Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial
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 b...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-11-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19490976.2020.1854639 |
| _version_ | 1818336921283198976 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jette Bornholdt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T14:47:00Z |
| format | Article |
| id | doaj.art-9243eb2759cc40ca901701ba70e54b10 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-12-13T14:47:00Z |
| publishDate | 2020-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-9243eb2759cc40ca901701ba70e54b102022-12-21T23:41:27ZengTaylor & Francis GroupGut Microbes1949-09761949-09842020-11-0112110.1080/19490976.2020.18546391854639Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trialJette Bornholdt0Christa Broholm1Yun Chen2Alfredo Rago3Stine Sloth4Jakob Hendel5Cathrine Melsæther6Christina V. Müller7Maria Juul Nielsen8Jesper Strickertsson9Lars Engelholm10Kristoffer Vitting-Seerup11Kim B. Jensen12Adam Baker13Albin Sandelin14University of CopenhagenUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenHerlev Hospital, University of CopenhagenHerlev Hospital, University of CopenhagenHuman Health DiscoveryUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenHuman Health DiscoveryUniversity of CopenhagenThe 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.http://dx.doi.org/10.1080/19490976.2020.1854639lactobacillus rhamnosus ggimmediate in vivo effectprobioticshuman transcriptomicsb cell activation |
| spellingShingle | 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 Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial Gut Microbes lactobacillus rhamnosus gg immediate in vivo effect probiotics human transcriptomics b cell activation |
| title | Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial |
| title_full | Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial |
| title_fullStr | Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial |
| title_full_unstemmed | Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial |
| title_short | Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial |
| title_sort | personalized b cell response to the lactobacillus rhamnosus gg probiotic in healthy human subjects a randomized trial |
| topic | lactobacillus rhamnosus gg immediate in vivo effect probiotics human transcriptomics b cell activation |
| url | http://dx.doi.org/10.1080/19490976.2020.1854639 |
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