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Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model.

Thomas DJ, Husmann RJ, Villamar M, Winship TR, Buck RH, Zuckermann FA - PLoS ONE (2011)

Bottom Line: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans.

View Article: PubMed Central - PubMed

Affiliation: Abbott Nutrition, Columbus, Ohio, United States of America. debra.thomas@abbott.com

ABSTRACT

Background: Probiotics have been studied as immunomodulatory agents of allergy. Several human probiotic trials tracking the development of eczema and other forms of allergy have yielded inconsistent results. A recent infant study demonstrated that pre and postnatal Lactobacillus rhamnosus HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported.

Objective: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.

Methods: Allergy was induced by a series of subcutaneous and intratracheal sensitizations with Ascaris suum allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted.

Results: In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.

Conclusions: Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans.

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Skin flare reactions 20 minutes post-intradermal challenge with ASA.ASA-sensitized pigs were intradermally inoculated with the indicated amounts of ASA. After 20 minutes the diameters of the resultant skin flares at the sites of inoculation were measured. Results are expressed as mean ± standard error of mean (SEM) for the respective group of pigs (n = 6). (A) Measurements made on study day 70 for control (triangles) and probiotic-fed (circles) groups. Differences between the responses of the two groups are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) and are not corrected for multiple comparison (Student's t test, unpaired). (B) Measurements made on study days 45 (open triangles) and 70 (filled triangles) for the control group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) (Student's t test, paired). (C) Measurements made on study days 45 (open circles) and 70 (filled circles) for the probiotic-fed group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) (Student's t test, paired).
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pone-0016577-g003: Skin flare reactions 20 minutes post-intradermal challenge with ASA.ASA-sensitized pigs were intradermally inoculated with the indicated amounts of ASA. After 20 minutes the diameters of the resultant skin flares at the sites of inoculation were measured. Results are expressed as mean ± standard error of mean (SEM) for the respective group of pigs (n = 6). (A) Measurements made on study day 70 for control (triangles) and probiotic-fed (circles) groups. Differences between the responses of the two groups are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) and are not corrected for multiple comparison (Student's t test, unpaired). (B) Measurements made on study days 45 (open triangles) and 70 (filled triangles) for the control group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) (Student's t test, paired). (C) Measurements made on study days 45 (open circles) and 70 (filled circles) for the probiotic-fed group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) (Student's t test, paired).

Mentions: In the current study, the extent of skin flare responses in the ASA-sensitized pigs to intradermal challenges with ASA were compared on a group and temporal basis to determine any influence due to probiotic supplementation or additional exposure to the allergen. There was no detectable difference in the degree of skin flare responses between the two groups on study day 45. However, after an interval of 25 days (study day 70) which encompassed two additional exposures to ASA (Figure 1), control pigs developed more severe reactions to allergen doses of 400 µg/mL (p = 0.024), 200 µg/mL (p = 0.005), 100 µg/mL (p = 0.027), 50 µg/mL (p = 0.024), and 25 µg/mL (p = 0.066 [trend]) than probiotic fed animals (Figure 3A); when adjusting for multiple comparisons, the p-value of the 200 µg/mL dose retained significance. Responses between the two groups to lower allergen doses were not significantly different (Figure 3A).


Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model.

Thomas DJ, Husmann RJ, Villamar M, Winship TR, Buck RH, Zuckermann FA - PLoS ONE (2011)

Skin flare reactions 20 minutes post-intradermal challenge with ASA.ASA-sensitized pigs were intradermally inoculated with the indicated amounts of ASA. After 20 minutes the diameters of the resultant skin flares at the sites of inoculation were measured. Results are expressed as mean ± standard error of mean (SEM) for the respective group of pigs (n = 6). (A) Measurements made on study day 70 for control (triangles) and probiotic-fed (circles) groups. Differences between the responses of the two groups are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) and are not corrected for multiple comparison (Student's t test, unpaired). (B) Measurements made on study days 45 (open triangles) and 70 (filled triangles) for the control group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) (Student's t test, paired). (C) Measurements made on study days 45 (open circles) and 70 (filled circles) for the probiotic-fed group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) (Student's t test, paired).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3046142&req=5

pone-0016577-g003: Skin flare reactions 20 minutes post-intradermal challenge with ASA.ASA-sensitized pigs were intradermally inoculated with the indicated amounts of ASA. After 20 minutes the diameters of the resultant skin flares at the sites of inoculation were measured. Results are expressed as mean ± standard error of mean (SEM) for the respective group of pigs (n = 6). (A) Measurements made on study day 70 for control (triangles) and probiotic-fed (circles) groups. Differences between the responses of the two groups are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) and are not corrected for multiple comparison (Student's t test, unpaired). (B) Measurements made on study days 45 (open triangles) and 70 (filled triangles) for the control group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) or ‡ (0.051≤p≤0.1) (Student's t test, paired). (C) Measurements made on study days 45 (open circles) and 70 (filled circles) for the probiotic-fed group. Differences between the responses of this group on day 45 versus day 70 are indicated by * (p≤0.05) (Student's t test, paired).
Mentions: In the current study, the extent of skin flare responses in the ASA-sensitized pigs to intradermal challenges with ASA were compared on a group and temporal basis to determine any influence due to probiotic supplementation or additional exposure to the allergen. There was no detectable difference in the degree of skin flare responses between the two groups on study day 45. However, after an interval of 25 days (study day 70) which encompassed two additional exposures to ASA (Figure 1), control pigs developed more severe reactions to allergen doses of 400 µg/mL (p = 0.024), 200 µg/mL (p = 0.005), 100 µg/mL (p = 0.027), 50 µg/mL (p = 0.024), and 25 µg/mL (p = 0.066 [trend]) than probiotic fed animals (Figure 3A); when adjusting for multiple comparisons, the p-value of the 200 µg/mL dose retained significance. Responses between the two groups to lower allergen doses were not significantly different (Figure 3A).

Bottom Line: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans.

View Article: PubMed Central - PubMed

Affiliation: Abbott Nutrition, Columbus, Ohio, United States of America. debra.thomas@abbott.com

ABSTRACT

Background: Probiotics have been studied as immunomodulatory agents of allergy. Several human probiotic trials tracking the development of eczema and other forms of allergy have yielded inconsistent results. A recent infant study demonstrated that pre and postnatal Lactobacillus rhamnosus HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported.

Objective: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.

Methods: Allergy was induced by a series of subcutaneous and intratracheal sensitizations with Ascaris suum allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted.

Results: In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.

Conclusions: Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans.

Show MeSH
Related in: MedlinePlus