Volume 5, Number 1:
Editorial. Intestinal flora and human health -- introductory remarks. PAUL J NESTEL
Abstracts:
Tomotari Mitsuoka, DVM, PhD
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 2-9
There is a growing interest in intestinal flora and human health and disease. The intestines of humans contain 100 trillion viable bacteria. These live bacteria, which make up 30% of the faecal mass, are known as the intestinal flora. There are two kinds o 1000 f bacteria in the intestinal flora, beneficial and harmful. In healthy subjects, they are well balanced and beneficial bacteria dominate. Beneficial bacteria play useful roles in the aspects of nutrition and prevention of disease. They produce essential nutrients such as vitamins and organic acids, which are absorbed from the intestines and utilised by the gut epithelium and by vital organs such as the liver. Organic acids also suppress the growth of pathogens in the intestines.
Other intestinal bacteria produce substances that are harmful to the host, such as putrefactive products, toxins and carcinogenic substances. When harmful bacteria dominate in the intestines, essential nutrients are not produced and the level of harmful substances rises. These substances may not have an immediate detrimental effect on the host but they are thought to be contributing factors to ageing, promoting cancer, liver and kidney disease, hypertension and arteriosclerosis, and reduced immunity. Little is known regarding which intestinal bacteria are responsible for these effects. A number of factors can change the balance of intestinal flora in favour of harmful bacteria. These include peristalsis disorders, surgical operations of stomach or small intestine, liver or kidney diseases, pernicious anaemia, cancer, radiation or antibiotic therapies, immune disorders, emotional stress, poor diet and ageing.
However, more importantly, the normal balance of intestinal flora may be maintained, or restored to a normal from an unbalanced state, by oral bacterio-therapy or by a well balanced diet. Oral bacterio-therapy using intestinal strains of lactic acid bacteria, such as lactobacillus and bifidobacteria, can restore normal intestinal balance and produce beneficial effects. Benefits include suppression of intestinal putrification so as to reduce constipation and other geriatric diseases; prevention and treatment of diarrhoea including antibiotic-associated diarrhoea; stimulation of the immune system; and increased resistance to infection.
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Patricia L Conway, MSc, PhD
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 10-14
Probiotics are preparations of live microorganisms which beneficially affect the host by improving the properties of the indigenous microbes. Since the human intestinal flora plays an important role in health and disease of man, probiotics are used to improve intestinal health and to stimulate the immune system. The microbes commonly used as probiotics for humans are the lactic acid bacteria (LAB). In early studies the strains used for fermenting milk products for human consumption were frequently used as probiotics. Subsequently, it was realised that it would be more appropriate if the strains originated from the human intestinal tract and that in addition to LABs, other microorganisms could be used either singly or in combination. Today, strict selection criteria are employed to obtain functional probiotic strains. It is generally agreed that the strain should be of host origin, well characterised, able to survive the rigours of the diges 1000 tive tract and possibly colonise, biologically active against the target as well as to be stable and amenable to commercial production and distribution. In addition, information on dosages and evidence of efficacy needs to be obtained. In vitro and in vivo studies are frequently combined to allow investigation of the various parameters, and ultimately clinical trials are required. Although lactic acid bacteria have been generally recognised as safe, the question of safety is discussed for LAB and non-LAB probiotic strains in terms of potential pathogenicity of the strains and risk to the individual and the community. Finally, even though the techniques for genetic manipulation of many probiotic strains are available, it is not envisaged that this issue will be addressed in the near future because of regulatory implications. It is proposed that when this type of selection criteria is employed, probiotics strains with demonstrable efficacy can be obtained.
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David L Topping, PhD
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 15-19
The colon is the major site of bacterial colonisation in the human gut and the resident species are predominantly anaerobes. They include potential pathogens but the greater proportion appear to be organisms which salvage energy through the metabolism of undigested carbohydrates and gut secretions. The major products of carbohydrate metabolism are the short chain fatty acids (SCFA), acetate, propionate and butyrate. In addition to general effects (such as lowering of pH) individual acids exert specific effects. All of the major SCFA appear to promote the flow of blood through the colonic vasculature while propionate enhances muscular activity and epithelial cell proliferation. Butyrate appears to promote a normal cell phenotype as well as being a major fuel for colonocytes. Important substrates for bacterial fermentation include non-starch polysaccharides (major components of dietary fibre) but it seems that starch which has escaped digestion in the small intestine (resistant starch) is the major contributor. Oligosaccharides are utilised by probiotic organisms and in the diet, act as prebiotics in promoting their numbers in faeces. High amylose starch is a form of RS and it appears to act as a prebiotic also. Although there is evidence that probiotics such as Bifidobacteria metabolise oligosaccharides and other carbohydrates, there appears to be little evidence to support a change in faecal SCFA excretion. It seems that any health benefits of probiotics are exerted through means other than SCFA.
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Charumati Mishra, MSc and John Lambert, MBBS, FRACP, PhD
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 20-24
Bacterial antagonism has been recognised for over a century but in recent years this phenomenon has received more scientific attention, particularly in the use of various strains of lactic acid bacteria (LAB). Antimicrobial compounds produced by LAB have provided these organisms with a competitive advantage over other microorganisms. Lactic acid bacteria have a natural ecological niche in many foods as well as in the intestinal tract. The efficacy and spectrum of antimicrobial products of lactic acid bacteria are broad and include lactic and acetic acid, hydrogen peroxide, carbon dioxide, diacetyl as well as bacteriocins or bacteriocin-like substances. Further screening for agents with a broad spectrum of activity is required. This will involve genetic or protein engineering of such compounds to commercialise these agents.
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DC Donohue, S Salminen
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 25-28
In recent years interest has been renewed in health promotion and disease prevention by the incorporation of probiotic bacteria into foods to counteract harmful bacteria in the intestinal tract. There is considerable interest in extending the range of foods containing probiotic organisms from dairy foods to infant formulae, baby foods, fruit juice-based products, cereal-based products and pharmaceuticals. New and more specific strains of probiotic bacteria are being sought. Traditional probiotic dairy strains of lactic acid bacteria have a long history of safe use and most strains are considered commensal microorganisms with no pathogenic potential. It cannot be assumed that these novel probiotic organisms share the historical safety of the traditional strains. Before their incorporation into products new strains should be carefully assessed and tested for the safety and efficacy of their proposed use. As yet, no general guidelines exist for the safety testing of probiotics. Different aspects of the safety of probiotic bacteria can be assessed using a panel of in vitro methods, animal models and human subjects.
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Masami Morotomi, PhD
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 29-30
Lactic acid bacteria are generally non-pathogenic. Before their presence became well known, lactic acid bacteria had been used empirically for the production of yoghurt and other types of fermented foods. Lactic acid bacteria are widely distributed in nature as a member of the indigenous intestinal microflora in man and mammals. Since Metchnikoff hypothesised the role of lactic acid bacteria in longevity in the early 1900's, the relations between lactic acid bacteria and human health have been studied from various view points. Today, as a term and a concept, 'probiotics' is used for 'a live microbial feed supplement which beneficially affects the host'.
Lactobacillus casei Shirota strain was isolated from human intestine in 1930. It has been used in the production of fermented milk since then. A number of animal and clinical studies indicating its effect in maintaining normal function of the digestive tract and inhibition of the growth of intestinal pathogens were reported. A focus of research is now the anti-tumour activity of this strain. That this topic is drawing special attention reflects the increasing health consciousness of the general public and the resulting awareness of cancer problems as well as the possibility and importance of 'dietary prevention' of cancer.
Parenteral administration of the Shirota strain is known to have anti-tumour and immuno-stimulating activities on experimentally implanted tumours. The same effects have been confirmed with oral administration. The oral administration of Shirota strain inhibited the growth of the subcutaneously implanted Meth A fibrosarcoma in mice. It also inhibited the growth of Meth A or Colon 26 implanted into the wall of mouse large intestine. Furthermore, by oral administration, a growth-inhibitory effect was observed in chemically induced tumours. In a clinical study, prophylactic effects of oral administration of Shirota strain on the recurrence of superficial bladder cancer have been reported.
The probiotic properties of the Shirota strain, as a lactic acid bacteria for cancer chemoprevention have increasing potential.
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John Lambert MBBS, PhD FRACP and Ron Hull PhD
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 31-35
Diseases of the oropharynx, oesophagus, stomach and duodenum are common. This review discusses the microflora of the upper gastrointestinal tract with particular reference to lactic acid bacteria and the effect of acid suppression. Probiotics can survive in these sites and evidence is presented for potential roles in disease prevention and treatment, particularly with regards to peptic ulcer disease, Helicobacter pylori infection and gastric cancer.
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Anthony G Catto-Smith, MD, FRACP, MRCP, DCH
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 36-38
The mucosal lining of the gastrointestinal tract is the route through which ingested nutrients are absorbed. It also serves to separate potentially toxic luminal contents and flora. These functions appear to be mutually incompatible, but are achieved by regional specialisations in epithelial structure and organ function. Enteric bacteria interact with enterocytes by influencing cellular electrolyte transport and tight junction permeability in the colon. The products of bacterial metabolism are essential for colonocyte nutrition.
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Peter H Katelaris, MBBS, FRACP, MD
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 39-43
Probiotics have been suggested to be of use in many diarrhoeal disorders, particularly in the prophylaxis and treatment of infectious diarrhoea. Several different preparations are available commercially and they are widely used but consistent scientific documentation of their efficacy is lacking. Although their putative mode of action is not known, non-pathogenic organisms may prevent or displace enteropathogens from colonising the gut. In vitro studies suggest that some probiotics may exert a direct inhibitory effect on pathogenic organisms. There is some clinical evidence suggesting a possible role for probiotics in the prophylaxis of infectious diarrhoea in some circumstances, but there is little evidence of a beneficial effect in the treatment of established diarrhoea, except in cases of relapsing C. difficile infection. There are no convincing data at present demonstrating efficacy of probiotics in non-infective diarrhoeal disorders. Although the use of probiotics in diarrhoeal diseases is conceptually appealing, their use for this indication is not clearly supported by the available scientific literature at present. Further research into the role of the human microflora in diarrhoeal diseases is needed to aid the selection of appropriate non-pathogenic bacteria for clinical studies. Well conducted controlled clinical trials are then needed in order to determine the place of probiotics in the prevention and treatment of diarrhoeal disorders.
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Graeme P Young, MD, FRACP
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 44-47
Any polysaccharide, whether starch or fibre (ie non-starch polysaccharides) may be fermented in the large bowel by resident microflora (anaerobic bacteria). Amongst other substances, the short chain fatty acid butyrate is produced during fermentation. Butyrate is important in the maintenance of normal epithelial biology; it is probably the means by which dietary fibre prevents colonic epithelial atrophy. Starch which escapes digestion in the small intestine (resistant starch) also prevents colonic epithelial atrophy. Dietary fibres differ greatly in their physicochemistry and also in their biological effects. As a general rule, resistant starch (especially of type 2) tend to behave more like soluble then insoluble nonstarch polysaccharides. In humans, resistant starch results in substantial production of butyrate in the colon. Butyrate can be shown to have "antitumour" effects at various levels (cell and molecular), and this could explain the important inverse association between starch intake and colon cancer incidence (on a country by country basis). The nature of the variables affecting butyrate production from dietary polysaccharides by resident microflora need to be explored with a view to better understanding the practical application of this to cancer prevention.
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Graeme H McIntosh, BUSc, PhD (ANU)
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 48-52
This review examines some of the evidence regarding probiotic bacteria as agents to reduce the risk of colon cancer in humans. While some of the evidence using rodent models of colon cancer is convincing for a reduction in cancer incidence and burden with the introduction orally of such bacteria as Bifidobacterium longum, Lactobacillus acidophilus and gg, convincing evidence in humans is more difficult to find. It consists of epidemiological studies or marker intervention studies using faecal enzymes, faecal bile acids or urinary/ faecal mutagens from microbial activity as measures of cancer risk, following probiotic introduction. Taken together these sources of data provide limited support for the hypothesis that probiotic bacteria are effective in cancer prevention.
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Salminen S, Isolauri E, Salminen E
Asia Pacific Journal of Clinical Nutrition (1996) Volume 5, Number 1: 53-56
Probiotic bacteria are used to treat disturbed intestinal microflora and altered gut permeability which are characteristic to many intestinal disorders. Examples include children with acute rotavirus diarrhoea, subjects with food allergy and patients undergoing pelvic radiotherapy. Altered intestinal microflora has been treated by oral intake of probiotic bacteria which are able to survive gastric conditions, colonise the intestine, at least temporarily, by adhering to the intestinal epithelium. Such probiotic microorganisms appear to be promising candidates for the treatment of clinical conditions with abnormal gut microflora and altered gut mucosal barrier functions.
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Copyright © 1996 [Asia Pacific Journal of Clinical Nutrition].
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Revised: January 19, 1999.