Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo

Department of Internal Medicine, Division of Gastroenterology & Hepatology, Maastricht University, Maastricht, The Netherlands.
BMC Genomics (Impact Factor: 3.99). 02/2008; 9(1):374. DOI: 10.1186/1471-2164-9-374
Source: PubMed


There is limited knowledge on the extent and dynamics of the mucosal response to commensal and probiotic species in the human intestinal lumen. This study aimed to identify the acute, time-dependent responses of intestinal mucosa to commensal Lactobacillus plantarum WCFS1 in vivo in two placebo-controlled human intervention studies in healthy volunteers. Transcriptional changes in duodenal mucosa upon continuous intraduodenal infusion of L. plantarum WCFS1 for one- and six h, respectively, were studied using oro- and nasogastric intubations with dedicated orogastric catheters and tissue sampling by standard flexible gastroduodenoscopy.
One- and six-h exposure of small intestinal mucosa to L. plantarum WCFS1 induced differential expression of 669 and 424 gene reporters, respectively. While short-term exposure to L. plantarum WCFS1 inhibited fatty acid metabolism and cell cycle progression, cells switched to a more proliferative phase after prolonged exposure with an overall expression profile characterized by upregulation of genes involved in lipid metabolism, cellular growth and development. Cell death and immune responses were triggered, but cell death-executing genes or inflammatory signals were not expressed. Proteome analysis showed differential expression of several proteins. Only the microsomal protein 'microsomal triglyceride transfer protein' was regulated on both the transcriptional and the protein level in all subjects.
Overall, this study showed that intestinal exposure to L. plantarum WCFS1 induced consistent, time-dependent transcriptional responses in healthy intestinal mucosa. This extensive exploration of the human response to L. plantarum WCFS1 could eventually provide molecular support for specific or probiotic activity of this strain or species, and exemplifies the strength of the applied technology to identify the potential bio-activity of microbes in the human intestine.

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    • "In agreement with other in vivo studies conducted with L. plantarum strain WCFS1 in humans (Bujalance et al. 2007; Troost et al. 2008; van Baarlen et al. 2009), our results also indicate that L. plantarum regulates the influx and/or enhances the proliferation and differentiation of lymphocytes in the intestine without inducing NFKB-mediated inflammatory processes. According to our predictions , and indicated by up-regulation of cell-specific marker genes, gene expression in CD4? lymphocytes, CD14? monocytes, adipocytes and B cells were regulated in response to L. plantarum 299v. "
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    • "Lactobacilli are generally viewed as conferring beneficial biological effects to the host. For example, in the gastrointestinal tract, lactobacilli promote immune stimulation and reinforcement of mucosal defence [7]. Amongst the lactobacilli, Lactobacillus fermentum is a common inhabitant of the gastrointestinal tract [8], including the oral cavity [9,10]. "
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    • "Treatment with L. plantarum WCFS1 was associated with profound skewing towards an immune regulatory phenotype within systemic T helper cells. These results are in line with studies that demonstrate L. plantarum-induced immune regulation in vitro [63], [64] as well as in the duodenum [38], [65]. The observed changes were accompanied by the infiltration of intestinal CD103+ DCs in the spleen. "
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