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The Influence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the Duration and Severity of Symptoms among Individuals with Covid-19
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2024
Abstract
Gut microbial irregularities can lead to increased gut inflammation and gut membrane damage in people with long covid. Symptoms such as cough and breathlessness are apparent in Covid 19 patients with harmful gut bacterial overgrowth. In Covid patients, antibiotic and dexamethasone treatment also aggravates gut microbial imbalances. Lactobacillus supplementation has been shown to lessen upper respiratory tract infection, increase gut bacterial diversity, improve gut wall integrity, reduce gastrointestinal symptoms and gut inflammation, decrease oxidative stress and improve immunity. This study analysed the efficacy of probiotics and prebiotics combined supplements in reducing the severity and longevity of symptomatic Covid infection. 126 participants with Covid symptoms consumed two capsules a day for a month of a supplement containing 5 species of Lactobacillus and chicory inulin. 32% of participants were in the early phase of infection, and 68% were in the late phase. Both early and late phase participants showed significant improvements in cough, fatigue, and subjective wellbeing after 30 days of intervention. The gut symptoms of 82% of the participants improved after a month of intervention. Inulin and Lactobacillus strains need to be studied further robustly to determine whether they provide additional benefits. Healthcare practitioners can use the results of this study to consider symbiotic interventions for those with Covid symptoms.
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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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Evaluation of Lactocare® Synbiotic Administration on the Serum Electrolytes and Trace Elements Levels in Psoriasis Patients: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial Study.
Akbarzadeh, A, Taheri, M, Ebrahimi, B, Alirezaei, P, Doosti-Irani, A, Soleimani, M, Nouri, F
Biological trace element research. 2022;200(10):4230-4237
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Psoriasis is an immune-mediated chronic inflammatory skin disorder characterised by plaques and lesions on the skin. While the etiopathogenesis of psoriasis is not completely understood, various mechanisms have been implicated, including changes in the composition of intestinal microbes, oxidative stress and changes in the levels of certain trace elements. Previous research has shown that fluctuations in trace minerals such as zinc and copper may contribute to the progression and progression of psoriasis. It is known that synbiotics, which are combinations of probiotics and prebiotics, have immune-modulating properties, and they may also enhance the absorption of trace minerals from food when consumed. This double-blind, randomised, placebo-controlled trial was conducted to randomly assign sixty-four patients with mild-to-moderate psoriasis to consume Lactocare, a symbiotic containing seven strains of probiotic bacteria and prebiotic fructooligosaccharide twice daily or a placebo for 12 weeks. Serum trace mineral levels were measured after 12 weeks of treatment, including Fe, K, Ca, Mg, P, Zn, Na, and Cu. A significant improvement in serum levels of zinc and calcium was observed in the symbiotic group after 12 weeks of treatment. Additionally, the symbiotic treatment significantly increased the levels of trace minerals such as Fe, Ca, Mg, P, Zn, and Na within the group compared to the baseline. Fe and Cu levels in the treatment group were affected by sex, with male participants showing significant differences. To evaluate the other benefits of symbiotic preparations in patients with psoriasis, further large-scale studies are required. Healthcare professionals can utilise the research to understand the immune-modulating and anti-inflammatory properties of symbiotic formulations such as Lactocare, as well as to understand how the consumption of Lactocare improves the absorption of trace minerals.
Abstract
BACKGROUND Despite the exact etiopathogenesis of psoriasis remains unknown, the increasing or decreasing of some trace elements and oxidative stress status are considered to play a role. In this study, the effect of Lactocare® synbiotic on the serum levels of trace elements including Zn, Cu, Mg, Na, Fe, P, Ca, and K in the patients with mild to moderate psoriasis was investigated. METHODS Sixty-four patients with mild to moderate psoriasis were included. Patients were randomly divided into treatment (n═32) and control (n═32) groups. The treatment group received Lactocare® and the control group received a placebo (two times daily for 12 weeks). Eight patients from the intervention group and 18 patients from the control group discontinued the study because of the recent COVID-19 condition. For routine trace element analysis, the blood samples were collected from all patients at the baseline as well as week 12 post-treatment. The serum was then isolated and the serum levels of trace elements including Fe, K, Ca, Mg, P, Zn, Na, and Cu were measured using an automatic electrolyte analyzer. For confirmation of the effect of Lactocare® on the alteration of serum levels of trace elements, intra-group analysis was performed at two interval times: baseline and week 12 post-treatment. RESULTS The serum levels of K, P, and Ca in the placebo group were significantly higher than that of the treatment group at baseline. Serum levels of Zn and Ca were significantly higher in the treatment group compared to the placebo group at week 12 post-treatment. Moreover, a significantly lower serum level of K, P, and Ca in the treatment group at the baseline compared to the placebo group was compensated on week 12 post-treatment. Intra-group analysis in the treatment group showed that the serum levels of Fe, Ca, Mg, P, Zn, and Na was significantly increased at week 12 post-treatment compared to baseline levels. Whereas, intra-group analysis in the control group showed only Ca has a significant difference between baseline and week 12 post-treatment. CONCLUSION The serum levels of Fe, Zn, P, Mg, Ca, and Na are increased significantly 12 weeks after oral administration of Lactocare® in psoriatic patients. The serum level of Fe and Cu is affected by sex at pre- and post-treatment. This study supports the concept that Lactocare® exerts beneficial effects in the gastrointestinal tract to improve mineral absorption in psoriatic patients.
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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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Microbiological and clinical effects of probiotics and antibiotics on nonsurgical treatment of chronic periodontitis: a randomized placebo- controlled trial with 9-month follow-up.
Morales, A, Gandolfo, A, Bravo, J, Carvajal, P, Silva, N, Godoy, C, Garcia-Sesnich, J, Hoare, A, Diaz, P, Gamonal, J
Journal of applied oral science : revista FOB. 2018;26:e20170075
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Chronic periodontitis is an inflammatory disease affecting the gums caused by the accumulation of dental bacterial plaque. There has been evidence that certain bacteria, like Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, are related to the development of chronic perdontitis. Research has shown that probiotic species such as Lactobacillus rhamnosus inhibit the growth of bacteria that cause gum disease. This parallel-arm, randomised, double-blinded, placebo-controlled clinical trial investigated the effects of Lactobacillus rhamnosus SP1 or Azithromycin tablets as an addition to non-surgical therapy on clinical and microbiological parameters of chronic periodontitis in healthy subjects. Participants in the intervention group consumed a probiotic sachet containing Lactobacillus rhamnosus SP1 and an antibiotic placebo daily for three months, whereas the placebo group consumed azithromycin 500 mg for five days and a probiotic placebo. At 6 weeks follow-up, both the probiotic group and the antibiotic group demonstrated improvements in clinical and microbiological parameters with a reduction in cultivable microbiota such as Tannerella forsythia, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The antibiotic group reduced the number of people with chronic periodontitis more effectively than the probiotic group, but there was no significant difference between the two. To identify the most effective probiotic therapy for chronic periodontitis, more robust studies are required. The results of this study can be used by healthcare professionals to learn about the effects of probiotic therapy in patients with chronic periodontitis.
Abstract
The aim of this double-blind, placebo-controlled and parallel- arm randomized clinical trial was to evaluate the effects of Lactobacillus rhamnosus SP1-containing probiotic sachet and azithromycin tablets as an adjunct to nonsurgical therapy in clinical parameters and in presence and levels of Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Forty-seven systemically healthy volunteers with chronic periodontitis were recruited and monitored clinically and microbiologically at baseline for 3, 6 and 9 months after therapy. Subgingival plaque samples were collected from four periodontal sites with clinical attachment level ≥1 mm, probing pocket depth ≥4 mm and bleeding on probing, one site in each quadrant. Samples were cultivated and processed using the PCR technique. Patients received nonsurgical therapy including scaling and root planing (SRP) and were randomly assigned to a probiotic (n=16), antibiotic (n = 16) or placebo (n = 15) group. L. rhamnosus SP1 was taken once a day for 3 months. Azithromycin 500mg was taken once a day for 5 days. All groups showed improvements in clinical and microbiological parameters at all time points evaluated. Probiotic and antibiotic groups showed greater reductions in cultivable microbiota compared with baseline. The placebo group showed greater reduction in number of subjects with P. gingivalis compared with baseline. However, there were no significant differences between groups. The adjunctive use of L. rhamnosus SP1 sachets and azithromycin during initial therapy resulted in similar clinical and microbiological improvements compared with the placebo group.
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Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study.
Eggers, S, Barker, AK, Valentine, S, Hess, T, Duster, M, Safdar, N
BMC infectious diseases. 2018;18(1):129
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The bacteria Staphylococcus aureus (S. aureus) is found in the digestive tract, nostrils, mouth and armpits. Methicillin-resistant S. aureus (MRSA) is responsible for several difficult-to-treat infections in humans. Probiotics are emerging as an alternative to antibiotics in preventing or treating bacterial infections. This randomised controlled trial aimed to determine the ability of Lactobacillus rhamnosus (L. rhamnosus) HN001 to reduce S. aureus at several different body sites. Participants in the study were mostly male, with an average age of 64 years, and all carriers of S. aureus in one or more body sites. Participants were organised into groups depending on whether S. aureus was found within the gastrointestinal tract (GI) or in other body sites (extra-GI), and given either L. rhamnosus HN001 probiotic, or a placebo for four weeks. Subjects given the probiotic had 15% lower levels of S. aureus in their stool samples than those given the placebo at the end of the trial. They also had 73% reduced odds of methicillin-susceptible S. aureus (MSSA) presence, and 83% reduced odds of any S. aureus presence in the stool sample compared to the placebo group. No other sampling sites showed a significant difference in colonisation between the two groups. The authors concluded that use of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites. The results of the study support the use of this probiotic strain for reducing the population of S. aureus in the gut. Further studies are needed to assess the effectiveness of different probiotic strains and to compare probiotics with antibiotics in reducing S. aureus in other body sites.
Abstract
BACKGROUND Infection by Staphylococcus aureus (S. aureus) is a major cause of morbidity and mortality. Colonization by S. aureus increases the risk of infection. Little is known about decolonization strategies for S. aureus beyond antibiotics, however probiotics represent a promising alternative. A randomized controlled trial was conducted to determine the efficacy of Lactobacillus rhamnosus (L. rhamnosus) HN001 in reducing carriage of S. aureus at multiple body sites. METHODS One hundred thirteen subjects, positive for S. aureus carriage, were recruited from the William S. Middleton Memorial Medical Center, Madison, WI, USA, and randomized by initial site of colonization, either gastrointestinal (GI) or extra-GI, to 4-weeks of oral L. rhamnosus HN001 probiotic, or placebo. Nasal, oropharyngeal, and axillary/groin swabs were obtained, and serial blood and fecal samples were collected. Differences in prevalence of S. aureus carriage at the end of the 4-weeks of treatment were assessed. RESULTS The probiotic and placebo groups were similar in age, gender, and health history at baseline. S. aureus colonization within the stool samples of the extra-GI group was 15% lower in the probiotic than placebo group at the endpoint of the trial. Those in the probiotic group compared to the placebo group had 73% reduced odds (OR 0.27, 95% CI 0.07-0.98) of methicillin-susceptible S. aureus presence, and 83% reduced odds (OR 0.17, 95% CI 0.04-0.73) of any S. aureus presence in the stool sample at endpoint. CONCLUSION Use of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01321606 . Registered March 21, 2011.
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The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature.
Reis, DJ, Ilardi, SS, Punt, SEW
PloS one. 2018;13(6):e0199041
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The microbiome-gut-brain axis in general and the possibility of altering the microbiome through administration of probiotics to support physical and mental health has received much attention in recent years. Here, a systematic review and meta-analysis were carried out to evaluate the clinical and preclinical evidence for the use of probiotics in anxiety. 22 preclinical (rodent) studies were included in the meta-analysis and showed an overall significant anxiolytic effect of probiotics in diseased, but not healthy, animals. Studies were heterogenous with regards to species and strains of probiotic used. Subgroup analysis showed that only Lactobacillus rhamnosus significantly reduced anxiety-like behaviour. 14 human studies were included in the meta-analysis and overall no anxiolytic effect was observed. Only three out of the 14 studies showed a positive effect (vs 12 out of the 22 animal studies), one of which used L. rhamnosus. Due to the small number of trials no subgroup analysis could be performed. Apart from the small number and heterogeneity of human studies, the authors discuss further possible reasons for the discrepancy between animal and human studies: • Dose: Dosages were typically 100 times higher (per kg) in animals than in humans. • Diseased vs healthy subjects: In animal studies, only those which investigated animals displaying anxiety related behaviour improved with probiotic administration. None of the human studies specifically recruited anxious individuals, eight of the studies included healthy subjects, the other six selected participants for other disorders, including four for irritable bowel syndrome. The authors conclude that more research into an anxiolytic effect of probiotics in humans is warranted, especially using L. rhamnosus, studying patients with anxiety, and using higher dosages and longer study duration.
Expert Review
Conflicts of interest:
None
Take Home Message:
- While preclinical animal studies suggest that probiotics may help reduce anxiety, such findings have not yet translated to clinical research in humans.
- Further investigation of probiotic treatment for clinically relevant anxiety is warranted, particularly with respect to the probiotic species L. rhamnosus.
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 review highlights how important it is for future studies to focus on clinically anxious patients and also to consider exploring the effects of differing doses of probiotics in this population.
Clinical practice applications:
Anxiety disorders affect as many as 3 in 10 people at some point during their lifetime. On that basis, it would be great to have a viable non-pharmaceutical option to help with some of the symptoms.
Considerations for future research:
If the results from the pre-clinical studies can be corroborated in human populations, this could have widespread clinical implications.
Abstract
BACKGROUND Probiotics have generated intensive research interest in recent years as a novel mode of treatment for physical and mental illness. Nevertheless, the anxiolytic potential of probiotics remains unclear. The present systematic review and meta-analysis aimed to evaluate the clinical and preclinical (animal model) evidence regarding the effect of probiotic administration on anxiety. METHODS The PubMed, PsycINFO, and Web of Science databases were reviewed for preclinical and clinical studies that met the defined inclusion and exclusion criteria. The effects of probiotics on anxiety-like behavior and symptoms of anxiety were analyzed by meta-analyses. Separate subgroup analyses were conducted on diseased versus healthy animals, specific preclinical probiotic species, and clinical versus healthy human samples. RESULTS Data were extracted from 22 preclinical studies (743 animals) and 14 clinical studies (1527 individuals). Overall, probiotics reduced anxiety-like behavior in animals (Hedges' g = -0.47, 95% CI -0.77 --0.16, p = 0.004). Subgroup analyses revealed a significant reduction only among diseased animals. Probiotic species-level analyses identified only Lactobacillus (L.) rhamnosus as an anxiolytic species, but these analyses were broadly under-powered. Probiotics did not significantly reduce symptoms of anxiety in humans (Hedges' g = -0.12, 95% CI -0.29-0.05, p = 0.151), and did not differentially affect clinical and healthy human samples. CONCLUSIONS While preclinical (animal) studies suggest that probiotics may help reduce anxiety, such findings have not yet translated to clinical research in humans, perhaps due to the dearth of extant research with clinically anxious populations. Further investigation of probiotic treatment for clinically relevant anxiety is warranted, particularly with respect to the probiotic species L. rhamnosus.