Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial

Abstract Probiotics have been widely tested for their effect on mental well-being, albeit with heterogeneous outcomes. Direct and indirect effects through the gut microbiome might lie at the basis of these observations. Here, in a post-hoc analysis, we assessed the effect of 4-week consumption of a...

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Main Authors: Jorge Francisco Vázquez-Castellanos, Lucas Ferreira Maciel, Lucas Wauters, Ann Gregory, Lukas Van Oudenhove, Karlien Geboers, Kristin Verbeke, Tamara Smokvina, Jan Tack, Tim Vanuytsel, Muriel Derrien, Jeroen Raes
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Biofilms and Microbiomes
Online Access:https://doi.org/10.1038/s41522-025-00776-w
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author Jorge Francisco Vázquez-Castellanos
Lucas Ferreira Maciel
Lucas Wauters
Ann Gregory
Lukas Van Oudenhove
Karlien Geboers
Kristin Verbeke
Tamara Smokvina
Jan Tack
Tim Vanuytsel
Muriel Derrien
Jeroen Raes
author_facet Jorge Francisco Vázquez-Castellanos
Lucas Ferreira Maciel
Lucas Wauters
Ann Gregory
Lukas Van Oudenhove
Karlien Geboers
Kristin Verbeke
Tamara Smokvina
Jan Tack
Tim Vanuytsel
Muriel Derrien
Jeroen Raes
author_sort Jorge Francisco Vázquez-Castellanos
collection DOAJ
description Abstract Probiotics have been widely tested for their effect on mental well-being, albeit with heterogeneous outcomes. Direct and indirect effects through the gut microbiome might lie at the basis of these observations. Here, in a post-hoc analysis, we assessed the effect of 4-week consumption of a probiotic candidate strain on the gut microbiome in students exposed to academic stress. Healthy students were randomized to consume a fermented milk product with Lacticaseibacillus rhamnosus CNCM I-3690 (N = 39) or an acidified non-fermented milk product (N = 40) twice daily for 4 weeks before academic exams. The gut microbiome was analysed by Quantitative Microbiome Profiling based on 16S rRNA gene amplicon and shotgun metagenomic sequencing. Stress and anxiety were assessed using both objective and self-reported markers. Changes of alpha-diversity markers and community shifts from baseline (beta diversity) were lower in L. rhamnosus treated individuals over controls, suggesting lower overall changes of gut microbiota during psychological stress in the Probiotic group. The intake of L. rhamnosus CNCM I-3690 induced differential abundance of some species, such as the maintenance of the quantitative abundance of Ruminococcus bicirculans, and co-varied with species, which differed according to visits (i.e., stress level), suggesting a potential beneficial effect of the strain before the highest increase of stress level. The higher quantitative abundance of F. prausnitzii induced by the probiotic intake was associated with lowered self-reported anxiety levels before the exam. Functional analysis revealed minor changes upon intake of the probiotic strain. Taken together, using a quantitative framework, we found that L. rhamnosus CNCM I-3690 has a potential effect on gut microbiome response to stress, although further studies are needed to better understand the precise interaction.
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spelling doaj-art-8f65b90fdbad4fceb83baca264f29bc82025-08-20T04:01:53ZengNature Portfolionpj Biofilms and Microbiomes2055-50082025-07-0111111210.1038/s41522-025-00776-wProbiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trialJorge Francisco Vázquez-Castellanos0Lucas Ferreira Maciel1Lucas Wauters2Ann Gregory3Lukas Van Oudenhove4Karlien Geboers5Kristin Verbeke6Tamara Smokvina7Jan Tack8Tim Vanuytsel9Muriel Derrien10Jeroen Raes11Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU LeuvenDepartment of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU LeuvenDepartment of Gastroenterology and Hepatology, University Hospitals LeuvenDepartment of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU LeuvenTranslational Research in Gastrointestinal Disorders (TARGID), department of Chronic Diseases and Metabolism (ChroMeta), KU LeuvenDepartment of Gastroenterology and Hepatology, University Hospitals LeuvenTranslational Research in Gastrointestinal Disorders (TARGID), department of Chronic Diseases and Metabolism (ChroMeta), KU LeuvenDanone Research & InnovationDepartment of Gastroenterology and Hepatology, University Hospitals LeuvenDepartment of Gastroenterology and Hepatology, University Hospitals LeuvenDanone Research & InnovationDepartment of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU LeuvenAbstract Probiotics have been widely tested for their effect on mental well-being, albeit with heterogeneous outcomes. Direct and indirect effects through the gut microbiome might lie at the basis of these observations. Here, in a post-hoc analysis, we assessed the effect of 4-week consumption of a probiotic candidate strain on the gut microbiome in students exposed to academic stress. Healthy students were randomized to consume a fermented milk product with Lacticaseibacillus rhamnosus CNCM I-3690 (N = 39) or an acidified non-fermented milk product (N = 40) twice daily for 4 weeks before academic exams. The gut microbiome was analysed by Quantitative Microbiome Profiling based on 16S rRNA gene amplicon and shotgun metagenomic sequencing. Stress and anxiety were assessed using both objective and self-reported markers. Changes of alpha-diversity markers and community shifts from baseline (beta diversity) were lower in L. rhamnosus treated individuals over controls, suggesting lower overall changes of gut microbiota during psychological stress in the Probiotic group. The intake of L. rhamnosus CNCM I-3690 induced differential abundance of some species, such as the maintenance of the quantitative abundance of Ruminococcus bicirculans, and co-varied with species, which differed according to visits (i.e., stress level), suggesting a potential beneficial effect of the strain before the highest increase of stress level. The higher quantitative abundance of F. prausnitzii induced by the probiotic intake was associated with lowered self-reported anxiety levels before the exam. Functional analysis revealed minor changes upon intake of the probiotic strain. Taken together, using a quantitative framework, we found that L. rhamnosus CNCM I-3690 has a potential effect on gut microbiome response to stress, although further studies are needed to better understand the precise interaction.https://doi.org/10.1038/s41522-025-00776-w
spellingShingle Jorge Francisco Vázquez-Castellanos
Lucas Ferreira Maciel
Lucas Wauters
Ann Gregory
Lukas Van Oudenhove
Karlien Geboers
Kristin Verbeke
Tamara Smokvina
Jan Tack
Tim Vanuytsel
Muriel Derrien
Jeroen Raes
Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial
npj Biofilms and Microbiomes
title Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial
title_full Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial
title_fullStr Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial
title_full_unstemmed Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial
title_short Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial
title_sort probiotic mediated modulation of gut microbiome in students exposed to academic stress a randomized controlled trial
url https://doi.org/10.1038/s41522-025-00776-w
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