Probiotics and Dietary Fiber (1998)

In 1998, Bengmark published a review article on the ecological control of the gastrointestinal tract and the role of the probiotic flora.1 Also this year, an international meeting was convened in Rome on "Probiotics and Fiber, and the Management of Human Intestinal Microflora."2 Both of these presentations bring up to date International Symposia that were published on Diet, Bacteria, and the Colon in 1976,3 and Intestinal Microbiology in 1970,4 1972,5 and 1974.6 The recent publication and meeting point out the advances in understanding of dietary fiber and short-chain fatty acids, mucosal immune function, adhesive relationship of bacteria and intestinal epithelia, and the prevention of disease by lactic acid producing bacteria, Lactobacillus rhamnosis strain GG and Lactobacillus plantarum.1 It is important to understand the concept of intestinal microecology to correctly use probiotic agents of today and tomorrow. THE ECOLOGIC UNIT Donald Luckey and others popularized the theory of the microecology of the gut.7-9 Luckey pointed out that the human body was exposed to the environment in three ways: (1) the skin, (2) the respiratory track, and (3) the gastrointestinal tract,8 the gastrointestinal tract being the hollow tube that receives food required for maintaining body metabolism. He noted that the gastrointestinal tract has a definite microecology. Later we stressed the four components of the microecology9: (1) the gastrointestinal wall that varies with unique histology and function from the mouth to the pharynx, to the esophagus, to the stomach, to the small and large intestine, and finally the rectum; (2) within that lumen are secretions from each part of the tract; (3) the foods that enter the tract; and last but not least, (4) the 500 species of microscopic organisms that live within the tract. Each component, the wall, the secretions, the foods, and the microflora, depend on each other for their nutrition and maintenance. The gut secretes approximately 6 to 7 L of fluid when one tabulates the salivary, the gastric, the pancreatic, biliary, and intestinal secretions. The types of food and fluids that are eaten vary this fluid milieu. Reproduction and growth of the microflora are affected by the content within the lumen. But the microflora in an individual is remarkably stable and varies only when disease occurs and when there are great fluxes in the fluids and foods that are eaten. Disturbance in any one of the four components making up the ecologic components of the gut results in disease. Clear examples of this are the obvious effect of an infectious agent, which damages the wall and rapidly changes the microflora environment. More subtle examples are long-term changes in dietary food intake, which are associated with chronic degenerative diseases. It is now clear that high-fat, low-fiber diets are associated with atherosclerosis, cancer, and degenerative gastrointestinal diseases. Although this is a long-term effect of dietary food intake or deficiency, degenerative diseases can be explained by a change in the microecology of the gut. Increased intake of salt, simple sugar, and high fat are clearly associated with chronic degenerative disease processes.1,3. THE MICROFLORA Our understanding of the role of the bacteriologic flora was greatly advanced by the work of Dubois and Schaedler.10 Their techniques helped characterize the anaerobic flora in animals. Before their work, the magnitude of the anaerobic flora, which is now recognized to be anywhere from 10 to 100 times more abundant than the aerobic flora, within the gut was not appreciated. After the technologic advance in animals, others, including our laboratories,3-6 developed techniques to identify the human anaerobic flora and its relationship to diseases. The magnificent work of Moore and Holdman in identifying and characterizing the human anaerobic flora further advanced our knowledge in this field.11 Many monographs were published that proved that theBacteroids spp, Lactobacillus spp, Peptostreptococcus spp, and Veillonella spp were some of the predominant organisms living in the gut. It is interesting that these organisms are great producers of short-chain fatty acids. It became obvious that a symbiotic relationship between these numbers of organisms existed to maintain the normal flora, which is very stable. Once again, a disturbance in the relationship of these organisms can result in disease. The clear example is pseudomembranous colitis that occurs when Clostridia difficile growth increases. The theory that balance in the ecology prevents disease is emphasized by the fact that Clostridia difficile growth can actually be controlled by fiber intake or by alteration in the flora. DIETARY FIBER The understanding of dietary fiber further advanced our understanding of the ecology of the microflora. It was clear from the landmark works of Burkitt, Trowell, and Walker12-14 that dietary fiber played a major role in varying the qualitative and quantitative component of the microflora. The importance of fiber to the flora was first stressed by Drasar and colleagues.15 Chemically there are two types of fibers: insoluble and soluble.14 The insoluble fibers are mostly made up of cellulose and lignins, whereas the soluble fibers are mostly hemicellulose. However, the chemistry of these fibers is extremely complex. Our knowledge of them is yet to evolve. Nevertheless, it is clear that soluble fibers are poorly or not digested at all by human enzymes. Within the ecology of the gut soluble fiber is digested by bacterial enzymes to produce short-chain fatty acids. Insoluble fibers are poorly digested and act to maintain certain physiochemical properties such as water holding, binding of chemicals and minerals, and the formation of gels.16 Soluble fibers are digested by bacterial enzymes, but do form gels in their passage through the small intestine. Bacterial fermentation of fibers into short-chain volatile fatty acids, the primary ones butyric, propionic, and acetic, make a major contribution to the metabolism of human beings.16 We now know that butyric acid is the major fuel for the colon epithelium and that both acetic and propionic are major contributors to the stability of cholesterol and lipid metabolism. The understanding of the fermentation of soluble fiber to produce short-chain fatty acids is a major advance in our understanding of human colonic physiology and its role in maintaining homeostasis. It is certain that much more information will come forth on this relationship. The early realization that butyric acid can be therapeutic in disease entities such as diversion colitis holds promise.17 Better understanding of this physiology will be therapeutic in certain diseases. PROBIOTIC FLORA Finally, control of a flora by the use of probiotic bacteria is a new approach in therapy. Bengmark defines probiotic bacteria as "live microorganisms belonging to the natural flora with low or no pathogenicity, but with functions of importance to the health and well being of the host."1 We have now had several demonstrations where the use of lactobacilli can correct systemic disease. It has been shown that they can control pathogens that affect both the gastrointestinal tract (such as Shigella) and the genital urinary tract.1 It is clear from all these advances that the ecology of the microflora is pivotal in maintaining health. Disturbance of the microecology of the flora may result in disease. We now move to an era where understanding how to maintain the normal flora, or understanding how to use organisms of the normal flora as therapeutic agents, holds great promise in prevention and treatment of disease. Martin H. Floch, M.D. Khalid Moussa, M.D. Gastroenterology Section; Department of Medicine; Norwalk Hospital/Yale University School of Medicine; Norwalk, Connecticut