Probiotics - Introduction
Probiotics are "live microbial feed supplements which benefit the host by improving its intestinal microbial balance and which upon ingestion in certain numbers induce health benefits beyond inherent basic nutrition" (6). Probiotic bacteria belong to the natural flora with low or no pathogenicity and show functions that are important for the health and well-being of the host. Therefore, the maintenance of this ecological flora is important to prevent diseases, especially infections of the gastrointestinal tract (7). Since the last decade there has been an increased awareness of the beneficial effects of probiotics. Bengmark (7) elegantly described the reasons for this interest in microbial interference treatment (Table I).
Increasing evidence shows that probiotic bacteria modify the gastrointestinal microflora in such a way that the bacterial activitiy is advantageous to the health of the host without colonizing the gastrointestinal tract, as it supresses gastrointestinal inflammation, and modulates the inflammatory response (8). However, further validatibn of probiotic properties in humans and clarification of their mechanisms of action are needed to better understand the role of probiotics in promoting human health.
According to Salminen et al. (9), probiotic bacteria may be used to treat disturbed intestinal microflora and increased gut permeability, characteristics of many intestinal disorders. Interesting examples that have been investigated, but for which no definitive studies exist, include children with acute diarrhea (with the exception of acute diarrhea caused by rotaviruses) (10, 11), subjects with food allergy, colonic motility disorders, patients undergoing pelvic radiotherapy and prevention of colon cancer. There is some evidence in favor of the use of probiotics in adult infectious diarrhea, antibiotic-associated diarrhea and lactose intolerance (12). Furthermore, data supporting the benefits of probiotics in alcoholic liver disease, hepatic encephalopathy (13) and Helicobacter pylori infection (14, 15) have been published. In some of these disease states, altered intestinal microflora, impaired gut barrier and different types of intestinal inflammation are present. Since probiotic bacteria may survive the low gastric pH, the effects of the bile and the transient colonization of the intestine by adhering to the intestinal epithelium make these bacteria potential candidates for the treatment of these clinical conditions (9).
In addition to lactobacilli and bifidobacteria, probiotics might also be of yeast origin, such as Saccharomyces, Aspergillus and Torulopsis. It should be noted that these agents are rather dangerous because in immunosuppressed subjects they can result in fungemia and fungal sepsis.
Although the mechanisms by which probiotics exert their effects in vivo have not yet been fully clarified, the luminal bacterial flora appears to play a major role in the initiation and perpetuation of chronic inflammatory bowel diseases in animal and human models. For example, colitis in the interleukin-10 (IL-10) gene-deficient mouse is associated with altered colonic microflora colonization, and may be modulated either by antibiotics or Lactobacillus subsp. treatment (16). In fact, most experimental animal models of intestinal inflammation require the presence of the microbial flora and do not develop disease in germ-free conditions. This was reported by Strober et al. (17): "in most if not all models the inflammation is driven by antigens in the normal mucosal microflora, which in effect means that it will be influenced by mitogens (e.g., lipopolysaccharides [LPS], CpGs) and superantigens associated with these organisms that tend to induce IL-12 production and thus Th1 responses".
To isolate potentially effective probiotic bacteria, the microbial population adhering to surgically resected segments of the ileum was screened by Dunne et al. (18). From the 1500 bacterial strains obtained, a small number of Lactobacillus and Bifidobacterium were selected. Of these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was shown to be acid and bile resistant. It adhered to epithelial cells, and in vitro it showed antagonism to pathogenic microorganisms (18). This specific strain is being widely investigated by several European groups led by a team of clinical scientists and food nutritionists in Cork, Ireland (18-20).
To date, the most common probiotics studied have been Bifidobacterium and Lactobacillus. Only a few strains have been characterized in vitro, in animal studies and in humans, and complete chromosome sequence has been obtained for L. acidophilus NCFM (21) and for the L. casei Shirota (personal communication).
One of the first Lactobacillus with therapeutic benefits isolated from human feces was Lactobacillus rhamnosus GG. It was administered during acute rotavirus diarrhea and promoted clinical recovery (22). In vitro, this Lactobacillus and Lactobacillus plantarum adhere to human mucosal cells (0.5-2.0 bacteria/cell) (23). Lactobacillus has a long history of safe use in the dairy industry and exists naturally in the human intestinal tract, which contains a myriad of microbes, collectively called microbiota. The microbial interference treatment is demonstrated by the use of lactobacilli, described by Sanders as promoters of human health (24). These bacteria were also effective in counteracting Gram-negative bacteria (7).
More recently members of the Bifidobacterium have been added to foods for probiotic purposes, probably encouraged by the discovery of their consistent presence as part of the normal microbiota of the human intestine. These bacteria are thought to be beneficial for the intestinal ecosystem and to provide protection against gastrointestinal infections and inflammatory bowel disease through their antagonistic activity against pathogens, their antiallergic effects and other positive effects on the immune system (25).
This review focuses on the different mechanisms of action of probiotics to maintain the normal ecology of the intestine and analyzes data supporting the role of probiotics in the suppression of inflammatory responses.
Table I: Reasons for new interest in probiotics (7).