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Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial

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  • Jette Bornholdt
  • Christa Broholm
  • Yun Chen
  • Alfredo Rago
  • Stine Sloth
  • Jakob Hendel
  • Cathrine Melsæther
  • Christina V Müller
  • Maria Juul Nielsen
  • Jesper Strickertsson
  • Lars Engelholm
  • Kristoffer Vitting-Seerup
  • Kim B Jensen
  • Adam Baker
  • Albin Sandelin
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The specific effects of administering live probiotics in the human gut are not well characterized. To this end, we investigated the immediate effect of Lactobacillus rhamnosus GG (LGG) in the jejunum of 27 healthy volunteers 2 h after ingestion using a combination of global RNA sequencing of human biopsies and bacterial DNA sequencing in a multi-visit, randomized, cross-over design (ClinicalTrials.gov number NCT03140878). While LGG was detectable in jejunum after 2 h in treated subjects, the gene expression response vs. placebo was subtle if assessed across all subjects. However, clustering analysis revealed that one-third of subjects exhibited a strong and consistent LGG response involving hundreds of genes, where genes related to B cell activation were upregulated, consistent with prior results in mice. Immunohistochemistry and single cell-based deconvolution analyses showed that this B cell signature likely is due to activation and proliferation of existing B cells rather than B cell immigration to the tissue. Our results indicate that the LGG strain has an immediate effect in the human gut in a subpopulation of individuals. In extension, our data strongly suggest that studies on in vivo probiotic effects in humans require large cohorts and must take individual variation into account.

Original languageEnglish
JournalGut Microbes
Volume12
Issue number1
Pages (from-to)1-14
Number of pages14
ISSN1949-0976
DOIs
Publication statusPublished - 9 Nov 2020

    Research areas

  • B cell activation, human transcriptomics, immediate in vivo effect, Lactobacillus rhamnosus GG, probiotics

ID: 61525216