title: Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study.
abstract: We examined gene expression of whole blood cells (WBC) from 11 healthy elderly volunteers participating on a Phase I open label study before and after oral treatment with Lactobacillus rhamnosus GG-ATCC 53103 (LGG)) using RNA-sequencing (RNA-Seq). Elderly patients (65-80 yrs) completed a clinical assessment for health status and had blood drawn for cellular RNA extraction at study admission (Baseline), after 28 days of daily LGG treatment (Day 28) and at the end of the study (Day 56) after LGG treatment had been suspended for 28 days. Treatment compliance was verified by measuring LGG-DNA copy levels detected in host fecal samples. Normalized gene expression levels in WBC RNA were analyzed using a paired design built within three analysis platforms (edgeR, DESeq2 and TSPM) commonly used for gene count data analysis. From the 25,990 transcripts detected, 95 differentially expressed genes (DEGs) were detected in common by all analysis platforms with a nominal significant difference in gene expression at Day 28 following LGG treatment (FDR<0.1; 77 decreased and 18 increased). With a more stringent significance threshold (FDR<0.05), only two genes (FCER2 and LY86), were down-regulated more than 1.5 fold and met the criteria for differential expression across two analysis platforms. The remaining 93 genes were only detected at this threshold level with DESeq2 platform. Data analysis for biological interpretation of DEGs with an absolute fold change of 1.5 revealed down-regulation of overlapping genes involved with Cellular movement, Cell to cell signaling interactions, Immune cell trafficking and Inflammatory response. These data provide evidence for LGG-induced transcriptional modulation in healthy elderly volunteers because pre-treatment transcription levels were restored at 28 days after LGG treatment was stopped. To gain insight into the signaling pathways affected in response to LGG treatment, DEG were mapped using biological pathways and genomic data mining packages to indicate significant biological relevance.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01274598.
authors: Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
authors: Gloria
authors: G
authors: Solano-Aguilar
authors: Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
authors: Aleksey
authors: A
authors: Molokin
authors: Division of Global Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Christine
authors: C
authors: Botelho
authors: Division of Global Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Anne-Maria
authors: AM
authors: Fiorino
authors: Statistics Group, Northeast Area, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
authors: Bryan
authors: B
authors: Vinyard
authors: Animal Genomics and Improvement Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
authors: Robert
authors: R
authors: Li
authors: Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
authors: Celine
authors: C
authors: Chen
authors: Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
authors: Joseph
authors: J
authors: Urban
authors: Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
authors: Harry
authors: H
authors: Dawson
authors: Division of Global Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Irina
authors: I
authors: Andreyeva
authors: Division of Global Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Miriam
authors: M
authors: Haverkamp
authors: Division of Global Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Patricia L
authors: PL
authors: Hibberd
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D052201:Lacticaseibacillus rhamnosus / Q000502:physiology*; D019936:Probiotics / Q000009:adverse effects / Q000494:pharmacology*; D017423:Sequence Analysis, RNA; D013997:Time Factors