Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial

ABSTRACT

Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 10⁸ colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 μg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 μg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168–1480] BAU/ml vs 111 [36.1–1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212–3449] BAU/ml vs (83.7 [22.8–2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9–976] BAU/ml vs 61.3 [26.7–97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

KEYWORDS:

• Probiotics
• SARS-CoV-2
• COVID-19
• immunology
• antibody

Acknowledgments

We are most grateful to the staff of Region Örebro Län’s Department of Clinical studies for their time and skillful assistance with the study visits. We would like to thank Anna Maria Delis and Martin Sundqvist from Örebro University Hospital for their efforts and expertise regarding the antibody analyses. We are also thankful to Patricia Ruiz Iglesias and all other colleagues at Nutrition-Gut-Brain Interactions Research Centre who kindly assisted with sample processing and study visits. Lastly, we sincerely thank all our study participants for their time and cooperation during the study.

Disclosure statement

JA and GG are employed at BioGaia AB. GG is also a member of BioGaia Pharma which is a subsidiary of BioGaia AB. JA and GG were involved in the study design and in the discussions about the data and the contents of this manuscript but were not involved in the data collection, laboratory analyses, or the statistical analyses of the final data set. RJB has received consulting fees from Chr Hansen A/S, Denmark, as well as participated in an expert panel discussion hosted by GSK Healthcare. The other authors declare no competing interests.

Author contributions

RJB conceptualized the study idea; RAF, JA, GG, SM, and RJB designed the study; RAF, JR, and KL-P recruited the study participants; RAF, JR, KL-P, and AK conducted the study visits as well as sample collection and storing; RAF and MGJT performed the laboratory analyses; MAHL developed the FFQ and collected the dietary intake data, RAF, SP, and SM performed the statistical analyses; RAF wrote the manuscript; all authors edited and reviewed the manuscript. RJB is the guarantor of the article and had the final responsibility of the manuscript. All authors read and approved the final version of the manuscript.

Data availability statement

Due to the nature of this research, participants of this study did not provide a written consent for their data to be shared publicly, so supporting data is not publicly available.

Ethical approval

The original study protocol and all protocol amendments were approved by the Central Ethical Review Board of Sweden (dnr: 2020–05519, dnr: 2021–00667, dnr: 2022–03403–02) and conducted according to principles of the Helsinki declaration and Good Clinical Practice. Participants gave informed consent for their study participation before taking part.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2229938

Additional information

Funding

This study is financially supported by BioGaia AB, Sweden, and by a grant from the Knowledge Foundation Sweden (nr 20110225). RAF is currently supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 896263.