The renaissance of probiotics and prebiotics

Comment From the Editors The Renaissance of Probiotics and Prebiotics etchnikoff proposed in 1908 that ingestion of Lactobacillus in yogurt might explain the unusual longevity of Russian peasants. The theory of “autointoxication,” popular in the late 19th century, held that intestinal bacteria released noxious agents that contributed to disease and aging. Yogurt with its mixture of “healthy” organisms could counteract these toxins and promote health and longevity. The theory of autointoxication was exploited by faddists, and, lacking any scientific basis, faded into obscurity. From this idea flowed the concept of a “probiotic”—a viable organism that when ingested could prevent or treat an intestinal disease. More recently, the term “prebiotic” has entered the medical lexicon as a dietary substance that promotes the growth of beneficial gut bacteria. For example, the feeding of oligofructose and insulin-polymers favors the growth of bifidobacteria, a probiotic organism that is part of the normal microflora. The best studied probiotic agents are Lactobacillus species, the organisms used to ferment milk products like yogurt. This organism secretes lactase, which hydrolyzes lactose to glucose and galactose. Lactose-deficient patients who consume live-cultured, unpasteurized yogurt benefit from the ability of the ingested Lactobacillus sp. to digest lactose in the small intestine, thus improving its absorption and preventing symptoms of diarrhea and gas. Besides this benefit, yogurt and other cultured dairy products contain proteins and carbohydrates other than lactose that are easier to digest and that improve growth when fed to cattle. L. acidophilus feeding delays the onset of experimental colon cancer in rats, possibly by competing with other organisms in the colon that are required in the luminal me-

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tabolism of the carcinogen to an active species. An exciting new development in this area is the recent discovery that probiotic therapy can influence the course of inflammatory bowel disease (see Gionchetti et al. in this issue of GASTROENTEROLOGY). Probiotics are also reported to treat or prevent intestinal infections in animals and humans and stimulate the immune response to rotavirus in children. For example, L. salivarius prevents experimental salmonellosis in chickens, and Lactobacillus GG shortens the course of rotaviral diarrhea in children. The latter probiotic agent is now available without prescription as a nutritional supplement, and has been reported in preliminary trials to be beneficial for prevention or treatment of traveler’s diarrhea, antibiotic-associated diarrhea, and Clostridium difficile–induced diarrhea and colitis. Probiotic therapy seems to be ideally suited for C. difficile infection. The normal intestinal microflora forms a natural barrier against pathogens that is disrupted with antibiotics. C. difficile colonizes the human intestine only when this barrier is unformed, as in newborns and infants, or weakened by antibiotic therapy in children and adults. Full recovery from this infection occurs only when the normal barrier flora is reestablished after antibiotics are stopped. What bacteria provide the barrier function of the colonic microflora? The normal flora of the human colon contains 1011 bacteria per gram of feces; of these approximately 99% are anaerobes comprising hundreds of individual strains. Of the 30 anaerobic genera in the human colon, Bacteroides, Clostridium, Eubacterium, Lactobacillus, and Bifidobacterium are the most numerous. These organisms provide a stable microenvironment that prevents pathogens like C. difficile from colonizing

and multiplying. Bacteroides species are considered to be an important component of the barrier because their number is reduced during antibiotic therapy and increased during recovery from C. difficile infection. Fecal enemas containing Bacteroides and other anaerobes have been shown to reverse C. difficile diarrhea in a small number of patients. This stubborn organism may also be eliminated by feeding microbes that compete for micronutrients. Saccharomyces boulardii is a nonpathogenic yeast shown to be effective in patients wih multiple relapses of C. difficile. Colonization in the hospitalized patient may also be prevented by feeding nontoxigenic strains of C. difficile that do not cause disease. Another potential mechanism that might explain the anti-infective properties of probiotic microbes is stimulation of the mucosal immune system. Yogurt made with multiple Lactobacillus and Bifidobacterium sp. was shown to significantly enhance the mucosal and systemic antibody responses in mice administered oral cholera toxin. Lactating mice fed live bifidobacteria for 12 days had significantly higher levels of immunoglobulin (Ig) A in milk and intestinal secretions. Similar results were observed in healthy children after administration of the probiotic. Immune stimulation has also been observed after feeding S. boulardii to suckling and weanling rats. The therapeutic possibilities of manipulating the bowel flora are just beginning to reach clinical development. Research in this field has been slow, but newer molecular technologies should allow us to unravel the complexities of our microbial world within.

J. THOMAS LAMONT Associate Editor doi:10.1053/gast.2000.16150 GASTROENTEROLOGY 2000;119:291