What are the mechanisms by which probiotics exert their effects?
Despite the benefits of probiotics being widely recognised, their mechanisms of action are often disputed, mainly due to strain specificity1. However, there are four main pathways through which probiotics are thought to act when studied in vitro.
1. Enhancement of the epithelial barrier
The intestinal barrier is a major defence mechanism for protection from the environment. Once this barrier is disrupted foreign antigens are able to pass through and trigger inflammatory responses(2). Consumption of probiotic bacteria can contribute to improving gut barrier function. Several studies have suggested that this may occur through enhancing the expression of genes involved in tight junction signalling(3). Tight junctions bind cells together, preventing unwanted molecules from passing through, thus maintaining gut integrity. Moreover, recent studies suggest probiotics may play a role in initiating repair of the gut barrier after it has been damaged, through reconstruction of the tight junction complex(4).
2. Increased adhesion to the intestinal mucosa
This is important for interaction between the probiotic and the host, making it one of the main selection criteria for new probiotic strains. One way in which effective strains are thought to achieve this is through interaction with the intestinal epithelial cells (IECs)(5). These cells secrete mucin, a component of mucus, which prevents the attachment of pathogenic bacteria. Probiotics are thought to interact with the IECs to increase their production of mucin preventing pathogen attachment(6).
3. Production of anti-microbial substances
Some probiotics are thought to have an inhibitory effect against pathogens through production of organic compounds such as lactic acid(7). Upon entering the bacterial cell, lactic acid is able to lower the intracellular pH, leading to death of the pathogen(8). Other probiotic strains produce antibacterial compounds such as bacteriocins. These can act on target cells through pore formation or inhibition of cell wall synthesis(9).
4. Modulation of the immune system
It is well understood that probiotics can suppress intestinal inflammation through down regulating the expression of toll like receptors (TLRs). The TLRs are an 11-protein family of transmembrane proteins expressed on various immune and non-immune cells. TLR-mediated signalling has been shown to control dendritic cell maturation, which in turn mediates a tolerant anti-inflammatory state(10).
The advances in our understanding of the importance of the microbiome and the mechanisms by which probiotics can effectively modulate it, may not only help to improve the credibility of probiotic supplementation but also prompt development of novel strategies for treatment or prevention of diseases.
- Bermudez-Brito M .Probiotic mechanisms of action. Ann Nutr Metab. 2012;61(2):160-74.
- Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI: Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001;291:881–884.
- Anderson RC, Cookson AL: Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation. BMC Microbiol 2010;10:316.
- Zyrek AA, Cichon C, Helms S,: Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKC redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol 2007;9:804–816.
- Collado MC, Gueimonde M, Hernández M, Sanz Y, Salminen S: Adhesion of selected Bifidobacterium strains to human intestinal mucus and the role of adhesion in enteropathogen exclusion. J Food Prot 2005;68:2672–2678.
- Ouwehand AC, Salminen S, Tolkko S, Roberts P, Ovaska J, Salminen E: Resected human colonic tissue: new model for characterizing adhesion of lactic acid bacteria. Clin Diag Lab Immunol 2002;9:184–186.
- Alakomi HL, Skytta E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM: Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 2000;66:2001–2005.
- Ouwehand AC: Antimicrobial components from lactic acid bacteria; in Salminen S, von Wright A (eds): Lactic Acid Bacteria: Microbiology and Functional Aspects. New York, Dekker, 1998, pp 139–159.
- Hassan M, Kjos M, Nes IF, Diep DB, Lotfipour F: Natural antimicrobial peptides from bacteria: characteristics and potential applications to fight against antibiotic resistance. J Appl Microbiol. 2012, DOI: 10.1111/j.1365-2672.2012.05338.
- Gómez-Llorente C, Muñoz S, Gil A: Role of Toll-like receptors in the development of immunotolerance mediated by probiotics. Proc Nutr Soc 2010;69:381–389.