Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
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Edited by Todd R. Klaenhammer, North Carolina State University, Raleigh, NC, and approved August 13, 2010 (received for review January 29, 2010)
Article Figures & SI
Figures
- Fig. 1.
Dendrogram visualizing similarity and distances between the microarray data. The second number of the array identification indicates each individual volunteer. Note that the clusters, representing the array datasets with higher similarity, are basically consisting of data from individual volunteers, not interventions. Clusters representing individuals are boxed. From the dendrogram, it is apparent that the differences between individuals, represented by the node-to-node distances, are larger than the differences between interventions.
- Fig. 2.
Ingenuity protein–protein interaction network reflecting immune response-related transcriptome changes after consumption of L. acidophilus. Nodes in the interaction network are encoded by differentially expressed genes with the following functional annotations: immune response, infectious disease, and inflammatory disease. Interactions between the nodes represent protein–protein interactions (binding and phosphorylation) as well as regulation of gene transcription by transcription factors. Chemokines without direct interactions are depicted as well (upper right corner). Transcriptional information was projected onto the interaction map such that up-regulated genes are depicted in shades of red and down-regulated genes are in shades of green. From this interaction map, it can be seen that the up-regulated transcription factors STAT3, CCAAT/enhancer binding protein (C/EBP), beta (CEBPB), CEBPD, RELB, and NFKB2 connect, by multiple outward pointing arrows, to multiple nodes. These nodes represent downstream genes that are known to be regulated by these transcription factors. Genes that participate in the immuno-regulatory pathways, NF-κB and IL-10 signaling, are indicated by the blue lines.
- Fig. 3.
Heat map visualization of transcriptional change (fold change) and coefficients of variation (CoVars) for those genes that encode the proteins that are represented in the interaction network depicted in Fig. 2. The values listed in the table correspond with the heat-map colors. An expression value represented in black indicates that the respective gene was not differentially expressed. From this, it can be seen that genes with functional annotations relating to the immune response are mainly regulated on consumption of L. acidophilus, not on consumption of the other two lactobacilli. Note that genes encoding proteins that occupy more central regulatory functions in the network of Fig. 2 tend to have lower CoVars compared with genes that encode proteins with more acute functions such as chemokines. This trend is also apparent in the responses to the other two lactobacilli (SI Appendix, SI Results, Figs. S8 and S9, and Tables S11 and S12).
Tables
- Table 1.
Connectivity-map analysis results for the interventions of healthy adults with L. acidophilus Lafti L10, L. casei CRL-431, and L. rhamnosus GG
Species Compound (medicine) Corr* Biochemical interactions Therapeutic usage L. acidophilus Phenoxy-benzamine (Dibenzyline) + Antagonist of α-adrenergic receptor activity Antihypertension (e.g., of blood vessels) 8-azaguanine + Guanine antagonist Treatment of acute leukemia Fludrocortisone (Florinef) + Synthetic corticosteroid Replacement for aldosterone hormone in adrenal insufficiency Luteolin (Lutimax) + Flavonoid Antioxidant, free-radical scavenger, preventer of inflammation, and immune-system modulator Tracazolate + Anxiolytic drug, modulation of GABA receptors Anxiolytic and anticonvulsant effects L. casei Adiphenine (Trasentine) − Cholinergic blocking agent (Smooth) muscle relaxant; can cause constipation Nadolol (Corgard) − Antagonist of β-adrenergic receptor activity Inhibition of water retention and vasoconstriction, may increase levels of plasma triglycerides and decrease HDL cholesterol Viomycin (Viocin) − Antibiotic; translation inhibitor Treatment of tuberculosis Etiocholanolone − Ketosteroid, metabolite of testosterone Causes fever, immunostimulation, and leukocytosis Medrysone (Medrisone Opththalmic, HMS) + Corticosteroid Treatment of (eye) inflammation caused by infections or injury L. rhamnosus Proscillaridin (Talusin) − Glycoside steroid, endogenous digitoxin-like Increase heart contractions; Na+/K+ ATPase inhibitor Cephaeline (related to emetine) + Alkaloid Promotes bowel movement, emetic, amoebicide Helveticoside − Glycoside Digitalis-like; Na+/K+ ATPase inhibitor Emetine + Alkaloid; protein synthesis inhibitor in eukaryotic cells Emetic, amoebicide; treatment of herpes zoster, protection against T-2 mycotoxin H-7 − Protein kinase C inhibitor Induction of apoptosis in human neuroblastoma cells through a p53-dependent pathway ↵*Correlation, indicated with a + or − sign, indicates if the corresponding compound induced (+) or repressed (−) the expression of the probe sets that feature as gene signatures in the ConnMap database. Statistics supporting significance and specificity of similarity can be found in SI Appendix, Table S5.
Data supplements
Supporting Information
Files in this Data Supplement:
Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways
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