Location: Diet, Genomics and Immunology Laboratory2012 Annual Report
1a. Objectives (from AD-416):
This project will characterize the whole blood response of healthy subjects to LGG using a select panel of cytokine and chemokine markers detected by real time PCR, and a more robust evaluation of transcriptomic changes detected prior to during and after feeding of LGG. Associations will be developed with the levels of LGG, Bifidobacterium and Lactobacillus spp. in the feces and naso-pharynx. The cooperator is interested in detecting LGG and evaluating the clinical effects in healthy adults fed LGG as part of a Phase I study to demonstrate safety strain.
1b. Approach (from AD-416):
ARS will acquire nucleic acids from whole blood PaxGene and fecal samples from treated subjects to detect specific bacterial genes and patterns of whole blood gene expression as was developed in-house using a pig model. The analysis will include Illumina-based deep sequencing of samples from subjects prior to feeding LGG, after 28 days of feeding, and 28 days after cessation of feeding. This information will be used by both ARS and the Cooperator to jointly develop studies that focus on the effects of probiotic bacteria LGG as a vaccine adjuvant. The Cooperator will collate this information with a comprehensive clinical evaluation of the subjects, including routine anaerobic culture – LGG recovery in naso-pharynx and GI tract.
3. Progress Report:
To establish safety and tolerability of Lactobacillus rhamnossus (LGG) ATCC 53103, 50 adult patients at Massachusetts General Hospital received a daily oral dose of LGG for 6 months with a six month follow-up period. Assessment of safety was determined by medical examination during and after the intervention and measurement of probiotic colonization was tracked by molecular detection of LGG in fecal samples collected at different times during a 12 month longitudinal study. Gene expression analysis using whole blood samples will indicate changes in gene expression associated with probiotic intervention and immune modulation. During FY-12 clinical samples from fifteen healthy elderly patients receiving LGG were also received and processed. Microbiota changes of commensal bacteria in fecal samples were tracked by real-time PCR. Whole transcriptome analysis in blood using next generation sequence technology will be used to detect biomarkers associated with probiotic colonization and immune modulatory effect.