Source: AGRICULTURAL RESEARCH SERVICE submitted to
PREVENTION AND TREATMENT OF MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS (MAP) INFECTION IN MICE BY LACTOBACILLUS ACIDOPHILUS NP51
Sponsoring Institution
Agricultural Research Service/USDA
Project Status
ACTIVE
Funding Source
Reporting Frequency
Annual
Accession No.
0413281
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jul 9, 2008
Project End Date
Jun 30, 2011
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Project Director
STABEL J R
Recipient Organization
AGRICULTURAL RESEARCH SERVICE
(N/A)
AMES,IA 50010
Performing Department
(N/A)
Non Technical Summary
(N/A)
Animal Health Component
30%
Research Effort Categories
Basic
40%
Applied
30%
Developmental
30%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113310100030%
3113410104070%
Goals / Objectives
1. To evaluate effects of Lactobacillus acidophilus NP51 on host immune response. 2. To evaluate effects of NP51 on the prevention of MAP infection. 3. To evaluate effects of NP51 on the treatment of MAP infection.
Project Methods
Mice will be fed NP51 before and after challenge with MAP to ascertain the effectiveness in prevention or treatment of the infection and colonization of target tissues such as spleen, ileum, and mesenteric lymph nodes. The host response to NP51 will be determined by evaluation of cytokine induction alone and in tandem with MAP infection.

Progress 10/01/10 to 09/30/11

Outputs
Progress Report Objectives (from AD-416) 1. To evaluate effects of Lactobacillus acidophilus NP51 on host immune response. 2. To evaluate effects of NP51 on the prevention of MAP infection. 3. To evaluate effects of NP51 on the treatment of MAP infection. Approach (from AD-416) Mice will be fed NP51 before and after challenge with MAP to ascertain the effectiveness in prevention or treatment of the infection and colonization of target tissues such as spleen, ileum, and mesenteric lymph nodes. The host response to NP51 will be determined by evaluation of cytokine induction alone and in tandem with MAP infection. The objective of this collaborative agreement was to examine whether feeding a probiotic, Lactobacillus acidophilus strain NP51, to mice challenged with Mycobacterium avium subspecies paratuberculosis (MAP), would increase cell-mediated immune responses and decrease progression of MAP infection. After conducting a preliminary experiment to optimize the dose of the probiotic, mice were fed the probiotic for 45 days before they were challenged with live or heat-killed MAP for an additional 135 days. Overall, feeding the probiotic significantly increased the frequency of CD8+ cytotoxic T cells in spleens of mice infected with viable MAP. Most importantly, MAP burden was decreased in the mesenteric lymph nodes, livers, and spleens of mice fed probiotic compared to the MAP-infected controls. These results suggest that feeding probiotic modifies the immune responses and prevents progression of MAP infection in the mouse model. Incorporation of this probiotic may reduce the incidence of Johne�s disease in dairy cattle. A study was conducted to determine effects of feeding the probiotic on general health of lactating dairy cows. Feeding the probiotic did not affect milk production but did demonstrate decreases in somatic cell counts. In addition, molar concentrations of volatile fatty acids in the rumen were observed, indicating an increase in energy availability. Results suggest the probiotic has potential to improve nutrient digestibility, energy availability, and udder health with good implications to dairy cows in other stages of lactation and the transition period. Progress was monitored via monthly phone calls, e-mails and meetings every 2-3 months.

Impacts
(N/A)

Publications


    Progress 10/01/09 to 09/30/10

    Outputs
    Progress Report Objectives (from AD-416) 1. To evaluate effects of Lactobacillus acidophilus NP51 on host immune response. 2. To evaluate effects of NP51 on the prevention of MAP infection. 3. To evaluate effects of NP51 on the treatment of MAP infection. Approach (from AD-416) Mice will be fed NP51 before and after challenge with MAP to ascertain the effectiveness in prevention or treatment of the infection and colonization of target tissues such as spleen, ileum, and mesenteric lymph nodes. The host response to NP51 will be determined by evaluation of cytokine induction alone and in tandem with MAP infection. This collaborative research project encompasses measures to ensure animal health through the control and management of the disease by improving knowledge of host immunity during infection. Feeding the probiotic, NP51, will allow us to determine if altering the gut ecology of the host will prevent colonization of Mycobacterium avium subspecies paratuberculosis (MAP) in the small intestine and associated tissues. As part of the study, we will attempt to determine if the mechanism of action of the probiotic is correlated with altered host immunity, both in the peripheral blood and at the site of infection. Gaining a further understanding into the host immune responses to MAP infection will add insight into the pathogenesis of this bacterium, providing us with information that will be helpful in potential treatments for infection in dairy cattle. Results from the first mouse study evaluating the appropriate dose of the probiotic to feed mice were analyzed. Feeding the highest level of probiotic did not affect the health of the mice. A second study was completed in which the probiotic was fed to mice prior to challenge with live MAP. Data demonstrate that the probiotic was very effective in preventing colonization of MAP in tissues of mice. In addition, the probiotic appeared to enhance T cell-mediated immunity in MAP-infected mice. These data will be useful in determining if probiotics can be used for the treatment and prevention of paratuberculosis in cattle. Progress will be monitored by associated parties via monthly phone calls and/or e-mails and meetings every 2-3 months.

    Impacts
    (N/A)

    Publications


      Progress 10/01/08 to 09/30/09

      Outputs
      Progress Report Objectives (from AD-416) 1. To evaluate effects of Lactobacillus acidophilus NP51 on host immune response. 2. To evaluate effects of NP51 on the prevention of MAP infection. 3. To evaluate effects of NP51 on the treatment of MAP infection. Approach (from AD-416) Mice will be fed NP51 before and after challenge with MAP to ascertain the effectiveness in prevention or treatment of the infection and colonization of target tissues such as spleen, ileum, and mesenteric lymph nodes. The host response to NP51 will be determined by evaluation of cytokine induction alone and in tandem with MAP infection. Significant Activities that Support Special Target Populations This collaborative research project between ARS National Animal Disease Center (NADC) and the Department of Animal Science, Iowa State University, encompasses measures to ensure animal health through the control and management of the disease by improving knowledge of host immunity during infection. Feeding the probiotic, NP51, will allow us to determine if altering the gut ecology of the host will prevent colonization of Mycobacterium avium subspecies paratuberculosis (MAP) in the small intestine and associated tissues. As part of the study, we will attempt to determine if the mechanism of action of the probiotic is correlated with altered host immunity, both in the peripheral blood and at the site of infection. Gaining a further understanding into the host immune responses to MAP infection will add insight into the pathogenesis of this bacterium, providing us with information that will be helpful in potential treatments for infection in dairy cattle. At the present time, one mouse study has been completed to evaluate the effects of feeding different levels of the probiotic on host immune responses and pathology of tissues. Feeding the highest level of probiotic did not affect the health of the mice. Data analyses are underway to determine effects of the probiotic on cell populations and immune cell function. A second study was completed in which the probiotic was fed to mice prior to challenge with live MAP. Data analyses are currently underway for this experiment as well. These data will be useful in determining if probiotics can be used for the treatment and prevention of paratuberculosis in cattle. Progress will be monitored by associated parties via monthly phone calls and/or e-mails and meetings every 2-3 months.

      Impacts
      (N/A)

      Publications


        Progress 10/01/07 to 09/30/08

        Outputs
        Progress Report Objectives (from AD-416) 1. To evaluate effects of Lactobacillus acidophilus NP51 on host immune response. 2. To evaluate effects of NP51 on the prevention of MAP infection. 3. To evaluate effects of NP51 on the treatment of MAP infection. Approach (from AD-416) Mice will be fed NP51 before and after challenge with MAP to ascertain the effectiveness in prevention or treatment of the infection and colonization of target tissues such as spleen, ileum, and mesenteric lymph nodes. The host response to NP51 will be determined by evaluation of cytokine induction alone and in tandem with MAP infection. Significant Activities that Support Special Target Populations This collaborative research project between ARS National Animal Disease Center (NADC) and the Department of Animal Science, Iowa State University, encompasses measures to ensure animal health through the control and management of the disease by improving knowledge of host immunity during infection. Feeding the probiotic, NP51, will allow us to determine if altering the gut ecology of the host will prevent colonization of Mycobacterium avium subspecies paratuberculosis (MAP) in the small intestine and associated tissues. As part of the study, we will attempt to determine if the mechanism of action of the probiotic is correlated with altered host immunity, both in the peripheral blood and at the site of infection. Gaining a further understanding into the host immune responses to MAP infection will add insight into the pathogenesis of this bacterium, providing us with information that will be helpful in potential treatments for infection in dairy cattle. At the present time, one mouse study has been completed to evaluate the effects of feeding different levels of the probiotic on host immune responses and pathology of tissues. Feeding the highest level of probiotic did not affect the health of the mice. Data analyses are underway to determine effects of the probiotic on cell populations and immune cell function. These data will be useful in determining if probiotics can be used for the treatment and prevention of paratuberculosis in cattle. Progress will be monitored by associated parties via monthly phone calls and/or e-mails and meetings every 2-3 months. This project addresses NP 103, component 6, problem statement 6A.

        Impacts
        (N/A)

        Publications