Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota–Gut–Brain Axis: A Pilot Clinical Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics, Recruitment, and Experimental Design
2.2. Dietary Intake, Physical Activity, Sleep, Mood, and Quality of Life
2.3. Anthropometrics and Biochemistry Parameter
2.4. Cytokine and Chemokine Levels
2.5. Microbiome Analysis
2.6. Statistical Analysis
3. Results
3.1. Anthropometrics, Dietary Intake, Biochemistry, Cytokines, and Chemokines Modulation
3.2. Sleep, Mood, Physical Activity, and Quality of Life Effects
3.3. Gut Microbiota Reshaping
3.4. Predictive Parameters of Microbiota Reshaping
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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LL1 (Long-Life 1) Capsules * | |
---|---|
Chromium (Cr) | 75 mcg |
Zinc (Zn) | 26 mg |
Magnesium (Mg) | 63.4 mg |
Fructooligosaccharide (FOS) | 45% |
Selenium | 140 mcg |
Galactooligosaccharide (GOS) | 10% |
1.3/1.6-(β-glycosidic bonds) yeast β-glucans (Saccharomyces cerevisiae) | 250 mg |
Silymarin Capsule | |
Silymarin extract (Silybum marianum (L.) Gaertn.) # | 150 mg |
LL1 + Silymarin | |||||
---|---|---|---|---|---|
Sample size (M/F) | 22 (7/15) | ||||
Age (years) | 58.54 ± 5.65 | ||||
Height (m) | 1.62 ± 0.10 | ||||
Anthropometrics | |||||
T0 | T180 | ||||
Mean ± SD | Mean ± SD | p | |||
BMI (kg/m2) | 28.9 ± 0.67 | 28.3 ± 0.76 | 0.0465 | ||
Neck (cm) | 36.3 ± 0.70 | 35.7 ± 0.73 | 0.0049 | ||
Plasmatic profile | |||||
Total Cholesterol (mg/dL) | 194 ± 7.81 | 208 ± 7.19 | 0.0255 | ||
HDL-C (mg/dL) | 45.7 ± 2.3 | 51.8 ± 2.61 | 0.0002 | ||
IgM (mg/dL) | 104 ± 10.4 | 107 ± 10.4 | 0.0106 | ||
Albumin (g/dL) | 4.65 ± 0.043 | 4.93 ± 0.052 | 0.0001 | ||
Creatinine (mg/dL) | 0.83 ± 0.36 | 0.90 ± 0.04 | 0.0007 | ||
TSH (mUI/L) | 2.02 ± 0.243 | 2.72 ± 0.352 | 0.0479 | ||
Thyroxine (ng/dL) | 0.981 ± 0.045 | 1.36 ± 0.043 | 0.0001 | ||
IL-8 (pg/mL) | 0.859 ± 0.231 | 0.422 ± 0.156 | 0.0161 | ||
T0 | T180 | ||||
Mean ± SD | CI 95% | Mean ± SD | CI 95% | p | |
Pittsburgh Sleep Quality Index (PSQI) | |||||
PSQI Global score | 6.39 ± 3.12 | 5.04–7.74 | 5.17 ± 2.77 | 3.97–6.37 | 0.0198 |
(C1) Sleep Quality | 1.17 ± 0.65 | 0.89–1.46 | 0.83 ± 0.57 | 0.57–1.08 | 0.0078 |
(C2) Sleep Latency | 1.09 ± 0.85 | 0.72–1.45 | 0.78 ± 0.16 | 0.44–1.13 | |
(C3) Sleep Duration | 1.17 ± 0.58 | 0.93–1.42 | 1.30 ± 0.87 | 0.93–1.68 | - |
(C4) Sleep Efficiency | 0.43 ± 0.73 | 0.12–0.75 | 0.43 ± 0.89 | 0.05–0.82 | - |
(C5) Sleep Disturbance | 1.13 ± 0.55 | 0.89–1.37 | 0.96 ± 0.47 | 0.75–1.16 | - |
(C6) Sleep Medication | 0.26 ± 0.75 | −0.06–0.59 | 0.13 ± 0.62 | −0.14–0.40 | - |
(C7) Daytime Dysfunction | 1.35 ± 1.43 | 0.73–1.97 | 0.68 ± 0.65 | 0.39–0.97 | 0.0042 |
Brunel Mood Scale (BRUMS) | |||||
BRUMS total score | 20.14 ± 1.31 | 17.40–22.89 | 21.62 ± 1.46 | 18.56–24.68 | - |
Tension | 3.90 ± 1.09 | 3.41–4.40 | 4.41 ± 1.71 | 3.65–5.17 | - |
Depression | 2.38 ± 1.66 | 1.63–3.14 | 3.77 ± 3.24 | 2.34–5.21 | - |
Anger | 3.19 ± 2.27 | 2.16–4.22 | 1.90 ± 1.61 | 1.17–2.64 | 0.0082 |
Confusion | 3.90 ± 1.04 | 3.43–4.38 | 4.62 ± 1.47 | 3.95–5.29 | 0.0199 |
Vigor | 3.48 ± 1.66 | 2.72–4.23 | 4.29 ± 1.55 | 3.58–4.99 | 0.0420 |
Fatigue | 3.10 ± 1.34 | 2.49–3.70 | 3.24 ± 1.30 | 2.65–3.83 | - |
% | R2 | IC 95% Min–Max | p | ||
---|---|---|---|---|---|
Body weight (kg) | Blautia producta | 0.71 | 0.22 | 1.21 | 0.009 |
WC-mid (cm) | Bacteroidetes | 26.66 | 2.3 | 308.01 | 0.009 |
Hip (cm) | Roseburia | 23.33 | 1.99 | 273.29 | 0.012 |
WC-IC (cm) | Parabacteroides | 17.5 | 1.59 | 191.89 | 0.019 |
Odoribacter | 19.99 | 1.67 | 238.62 | 0.018 | |
WHR | Actinobacteria | 0.15 | 0.011 | 2.055 | 0.155 |
Coprococcus | 12.01 | 1.58 | 91.08 | 0.016 | |
WHtR | Bacteroidetes | 17.5 | 1.59 | 191.89 | 0.019 |
TNF-α/IL-10 ratio | Anaerostipes | 56.01 | 2.92 | 1071.63 | 0.008 |
R. Ruminococcus | 15.75 | 1.42 | 174.24 | 0.025 | |
IL-6 (pg/mL) | Prevotella | 10.5 | 1.11 | 98.91 | 0.04 |
Oscillospira | 7.11 | 1.08 | 46.44 | 0.04 | |
Bilophila | 13.5 | 1.19 | 152.21 | 0.035 | |
RANTES (pg/mL) | α-diversity chao1 index | 12.01 | 1.11 | 128.83 | 0.04 |
α-diversity Faith’s PD | 12.01 | 1.11 | 128.83 | 0.04 | |
α-diversity Obs features | 12.01 | 1.11 | 128.83 | 0.04 | |
CXCL10/IP-10 (pg/mL) | Oscillospira | 7.11 | 1.08 | 46.44 | 0.04 |
R. Ruminococcus | 7.11 | 1.08 | 46.44 | 0.04 | |
BRUMS Anger | α-diversity chao1 index | 21.01 | 1.5 | 293.25 | 0.024 |
α-diversity Obs features | 21.01 | 1.5 | 293.25 | 0.024 | |
α-diversity Shanon entropy | 21.01 | 1.5 | 293.25 | 0.024 | |
BRUMS Depression | Bacteroidetes | 32.01 | 2.39 | 427.74 | 0.009 |
Bacteroides uniformis | 8.166 | 1.027 | 64.93 | 0.047 | |
Alistipes onderdonkii | 30.01 | 1.471 | 611.79 | 0.027 | |
Lachnospira | 0.122 | 0.015 | 0.973 | 0.047 | |
BRUMS Vigor | Ruminococcus bromii | 24.01 | 1.14 | 505.19 | 0.041 |
BRUMS Fatigue | Streptococcus | 14.01 | 1.13 | 172.64 | 0.039 |
Variable | (%) | Coef | IC 95% Min–Max | p | |
---|---|---|---|---|---|
↓TNF-α/IL-10 ratio | Bilophila | −4.4251 | −7.7851 | −1.0650 | 0.016 |
Bifidobacterium | −0.1032 | −0.1740 | −0.0323 | 0.012 | |
Clostridium spiroforme | −3.2441 | −4.9353 | −1.5529 | 0.009 | |
Ruminococcus gnavus | −0.3283 | −0.5890 | −0.0677 | 0.022 | |
Ruminococcus lactaris | 2.6987 | 0.1400 | 5.2573 | 0.042 | |
↓IL-6 (pg/mL) | Catenibacterium | −0.1599 | −0.2459 | −0.0739 | 0.003 |
Ruminococcus callidus | 0.7058 | 0.2054 | 1.2062 | 0.012 | |
Faecalibacterium prausnitzii | 0.4652 | 0.2876 | 0.6428 | <0.0001 | |
Parabacteroides distasonis | 0.1206 | 0.0121 | 0.2291 | 0.032 | |
↑IL-10 (pg/mL) | Desulfovibrio | 1.3290 | 0.0201 | 2.6379 | 0.047 |
Prevotella | −0.9742 | −1.6373 | −0.3110 | 0.008 | |
↓IL-12p70 (pg/mL) | Holdemania | 0.8647 | 0.0005 | 1.7289 | 0.05 |
Catenibacterium | −0.1341 | −0.2282 | −0.0401 | 0.01 | |
Faecalibacterium prausnitzii | 0.4129 | 0.1619 | 0.6639 | 0.003 | |
Parabacteroides distasonis | 0.1785 | 0.0859 | 0.2711 | 0.001 | |
↓IL-8 (pg/mL) | Ruminococcus bromii | 5.4948 | 2.0311 | 8.9585 | 0.012 |
Bacteroidetes | 1.6105 | 0.0040 | 3.2169 | 0.05 | |
Alistipes | −0.814 | −1.590 | −0.039 | 0.041 | |
α-diversity Faith’s PD | 2.021 | 0.258 | 3.784 | 0.027 | |
Ruminococcus gnavus | 0.280 | 0.028 | 0.532 | 0.033 | |
↓RANTES (pg/mL) | Actinomyces | −0.802 | −1.253 | −0.351 | 0.003 |
α-diversity Faith’s PD | −1.381 | −2.752 | −0.011 | 0.048 | |
↓Depression (BRUMS) | Desulfovibrio | −1.693 | −2.670 | −0.715 | 0.005 |
Paraprevotella | −1.172 | −1.636 | −0.709 | 0.002 | |
↓Anger (BRUMS) | Roseburia faecis | 0.302 | 0.085 | 0.519 | 0.010 |
Blautia producta | −0.303 | −0.597 | −0.009 | 0.045 | |
↓Confusion (BRUMS) | Alistipes | 0.182 | 0.011 | 0.353 | 0.038 |
Firmicutes | −0.220 | −0.388 | −0.053 | 0.013 | |
↓PSQI (C2) Sleep Latency | Ruminococcus lactaris | 0.142 | 0.116 | 0.167 | 0.002 |
↓PSQI (C3) Sleep Duration | Faecalibacterium | 0.279 | 0.011 | 0.548 | 0.042 |
↓PSQI (C4) Sleep Efficiency | Faecalibacterium prausnitzii | −0.608 | −0.785 | −0.431 | 0.002 |
Alistipes indistinctus | −0.127 | −0.182 | −0.072 | 0.022 | |
↓PSQI (C5) Sleep Disturbance | Phascolarctobacterium | 0.136 | 0.044 | 0.229 | 0.009 |
Faecalibacterium | 0.410 | 0.224 | 0.596 | <0.0001 | |
Clostridium spiroforme | −0.378 | −0.511 | −0.246 | 0.001 | |
Bacteroides caccae | −0.102 | −0.191 | −0.013 | 0.030 | |
↓PSQI Global score | Eubacterium biforme | 0.507 | 0.128 | 0.886 | 0.014 |
Ruminococcus callidus | 2.352 | 0.876 | 3.829 | 0.006 | |
Coprococcus catus | 1.094 | 0.182 | 2.007 | 0.022 | |
F/B ratio | 0.785 | 0.102 | 1.468 | 0.027 |
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Santamarina, A.B.; Nehmi Filho, V.; Freitas, J.A.d.; Franco, L.A.M.; Fonseca, J.V.; Martins, R.C.; Turri, J.A.O.; Silva, B.F.R.B.d.; Gusmão, A.F.; Olivieri, E.H.R.; et al. Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota–Gut–Brain Axis: A Pilot Clinical Study. Nutrients 2024, 16, 3049. https://doi.org/10.3390/nu16183049
Santamarina AB, Nehmi Filho V, Freitas JAd, Franco LAM, Fonseca JV, Martins RC, Turri JAO, Silva BFRBd, Gusmão AF, Olivieri EHR, et al. Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota–Gut–Brain Axis: A Pilot Clinical Study. Nutrients. 2024; 16(18):3049. https://doi.org/10.3390/nu16183049
Chicago/Turabian StyleSantamarina, Aline Boveto, Victor Nehmi Filho, Jéssica Alves de Freitas, Lucas Augusto Moysés Franco, Joyce Vanessa Fonseca, Roberta Cristina Martins, José Antônio Orellana Turri, Bruna Fernanda Rio Branco da Silva, Arianne Fagotti Gusmão, Eloísa Helena Ribeiro Olivieri, and et al. 2024. "Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota–Gut–Brain Axis: A Pilot Clinical Study" Nutrients 16, no. 18: 3049. https://doi.org/10.3390/nu16183049