-55.
(13) Duchmann, R. et al. (1995) ' Tolerance exists towards resident intestinal flora but is broken down in active inflammatory dowel diease (IBD).' Clin Exp Immunol 102: 448-455.
(14) Reddy, B.S. et al. (1997) ' Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition.' Carcinogenesis Vol 18, No 7: 1371-4.
(15) Kullen, M.J. et al. (1997) ' Differentiation of ingested and endogenous bifidobacteria by DNA fingerprinting demonstates.' J Nutri 127: 89-94.
(16) Berg, R.D. (1998) ' Probiotics, prebiotics or 'conbiotics'. '
Trends in Microbiology Vol 6, no3: 89-92.
(17) Gibson, G.R. & Roberfroid, M.B. (1995) ' Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics.' J Nutr 125: 1401-12.
(18) Delzenne,N.M. & Roberfroid, M.B. (1994) ' Physiological effects of Non-Digestible Oligosaccharides.' Lebensm. Wiss. Technol 27: 1-6.
(19) Roberfroid, M.B. (1993) ' Dietary fibre, inulin and oligofructose: a review comparing their physiological effects.' Crit Rev , Food Sci Technol. 33: 103-48.
(20) Crittendon R.G. & Playne M.J. (1996) ' Production, properties and applications of food-grade oligosaccharides.' Trends in Food Science and Technology Vol 7; 353-61
(*) Leeds, A.R. & Rowland,I.R. (1996) Editors of ' Gut flora and health- past, present and future.' Royal Society of Medicine Press Limited. ISBN 1-85315-303-6.