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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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Effect of probiotics on NF-κB (A) and IL-8 (B) response to pathogen.Results are shown from 6 replicate experiments and are expressed as mean + S.E.M. * p≤0.05, ** p≤0.01 and *** p≤0.001.
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pone-0026507-g002: Effect of probiotics on NF-κB (A) and IL-8 (B) response to pathogen.Results are shown from 6 replicate experiments and are expressed as mean + S.E.M. * p≤0.05, ** p≤0.01 and *** p≤0.001.

Mentions: Monolayers of Caco-2 and T84 cells were treated with the three potential probiotic bacterial strains in combination with pathogenic E. coli strains in order to determine the effect of probiotic on either of these pro-inflammatory signalling events. NF-κB signalling in Caco-2 cells was upregulated by 491% (p = 0.002) compared to controls following infection with E. coli K12 and by 247% (p = 0.002) following AIEC HM427 treatment. However, this induction was reduced by the addition of all three probiotic strains: L. acidophilus ASF360 reduced the NF-κB response to E. coli K12 by 50% (p = 0.006) and AIEC HM427 by 28% (p = 0.007); S. thermophilus NCIMB 41856 reduced the NF-κB response to E. coli K12 by 58% (p = 0.002) and AIEC HM427 by 49% (p = 0.005); and E. coli Nissle 1917 reduced the NF-κB response to E. coli K12 by 79% (p = 0.0005) and AIEC HM427 by 68% (p = 0.004) (Figure 2A). S. thermophilus NCIMB 41856 also reduced NF-κB signalling by 48% in untreated cells (p = 0.003) (Figure 2A). Following NF-κB signalling, IL-8 production was increased by 1566% in response to E. coli K12 (p = 0.001), 1104% in response to AIEC HM427 (p = 0.004) and 363% in response to HM615 (p = 0.02), as well as a 1498% increase following addition of E. coli Nissle 1917 (p = 0.004). The IL-8 response to E. coli K12 was reduced by 22% following addition of S. thermophilus NCIMB 41856 (p = 0.02) and the response to AIEC HM427 was reduced by both L. acidophilus ASF360 and S. thermophilus NCIMB 41856 by 17% (p = 0.02) and 39% (p = 0.02) respectively (Figure 2B).


Identification and characterisation of an iron-responsive candidate probiotic.

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

Effect of probiotics on NF-κB (A) and IL-8 (B) response to pathogen.Results are shown from 6 replicate experiments and are expressed as mean + S.E.M. * p≤0.05, ** p≤0.01 and *** p≤0.001.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3198401&req=5

pone-0026507-g002: Effect of probiotics on NF-κB (A) and IL-8 (B) response to pathogen.Results are shown from 6 replicate experiments and are expressed as mean + S.E.M. * p≤0.05, ** p≤0.01 and *** p≤0.001.
Mentions: Monolayers of Caco-2 and T84 cells were treated with the three potential probiotic bacterial strains in combination with pathogenic E. coli strains in order to determine the effect of probiotic on either of these pro-inflammatory signalling events. NF-κB signalling in Caco-2 cells was upregulated by 491% (p = 0.002) compared to controls following infection with E. coli K12 and by 247% (p = 0.002) following AIEC HM427 treatment. However, this induction was reduced by the addition of all three probiotic strains: L. acidophilus ASF360 reduced the NF-κB response to E. coli K12 by 50% (p = 0.006) and AIEC HM427 by 28% (p = 0.007); S. thermophilus NCIMB 41856 reduced the NF-κB response to E. coli K12 by 58% (p = 0.002) and AIEC HM427 by 49% (p = 0.005); and E. coli Nissle 1917 reduced the NF-κB response to E. coli K12 by 79% (p = 0.0005) and AIEC HM427 by 68% (p = 0.004) (Figure 2A). S. thermophilus NCIMB 41856 also reduced NF-κB signalling by 48% in untreated cells (p = 0.003) (Figure 2A). Following NF-κB signalling, IL-8 production was increased by 1566% in response to E. coli K12 (p = 0.001), 1104% in response to AIEC HM427 (p = 0.004) and 363% in response to HM615 (p = 0.02), as well as a 1498% increase following addition of E. coli Nissle 1917 (p = 0.004). The IL-8 response to E. coli K12 was reduced by 22% following addition of S. thermophilus NCIMB 41856 (p = 0.02) and the response to AIEC HM427 was reduced by both L. acidophilus ASF360 and S. thermophilus NCIMB 41856 by 17% (p = 0.02) and 39% (p = 0.02) respectively (Figure 2B).

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