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


RESULTS
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.


CONCLUSIONS
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.
Troost
Freddy J
FJ
Department of Internal Medicine, Division of Gastroenterology & Hepatology, Maastricht University, Maastricht, The Netherlands. f.troost@intmed.unimaas.nl
van Baarlen
Peter
P
Lindsey
Patrick
P
Kodde
Andrea
A
de Vos
Willem M
WM
Kleerebezem
Michiel
M
Brummer
Robert-Jan M
RJ
D016923:Cell Death / Q000235:genetics; D049109:Cell Proliferation; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006262:Health; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology*; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology; D048191:Lactiplantibacillus plantarum / Q000502:physiology*; D008055:Lipids / Q000096:biosynthesis / Q000235:genetics; D010477:Perfusion; D019936:Probiotics; D040901:Proteomics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D005227:Fatty Acids; D008055:Lipids; D014157:Transcription Factors