Current probiotics are naturally occurring indigenous microbes that are aimed to restore lost bacteria or metabolic activities in colonized organs, restore a balanced immune response similar to that induced by the usual indigenous microbiota, or to suppress pathogenic microbes (Kalliomaki and Isolauri 2003
). The scope of probiotics being used is narrow: several intestinal species predominate, including Bifidobacterium
species, Streptococcus thermophilus
species, E. coli
and yeasts, including Sacharomyces boulardii
Preliminary studies indicate that probiotics can affect innate immunity, as evidenced by oral tolerance, which cannot be achieved in germ-free animals (Sudo, Sawamura et al. 1997
), is reduced by antibiotic use (Bashir, Louie et al. 2004
), and can be restored by administering probiotics (Braat, van der Brande et al. 2004
). Probiotics also protect against pathogens by strengthening the intestinal mucosal (immune) barrier, decreasing pathogen adherence (Mack, Michail et al. 1999
), or by production of acid or antibiotics inhibitory to pathogens (Gibson, McCartney et al. 2005
). Our scientific understanding of currently used probiotics is limited; their beneficial effects are usually low, with strong placebo effects, and a substantial lack of robustness across experiments.
Modern era lifestyles are impacting our microbiome in ways we are just beginning to elucidate. We might need to have a probiotic in our future, but first, well-designed clinical trials are needed. The future of probiotics might expand in several ways:
1. Use of non-bacterial members of the human microbiota as probiotics
Fungi also are known to be constituents of the intestinal microbiota in mice (Scupham, Presley et al. 2006
), fish (Andlid, Blomberg et al. 1999
) and humans, and they are being investigated as intestinal probiotics (Martins, Nardi et al. 2005
). S. boulardii
may bind pathogenic Escherichia coli
strain and salmonellae (Buts, Dekeyser et al. 2006
)]. Effective probiotics for the skin, vagina, nose, and ear microbiota are yet to be discovered. It also is possible that constituents of other microbiomes from other animals might have specific utilities for humans; these, too, would need to be carefully tested so that the zoonotic costs do not exceed the potential benefits.
2. Administration of bacteriophages
Bacteriophages may be considered as either probiotics or as prebiotics , in the sense that they would inhibit specific bacterial populations, promoting the growth of other species. Bacteriophages also are potential alternatives to antibiotics (Sulakvelidze and Morris 2001
). Discovered independently by Frederick W. Twort and Felix d’Herelle (Stone 2002
), phages have been extensively used to prevent and treat bacterial infections, mainly in Eastern Europe and the former Soviet Union (Shasha, Sharon et al. 2004
). Phages have been used in humans against diarrheal diseases caused by E. coli, Shigella
, and to eliminate Campylobacter
in farm animals (Lederberg 1996
; Sulakvelidze and Morris 2001
). Although more specific, the lysogenic (non-lytic) pathway can limit the effectiveness of phage therapy.
3. Development of new prebiotics
Deeper knowledge of human microbial ecology will lead to specific prebiotic approaches to promote growth of favorable microbes, or to provide substrate for favorable metabolic pathways. In that sense, lactulose, a non-absorbable polysaccharide currently used as a prebiotic to treat hepatic encephalopathy, has multiple effects; next generation prebiotics may have much greater specificity.