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Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials.
Shu, Q, Kang, C, Li, J, Hou, Z, Xiong, M, Wang, X, Peng, H
PloS one. 2024;19(1):e0296733
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The gut microbiome is thought to play a role in thyroid disorders, mediated by regulating iodine uptake, degradation and enterohepatic cycling of thyroid hormones, and differences in microbiome composition between patients with thyroid disorders and healthy individuals have been observed. The aim of this systematic review and meta-analysis was to evaluate the effect of pro-, pre- and synbiotics on thyroid function (thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) and thyroid stimulating hormone receptor antibody (TRAb)) in patients with and without thyroid disorders. 8 randomised controlled trials including 367 participants were included in the review and meta-analysis. Neither pro-, pre- nor synbiotics had a significant effect on TSH, fT4 or fT3 but pre- and probiotics lead to a significant reduction in TRAb in patients with Graves’ disease.
Abstract
BACKGROUND Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels. METHODS We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement. RESULTS A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: -0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: -0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: -0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found. CONCLUSIONS Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves' disease.
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Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial.
Li, X, Hu, S, Yin, J, Peng, X, King, L, Li, L, Xu, Z, Zhou, L, Peng, Z, Ze, X, et al
Gut microbes. 2023;15(2):2247025
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The gut microbiota is involved in regulating immunity and synbiotics, that is combinations of pro- and prebiotics, may therefore modulate immunity via the gut microbiota. The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the immune-modulatory effects of a synbiotic supplement (containing Bifidobacterium lactis HN019, Lactobacillus rhamnosus HN001 and fructo-oligosaccharide) in healthy adults. Outcome measures included C-reactive protein (CRP, an inflammatory marker), various pro- and anti-inflammatory cytokines, stool and salivary secretory IgA (sIgA), leukocytes, microbial stool analysis and occurrence, duration, and severity of upper respiratory tract infections (URTI). Compared to the control group, a significant reduction in the inflammatory markers CRP and interferon-gamma and an increase in the anti-inflammatory interleukin-10 and stool sIgA were observed in the supplementation group. There were no differences in types of leukocytes or URTIs between groups. Significant favourable changes in microbiome analysis were observed in the supplemented group which correlated with the observed improvements in inflammatory markers. These changes were dependent on the baseline composition of the microbiome. No adverse events were reported. The authors conclude that the data show that synbiotics are of benefit to healthy adults and support the concept of personalised supplementation.
Abstract
Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.
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Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.
Sims, MD, Khanna, S, Feuerstadt, P, Louie, TJ, Kelly, CR, Huang, ES, Hohmann, EL, Wang, EEL, Oneto, C, Cohen, SH, et al
JAMA network open. 2023;6(2):e2255758
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Clostridioides difficile infection (CDI) is most commonly caused by treatment with broad-spectrum antibiotics. Antibiotic treatment of CDI is generally successful but recurrences of CDI occur in 15-25% of patients after the first episode, and up to 40% of patients with a previous recurrence. This is thought to be due to persistent microbiome disruption, including a depletion of Firmicutes bacteria. The aim of this single-arm, open-label trial was to evaluate the safety and effectiveness of an investigational, microbiome therapeutic composed of purified Firmicutes spores (SER-109) to prevent CDI recurrences. 263 patients were enrolled in the study and received SER-109 on 3 consecutive days, started within 4 days of completion of antibiotic treatment for CDI recurrence. Follow-up was 24 weeks. Most patients were aged 65 years or older and had a high prevalence of comorbidities. There were no reports of serious adverse events which were considered related to SER-109. By week 24, 36 patients (13.7%) had experienced a CDI recurrence. This was independent of demographics, type of antibiotic treatment and number of prior recurrences. The authors concluded that the data suggest a role of SER-109 in the management of recurrent CDI.
Abstract
IMPORTANCE A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. OBJECTIVES To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. DESIGN, SETTING, AND PARTICIPANTS This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. INTERVENTIONS SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. MAIN OUTCOMES AND MEASURES The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. RESULTS Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). CONCLUSIONS AND RELEVANCE In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03183141.
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Effect of an enzyme-containing mouthwash on the dental biofilm and salivary microbiome in patients with fixed orthodontic appliances: a randomized placebo-controlled pilot trial.
Hoffstedt, T, Skov Hansen, LB, Twetman, S, Sonesson, M
European journal of orthodontics. 2023;45(1):96-102
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Fixed orthodontic appliances are associated with dysbiosis in the oral cavity which may result in demineralisations of the enamel. Antiseptic mouthwashes have been shown to control the formation of cariogenic biofilm but may have negative effects on the salivary microbiome. The aim of this 8-day double-blind, randomised, placebo-controlled trial, including 35 adolescents with fixed orthodontics, was to evaluate the effect of an enzyme-based mouthwash (EBM), used twice daily, on dental biofilm (plaque) formation and salivary microbiome. At 8 days, a statistically and clinically significant decrease in the orthodontic plaque index was seen in the EBM group, whilst no change was seen in the placebo group. There were no statistically significant changes in microbiome between groups but a trend to increased richness in the placebo group. The authors concluded that the use of an enzyme-based mouthwash alongside regular toothbrushing reduced dental biofilm in adolescents with orthodontics without affecting the salivary microbiome.
Abstract
BACKGROUND Mouthwashes containing oral antiseptics or enzymes are suggested suitable for controlling biofilm accumulation in patients with fixed appliances and thereby limiting unwanted side effects during the orthodontic treatment. OBJECTIVES To evaluate the effect of an enzyme-based mouthwash on the amount of dental biofilm and the composition of the salivary microbiome in patients undergoing treatment with fixed orthodontic appliances. TRIAL DESIGN Randomized double-blind placebo-controlled trial. MATERIAL AND METHODS In total, 35 young adolescents (14-18 years) under treatment with fixed appliances were consecutively enrolled and randomly allocated to an experimental or a placebo group by opening a computer-generated numbered envelope. The subjects were instructed to rinse twice daily during an intervention period of 8 days with experimental mouthwash or placebo without active enzymes. Unstimulated whole saliva samples were collected at baseline and after 8 days. The participants and examiner were blinded for the allocation. The primary outcome was the Orthodontic Plaque Index (OPI) and the secondary was the composition of the salivary microbiome. RESULTS In total, 28 adolescents (21 females and 7 males) completed the trial and there were no differences in age, clinical, or microbial findings between the test (n = 14) and the placebo group (n = 14) at baseline. We found a decreased OPI in the test group after 8 days and the difference was statistically significant compared with the placebo group (P < 0.05). There were no significant treatment effects on the richness and global composition of the salivary microbiome. HARMS In total, one participant in the test group claimed nausea and abandoned the project. In total, two participants did not like the taste of the mouthwash but used it as instructed. No other adverse events or side effects were reported. LIMITATIONS Short-term pilot trials may by nature be sensitive for selection and performance biases and are not designed to unveil persisting effects. CONCLUSION Daily use of enzyme-containing mouthwash reduced the amount of dental biofilm in adolescents under treatment with the fixed orthodontic appliances, without affecting the composition of the salivary microbiota. ETHICAL APPROVAL Approved by the Regional Ethical Board, Lund, Sweden (Dnr 2020-05221). CLINICAL TRIAL REGISTRATION NCT05033015.
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The right bug in the right place: opportunities for bacterial vaginosis treatment.
Wu, S, Hugerth, LW, Schuppe-Koistinen, I, Du, J
NPJ biofilms and microbiomes. 2022;8(1):34
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The vaginal microbiome is generally dominated by Lactobacilli bacteria. However, variations exist, and in some ethnic groups a dominance of non-Lactobacilli species is more common. Lactobacilli produce various antimicrobial substances which keep growth of other bacteria in check. Bacterial vaginosis (BV) is characterized by a disturbance of the vaginal microbe balance and deficiency of Lactobacilli, giving rise to the overgrowth of certain bacteria, such as Gardnerella, Atopobium, Megasphaera, Prevotella, and Sneathia. In some countries, BV can affect over half of the women. This review discusses the advantages and challenges of the current treatment options for BV and postulates directions for future research. The article examines the use of antibiotics, their effectiveness and difficulties in obtaining long-term remission, their negative impact on the existing vaginal microbiome, the risk of antibiotic resistance and the benefits and challenges of local antibiotic applications. Following this, the authors discussed the use of prebiotics and probiotics, possible reasons why clinical trials in the past showed mixed results, and what strains may be of particular importance in vaginal health, with L. crispatus and L. iners being of particular interest here. Considered are also factors that influence and enhance bacterial colonization. Lastly, the article summarizes some current thinking on Vaginal Microbiome Transplantation, which is the transfer of vaginal microbes and fluids from a healthy donor, what benefits they may have, the associated safety risks and legislative challenges. This review is a comprehensive summary of BV treatment options, their current evidence, efficacy and drawbacks, yielding useful information to consider in the clinical management of BV.
Abstract
Bacterial vaginosis (BV) is a condition in which the vaginal microbiome presents an overgrowth of obligate and facultative anaerobes, which disturbs the vaginal microbiome balance. BV is a common and recurring vaginal infection among women of reproductive age and is associated with adverse health outcomes and a decreased quality of life. The current recommended first-line treatment for BV is antibiotics, despite the high recurrence rate. Live biopharmaceutical products/probiotics and vaginal microbiome transplantation (VMT) have also been tested in clinical trials for BV. In this review, we discuss the advantages and challenges of current BV treatments and interventions. Furthermore, we provide our understanding of why current clinical trials with probiotics have had mixed results, which is mainly due to not administering the correct bacteria to the correct body site. Here, we propose a great opportunity for large clinical trials with probiotic strains isolated from the vaginal tract (e.g., Lactobacillus crispatus) and administered directly into the vagina after pretreatment.
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Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial.
Dierikx, T, Berkhout, D, Eck, A, Tims, S, van Limbergen, J, Visser, D, de Boer, M, de Boer, N, Touw, D, Benninga, M, et al
Gut. 2022;71(9):1803-1811
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Early-life microbiome acquisition and development can be compromised by external perturbations such as delivery via caesarean section (CS), formula feeding and antibiotics. Currently, based on revised international guidelines, all infants born by CS are exposed to broad-spectrum antibiotics via the umbilical cord. Even though there was not an increase in the incidence of neonatal sepsis, the effects on the gut microbiota colonisation and long-term health consequences remain largely unknown. The hypothesis for this study was that exposure to antibiotics in children delivered by CS, related to the revised international guidelines, influences the microbial colonisation process and may impact health outcome. This study is a randomised controlled trial on the microbiome and health state of infants up to 3 years of age. The study enrolled women delivering via CS who received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20) and women who had a vaginal delivery (n=23). Results show that CS delivery in general leads to a profound impact on the initial microbial colonisation. Furthermore, maternal antibiotic administration prior to CS does not lead to a ‘second hit’ on the already compromised microbiome in CS born infants. Authors conclude that early-life microbiome development is strongly affected by mode of delivery.
Abstract
OBJECTIVE Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants. DESIGN In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing. RESULTS Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points. CONCLUSION We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.
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Probiotic treatment with specific lactobacilli does not improve an unfavorable vaginal microbiota prior to fertility treatment-A randomized, double-blinded, placebo-controlled trial.
Jepsen, IE, Saxtorph, MH, Englund, ALM, Petersen, KB, Wissing, MLM, Hviid, TVF, Macklon, N
Frontiers in endocrinology. 2022;13:1057022
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Efforts to improve pregnancy rates remain largely focused on enhancing the quality of the transferred embryo. However, there is increasing awareness of the potential role of the intra-uterine environment as a determinant for success. The aim of this study was to determine if lactobacilli-loaded vaginal capsules are superior to placebo in improving a vaginal microbiota reported as unfavourable to implantation in women scheduled for fertility treatment. This study is a single-centre, two-arm, double-blinded, randomised controlled study. The study enrolled women aged 18–40 years who were referred to the Fertility Clinic and whose vaginal microbiota prior to fertility treatment had been diagnosed as an unfavourable. Participants (n=77) were randomised in a 1:1 ratio to either lactobacilli-loaded vaginal capsules or placebo. Results did not show any significant effect of treatment with lactobacilli-loaded vaginal capsules on the unfavourable vaginal microbiota profile among women referred to fertility treatment. However, the study showed the highly dynamic nature of the vaginal microbiota, with a spontaneous improvement rate of 34.2% (of the patients) one to three months after the baseline sample. Authors conclude that probiotics use for the improvement of vaginal microbiota should be tempered with some caution. More studies of both the vaginal and endometrial microbiota are required to confirm the efficacy of specific vaginal probiotics before they can be considered as a therapeutic solution.
Abstract
OBJECTIVE To investigate whether treatment with proprietary lactobacilli-loaded vaginal capsules improves an unfavorable vaginal microbiome diagnosed using a commercially available test and algorithm. DESIGN A randomized, double-blinded, placebo-controlled study was conducted in 74 women prior to undergoing fertility treatment at a single university fertility clinic between April 2019 and February 2021. The women were randomly assigned in a 1:1 ratio to receive one vaginal capsule per day for 10 days containing either a culture of more than 108 CFU of Lactobacillus gasseri and more than 108 CFU Lactobacillus rhamnosus (lactobacilli group) or no active ingredient (placebo group). Vaginal swabs for microbiota analysis were taken at enrollment, after treatment and in the cycle following treatment. PARTICIPANTS AND METHODS Women aged 18-40 years who prior to fertility treatment were diagnosed with an unfavorable vaginal microbiota, characterized by either a low relative load of Lactobacillus or a high proportion of disrupting bacteria using the criteria of the IS-pro™ diagnostic system (ARTPred, Amsterdam, the Netherlands), were enrolled in the study. The primary outcome measure was the proportion of women with improvement of the vaginal microbiota after intervention. RESULTS The vaginal microbiota improved after intervention in 34.2% of all participants (lactobacilli group 28.9%, placebo group 40.0%), with no significant difference in the improvement rate between the lactobacilli and placebo groups, RR = 0.72 (95% CI 0.38-1.38). CONCLUSION This study indicates that administering vaginal probiotics may not be an effective means of modulating the vaginal microbiome for clinical purposes in an infertile population. However, a spontaneous improvement rate of 34.2% over a period of one to three months, confirming the dynamic nature of the vaginal microbiota, indicates that a strategy of postponing further IVF treatment to await microbiota improvement may be relevant in some patients, but further research is needed. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT03843112.
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Effects of Lactococcus lactis subsp. cremoris YRC3780 daily intake on the HPA axis response to acute psychological stress in healthy Japanese men.
Matsuura, N, Motoshima, H, Uchida, K, Yamanaka, Y
European journal of clinical nutrition. 2022;76(4):574-580
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The hypothalamic-pituitary-adrenal (HPA) axis is involved in the stress response and is linked to the microbiome through a number of possible mechanisms, including immune-related ones. Lactococcus lactis subsp. cremoris YRC3780 (YRC3780), a probiotic isolated from kefir, has been shown to have beneficial immune-modulatory properties. The aim of this double-blind, placebo-controlled trial, which included 27 healthy young men, was to assess sleep quality, mental health, HPA axis activity (salivary cortisol) and response to an acute stress test during/after 8 weeks of supplementation with YRC3780. At 8 weeks, salivary morning cortisol levels were significantly reduced in the probiotic compared to the placebo group. The effect on the stress test depended on whether or not participants were considered “cortisol-responders” or not. Improvements in sleep quality were seen at 6 weeks (but not at any other time points) in 1 out of 2 sleep questionnaires in the YRC3780 group, whilst no significant differences were observed in actigraphy-measured sleep efficiency. There were no differences in mood between groups, but significant improvements in general health in the probiotic group. Interestingly, no changes in the microbiome of the probiotic group were seen, suggesting that the observed effects may be mediated via the immune system.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Research indicates a bidirectional interaction between the gut microbiome and the central nervous system, affecting the functions of the brain and spinal cord.
- This clinical trial suggests that daily intake of Lactococcus lactis subsp. cremoris (YRC3780) may enhance the HPA axis response to acute psychological stress, potentially linked to a reduction in morning cortisol levels.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomized, placebo-controlled, double-blind clinical trial was conducted to investigate the influence of Lactococcus lactis subsp. cremoris (YRC3780), isolated from kefir, on stress response, sleep quality, and mental health.
Method
Twenty-seven healthy young men, with an average age of 23.5 years, and mean body mass index of 21.5 kg/m2 , were randomly assigned to either the YRC3780 group or the placebo group. Participants were administered YRC3780 or a placebo daily for 8 weeks.
Throughout the study, participants completed assessments, including the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ-28), and the Profile of Mood States 2nd Edition-Adult Short, Total Mood Disturbance subscale (POMS 2 TMD), every 2 weeks. Additionally, diurnal rhythms of HPA axis activity were assessed every 2 weeks through saliva samples collected at 2-hour intervals during the day. At the end of the 8-week supplementation period, participants underwent the Trier Social Stress Test (TSST) to evaluate the effects of daily YRC3780 intake on the HPA axis stress response. In addition, three fecal samples were collected to analyse the gut microbiome (on the last day of baseline, and at 4 and 8 weeks).
A total of 27 out of 33 subjects (81%) completed the study, with six participants withdrawing without providing explanations.
Results
The primary findings of this study were as follows:
- At week 6 of YRC3780 supplementation, salivary cortisol levels at 2 hours and 6 hours after waking were significantly lower in the YRC3780 group compared to the placebo group (p=0.05).
- Salivary cortisol concentrations at 40 minutes after the TSST were significantly lower in the YRC3780 group (4.2 ± 4.4 nmol/L, mean ± SD) than in the placebo group (7.6 ± 4.7 nmol/L) (p=0.043).
- AIS scores at 6 weeks and GHQ-28 scores at 8 weeks were significantly lower in the YRC3780 group compared to the placebo group (AIS, p=0.031; GHQ-28, p=0.038) indicating better sleep quality and a better mental state.
Conclusion:
Oral supplementation with YRC3780 may have beneficial effects on the HPA axis response to acute psychological stress, potentially associated with a decrease in morning cortisol levels. Additionally, the study suggests that the lower basal activity and stress reactivity of the HPA axis may lead to improvements in subjective sleep quality and mental health.
Clinical practice applications:
- The precise mechanisms underlying the correlation between the gut microbiota and the gut-brain axis remain incompletely understood, emphasising the need for further research.
- This clinical trial demonstrated that daily intake of YRC3780 decreased morning salivary cortisol levels at 6 and 8 weeks and reduced the salivary cortisol response to acute psychological stress.
Considerations for future research:
- Larger, adequately powered clinical trials are required to provide deeper insights into the mechanisms responsible for the stress-reducing and sleep-improving effects of Lactococcus lactis subsp. cremoris.
- Furthermore, investigations into optimal dosage and duration of probiotic supplementation are warranted for a more comprehensive understanding, particularly in diverse demographic groups.
- Comparative research is needed to explore the effects of various probiotic strains on objective stress responses.
Abstract
BACKGROUND Lactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans. METHODS Effects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups. RESULTS The results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo. CONCLUSIONS Our study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.
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Characterization of the Oral and Gut Microbiota in Patients with Psoriatic Diseases: A Systematic Review.
Todberg, T, Kaiser, H, Zachariae, C, Egeberg, A, Halling, AS, Skov, L
Acta dermato-venereologica. 2021;101(7):adv00512
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Psoriasis is a common inflammatory skin disease that results in patches of dry, scaly skin that can be itchy or sore. Psoriatic arthritis is an inflammatory arthritis that affects up to 30% of psoriasis patients. There is growing interest in the association between the microbiome and inflammatory conditions. This systematic review examined the role of the oral and gut microbiota and the effect of probiotics in patients with psoriasis and/or psoriatic arthritis. 23 studies were included in the analysis. Studies examined the microbiota using culture or 16S ribosomal RNA gene sequencing analysis. The results showed an increased presence of Candida in the mouth, and an altered gut microbiota in patients with psoriatic disease compared with healthy controls. Probiotics were associated with a significant decrease in psoriasis severity, but the microbiota was unchanged. The study authors concluded that further research is required into the role of the microbiome in patients with psoriasis.
Abstract
Advances in technology have led to an increased number of studies investigating the microbiome in patients with psoriasis. This systematic review examined data regarding the oral and gut microbiota in patients with psoriasis and/or psoriatic arthritis and the effect of probiotics on the microbiota and severity of psoriasis. Of 1,643 studies, 23 were included (22 observational, 1 interventional). Studies examined the microbiota using culture or 16S rRNA gene sequencing analysis. All culture-based studies identified an increased presence of oral Candida in patients with psoriasis, whereas small variations in the oral microbiota were found in a 16S rRNA gene-based study. All 16S rRNA gene sequencing based studies agreed that the gut microbiota of patients with psoriatic disease differed from that of healthy controls, but the results were heterogeneous. Probiotics were associated with a significant improvement in the severity of psoriasis, but did not change microbiota. Overall, studies lacked relevant inclusion criteria and baseline information. In conclusion, the role of the microbiota in patients with psoriasis requires further investigation using more robust methods.
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Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.
Siena, M, Laterza, L, Matteo, MV, Mignini, I, Schepis, T, Rizzatti, G, Ianiro, G, Rinninella, E, Cintoni, M, Gasbarrini, A
Microorganisms. 2021;9(3)
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During pregnancy, several adaptations occur in the female organism. In fact, from fertilization until delivery, the maternal body changes and activates a series of physiological transformations to welcome the new life. The microbiota as a component of human bodies is subject to these modifications. This study is a review that focused on gut and reproductive tract microbiota variations during physiologic pregnancy and in case of pregnancy complications, particularly gestational diabetes mellitus (GDM), pre-eclampsia (PE), and preterm birth (PTB). Results show that: - during pregnancy, major changes have been seen in mothers’ gut microbiota. Between the first and third trimester of pregnancy, to support the foetus growth, there is a shift towards communities of microbes implicated in energy production and storage. - in nonpregnant women, vaginal microbiota could be classified into five major types, representing the community state types. - meconium’s microbes seems to be dominated by the Enterobacteriaceae family, suggesting prenatally stepwise colonization. - gut microbiota may contribute to enhanced insulin resistance in early pregnancy (1st and 2nd trimester). - microbiota imbalances in PE women are related not only with blood pressure levels but also with markers of kidney dysfunction. Thus, it is of key importance to understand the role of microbiota and other factors involved in the etiopathogenesis of PE - dysbiosis is related to PTB (however, further studies are necessary to better understand the correlation between this pregnancy complication and the specific microbiota alteration). Authors conclude that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
Abstract
Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.