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

Bornholdt, Jette ; Broholm, Christa ; Chen, Yun ; Rago, Alfredo LU ; Sloth, Stine ; Hendel, Jakob ; Melsæther, Cathrine ; Müller, Christina V ; Juul Nielsen, Maria and Strickertsson, Jesper , et al. (2020) In Gut microbes 12(1). p.1-14
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Adult, B-Lymphocytes/immunology, Cross-Over Studies, DNA, Bacterial/genetics, Female, Gastrointestinal Microbiome/drug effects, Gene Expression/genetics, Gene Expression Regulation/genetics, Healthy Volunteers, Humans, Jejunum/immunology, Lactobacillus rhamnosus/immunology, Lymphocyte Activation/immunology, Male, Probiotics/pharmacology, Sex Factors, Young Adult
in
Gut microbes
volume
12
issue
1
article number
e1854639
pages
1 - 14
publisher
Taylor & Francis
external identifiers
  • scopus:85097120980
  • pmid:33274667
ISSN
1949-0976
DOI
10.1080/19490976.2020.1854639
language
English
LU publication?
no
id
dc790a1d-137f-401f-8874-4d3b4854594f
date added to LUP
2022-01-26 12:15:59
date last changed
2024-05-18 23:07:56
@article{dc790a1d-137f-401f-8874-4d3b4854594f,
  abstract     = {{<p>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.</p>}},
  author       = {{Bornholdt, Jette and Broholm, Christa and Chen, Yun and Rago, Alfredo and Sloth, Stine and Hendel, Jakob and Melsæther, Cathrine and Müller, Christina V and Juul Nielsen, Maria and Strickertsson, Jesper and Engelholm, Lars and Vitting-Seerup, Kristoffer and Jensen, Kim B and Baker, Adam and Sandelin, Albin}},
  issn         = {{1949-0976}},
  keywords     = {{Adult; B-Lymphocytes/immunology; Cross-Over Studies; DNA, Bacterial/genetics; Female; Gastrointestinal Microbiome/drug effects; Gene Expression/genetics; Gene Expression Regulation/genetics; Healthy Volunteers; Humans; Jejunum/immunology; Lactobacillus rhamnosus/immunology; Lymphocyte Activation/immunology; Male; Probiotics/pharmacology; Sex Factors; Young Adult}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{1--14}},
  publisher    = {{Taylor & Francis}},
  series       = {{Gut microbes}},
  title        = {{Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects : a randomized trial}},
  url          = {{http://dx.doi.org/10.1080/19490976.2020.1854639}},
  doi          = {{10.1080/19490976.2020.1854639}},
  volume       = {{12}},
  year         = {{2020}},
}