Microbial Ecology of the Intestinal Microflora: Influence of Interactions with the Host Organism

Prohiotics, Other Nutritional Factors, jwd Intestinal Microflora, edited by Lars A. Hanson and Robert H. Yolken, Nestle Nutrition Workshop Series, Vol. 42, Nestec Ltd.. Vevey/Lippineott-Raven Publishers, Philadelphia © 1999. Microbial Ecology of the Intestinal Microflora: Influence of Interactions with the Host Organism Dirk van der Waaij Retired Professor of Medical Microbiology, University of Groningen, Groningen, The Netherlands As a medical doctor specializing in medical microbiology, my scientific interest is the patient-related importance of the gastrointestinal microflora. This concerns the defense function of the microflora, the conditions that lead to distortion of this "win-win" arrangement, the medical consequences of such distortions, and a sim- plified classification of microorganisms that can cause infectious disease. The current terminology used to identify the various fractions and stages of the intestinal microflora has been reviewed by Rusch (1). The normal or indigenous microflora of humans is known to consist of a rather static resident (autochthonous) part and a transient part. Under normal circumstances, the microflora has a dynami- cally changing composition. The turnover of the transient part depends on the composition of the autochthonous microflora, the gut ecosystem of the host, and the influx of new microorganisms. This influx is determined by the degree of contamination of ingested food and beverages, which relates to the hygienic condition of the envi- ronment. As will be outlined later, the net result of a contamination with foreign bacteria is determined by the dose (the number of microbes ingested) and the composition of the endogenous ecosystem. Another point of practical importance concerns antibiotics. Since antimicrobial treatment is rapidly losing ground because of the development of multiple resistance, including resistance to new antibiotics brought on the market, there is a need for new antimicrobial strategies. The problem of multiple resistance of microorganisms is worldwide (2,3). An international study group of biomedical scientists has under- taken to try to find a solution to this problem. This group, named the International Study Group on New Antimicrobial Strategies (ISGNAS) (4), has indicated that an important key to a new strategy could be the modulation of gastrointestinal tract microflora and its many complex interactions with the host defense system. For successful modulation of gut microflora, however, more research is needed on these interactions. 2 MICROBIAL ECOLOGY OF INTESTINAL MICROFLORA Insight into the development of miraculously stable bacterial ecosystems such as our intestinal microflora and into the role of the autochthonous microflora in the defense system may be gained from information on the development of these systems during evolution. This information may also help in understanding the development of resistance to antibiotics by microorganisms each time a new antibiotic becomes available. GROUPING OF BACTERIA ACCORDING TO THEIR DEGREE OF PATHOGENICITY For practical (medical) purposes, all existing bacteria can be placed in one of three dominant groups, each group of different (from 1 -3 increasing) pathogenicity. The composition of these groups may differ slightly between man and animals and among animal species. In particular, the first two groups may differ among animal species. Nonpathogenic By far the largest group is not pathogenic at all, or only in extremely compromised individuals. Bacteria belonging to this group can be found in the digestive tract and on the skin of all healthy human subjects, as well as on the skin of animals and plants. These bacteria live in peaceful coexistence with the defense (immune) system of the host. They may permanently induce or maintain suppression of the so-called gut-associated lymphoid tissue (GALT) and in this way avoid inducing a chronic inflammatory response (see below). Potentially Pathogenic A second and smaller group is potentially pathogenic. In healthy subjects, these bacteria are kept well under control by the immune system of the digestive tract, the GALT, as well as some nonspecific defense factors. We all experience daily the fact that this control occurs without causing any signs or symptoms of disease. Representatives of this group, which are also called opportunistic, can be found in practically every healthy human subject, in every animal, and on many plants. In compromised subjects, however, they may cause infections. Pathogenic The third group, a small one, comprises the pathogenic organisms. Following contamination in sufficient numbers, these microorganisms can cause disease in noncompromised healthy subjects. In unvaccinated individuals, these bacteria are not readily controlled by the immune system. In contrast to representatives of groups 1 and 2, bacteria of group 3 are not normally cleared without signs of disease (an inflammatory response) and are not found in healthy subjects. If they are present, the host organism is called a carrier and is regarded as infectious. MICROBIAL ECOLOGY OF INTESTINAL MICROFLORA 3 DEVELOPMENT OF THE MICROFLORA AND A DEFENSE SYSTEM IN EVOLUTION First Ecosystem on Earth: Ancestor of Our Microflora The earliest life on earth may have consisted of a photosynthesizing species of auxotrophic bacteria. During the subsequent millions of years, more and more of these species will have developed. With the appearance of these first bacterial species, our planet may have provided a spectacular sight from space, with purple-, red-, and later green-colored islands. Land may have been covered by a dense bacterial population, but the sea may also have had a rich bacterial life (5). When one realizes that many bacterial species may divide for reproduction every 20 minutes, one may question why our planet has not been entirely taken over by bacteria. An important reason for restricted growth has been, and still is, competition for nutrients. Even in niches with an adequate nutrient supply, bacteria have to compete with each other for practically every morsel. An important source of nutrients for the great majority of more recently developed nonauxotrophic bacteria is other organisms, both living and dead. Bacterium have only a restricted enzymatic capacity for digestion, however, regardless of the species, and they cannot digest the larger and more complex molecules by themselves. Thus, bacteria must cooperate with other bacterial species to digest the more complex molecules. Only in concert with other species, for exam- ple, in ecosystems, can they form the enzymatic pattern required for the breakdown and digestion of dead organisms and other complex nutrients (the process of decom- position). Nucleated Cells Developed from Bacterial Ecosystems A major change occurred in the first eons when certain bacteria developed that produced oxygen. The increasing presence of oxygen in the atmosphere made a change from anaerobic to aerobic metabolism possible. The emergence of aerobes changed life on earth completely, as it made possible the development of nucleated cells, presumably from bacterial aggregates (6). Later on, the development of plants and animals could follow from these cells. Maintenance of Bacterial Ecosystems by Antibiosis and Development of Resistance Most bacterial populations in nature exist in "open systems" with continuous influx of new (foreign) bacteria along many different routes. Therefore, in ecosystems, indigenous bacteria have to protect the nutrient sources of their community. The numerous bacterial ecosystems that were formed during evolution have developed the means to defend their communities by antibiosis. Antibiosis means the production of substances that are either "static" (growth inhibiting) or "cidal" (toxic and directly killing) to most, and preferably all, incoming bacteria and fungi that are foreign to the ecosystem and do not contribute to it in any way. All permanent 4 M1CR0BIAL ECOLOGY OF INTESTINAL MICROFLORA members of the ecosystem are obviously resistant to these static/cidal substances. Conversely, newly arrived microorganisms that produce antibiotic-like substances that are effective against members of the ecosystem may cause relatively little harm to the system. These usually enter the ecosystem in relatively small numbers and consequently release relatively little antibiotic substance. In addition, their antibiotic may rapidly become inactivated. This inactivation occurs either by chemical binding to organic material in the system or, after an adaptation period, by enzymatic inactivation. This is an assumption based on observations in the human gut microflora (7). Development of a Defense System to Microorganisms Small animals with a short life span were the first that developed from nucleated cells. They could live with a primitive nonspecific defense system, that is, microbial adherence and subsequent phagocytosis and killing. In higher, longer living animals and humans, additional means for protection against bacterial invasion developed. An increasingly complex defense system, known as the immune system (8), was formed stepwise. With the increasing life span of animals, the complexity of the immune system became enhanced, and a "learning system" was needed and developed. This learning system enabled the host to distinguish between bacteria of their own ecosystem and newly ingested foreign (potentially invasive) bacteria. This makes it plausible that host organisms play an important role in maintaining the

Load more