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Bifidobacterium longum subsp. longum Reduces Perceived Psychological Stress in Healthy Adults: An Exploratory Clinical Trial.
Boehme, M, Rémond-Derbez, N, Lerond, C, Lavalle, L, Keddani, S, Steinmann, M, Rytz, A, Dalile, B, Verbeke, K, Van Oudenhove, L, et al
Nutrients. 2023;15(14)
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Plain language summary
Psychosocial stress is a common issue and one way in which nutrition may modulate the stress response is via the microbiota-gut-brain axis. This 6-week randomised, double-blind, placebo-controlled trial of 45 healthy adults with mild-to-moderate stress evaluated the effects of Bifidobacterium longum (BL) NCC3001 on psychological and physiological markers of stress and the response to an acute stress test. Outcome measures included cortisol awakening response, heart rate, heart rate variability and various questionnaires assessing stress, anxiety, depression, sleep and gastrointestinal symptoms. Compared to placebo, probiotic intake led to a significant decrease in perceived stress and an improvement in subjective sleep after 6 weeks. There was no difference in cortisol awakening response. The subjects in both groups did not experience significant gastrointestinal symptoms and scored low on anxiety and depression at baseline. In response to the acute stress test, cortisol levels were higher in the probiotic than the placebo group, whilst no clear differences were seen in heart rate and heart rate variability. Subjects in the probiotic group had a lower pain experience during the stress test whilst subjects in the placebo group had an increase in positive mood following the test. The authors conclude that these results support their hypothesis that BL NCC3001 may alleviate stress and improve sleep in adults with moderate stress levels.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There is mounting evidence to suggest that nutritional interventions can influence our stress responses. One of the routes by which nutrition can influence physiological and psychological stress responses involves the microbiota– gut–brain-axis.
- This exploratory trial suggests that supplementation with Bifidobacterium longum (BL) strain NCC3001 leads to a beneficial effect on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.
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 randomised, placebo-controlled, two-arm, parallel, double-blind exploratory clinical trial was conducted to investigate the effect Bifidobacterium longum (BL) strain NCC3001 on stress-related psychological and physiological parameters and acute stress in healthy adults who typically experience mild-to-moderate-levels of stress.
Method
47 Participants between the ages of 25-65 years old with mild-to-moderate psychological stress received 1x1010 CFU of Bifidobacterium longum (BL) strain NCC3001 daily or a placebo for 6 weeks.
Participants completed the Perceived Stress Scale (PSS), the Hospital Anxiety and Depression Scales (HAD-A and HADS-D), the Gastrointestinal Symptom Rating Scale (GSRA), the Pittsburgh Sleep Quality Index (PSQI) questionnaire, the Positive and Negative Affect Schedule (PANAS), the State Trait Anxiety Inventory (STAI-6), the Maastricht Acute Stress Test (MAST) and the Visual Analog Scales (VAS, which measures pain intensity) during the clinical study. The Depression, Anxiety and Stress Scale (DASS-42) questionnaire was also used to depict the progression of the participants through the study.
Faecal samples were taken at baseline and 6 weeks and awakening saliva samples were taken at baseline, 2, 4, 6 and 8 weeks. At the endpoint, 45/49 (91%) of the subjects completed the study. One participant reported an adverse event and the other withdrew without an explanation. Two participants were excluded from the full analysis.
Results
The primary outcomes were:
- After 6-week of the probiotic intervention, there was a significant decrease in perceived stress in the probiotic group (21.4%) compared to the placebo group (-10.2%), p = 0.017.
- There was a significant improvement in subjective sleep in the probiotic group compared to the placebo group (p = 0.037).
- There was a significant decrease in the positive PANAS change score from the pre-stressor stage in the probiotic group compared to the placebo group (p = 0.01).
- There were lower pain values (VAS) scores from pre-stressor to post-stressor in the probiotic group compared to the placebo group (p = 0.05).
- There was no significant difference between groups in anxiety (HADS-A) and Depression (HADS_D) scores.
Conclusion
Oral supplementation with BL NCC3001 may have beneficial effects on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.
Clinical practice applications:
- While the mechanism underlying the correlation between the microbiota and the gut-brain-axis is not fully understood, it is thought to play a critical role in the links between the microbiota, mood, stress, and brain health.
- This exploratory trial additionally supports the potential of specific probiotics being used to reduce perceived stress and improve subjective sleep quality in healthy adults.
Considerations for future research:
- Larger, powered clinical trials are needed to provide further insights into the mechanisms underlying the stress-relieving and sleep-improving effect of Bifidobacterium longum.
- Furthermore, the dosage and duration of the probiotics need further investigation in a larger healthy population.
- Comparative research is needed to help investigate the effect of different probiotic strains on stress relief and sleep quality.
Abstract
Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with Bifidobacterium longum (BL) NCC3001 (1 × 1010 CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into BL NCC3001 to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.
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Nutritional and lifestyle management of the aging journey: A narrative review.
Kassis, A, Fichot, MC, Horcajada, MN, Horstman, AMH, Duncan, P, Bergonzelli, G, Preitner, N, Zimmermann, D, Bosco, N, Vidal, K, et al
Frontiers in nutrition. 2022;:1087505
Abstract
With age, the physiological responses to occasional or regular stressors from a broad range of functions tend to change and adjust at a different pace and restoring these functions in the normal healthy range becomes increasingly challenging. Even if this natural decline is somehow unavoidable, opportunities exist to slow down and attenuate the impact of advancing age on major physiological processes which, when weakened, constitute the hallmarks of aging. This narrative review revisits the current knowledge related to the aging process and its impact on key metabolic functions including immune, digestive, nervous, musculoskeletal, and cardiovascular functions; and revisits insights into the important biological targets that could inspire effective strategies to promote healthy aging.
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Extruded Wheat Bran Consumption Increases Serum Short-Chain Fatty Acids but Does Not Modulate Psychobiological Functions in Healthy Men: A Randomized, Placebo-Controlled Trial.
Dalile, B, La Torre, D, Kalc, P, Zoppas, F, Roye, C, Loret, C, Lamothe, L, Bergonzelli, G, Courtin, CM, Vervliet, B, et al
Frontiers in nutrition. 2022;:896154
Abstract
BACKGROUND Incorporation of wheat bran (WB) into food products increases intake of dietary fiber, which has been associated with improved mood and cognition and a lower risk for psychiatric disorders such as depression, with short-chain fatty acids (SCFAs) as candidate mediators of these effects. Modifying WB using extrusion cooking increases SCFA production in vitro relative to unmodified WB. OBJECTIVE The aim of this study was to evaluate the effects of extruded WB on psychobiological functioning and the mediating role of SCFAs. METHODS In a randomized, triple-blind, placebo-controlled trial, 69 healthy male participants consumed 55 g of breakfast cereal containing either extruded WB or placebo daily for 28 days. At pre- and post-intervention visits, the cortisol response to experimentally induced stress was measured as a primary outcome. In addition, serum SCFAs and brain-derived neurotrophic factors were quantified as potential mediators. Secondary psychobiological outcomes included subjective stress responses, responses to experimentally induced fear, cortisol awakening response, heart rate variability, and retrospective subjective mood ratings. Intestinal permeability, fecal SCFAs, and stool consistency were measured as secondary biological outcomes. RESULTS Extruded WB increased serum acetate and butyrate (p < 0.05). None of the primary or secondary outcomes were affected by the intervention. Participants who consumed a placebo exhibited an increase in the percentage of fecal dry weight but did not report increased constipation. Despite these statistically significant effects, these changes were small in magnitude. CONCLUSIONS Extruded WB consumption increased serum short-chain fatty acids but did not modulate psychobiological functions in healthy men. Effective modulation of psychobiological functions may require greater increases in SCFAs than those achieved following extruded WB consumption. Rather than attempting to induce health benefits with a single fiber-rich food, combinations of different fibers, particularly highly fermentable ones, might be needed to further increase SCFA production and uptake in the systemic circulation to observe an effect on psychobiological processes.
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Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: a randomized, placebo-controlled trial.
Dalile, B, Vervliet, B, Bergonzelli, G, Verbeke, K, Van Oudenhove, L
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2020;(13):2257-2266
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Abstract
Short-chain fatty acids (SCFAs) are products of microbial fermentation of dietary fiber in the colon and may mediate microbiota-gut-brain communication. However, their role in modulating psychobiological processes that underlie the development of stress- and anxiety-related disorders is not mechanistically studied in humans. In this triple-blind, randomized, placebo-controlled intervention trial, we examine in a parallel group design the effects of 1-week colonic SCFA-mixture delivery in doses equivalent to fermentation of 10 g or 20 g of arabinoxylan oligosaccharides on responses to psychosocial stress and fear tasks in 66 healthy men. We demonstrate that low and high doses of SCFAs significantly attenuate the cortisol response to psychosocial stress compared to placebo. Both doses of SCFAs increase serum SCFA levels and this increase in circulating SCFAs co-varies significantly with the attenuation of the cortisol response to psychosocial stress. Colonic SCFA delivery does not modulate fecal SCFA concentrations, serum brain-derived neurotrophic factor, cortisol awakening response, fear learning and extinction, or subjective mood ratings. These results demonstrate that colon-delivered SCFAs modulate hypothalamic-pituitary-adrenal axis reactivity to psychosocial stress, thereby supporting their hypothesized role in microbiota-gut-brain communication.
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Short-Term Daily Intake of Polydextrose Fiber Does Not Shorten Intestinal Transit Time in Constipated Adults: A Randomized Controlled Trial.
Duncan, PI, Enters-Weijnen, CF, Emami, N, McLean, P, Nunes, T, Beaumont, M, Crabbe, R, Whelan, K, Scott, SM, deWit, NJ, et al
Nutrients. 2018;(7)
Abstract
Chronic constipation (CC) remains a common gastrointestinal (GI) disorder that conveys a substantial healthcare burden. Expert guidelines recommend increasing fiber intake, yet the clinical evidence to support this needs strengthening for specific fibers. The aim was to evaluate changes in intestinal transit time and GI symptoms in CC patients who consumed polydextrose. In a randomized, double-blind, placebo-controlled trial, 128 adults with CC received 8 g or 12 g polydextrose, or placebo, daily for 4 weeks. Transit time, as primary outcome, was assessed by radiopaque marker distribution after 2-weeks intervention. Bowel habits, GI symptoms and quality of life (QOL) were assessed by questionnaire, including the Patient-Assessment of Constipation (PAC) Symptoms (SYM), and PAC-QOL. Following 2-weeks intervention, no reduction was seen in transit time in any group and following 2- or 4-weeks intervention, no improvements were seen in stool frequency or consistency in any group. After 2-weeks intervention with 8 g/day polydextrose an improvement was seen in the PAC-SYM rectal score (p = 0.041). After 4-weeks intervention both rectal (p = 0.049) and stool (p = 0.029) scores improved while improvement in the QOL satisfaction score did not reach significance (p = 0.071). Overall, the results suggest that 2-weeks consumption of 8 or 12 g/day polydextrose does not significantly improve physiological measures of gut function in CC adults. Longer term consumption may improve clinical measures, but further studies will be required to substantiate this.
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Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.
Pinto-Sanchez, MI, Hall, GB, Ghajar, K, Nardelli, A, Bolino, C, Lau, JT, Martin, FP, Cominetti, O, Welsh, C, Rieder, A, et al
Gastroenterology. 2017;(2):448-459.e8
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Abstract
BACKGROUND & AIMS Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. METHODS We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. RESULTS At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites. At week 10, depression scores were reduced in patients given BL vs placebo. CONCLUSION In a placebo-controlled trial, we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS. These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity. ClinicalTrials.gov no. NCT01276626.
