The Cancer Journal - Volume 9, Number 5 (September-October 1996)
Antibiotic resistance and the intestinal flora
Academic medicine breeds resistant microbes - Microbial resistance to antibiotics is a growing threat to patients. Academic medicine is breeding a destructive device, the hospital strain. A dangerous microbe, resistant to all antibiotics, that evolves in a Darwinian fashion (1). Microbe breeding does not differ from cattle breeding, where the best parents are selected for mating. Here, antibiotic treatment selects parents that endow their progeny with antibiotic resistance. Microbe breeding is unintended and unwanted and can be averted only by a total ban on antibiotics, which is unthinkable since medicine and our society are addicted to antibiotics. The hospital strain highlights an inadequacy of academic medicine, total subjection to technology. By breeding hospital strains, academic medicine is iatrogenic and dangerous to patients. The threat may, however, be alleviated in several ways: by boosting our resistance to microbes, e.g., vaccination, by relying more on the wisdom of our body in handling microbes (2) (3), and by mobilizing our own flora.
Microbes ensure our existence on earth - Pasteur and other microbe hunters taught us that microbes are enemies that should be destroyed. Yet these tiny creatures are responsible for our existence. They appeared on earth one billion years after its formation. For 3.5 billion years they prepared our planet for the evolution of all life-forms (4). Their most important achievement was the maintenance of oxygen and carbon dioxide in the atmosphere, without which life would not have evolved. Today they are the first and most important link in the food chain of our planet. Solar energy trapped by plants is converted mainly into cellulose, that is indigestible by us, since we lack cellulose-degrading enzymes. Cellulose is degraded solely by microorganisms. Microbes and degradation products are ingested by protozoa. These in turn are ingested by higher live forms and so on. At the high end of this food chain are the animals that serve as our food.
The intestinal eco-system - Microbes are everywhere, and inhabit our skin and intestine. The newborn baby receives its microbial flora from its mother, that already infects it at birth. Bifido-bacterium and Lactobacilli are the first to colonize its gastrointestinal tract (4). Then come the facultative anaerobes, such as Escherichia coli and Streptococcus fecalis, that are followed by strictly anaerobic bacteria, e.g., Bacteroides. At the time of weaning, populations of obligate anaerobes become dominant. The development of our personal microbial community, known as primary succession, involves an ordered sequential change in the microbial populations of the community. Succession ends when the community consists of up to 400 different species, and attains homeostasis. It is stable, resists any change in its content, and repels unwelcome microbes like the hospital strain.
Eco-system evolution is a complex process that repeats itself in every growing child. By infecting the baby, its mother transmits to it the best microbial populations that she has gathered. It is a vertical inheritance of a protecting eco-system that is adapted later to the needs of the adult. In the intestine, anaerobic bacteria outnumber aerobic bacteria by 100:1 or 1,000:1 (5). Since anaerobes preferentially colonize the intestinal mucous layer, they might hinder aerobes from accessing the mucous layer and crossing it.
Antibiotics induce an ecological catastrophe in the intestine - Antibiotics disrupt our stable ecosystem, that either adapts to the trauma or is invaded by resistant microbes. It is an ecological catastrophe like water pollution. Changes observed in the "ailing" ecosystems are called secondary succession. Clinically, this catastrophe is manifested by "antibiotic associated-diarrhea", a pseudo-membranous colitis caused by Clostridium difficile (6). Its overgrowth is also induced by combination chemotherapy, and radiotherapy of the lower abdomen. In 20% of treated patients diarrhea may relapse several times, particularly following vancomycin, and metronidazole treatment. Treatment, called bacteriotherapy, or biotherapy, attempts to restore the original eco-system. This idea was raised last century, by Metchnikov, who noted that lactobacilli inhibit the growth of putrefactive organisms. He concluded that fermented milk, e.g., yogurt, kefir, or buttermilk, might be good for diarrhea. Today, live bacteria, e.g., L. acidophilus and L. bulgaricus, in dried form, are given as granules or packed in capsules. Their effect was examined in several clinical trials (6). Other treatments include enema of mixed microbe populations, and biotherapy with yeast.
Apparently some microorganisms may activate heterocyclic amines, and make them carcinogenic (7). If so, by preventing their access to the intestine, our eco-system might also protect us against cancer. This could be also the rationale for diets rich in fibers. These examples illustrate the importance of our microflora, a yet neglected organ, that waits to be explored (8). p
H.H. Humphrey Center for Experimental Medicine and Cancer Research, P.O.Box 12272, Jerusalem 91120, Israel.
Internet home page: http://www6.huji.ac.il/md/home.html
1. Zajicek G. How to diminish microbial resistance to antibiotics. Cancer J 6, 52, 1993
2. Zajicek G. Wisdom of the body. Cancer J 7, 212-213, 1994.
3. Zajicek G. Microbial resistance to antibiotics and the wisdom of the body.Cancer J 7, 168-169, 1994.
4. Atlas RM., Bartha R. Microbial Ecology. The Benjamin/Cummings Publishing Co. Inc. Redwood City CA, 1993.
5. Wells CL, Maddaus MA, Simmons RL. Proposed mechanisms for translocation of intestinal bacteria. Rev Infectious Dis 10, 958-979, 1988.
6. Roffe C. Biotherapy for antibiotic-associated and other diarrheas. J Infection. 32, 1-10, 1996.
7. Kadlubar FF. Rethinking the role of intestinal microflora in bioactivation of food-borne heterocyclic amine carcinogens. J Natl Canc Inst 86, 5, 1994.
8. Bocci V. The neglected organ: bacterial flora has a crucial immunostimulatory role. Persp Biol Med 35, 251-260, 1992.