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Randomized Controlled Trial
. 2021 Jul 30;13(8):2660.
doi: 10.3390/nu13082660.

Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial

Hyuk Joo Lee  1   2 , Jung Kyung Hong  3 , Jeon-Kyung Kim  4 , Dong-Hyun Kim  4 , Seok Won Jang  5 , Seung-Won Han  5 , In-Young Yoon  3   6
Affiliations
Randomized Controlled Trial

Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial

Hyuk Joo Lee et al. Nutrients. .

Abstract

The human gut microbiome is closely linked to mental health and sleep. We aimed to verify the efficacy and safety of probiotic NVP-1704, a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98, in improving stress, depression, anxiety, and sleep disturbances, along with the measurement of some blood biomarkers. A total of 156 healthy adults with subclinical symptoms of depression, anxiety, and insomnia were retrospectively registered and randomly assigned to receive either NVP-1704 (n = 78) or a placebo (n = 78) for eight weeks. Participants completed the Stress Response Inventory, Beck's Depression and Anxiety Inventory, Pittsburg Sleep Quality Index, and Insomnia Severity Index at baseline, at four and eight weeks of treatment. Pre- and post-treatment blood tests for biomarkers were conducted. After intervention, gut microbiota composition was quantified by pyrosequencing the bacterial 16S rRNA gene. The NVP-1704 group had a more significant reduction in depressive symptoms at four and eight weeks of treatment, and anxiety symptoms at four weeks compared to the placebo group. Those receiving NVP-1704 also experienced an improvement in sleep quality. NVP-1704 treatment led to a decrease in serum interleukin-6 levels. Furthermore, NVP-1704 increased Bifidobacteriaceae and Lactobacillacea, whereas it decreased Enterobacteriaceae in the gut microbiota composition. Our findings suggest that probiotic NVP-1704 could be beneficial for mental health and sleep.

Keywords: anxiety; depression; gut microbiome; probiotic; sleep.

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Conflict of interest statement

Jang S.W. and Han S.-W. are employees of Navipharm Inc., which provided study products. Other authors declare that there are no potential conflicts of interest.

Figures

Figure 1
Figure 1
Timeline of the study protocol. SRI, Stress Response Inventory; BDI-II, Beck’s Depression Inventory-II; BAI, Beck’s Anxiety Inventory; PSQI, Pittsburgh Sleep Quality Index; ISI, Insomnia Severity Scale.
Figure 2
Figure 2
Flow chart of study participants.
Figure 3
Figure 3
Effects of NVP-1704 on mood parameters such as SRI score (A), BDI-II score (B), BAI score (C), and the sum of BDI-II and BAI scores (D). Scores are shown as 4- and 8-week mean changes from baseline during the study period. Independent t-tests were performed. Data values are described as the mean ± standard error of the mean. Asterisks indicates a statistically significant difference between the two groups (* p < 0.05, ** p < 0.01). SRI, Stress Response Inventory; BDI-II, Beck’s Depression Inventory; BAI, Beck’s Anxiety Inventory.
Figure 4
Figure 4
Effects of NVP-1704 on sleep parameters such as the PSQI score (A), ISI score (B), and the fraction of subjects with improvements in PSQI and ISI scores (C). Scores are shown as 4- and 8-week mean changes from baseline during the study period. The improvement is defined as a score reduction above or equal to the minimal clinically important difference for each scale. Independent t-tests were performed for analysis of the PSQI and ISI scores. Chi-squared tests were performed for the comparison of the fraction of participants with improvement. Data values are described as means ± standard errors of the mean. Asterisks indicates a statistically significant difference between the two groups (* p < 0.05, ** p < 0.01). PSQI, Pittsburgh Sleep Quality Index; ISI, Insomnia Severity Scale.
Figure 5
Figure 5
Effect of NVP-1704 on blood levels of IL-6, BDNF, and the ratio of IL-6 to log (BDNF). (A) Changes in the level of IL-6 and (B) log (BDNF) in serum from baseline to 8 weeks of treatment. (C) The ratio of IL-6 to log (BDNF) as individual values at each time point in the NVP-1704 and placebo groups. IL-6, interleukin-6; BDNF, brain-derived neurotrophic factor.
Figure 6
Figure 6
Effects of NVP-1704 on the gut microbiota composition. Effect on the α-diversity (estimated operational taxonomic units, OTUs) (A) and β-diversity (principal coordinate analysis [PCoA] plot based on Jansen-Shannon) (B). Effects on gut bacteria composition at the phylum (C) and cladogram (F) generated by linear discriminant analysis effect size indicating significant differences in gut microbial abundances. (D) Effect on the Actinobacteria (a) and Proteobacteria populations (b) and their ratio (c) at the phylum level. (E) Effect on the Bifidobacteriaceae (a), Enterobacteriaceae (b) and Lactobacillaceae populations (c) and as their ratio, Enterobacteria per Bifidobacteriaceae (d) and Lactobacillaceae per Enterobacteriaceae (e) at the family level. The composition of Actinobacteria, Proteobacteria, Bifidobacteriaceae, Enterobacteriaceae, and Lactobacillaceae populations was indicated as log (composition percent + 1). Data indicate mean ± standard deviation. * The significance was analyzed by one-tailed Mann–Whitney test (p < 0.05).
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