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Identification and characterisation of an iron-responsive candidate probiotic.

Bailey JR, Probert CS, Cogan TA - PLoS ONE (2011)

Bottom Line: The isolate of S. thermophilus selected was able to reduce epithelial cell death as well as NF-κB signalling and IL-8 production triggered by pathogens.It was capable of crossing an epithelial cell barrier in conjunction with E. coli and downregulating Th1 and Th17 responses in primary human intestinal leukocytes.Therefore, we offer an alternative paradigm which considers that probiotics should be able to be competitive during periods of intestinal bleeding, trauma or stress.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Microbiology, School of Veterinary Sciences, University of Bristol, Bristol, United Kingdom.

ABSTRACT

Background: Iron is an essential cofactor in almost all biological systems. The lactic acid bacteria (LAB), frequently employed as probiotics, are unusual in having little or no requirement for iron. Iron in the human body is sequestered by transferrins and lactoferrin, limiting bacterial growth. An increase in the availability of iron in the intestine by bleeding, surgery, or under stress leads to an increase in the growth and virulence of many pathogens. Under these high iron conditions, LAB are rapidly out-competed; for the levels of probiotic bacteria to be maintained under high iron conditions they must be able to respond by increasing growth rate to compete with the normal flora. Despite this, iron-responsive genera are poorly characterised as probiotics.

Methodology/principal findings: Here, we show that a panel of probiotics are not able to respond to increased iron availability, and identify an isolate of Streptococcus thermophilus that can increase growth rate in response to increased iron availability. The isolate of S. thermophilus selected was able to reduce epithelial cell death as well as NF-κB signalling and IL-8 production triggered by pathogens. It was capable of crossing an epithelial cell barrier in conjunction with E. coli and downregulating Th1 and Th17 responses in primary human intestinal leukocytes.

Conclusions/significance: We propose that an inability to compete with potential pathogens under conditions of high iron availability such as stress and trauma may contribute to the lack of efficacy of many LAB-based probiotics in treating disease. Therefore, we offer an alternative paradigm which considers that probiotics should be able to be competitive during periods of intestinal bleeding, trauma or stress.

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Maintenance of tight cell junctions by probiotics.Expression of occudin (red) in epithelial cell monolayers (A). Proportion of pixels positive for occludin staining relative to entire field of view in T84 (B) and Caco-2 cells (C). Results are expressed as mean+S.E.M. * p≤0.05 and ** p≤0.01.
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pone-0026507-g004: Maintenance of tight cell junctions by probiotics.Expression of occudin (red) in epithelial cell monolayers (A). Proportion of pixels positive for occludin staining relative to entire field of view in T84 (B) and Caco-2 cells (C). Results are expressed as mean+S.E.M. * p≤0.05 and ** p≤0.01.

Mentions: Caco-2 and T84 cells were grown in a Transwell system and infected with AIEC HM615; S. thermophilus NCIMB 41856 was added to determine its effect on the tight cell junction protein occludin. AIEC HM615 caused the breakdown of tight cell junctions in Caco-2 and T84 monolayers, illustrated by decreased occludin (61% and 56% respectively) (Figure 4). AIEC HM615 also caused a 24% decrease in nuclear staining of T84 cells (data not shown), indicating that it was inducing cell death. The addition of S. thermophilus NCIMB 41856 to the monolayers in conjunction with AIEC HM615 prevented AIEC-induced tight cell junction breakdown and cell death; levels of nuclear and occludin staining were unchanged from control monolayers (Figure 4).


Identification and characterisation of an iron-responsive candidate probiotic.

Bailey JR, Probert CS, Cogan TA - PLoS ONE (2011)

Maintenance of tight cell junctions by probiotics.Expression of occudin (red) in epithelial cell monolayers (A). Proportion of pixels positive for occludin staining relative to entire field of view in T84 (B) and Caco-2 cells (C). Results are expressed as mean+S.E.M. * p≤0.05 and ** p≤0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198401&req=5

pone-0026507-g004: Maintenance of tight cell junctions by probiotics.Expression of occudin (red) in epithelial cell monolayers (A). Proportion of pixels positive for occludin staining relative to entire field of view in T84 (B) and Caco-2 cells (C). Results are expressed as mean+S.E.M. * p≤0.05 and ** p≤0.01.
Mentions: Caco-2 and T84 cells were grown in a Transwell system and infected with AIEC HM615; S. thermophilus NCIMB 41856 was added to determine its effect on the tight cell junction protein occludin. AIEC HM615 caused the breakdown of tight cell junctions in Caco-2 and T84 monolayers, illustrated by decreased occludin (61% and 56% respectively) (Figure 4). AIEC HM615 also caused a 24% decrease in nuclear staining of T84 cells (data not shown), indicating that it was inducing cell death. The addition of S. thermophilus NCIMB 41856 to the monolayers in conjunction with AIEC HM615 prevented AIEC-induced tight cell junction breakdown and cell death; levels of nuclear and occludin staining were unchanged from control monolayers (Figure 4).

Bottom Line: The isolate of S. thermophilus selected was able to reduce epithelial cell death as well as NF-κB signalling and IL-8 production triggered by pathogens.It was capable of crossing an epithelial cell barrier in conjunction with E. coli and downregulating Th1 and Th17 responses in primary human intestinal leukocytes.Therefore, we offer an alternative paradigm which considers that probiotics should be able to be competitive during periods of intestinal bleeding, trauma or stress.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Microbiology, School of Veterinary Sciences, University of Bristol, Bristol, United Kingdom.

ABSTRACT

Background: Iron is an essential cofactor in almost all biological systems. The lactic acid bacteria (LAB), frequently employed as probiotics, are unusual in having little or no requirement for iron. Iron in the human body is sequestered by transferrins and lactoferrin, limiting bacterial growth. An increase in the availability of iron in the intestine by bleeding, surgery, or under stress leads to an increase in the growth and virulence of many pathogens. Under these high iron conditions, LAB are rapidly out-competed; for the levels of probiotic bacteria to be maintained under high iron conditions they must be able to respond by increasing growth rate to compete with the normal flora. Despite this, iron-responsive genera are poorly characterised as probiotics.

Methodology/principal findings: Here, we show that a panel of probiotics are not able to respond to increased iron availability, and identify an isolate of Streptococcus thermophilus that can increase growth rate in response to increased iron availability. The isolate of S. thermophilus selected was able to reduce epithelial cell death as well as NF-κB signalling and IL-8 production triggered by pathogens. It was capable of crossing an epithelial cell barrier in conjunction with E. coli and downregulating Th1 and Th17 responses in primary human intestinal leukocytes.

Conclusions/significance: We propose that an inability to compete with potential pathogens under conditions of high iron availability such as stress and trauma may contribute to the lack of efficacy of many LAB-based probiotics in treating disease. Therefore, we offer an alternative paradigm which considers that probiotics should be able to be competitive during periods of intestinal bleeding, trauma or stress.

Show MeSH
Related in: MedlinePlus