Bacteriotherapy: the time has come

The worldwide emergence of bacterial resistance to antibacterial agents has produced a need for new methods of combating bacterial infections. This need is forced on us by the long time lag in developing new antibacterial agents. And even though new agents may be in the pipeline, they will not solve all current resistance problems. In addition, we also have to recognise that the use of antibacterial agents not only selects resistant bacteria but also disturbs normal human flora, which may itself further inhibit our defence against infection. Bacteriotherapy—using harmless bacteria to displace pathogenic organisms—is an alternative and promising way of combating infections.¹

A recent paper in the BMJ by Roos et al showed how commensal α haemolytic streptococci were used to replace the normal nasopharyngeal flora in children with recurrent otitis media.² The results were astonishing. After treatment, recurrences of otitis media fell to half of those in the control group; at three months 42% of children given streptococci in nasal spray were healthy compared with 22% of the controls; and the need for new courses of antibacterial treatment decreased. This study is not the first of its kind from this group: Roos et al have also successfully used α haemolytic streptococci in preventing recurrent streptococcal tonsillitis.³

This approach to treatment is not new.¹ Bacterial interference was once widely studied, and attempts to influence colonisation of pathogenic bacteria with “harmless” bacteria were carried out some decades ago. In human health bacteriotherapy was probably forgotten because of the continuous development of new, more potent antibacterial agents and because of fears about possible side effects. Avirulent bacterial strains can, in principle, also cause infections. Though otherwise effective, Staphylococcus spp 502A caused minor skin lesions in a few individuals when it was introduced into the skin flora to interfere with a virulent strain of S aureus.¹ Nevertheless, bacteriotherapy has already long been used in animals—for example, to prevent salmonellosis in chickens.⁴

The results of Roos et al show also that antibiotic treatment itself increases the risk of recurrent otitis media, and we know that antibiotic treatment for any purpose increases the risk of urinary tract infections in young women.⁵ Again, this increased risk is probably caused by the antibiotics disturbing the balance of normal genital and perianal flora.

Bacteriotherapy has also been used for other indications. Faeces or a mixture of faecal bacterial strains have been used to treat recurrent Clostridium difficile infection.⁶ Although the efficacy of this treatment method still remains undecided because no randomised trials have been performed, Saccharomyces bourlardii yeast was used for the same indication in a randomised trial, with good results.⁷ Milk containing Lactobacillus GG, given to children in day care centres, seems to reduce the rate and severity of respiratory infections.⁸ Lactobacilli have been used in various clinical conditions—for example, for prophylaxis of antibiotic induced diarrhoea (decreasing the diarrhoea rate to one third compared with placebo) but also in promoting recovery from acute diarrhoea in children.⁹ Moreover, non-pathogenic Escherichia coli have successfully been used to treat ulcerative colitis.¹⁰

Why are strategies such as bacteriotherapy arousing more interest in our attempts to combat antibacterial resistance? Although restrictions on use of antibacterial drugs in hospitals are effective in reducing bacterial resistance, the increasing number of immunocompromised patients in hospitals nevertheless tends to increase their use. And although we have shown that the reduction of antibiotics used in the community can reduce bacterial resistance,¹¹ this is a long row to hoe. Also, it may be that bacterial resistance is still too remote a problem for most physicians, patients, decision makers, and the medical industry to cause any concerted action in reducing antibacterial consumption. We do not even know the total consumption of antibacterial agents among humans in the European Union.¹²

In addition to bacteriotherapy, other strategies to reduce infection and bacterial resistance include improved hygiene measures, especially in hospitals but also in day care centres, and new bacterial vaccines.¹² In the future, treatment opportunities may include antibody treatment and bacteriophage therapy.

In the meantime bacteriotherapy seems to be a promising candidate for the future treatment and prevention of respiratory tract and gastrointestinal infections. Several questions remain open, however, such as safety. The α haemolytic streptococci chosen by Roos et al were selected for their superior ability to inhibit the growth of respiratory tract pathogens. Even if bacteriotherapy is safe for individual patients, the possibility remains that large quantities of active bacteria used clinically might change the human flora at population level.

Indeed, we still know very little about the complex system of human flora. There is an immediate need for basic research, and new molecular techniques should help.¹³ This research is needed not only to develop bacteriotherapy and other medical treatments but also to better understand the role of human flora—for example, in food processing. Certainly the human microbiome will present plenty of challenges to eager explorers over the next few years.