Impact of Bifidobacterium longum and Lactobacillus acidophilus on the intestinal microflora and bioavailability of some food mutagens

University dissertation from Stockholm : Karolinska Institutet, Department of Immunology, Microbiology, Pathology and Infectious Diseases

Abstract: The gastrointestinal microflora is a complex ecological system, normally characterised by a flexible equilibrium. The most important role of the microflora, from the point of view of the host, is probably to act in colonisation resistance against exogenous, potentially pathogenic, microorganisms. The microflora also performs an important metabolic activity, breaking down and transforming compounds, in the intestine. Bifidobacteria and lactobacilli are Gram positive lactic acid producing bacteria constituting a major part of the intestinal microflora in humans and other mammals. Administration of antimicrobial agents may cause disturbances in the ecological balance of the gastrointestinal microflora with several unwanted side effects such as colonisation by potential pathogens. To maintain or reestablish the balance in the flora supplements of intestinal microorganisms, mainly bifidobacteria and lactobacilli, sometimes called probiotics, have been used. Lactic acid producing bacteria have also been reported to have antimutagenic and anticarcinogenic properties in vitro and in vivo. The aims of this thesis were to determine the effect of the two lactic acid producing bacteria, Bifidobacterium longum BB 536 and Lactobacillus acidophilus NCFB 1748, originally isolated from humans, on the intestinal microflora by ingestion with or without antimicrobial treatment and to determine their effect on the bioavailability of some mutagenic heterocyclic amines. Oral supplementation of B. longum BB 536 in a fermented milk product to healthy volunteers did not cause any major effects on the intestinal microflora nor any clinical side effects. When B. longum BB 536 and L. acidophilus NCFB 1748 were administered together with clindamycin, there was a smaller reduction of anaerobic microorganisms in the microflora compared to administration of the antimicrobial agent with placebo or together with only B. Longum. The differences were mainly due to higher numbers of bifidobacteria and Bacteroides in the group supplemented with the two organisms. There was also a smaller incidence of gastrointestinal discomfort in this group. Administration of the two microorganisms together with cefpodoxime proxetil and oligofructose resulted in a significantly lower colonisation by Clostridium difficile compared to administration of the antimicrobial agent with only oligofructose or placebo. In the other groups of the anaerobic microflora there were dramatic decreases, especially a loss of bifidobacteria in all groups, but at the end of cefpodoxime proxetil administration the number of lactobacilli was higher in the bacteria supplemented group than in the placebo group. The administered strain of B. Longum was recovered in one and L. acidophilus in six of nine volunteers. B. Longum BB 536 and L. acidophilus NCFB 1748, together with some other lactic acid producing or intestinal strains, were shown to bind the mutagenic heterocyclic amines Trp-P-2, PhIP, IQ and MeIQx, produced by cooking of protein rich food, in vitro. There were only minor differences in the binding capacities of the tested strains but the compounds were bound with different efficiencies. Oral administration of the two microorganisms, together with Trp-P-2, to mice resulted in a lower absorption of the compound, compared to mice not administered the bacteria. The results indicate that a binding between the microorganisms and the compound may have occurred in the gastrointestinal tract thus decreasing the bioavailability of the mutagen. In conclusion, the results indicate intestinal microflora preserving effects by administration of the two strains of lactic acid producing bacteria. They also suggest that the bioavailability of mutagenic heterocyclic amines originating from cooked food may be decreased by binding to the microorganisms.

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