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Peer-reviewedCC BY 4.0Frontiers in Immunology

Effects of a multistrain probiotic formulation on immune response and microbiome modulation following influenza vaccination in adults: a randomised, triple-blind, placebo-controlled trial

  • Malwina Naghibi1
  • Eric Climent Sanz2
  • Andrea Rodenes-Gavidia2
  • Vanessa Illescas-Armijo2
  • Arnaud Jouve1
  • Vineetha Vijayakumar1
  • Araceli Lamelas2
  • Juan F. Martinez-Blanch2
  • Maria Theodoridou3
  • Panagiota Tselou3
  • Richard Day1
  1. 1R&D Medical, ADM Health & Wellness
  2. 2R&D Biopolis, ADM Nutrition, University of Valencia Science Park (Parc Científic de la Universitat de València)
  3. 3NEXT CRO
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Abstract

Background: Seasonal influenza remains a major global health burden, despite widespread vaccination. Vaccine responsiveness varies considerably between individuals and is increasingly recognised to be influenced by host factors, including the gut microbiome. Probiotics have been proposed as a strategy to modulate microbiome–immune interactions, although their effects on vaccine responses and the underlying microbial mechanisms remain incompletely understood.

Objective: To investigate the effects of a probiotic formulation on immune responses and gut microbiome dynamics following seasonal influenza vaccination in healthy adults.

Methods: In this randomised, triple-blind, placebo-controlled, multicentre trial, 120 healthy adults received either a 14-strain probiotic formulation (14 bacterial strains; 8 × 10 ⁹ CFU/day, 40 mg vitamin C, and 2.5 μg vitamin B ₁₂ ) or placebo for six weeks, commencing three weeks before influenza vaccination and continuing for three weeks afterwards. The primary endpoint was change in strain-specific haemagglutination inhibition (HAI) antibody titres. Secondary endpoints included seroprotection and seroconversion rates, microneutralization activity, serum immune biomarkers and shotgun metagenomic analysis of the gut microbiome.

Results: Vaccination induced the expected increases in HAI antibody titres in both groups, with no significant differences between the active and placebo groups. The probiotic formulation was, however, associated with selective changes in the gut microbiome, including enrichment of the butyrate-producing species Roseburia inulinivorans and alterations in predicted microbial metabolic pathways, without affecting overall microbiome diversity. Participants who achieved seroprotection exhibited distinct compositional and functional microbiome responses to vaccination. These patterns included community-level changes that occurred predominantly in the active group, alongside taxonomic and functional differences associated with seroprotection.

Conclusions: Although supplementation with the probiotic formulation did not increase influenza antibody responses, it did alter the gut microbiome response to vaccination, with selective changes in microbial composition and predicted functional potential while maintaining overall community diversity. Importantly, seroprotection was associated with distinct compositional and functional microbiome adaptations, and community-level changes associated with seroprotection occurred predominantly in the active group. Collectively, these findings support a microbiome-conditioning model in which the probiotic formulation shapes the gut microbiome response during vaccination, rather than acting as a direct immunostimulant. Future studies are required to determine whether these microbiome adaptations contribute causally to vaccine responsiveness.

Clinical Trial Registration: https://clinicaltrials.gov/study/NCT06103994 , identifier NCT06103994

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Cite

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BibTeX
@article{naghibi2026effects,
  title = {{Effects of a multistrain probiotic formulation on immune response and microbiome modulation following influenza vaccination in adults: a randomised, triple-blind, placebo-controlled trial}},
  author = {Malwina Naghibi and Eric Climent Sanz and Andrea Rodenes-Gavidia and Vanessa Illescas-Armijo and Arnaud Jouve and Vineetha Vijayakumar and Araceli Lamelas and Juan F. Martinez-Blanch and Maria Theodoridou and Panagiota Tselou and Richard Day},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = nov,
  doi = {10.3389/fimmu.2026.1952476},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952476/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Effects of a multistrain probiotic formulation on immune response and microbiome modulation following influenza vaccination in adults: a randomised, triple-blind, placebo-controlled trial
AU  - Malwina Naghibi
AU  - Eric Climent Sanz
AU  - Andrea Rodenes-Gavidia
AU  - Vanessa Illescas-Armijo
AU  - Arnaud Jouve
AU  - Vineetha Vijayakumar
AU  - Araceli Lamelas
AU  - Juan F. Martinez-Blanch
AU  - Maria Theodoridou
AU  - Panagiota Tselou
AU  - Richard Day
PY  - 2026
DA  - 2026/11/02
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1952476
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952476/full
AB  - Background: Seasonal influenza remains a major global health burden, despite widespread vaccination. Vaccine responsiveness varies considerably between individuals and is increasingly recognised to be influenced by host factors, including the gut microbiome. Probiotics have been proposed as a strategy to modulate microbiome–immune interactions, although their effects on vaccine responses and the underlying microbial mechanisms remain incompletely understood.  Objective: To investigate the effects of a probiotic formulation on immune responses and gut microbiome dynamics following seasonal influenza vaccination in healthy adults.  Methods: In this randomised, triple-blind, placebo-controlled, multicentre trial, 120 healthy adults received either a 14-strain probiotic formulation (14 bacterial strains; 8 × 10 ⁹ CFU/day, 40 mg vitamin C, and 2.5 μg vitamin B ₁₂ ) or placebo for six weeks, commencing three weeks before influenza vaccination and continuing for three weeks afterwards. The primary endpoint was change in strain-specific haemagglutination inhibition (HAI) antibody titres. Secondary endpoints included seroprotection and seroconversion rates, microneutralization activity, serum immune biomarkers and shotgun metagenomic analysis of the gut microbiome.  Results: Vaccination induced the expected increases in HAI antibody titres in both groups, with no significant differences between the active and placebo groups. The probiotic formulation was, however, associated with selective changes in the gut microbiome, including enrichment of the butyrate-producing species Roseburia inulinivorans and alterations in predicted microbial metabolic pathways, without affecting overall microbiome diversity. Participants who achieved seroprotection exhibited distinct compositional and functional microbiome responses to vaccination. These patterns included community-level changes that occurred predominantly in the active group, alongside taxonomic and functional differences associated with seroprotection.  Conclusions: Although supplementation with the probiotic formulation did not increase influenza antibody responses, it did alter the gut microbiome response to vaccination, with selective changes in microbial composition and predicted functional potential while maintaining overall community diversity. Importantly, seroprotection was associated with distinct compositional and functional microbiome adaptations, and community-level changes associated with seroprotection occurred predominantly in the active group. Collectively, these findings support a microbiome-conditioning model in which the probiotic formulation shapes the gut microbiome response during vaccination, rather than acting as a direct immunostimulant. Future studies are required to determine whether these microbiome adaptations contribute causally to vaccine responsiveness.  Clinical Trial Registration: https://clinicaltrials.gov/study/NCT06103994 , identifier NCT06103994
SN  - 1664-3224
ER  -