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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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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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A randomized trial of probiotic supplementation in nurses to reduce stress and viral illness.
Slykerman, RF, Li, E
Scientific reports. 2022;12(1):14742
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Dynamic communication occurs between the gut microbiota and the central nervous system along multiple physiological pathways. Stress increases glucocorticoid production and activation of the hypothalamic–pituitary–adrenal axis, affecting immunological function and neuronal changes. The aim of this study was to investigate whether supplementation with the probiotic Lactobacillus rhamnosus HN001 could reduce symptoms of stress and anxiety and improve psychological wellbeing in nurses working during the COVID19 pandemic. This study was a large double-blind, placebo-controlled randomised trial of probiotic supplementation with two parallel arms and a ratio of allocation to probiotic or placebo of 1:1. Results showed that following the intervention, stress, anxiety, and psychological wellbeing were not significantly different between nurses supplemented with the probiotic and those who received the placebo. Furthermore, the average number of days per week that nurses reported symptoms of cold or flu-like illness did not significantly differ between the probiotic and placebo supplemented groups. Authors conclude that there weren’t significant differences in outcomes between the probiotic and placebo groups.
Abstract
Animal studies demonstrate how the gut microbiota influence psychological health and immunity to viral infections through their actions along multiple dynamic pathways in the body. Considerable interest exists in probiotics to reduce stress and illness symptoms through beneficial effects in the gut, but translating pre-clinical evidence from animal models into humans remains challenging. We conducted a large trial in nurses working during the 2020 COVID19 pandemic year to establish whether daily ingestion of the probiotic Lactobacillus rhamnosus HN001 reduced perceived stress and the number of days participants reported symptoms of a viral illness. Our results showed no significant difference in perceived stress or the average number of illness days between probiotic supplemented nurses and the placebo group. Stress and viral illness symptoms reduced during the study for all participants, a trajectory likely influenced by societal-level factors. The powerful effect of a well-managed public health response to the COVID19 pandemic and the elimination of COVID19 from the community in 2020 may have altered the trajectory of stress levels and reduced circulating viral infections making it difficult to detect any effect of probiotic supplementation. Our study highlights the challenge in controlling environmental factors in human trials.
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Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.
Quero, CD, Manonelles, P, Fernández, M, Abellán-Aynés, O, López-Plaza, D, Andreu-Caravaca, L, Hinchado, MD, Gálvez, I, Ortega, E
Nutrients. 2021;13(4)
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Synbiotic, a mixture of prebiotics and probiotics, is known to improve neurotransmitter interactions, immune, inflammatory, and stress responses by modulating the gut microbial composition. It is also believed that physical activity plays an important role in the modulation of immune function and stress response. The purpose of this triple-blinded, randomized, placebo-controlled pilot study was to evaluate the health benefits of symbiotic intervention in fourteen sedentary students and thirteen soccer players, especially in terms of improving immunophysiological and metabolic parameters. The 300mg of symbiotic intervention contained Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, Bifidobacterium longum ES1(109 colony-forming unit), and fructooligosaccharides (200 mg) plus 1.5 mg of zinc, 8.25 µg of selenium, 0.75 µg of vitamin, and maltodextrin. Following a one-month intervention with synbiotic formulation, soccer players showed improvements in anxiety, sleep quality and stress, a slight reduction in proinflammatory cytokine IL-1β, an exercise-induced significant increase in dopamine and a slight elevation of corticotropin-releasing hormone. For confirmation of results of this pilot study and to assess more significant effects of symbiotic intervention in athletes as well as in the general population, longer-term robust studies are required. The findings of this study can help healthcare professionals understand the extensive health benefits of synbiotic intervention and its relationship to physical activity.
Abstract
The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.
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Gut dysbiosis: a potential link between increased cancer risk in ageing and inflammaging.
Biragyn, A, Ferrucci, L
The Lancet. Oncology. 2018;19(6):e295-e304
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This study looks at the important role our gut bacterial and commensal microbes play in supporting immunity and potentially reducing the risk of cancer from aging. Cancer risk increases as we age and is one of the main causes of reduced life expectancy. Our gut microbiome changes continually in response to diet, lifestyle, infection, and activation of immune responses. Gut dysbiosis is characterised by a shift towards proinflammatory commensals and a reduction of beneficial microbes, which can cause impairment and leakiness of the intestinal barrier. This is thought to trigger inflammaging or rather aging in a state of continual inflammation, where the immune system is in a heightened state of activation, and the body essentially creates an environment conducive to cancer. The gut is populated by trillions of species of bacteria which work together with our immune cells. As we age the diversity and density of these beneficial bacteria reduce. Therapies which support the balance of our commensal bacteria may prove effective at reducing rates of cancer in the elderly.
Abstract
Cancer incidence substantially increases with ageing in both men and women, although the reason for this increase is unknown. In this Series paper, we propose that age-associated changes in gut commensal microbes, otherwise known as the microbiota, facilitate cancer development and growth by compromising immune fitness. Ageing is associated with a reduction in the beneficial commensal microbes, which control the expansion of pathogenic commensals and maintain the integrity of the intestinal barrier through the production of mucus and lipid metabolites, such as short-chain fatty acids. Expansion of gut dysbiosis and leakage of microbial products contributes to the chronic proinflammatory state (inflammaging), which negatively affects the immune system and impairs the removal of mutant and senescent cells, thereby enabling tumour outgrowth. Studies in animal models and the importance of commensals in cancer immunotherapy suggest that this status can be reversible. Thus, interventions that alter the composition of the gut microbiota might reduce inflammaging and rejuvenate immune functions to provide anticancer benefits in frail elderly people.
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Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Nagy-Szakal, D, Williams, BL, Mishra, N, Che, X, Lee, B, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, et al
Microbiome. 2017;5(1):44
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, swollen lymph glands and irritable bowel syndrome (IBS). It is associated with gut bacterial dysbiosis, systemic inflammation and both gastro intestinal (GI) and neurological disturbances. The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. This experiment looked at fecal bacterial samples and metabolic pathway markers in 50 ME/CFS patients and 50 healthy controls. In ME/CFS subgroups, measures of symptom severity including pain, fatigue, and reduced motivation were correlated with the amounts and types of gut bacteria and certain metabolic pathways. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. This may enable more accurate diagnosis and the development of specific therapeutic strategies.
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.