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临床试验/NCT05567653
NCT05567653已完成不适用

Effects of 3-month Probiotic Mix Supplementation (L. Helveticus R-0052, B. Longum R-0175) on Gut Microbiota and Metabolome, Endocannabinoid and Immune Systems Activation, Along With Symptoms of Fatigue in Professional Dancers

Poznan University of Physical Education1 个研究点 分布在 1 个国家目标入组 26 人开始时间: 2022年10月1日最近更新:
适应症
干预措施

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
26
试验地点
1
主要终点
Qualitative Assessment of Intestinal Microbiota in Stool Samples

研究概览

简要总结

The aim of the planned research is to assess the dynamics of changes in the elements of the gut-brain axis (GBA), the cytokine profile and the endocannabinoid system markers, after dietary supplementation with probiotics Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175 by professional dancers. Although in recent years there has been growing interest in the influence of the gut microbiota on the body's adaptation to stress stimuli and on overall health, there is a lack of information on the influence of probiotics on systems involved in maintaining neuropsychiatric balance, such as the endocannabinoid system.

In order to determine the validity of the applied therapy with selective probiotics, the following will be assessed: intestinal bacteria and bacterial metabolites in the stool, cannabinoids and cannabinoid receptors and enzymes in the blood, indicators of mental distress in the blood, cytokines responsible for the modulation of the gut-brain axis in the blood, as well as questionnaires regarding the functioning of the digestive tract, fatigue, stress and sleep quality.

The study will involve active dancers of the Polish Theater in Poznan, the Polish Dance Theater, the Private School of Dance Art in Poznan and students of the Academy of Physical Education in the field of Dance. Dancers are a group of athletes that is exposed to particular injuries and work-overload. Professional dancers spend multiple hours a week on intensive physical training. The largest percentage of injuries occurring in the group of professional dancers are chronic injuries, including: inflammation of soft tissues, muscle strains and tears.

Professional dance is one of the most physically demanding forms of physical activity, and at the same time it is associated with a high burden on the nervous system problems caused by performances in front of an audience or subjective jury, frequent traveling and disturbances in the circadian rhythm.

详细描述

Professional dancers are often referred to as artistic athletes due to their high level of physical activity and competition. Training dance for over 11.5 hours a week increases the risk of injury (women - mostly bone injuries, men - mostly bruises and tendon injuries). One of the reasons for the increased susceptibility to injuries among dancers is psychological stress. The observations results indicate that dancers often decide to continue training despite feeling pain, which limits the smoothness of their movements and leads to a further increase of stress. Highly physically active groups of people are more exposed to functional dyspepsia (FD) and irritable bowel syndrome (IBS), which occurence is correlated to chronic stress. As a result of chronic stress and the activation of the hypothalamic pituitary-adrenal axis (HPA), inflammatory processes in the gastrointestinal mucosa are initiated. The presence of noradrenaline increases the adhesion of bacteria and viruses to the epithelium, which in turn modulates the immune system within the intestines and increases their inflammation. Systemically acting cortisol causes the leakage of tight junctions (TJ) cells and an increase in the permeability of the intestinal barrier. Inflammation stimulates the secretion of cortisol, which initiates the further cycle of inflammation and weakening of the intestinal barrier function. As a consequence, cytokines and inflammatory mediators released in the course of inflammation act directly on the nerve endings that transmit these afferent nerve signals to the brain, becoming an endogenous stressor.

When exogenous and endogenous stress factors overlap, the body's perception of stress increases, which ultimately leads to psychological, physiological and behavioral changes.

Pain and depression are common comorbidities of neuropsychiatric origin. One of the body's regulatory systems, which in both cases is dysfunctional, is the endocannabinoid system (ECS). It has been suggested that these diseases can be caused by intense and prolonged exercise, which disrupts the intestinal barrier, causing changes in the profile of metabolites and the function of the intestinal microbiota. Overtraining leads to an increase in the levels of cortisol, adrenaline and noradrenaline, and to the translocation of lipopolysaccharide (LPS) outside the gut, increasing the concentration of pro-inflammatory cytokines in the body. This results in dysregulation of the balance between serotonin (5-HT), dopamine (DA) and gamma-aminobutyric acid (GABA) and fatigue. These changes lead to further activation of the endocannabinoid system and, in the long-term, weakening of adaptive abilities.

The neuromodulatory properties of the cannabinoid system are manifested e.g. in short- and long-term synaptic plasticity and modulation of pain conduction. Research results indicate that the endocannabinoid system, in addition to its key role in regulating intestinal motility, also affects the secretory functions of the gastrointestinal tract and the integrity of the intestinal epithelium, which may be an alternative way to regulate the immune system and inflammation in the intestines.

Type 1 cannabinoid receptors (CB1) are located presynaptically in the cell membrane of central and peripheral nervous system neurons, and their activation inhibits the release of many neurotransmitters, i.e. acetylcholine, noradrenaline, dopamine, serotonin, glutamate and γ-aminobutyric acid. Type 2 cannabinoid receptors (CB2) are found mainly on the surface of cells of the immune system, especially B-lymphocytes, macrophages and monocytes. Their activation inhibits pro-inflammatory cytokines release and increases the release of anti-inflammatory cytokines.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Triple (Participant, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 36 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • Age > 18, <36 years old;
  • Professional dancing activity with over 8 hours of training per week.

排除标准

  • Age <18,> 36 y.o.;
  • Being injured within 3 months from the start of the study;
  • Taking pre- and / or probiotics in the last 3 months before the study;
  • Hospitalization during the last 4 weeks before starting of the study;
  • Traveling to tropical countries during the last 4 weeks before study;
  • Taking antibiotics, steroids and anabolic steroids in the last 4 weeks before study.

研究组 & 干预措施

Placebo group

Placebo Comparator

ca. 30 participants

干预措施: Starch (placebo) (Dietary Supplement)

Probiotic treatment group

Experimental

ca. 30 participants

干预措施: Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175 (Sanprobi Stress) (Dietary Supplement)

结局指标

主要结局

Qualitative Assessment of Intestinal Microbiota in Stool Samples

时间窗: Baseline and 3 months

• gut bacteria species in stool will be assessed using the shallow shotgun sequencing method, NGS (Next-Generation Sequencing);

Quantitive Change in Intestinal Microbiota in Stool Samples

时间窗: Baseline and 3 months

• determination of quantitative (Colony forming units - CFU) changes in bacteria in the stool - the shallow shotgun sequencing method, NGS (Next Generation Sequencing) molecular analysis will be used to assess the changes;

Intestinal Metabolome in Stool Samples

时间窗: Baseline and 3 months

Metabolites with fold change \>1.5 and p\<0.05 were considered significantly altered. The reported values represent the number of metabolites meeting these criteria in the probiotic group. • metabolomic analysis (non-targeted metabolome, short-chain fatty acids, trimethylamines, tryptophan catabolites) will be performed on a quadrupole mass spectrometer coupled with a time-of-flight (QToF) analyzer connected to the high performance liquid chromatograph (UHPLC).

Quantitive Change in Endocannabinoids Levels in Blood Samples

时间窗: Baseline and 3 months

• determination of endocannabinoids and cannabinoid receptors: anandamide (AEA) using ELISA Kit (nanograms per millilitre (ng/mL));

Quantitive Change in Endocannabinoids' Receptors Levels in Blood Samples

时间窗: Baseline and 3 months

• determination of cannabinoid receptors: Endocannabinoid Receptor 2 (CNR2) using ELISA Kit (nanograms per millilitre (ng/mL));

Quantitive Change in Endocannabinoids Metabolism Enzymes in Blood

时间窗: Baseline and 3 months

• determination of cannabinoid metabolism enzymes: fatty acid amide hydrolase (FAAH) using ELISA Kit (nanograms per millilitre (ng/mL));

Quantitive Change in Intestinal Barrier Proteins in Blood Samples

时间窗: Baseline and 3 months

• determination of blood biomarkers of a disturbed intestinal barrier concentrations: zonulin, calprotectin (CALPRO) using ELISA Kit (nanograms per millilitre (ng/mL));

Quantitive Change in Intestinal Barrier Biomarkers in Blood Samples

时间窗: Baseline and 3 months

• determination of blood biomarkers of a disturbed intestinal barrier concentrations: lipopolysaccharide (LPS), using ELISA Kit (picograms per millilitre (pg/mL));

Quantitive Change in Tumor Necrosis Factor-alpha (TNF-α) in Blood Samples

时间窗: Baseline and 3 months

• determination of blood tumor necrosis factor-alpha (TNF-α) concentration using ELISA Kit (nanograms per millilitre (ng/mL));

Quantitive Change in Leukemia Inhibitory Factor (LIF) in Blood Samples

时间窗: Baseline and 3 months

• determination of blood leukemia inhibitory factor (LIF) concentration using ELISA Kit (nanograms per millilitre (ng/mL));

Quantitive Change in Blood Interleukins Profile

时间窗: Baseline and 3 months

• determination of interleukins concentrations: IL-1β (interleukin-1beta), using ELISA Kit (picograms per millilitre (pg/mL));

Quantitive Change in Chronic Stress Biomarker in Blood Samples - Cortisol

时间窗: Baseline and 3 months

• determination of blood cortisol concentration using ELISA Kit (nanograms per millilitre (ng/mL)) - Instead of cortisol, IL-10 levels were analyzed as a marker of anti-inflammatory response \[pg/mL\].

Quantitive Change in Inflammation Biomarker in Blood Samples - C-reactive Protein

时间窗: Baseline and 3 months

• determination of C-reactive protein (CRP) concentration using ELISA Kit (picograms per millilitre (pg/mL));

次要结局

  • Changes in Hemoglobin Level(Baseline and 3 months)
  • Body Mass Analysis (BMI, kg/m^2)(Baseline and 3 months)
  • Changes in Hematocrit(Baseline and 3 months)
  • Coping With Stress Questionnaire(Baseline and 3 months)
  • Fatigue Questionnaire(Baseline and 3 months)
  • Gastrointestinal Disorders Questionnaire(Baseline and 3 months)
  • Sleep Quality Questionnaire(Baseline and 3 months)
  • Body Composition Analysis (Percent of Total Body Mass)(Baseline and 3 months)
  • Composite Measure of Diet Composition Assessed by Food Diaries(Baseline and 3 months)
  • Pain Threshold Test (Newtons)(Baseline and 3 months)
  • Changes in Red Blood Cells Count(Baseline and 3 months)
  • Changes in White Blood Cells Count(Baseline and 3 months)
  • Changes in Platelets Counts(Baseline and 3 months)

研究者

发起方
Poznan University of Physical Education
申办方类型
Other
责任方
Principal Investigator
主要研究者

Jakub Wiącek

Principal Investigator

Poznan University of Physical Education

研究点 (1)

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