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Frequent association of Lactobacillus acidophilus and Streptococcus mutans with caries activity gave credence to their being specific cariogens. However, dental caries occurrence in their absence, and the presence of other bacteria able to produce substantial amounts of acid from fermentable carbohydrate, provided arguments for non-specificity. In the 1940s, Stephan found that the mixed bacteria in dental plaque produced a rapid drop in pH following a sugar rinse and a slow pH return toward baseline. This response became a cornerstone of plaque and mixed-bacterial involvement in dental caries causation when Stephan showed that the pH decrease was inversely and clearly related to caries activity. Detailed examination of the pH (acid-base) metabolisms of oral pure cultures, dental plaque, and salivary sediment identified the main bacteria and metabolic processes responsible for the pH metabolism of dental plaque. It was discovered that this metabolism in different individuals, in plaque in different dentition locations within individuals, and in individuals of different levels of caries activity could be described in terms of a relatively small number of acid-base metabolic processes. This led to an overall bacterial metabolic vector concept for dental plaque, and helped unravel the bacterial involvement in the degradation of the carbohydrate and nitrogenous substrates that produce the acids and alkali that affect the pH and favor and inhibit dental caries production, respectively. A central role of oral arginolytic and non-arginolytic acidogens in the production of the Stephan pH curve was discovered. The non-arginolytics could produce only the pH fall part of this curve, whereas the arginolytics could produce both the fall and the rise. The net result of the latter was a less acidic Stephan pH curve. Both kinds of bacteria are numerous in dental plaque. By varying their ratios, we were easily able to produce Stephan pH curves indicative of different levels of caries activity. This and substantial related metabolic and microbial data indicated that it is the proportions and numbers of acid-base-producing bacteria that are at the core of dental caries activity. The elimination of S. mutans, as with a vaccine, was considered to have little chance of success in preventing dental caries in humans, since, in most cases, this would simply make more room for one or more of the many acidogens remaining. An understanding of mixed-bacterial metabolism, knowledge of how to manipulate and work with mixed bacteria, and the use of a bacterial metabolic vector approach as described in this article have led to (1) a more ecological focus for dealing with dental caries, and (2) new means of developing and evaluating anti-caries agents directed toward microbial mixtures that counter excess acid accumulation and tooth demineralization. <\/jats:p>","DOI":"10.1177\/154411130201300202","type":"journal-article","created":{"date-parts":[[2009,1,9]],"date-time":"2009-01-09T00:40:32Z","timestamp":1231461632000},"page":"108-125","source":"Crossref","is-referenced-by-count":247,"title":["A M<scp>ixed-bacteria<\/scp> E<scp>cological<\/scp> A<scp>pproach to<\/scp>                   U<scp>nderstanding the<\/scp> R<scp>ole of the<\/scp> O<scp>ral<\/scp> B<scp>acteria in<\/scp>                   D<scp>ental<\/scp> C<scp>aries<\/scp> C<scp>ausation: an<\/scp> A<scp>lternative to<\/scp>                   S<scp>treptococcus mutans and the<\/scp> S<scp>pecific-plaque<\/scp> H<scp>ypothesis<\/scp>"],"prefix":"10.1177","volume":"13","author":[{"given":"I.","family":"Kleinberg","sequence":"first","affiliation":[{"name":"Department of Oral Biology and Pathology, State University of New York, Stony\r               Brook, New York 11794-8702"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2002,3,1]]},"reference":[{"key":"AFONSKY-1961","unstructured":"Afonsky D (1961). 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