Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy
Introduction
The bacterial flora of the gastrointestinal tract play a major role in human physiology, modulating metabolic and immunological processes and providing colonisation resistance, which is the prevention of overgrowth of opportunistic microorganisms. Administration of antimicrobial agents, whether therapeutically or prophylactically, disturbs the ecological balance between the host and the normal microbiota [1]. The extent of the disturbance depends on the nature of the antimicrobial agent, the absorption, the route of elimination and any potential enzymatic degradation and/or binding to faecal material. However, predicting the effects of an antibiotic on the microbiota can be difficult due to the complex relationships among the components of the microbiota [2].
Disturbance of the microbiota is frequently associated with diarrhoea, gastritis, glossitis and pruritus [3] as well as fungal infections. In addition, altered sensitivity to secondary infection can occur. A single oral dose of streptomycin can enhance susceptibility of laboratory animals to challenge by Salmonella spp. by at least 100 000-fold [4]. Another important and growing area of concern is the effect of antibiotics on the colonisation resistance properties of the indigenous microbiota resulting in the emergence and spread of resistant strains between patients and the dissemination of resistance determinants between microorganisms [1]. Reid and Friendship [5] state that in 1998 the World Health Organization cited diarrhoeal diseases as the second most common cause of disability-adjusted life-years lost and of death (2.2 million). However, in many instances there is an essential requirement for the administration of antibiotics, and hence it is necessary to identify means of minimising the adverse effects of antibiotics whilst maximising their potential benefits. One method is to select for antimicrobial agents that do not disturb the microbial colonisation resistance, but this is not always possible.
Beneficial effects have been observed when probiotics have been used for the prevention and treatment of gastrointestinal disturbance [6], [7]. Trials have shown the potential for the use of probiotics in the treatment of rotavirus infections, antibiotic-associated diarrhoea, traveller's diarrhoea, infantile diarrhoea, relapsing Clostridium difficile colitis, inflammatory bowel disease, irritable bowel syndrome, atopy in at-risk infants and chronic sinusitis [8], [9], [10], [11], [12], [13], [14], [15].
For the purposes of this study, a cohort of Helicobacter pylori-infected patients receiving the triple therapy antibiotic treatment regimen was selected for investigation.
The aim was to determine the effects of probiotic supplementation during triple therapy on the composition of the intestinal re-growth population, looking both at numbers and types of microorganisms and on the incidence of antibiotic resistance in the intestinal microbiota.
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Subjects
One hundred and sixty-two patients infected with H. pylori were enrolled into a study at Addenbrooke's Hospital, Cambridge, UK. The H. pylori infection was verified by positive serology and histology by the Public Health Laboratory Service at Addenbrooke's Hospital. Patients provided written consent and had no other gastrointestinal disorders apart from peptic ulcers thought to be related to their H. pylori infection. None had received any antibiotics or been subject to any dietary intervention
Results
In the placebo and active groups, the total bacterial numbers decreased during antibiotic therapy, with a small clinical significance (P < 0.05), and increased post therapy (Table 1, Table 2). There were no significant differences between the numbers at days 1 and 35.
Discussion
Administration of antibiotics often causes disturbances in the normal intestinal microbiota [19], [20]. In the present study, the total bacterial and total facultative anaerobe population results indicate that despite the probiotic supplement the microbiotas of both the placebo and active groups were susceptible to the effects of the antibiotics administered to eradicate H. pylori. It appeared that there was recovery of the majority of the components of the microbiota post antibiotic therapy,
Acknowledgments
We would like to thank Dr Martin Day of Cardiff University, UK, and Dr Asa Sullivan of Karolinska University Hospital, Huddinge, Sweden, for their expert advice and knowledge of antibiotic resistance. We would like to express our sincere thanks posthumously to Prof. Denver Russell of Cardiff University, UK, for his support and guidance until his recent death.
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