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Effects of probiotic supplementation on serum trimethylamine-N-oxide level and gut microbiota composition in young males: a double-blinded randomized controlled trial

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

To explore whether probiotic supplementation could attenuate serum trimethylamine-N-oxide (TMAO) level and impact the intestinal microbiome composition.

Design

Forty healthy males (20–25 years old) were randomized into the probiotic group (1.32 × 1011 CFU live bacteria including strains of Lactobacillus acidophilus, Lactobacillus rhamnosus GG, Bifidobacterium animalis, and Bifidobacterium longum daily) or the control group for 4 weeks. All participants underwent a phosphatidylcholine challenge test (PCCT) before and after the intervention. Serum TMAO and its precursors (TMA, choline and betaine) were measured by UPLC-MS/MS. The faecal microbiome was analyzed by 16S rRNA sequencing.

Results

Serum TMAO and its precursors were markedly increased after the PCCT. No statistical differences were observed in the probiotic and the control group in area under the curve (AUC) (14.79 ± 0.97 μmol/L 8 h vs. 19.17 ± 2.55 μmol/L 8 h, P = 0.106) and the pre- to post-intervention AUC alterations (∆AUC) (− 6.33 ± 2.00 μmol/L 8 h vs. − 0.73 ± 3.04 μmol/L 8 h, P = 0.131) of TMAO; however, higher proportion of participants in probiotic group showed their TMAO decrease after the intervention (78.9% vs. 45.0%, P = 0.029). The abundance of Faecalibacterium prausnitzii (P = 0.043) and Prevotella (P = 0.001) in the probiotic group was significantly increased after the intervention but without obvious differences in α- and β-diversity.

Conclusions

The current probiotic supplementation resulted in detectable change of intestinal microbiome composition but failed to attenuate the serum TMAO elevation after PCCT.

Clinicaltrials.gov Identifier

NCT03292978.

Clinicaltrials.gov website

https://clinicaltrials.gov/ct2/show/NCT03292978.

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Abbreviations

TMA:

Trimethylamine

TMAO:

Trimethylamine-N-oxide

PCCT:

Phosphatidylcholine challenge test

UPLC–MS:

Ultrahigh-performance liquid chromatography–tandem mass spectrometry

FMO3:

Flavin-containing monooxygenase 3

CVDs:

Cardiovascular diseases

CRF:

Case report form

TBA:

tert-butyl bromoacetate

USDA:

United States Department of Agriculture

ITT:

Intent-to-treat analysis method

ANOVA:

Analysis of variance

NMDS:

Non-metric multi-dimensional scaling

MET:

Metabolic equivalent

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Acknowledgements

The study sponsors were not involved in the study design, data collection, analysis or interpretation of the results; the writing of the manuscript; or in the decision to submit the manuscript for publication. This study was supported by the National Natural Science Foundation of China (Grant number: 81472966); and the Dietary Nutrition Research and Education Foundation of Danone, China (Grant number: DIC2016-08). Special thanks go to the Danisco Culture for providing the study products in kind.

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Authors and Affiliations

  1. Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhongshan II Road, Guangzhou, 510080, People’s Republic of China

    Si Chen, Ping-ping Jiang, Gong-cheng Liao, Shang-ling Wu, Ai-ping Fang, Pei-yan Chen, Xiao-yan Wang, Yun Luo, Jing-an Long, Rong-huan Zhong, Zhao-yan Liu, Chun-lei Li, Dao-ming Zhang & Hui-lian Zhu

  2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China

    Si Chen, Ping-ping Jiang, Gong-cheng Liao, Shang-ling Wu, Ai-ping Fang, Pei-yan Chen, Xiao-yan Wang, Yun Luo, Jing-an Long, Rong-huan Zhong, Zhao-yan Liu, Chun-lei Li, Dao-ming Zhang & Hui-lian Zhu

  3. Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, 37203, USA

    Danxia Yu

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Conflict of interest

S.C. and H.-L.Z. designed the research. S.C., G.-C.L. and S.-L.W., P.-Y.C., X.-Y.W., Y.L., J.-A.L., R.-H.Z., Z.-Y.L and D.-M.Z. conducted the research. C.-L.L. created the randomization sequences and performed the masking procedure. S.C. and A.-P.F analyzed data. S.C., D.X.Y. and H.-L.Z. contributed to the interpretation of the results. S.C., P.-P.J., D.X.Y. and H.-L.Z. wrote the paper. H.-L.Z. had primary responsibility for final content. All authors read and approved the final manuscript. All authors have no conflicts of interest.

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Chen, S., Jiang, Pp., Yu, D. et al. Effects of probiotic supplementation on serum trimethylamine-N-oxide level and gut microbiota composition in young males: a double-blinded randomized controlled trial. Eur J Nutr 60, 747–758 (2021). https://doi.org/10.1007/s00394-020-02278-1

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