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Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial.
Wauters, L, Van Oudenhove, L, Accarie, A, Geboers, K, Geysen, H, Toth, J, Luypaerts, A, Verbeke, K, Smokvina, T, Raes, J, et al
Gut microbes. 2022;14(1):2031695
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Plain language summary
Previous research has shown a bidirectional relationship between the gut and psychological stress, which could be mediated by intestinal permeability followed by an immune and inflammatory response. However, the exact mechanisms of this relationship are yet to be elucidated. This randomised, double-blind, placebo-controlled trial evaluated the beneficial effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress markers during a public speech in healthy students. Participants consumed either milk containing Lactobacillus rhamnosus CNCM I-3690 or acidified milk twice daily for four weeks to assess subjective and objective stress markers and markers of intestinal permeability. Lactobacillus rhamnosus CNCM I-3690 reduced the stress-induced hyperpermeability to mannitol and subjective stress markers (State-Trait Anxiety Inventory/ STAI). A subgroup of healthy students with stress-induced cortisol >P90 of baseline showed a reduction in perceived stress score following Lactobacillus rhamnosus CNCM I-3690 intervention. To evaluate the additional effects of Lactobacillus rhamnosus CNCM I-3690 on stress and gut health, further robust studies are needed. Healthcare professionals can use the findings of this study to understand the anxiolytic effects of Lactobacillus rhamnosus CNCM I-3690.
Abstract
Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose-mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.
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Effects of Lactobacillus gasseri CP2305 on Mild Menopausal Symptoms in Middle-Aged Women.
Sawada, D, Sugawara, T, Hirota, T, Nakamura, Y
Nutrients. 2022;14(9)
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The gastrointestinal tract represents the largest interface and interaction between the host and microorganisms. This collection of microorganisms is called the enteric or gut microbiota, and co-evolved with their hosts in an intricate, mutually beneficial relationship. One of the most important interactions is the brain–gut interaction, which maintains both intestinal homeostasis and brain function. The aim of this study was to analyse the influence of Lactobacillus gasseri CP2305 (CP2305) intake on the hypothalamic– pituitary–gonadal axis and its effects on mild symptoms associated with menopause. This study was a double-blind, placebo-controlled, parallel-group clinical trial. The enrolled subjects were randomly assigned to either the CP2305 group or placebo group. Results showed that consumption of CP2305 improves mild psychological symptoms that are unique to menopausal women, and improves the most common vasomotor symptoms, such as hot flashes. Authors concluded that the consumption of CP2305 may be used as an alternative treatment to alleviate menopausal symptoms.
Abstract
Lactobacillus gasseri CP2305 (CP2305) is a paraprobiotic that exhibits beneficial effects on the intestinal function and microbiota, and increases resistance to psychological stress. The stress response mechanism mainly involves the hypothalamic-pituitary-adrenal axis, which is influenced by the gut-brain axis. Furthermore, the gut-brain axis also communicates bidirectionally with the intestinal microbiota. Additionally, the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes share a common route that affects both mental and health aspects in women. This double-blind, placebo-controlled, parallel-group clinical trial aimed to analyze the influence of the intake of CP2305 on mild symptoms associated with menopause. Eighty women aged 40-60 years ingested CP2305 or placebo tablets for six consecutive menstrual cycles. Assessment was based on the observation of climacteric symptoms with two validated questionnaires-the Simplified Menopausal Index (SMI) and the Greene Climacteric Scale (GCS). The results showed that CP2305 provided significant relief in the SMI total score, SMI vasomotor score, SMI psychological score, GCS total score, GCS somatic score, and GCS vasomotor score compared to the placebo. The percentage of women with symptom relief for the SMI total score was 75.0%, with 30 of 40 women in the CP2305 group, and 55.0%, with 22 of 40 women in the placebo group (p = 0.0594). These findings provide new insights into the function of paraprobiotic CP2305 in relieving mild climacteric symptoms in women.
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Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population.
Berding, K, Bastiaanssen, TFS, Moloney, GM, Boscaini, S, Strain, CR, Anesi, A, Long-Smith, C, Mattivi, F, Stanton, C, Clarke, G, et al
Molecular psychiatry. 2022
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Psychobiotic describe any exogenous intervention that leads to a bacterially mediated impact on the brain. Probiotics and prebiotics have shown promising results as psychobiotic agents in both animal and human studies. The aim of this study was to investigate the potential of a whole diet psychobiotic approach to modulate the microbiota composition and function, affect responses to and feelings of stress and improve mood in a healthy population. This study is a single-blind, randomized, controlled study which recruited healthy adult (male and female) participants with poor dietary habits, aged 18–59 years. Participants were block randomized (block of 4, stratified by gender) into either intervention or control group using randomly permuted blocks and were instructed to follow their respective diet for 4 weeks. Results show that a short term psychobiotic dietary intervention improved perceived stress in a healthy population, while eliciting specific metabolic changes in the gut microbiota. Authors conclude that underlying microbial influences need to be investigated and future preclinical experiments are required to explore causality and decipher mechanistic pathways.
Expert Review
Conflicts of interest:
None
Take Home Message:
Eating foods known to have a positive influence on gut microbial composition could elicit benefits in terms of reducing perceived stress and improving sleep quality.
Evidence Category:
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X
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:
This RCT explored the impact of a psychobiotic diet, compared to a control diet, on perceived stress, sleep and gut microbiota.
A high psychobiotic diet is one high in prebiotic and fermented foods. In this study, a psychobiotic diet included daily recommended consumption and servings of the following:
- High prebiotic fruit & veg (6-8)
- Grains (5-8)
- Fermented foods (2-3)
- Legumes (3-4 per week)
Methodology:
- A single-blind, randomised, controlled study
- 45 healthy adults (18-59 years) with poor dietary habits
- Sample size determined by previous microbiome research - target not reached due to introduction of covid restrictrictions
- Active intervention (n=24) received dietitian advice to follow psychobitoic diet
- Control intervention (n=21) received dietitian advice largely based on the Irish Healthy Eating Guidelines food pyramid
- Intervention duration 4 weeks.
- Assessed on questionnaire measures of perceived stress and sleep, pre and post-intervention (no primary outcome defined)
- Shotgun microbiome analysis on stool samples, pre and post-intervention
Results:
- Perceived stress improved in the psychobiotic diet group
- Subjective sleep quality improved in the psychobiotic diet group
- Only subtle changes in microbial composition and function
- More stable microbiota throughout the study (regardless of diet) was correlated with greater changes in perceived stress
- Neither cortisol awakening response nor measured immune markers were affected by dietary intervention
Conclusions:
- Using a diet targeted to positively modulate gut-brain communication may have the potential for reducing stress and improving sleep
- Although improvements in stress were only observed for the intervention group – the post-intervention stress levels were not significantly different between the groups.
- Thus, we should interpret the results with some caution
Clinical practice applications:
- Providing advice on dietary intake of foods known to positively impact gut microbiota may be helpful for individuals affected by stress or sleep problems
- The inclusion of the following foods may be helpful:
- High prebiotic fruit & veg (6-8 per day)
- Grains (5-8 per day)
- Fermented foods (2-3 per day)
- Legumes (3-4 per week)
Considerations for future research:
- Important to replicate these results in a larger sample
- It might be helpful to investigate individual aspects of the diet separately, to assess their individual impact
- Objective measures of sleep (such as actigraphy recordings) might provide additionally useful findings
- It would be interesting to explore the effect of the psychobiotic diet in other conditions
- Chronobiology or chrononutrition - i.e. looking at timing of the foods proposed in the section above
Abstract
The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.