Effects of Lactobacillus GG on genes expression pattern in small bowel mucosa.
OBJECTIVE
Probiotics have been used for cure and prevention of several clinical conditions. However, further insights into the mechanism of action are needed to understand the rationale of their use. The aim of this study was to investigate the influence of Lactobacillus GG on the genetic expression patterns in the small bowel mucosa.


METHODS
Six male patients (38+/-5 years) with endoscopically proven oesophagitis were enrolled. All patients were treated for 1 month with esomeprazole and randomised to receive Lactobacillus GG or placebo. After 1 month of treatment, upper endoscopy was repeated. Biopsies of the duodenal mucosa were taken prior to and after the treatment, and the genes expression patterns were assessed using GeneChip Human U133A array. Genes with significant expression changes were selected and analysed to identify specific cellular pathways modified by Lactobacillus GG. To support the array data, 10 target genes were studied using Syber-Green PCR.


RESULTS
Microarray analysis showed that Lactobacillus GG administration determined the up- and down-regulation of 334 and 92 genes, respectively. Real-time PCR confirmed the reliability of the analysis. Lactobacillus GG mainly affected the expression of genes involved in immune response and inflammation (TGF-beta and TNF family members, cytokines, nitric oxide synthase 1, defensin alpha 1), apoptosis, cell growth and cell differentiation (cyclins and caspases, oncogenes), cell-cell signalling (ICAMs and integrins), cell adhesion (cadherins), signal transcription and transduction.


CONCLUSIONS
These data indicate that administration of Lactobacillus GG is associated with a complex genetic response of the duodenal mucosa, reflected by the up- and down-regulation of several genes involved in specific cellular pathways.
Di Caro
S
S
Department of Gastroenterology, Catholic University of Rome, Largo Gemelli 1, 00168 Rome, Italy.
Tao
H
H
Grillo
A
A
Elia
C
C
Gasbarrini
G
G
Sepulveda
A R
AR
Gasbarrini
A
A
D000328:Adult; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells; D004941:Esophagitis / Q000188:drug therapy / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007778:Lactobacillus; D008297:Male; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D020411:Oligonucleotide Array Sequence Analysis; D019936:Probiotics / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II