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临床试验/NCT06133530
NCT06133530Enrolling By Invitation不适用

Effects of Human Milk Oligosaccharides (HMOs) on Gut Microbiota, Immune System and Metabolism in Adults Wintering Over in Antarctica

IU University of Applied Sciences2 个研究点 分布在 1 个国家目标入组 26 人开始时间: 2023年9月24日最近更新:
适应症

试验速览

阶段
不适用
状态
Enrolling By Invitation
发起方
入组人数
26
试验地点
2
主要终点
Insulin resistance

研究概览

简要总结

Human milk oligosaccharides (HMOs) are the third-most abundant component in mothers' milk and are an important prebiotic factor for the development of the gut microbiota of infants, promoting the growth of certain beneficial bacterial strains and providing protection against many bacterial and viral infections. HMOs induce immunomodulatory activity by affecting immune cell populations and functions. In a simulator of the adult human intestinal microbial ecosystem, fermentation of HMOs led to an increase of bifidobacteria in parallel with an increase in short-chain fatty acids as well as a reduction in inflammation markers, supporting the potential of HMOs to provide health benefits also in adults. Long-term stay in microgravity induces many physiological responses, including diminished immune function and impaired glucose tolerance which may lead to rather severe consequences. Similarly, hypoxia conditions as in the Concordia station, affects the immune system and may lead to impaired glucose tolerance and insulin resistance. The hypothesis is that HMOs as a prebiotic supplement will mitigate changes in immune function, glucose tolerance, lipid homeostasis, and neurotransmitter production. It is expected that HMO supplementation will

  • Modulate gut microbiota composition and function
  • Improve inflammation status
  • Improve immune function
  • Improve glucose tolerance
  • Improve nutritional status
  • Prevent changes in neurotransmitters associated with anxiety and depression. During the stay in Antarctica an HMO blend will be supplemented to the verum group of volunteers. The control group will receive a placebo. Experiment days with blood drawing, an oral glucose tolerance test, saliva sampling, and feces samples are planned once before, about every second month in Concordia, and once after return.

详细描述

The aim of this study is to investigate the effect of supplementation with prebiotics, a specific mixture of carbohydrates found in breast milk (HMOs), as a measure to improve intestinal flora, inflammatory processes in the gut, general immune status, carbohydrate regulation, fat and bone metabolism and neurological changes in Antarctica. The approximately one-year stay at Concordia Station (Antarctica) at an altitude of about 3200 m includes a long journey and subsequent extreme environmental conditions as well as corresponding adaptation mechanisms and is therefore a very good terrestrial model (analogue model) for investigating changes during space stays. Long-term (i.e. > 6 months) exposure to microgravity leads to numerous physiological responses, including impaired glucose tolerance, reduced immune function and bone loss, which can lead to quite severe health consequences. In this analogue model, similar changes, albeit less severe, are observed with regard to the immune system or glucose tolerance as in space flight.

The composition of the diet significantly influences the composition of the intestinal flora. In particular, dietary carbohydrates provide the substrate for certain bacteria that could have a positive effect on health. Prebiotics are defined as substrates that are selectively used by host microorganisms and that provide health benefits. Prebiotics are digested only by gut microorganisms and stimulate the growth or activity of bacteria in the gut that have shown health benefits or improved well-being. The main nutrients for bacterial growth are non-digestible carbohydrates, which by definition are not digested by the host, in this case the human organism (host). Non-digestible carbohydrates include, for example, resistant starch and dextrins, non-starch polysaccharides (NSPs) (e.g. pectins) and non-digestible oligosaccharides (e.g. Raffinose, inulin, etc.). These carbohydrates are fermented by the intestinal bacteria to short-chain fatty acids (SCFAs), mainly acetic acid, propionic acid and butyric acid. This process takes place mainly in the large intestine, but also in the small intestine. SCFAs are rapidly absorbed by the mucosa of the large intestine and exert whole-body effects, contributing, for example, to the host's energy needs or mediating gut-brain communication, which has a major impact on the physiology and health of the host.

HMOs are also prebiotics and are the third most abundant solid component in breast milk. Most of the research published to date on the effects of HMOs has therefore been conducted on infants. HMOs are not digested in the intestine and are mainly utilised in the large intestine by the bacteria that reside there. In infants, it has been shown that HMOs not only promote a healthy composition of the intestinal flora, but also impair the growth of pathogens and modulate the expression of genes involved in inflammation. Several in vitro and in vivo studies have shown antiviral properties of HMOs against various viruses such as rotavirus, norovirus, HIV and influenza. HMOs play a significant role in the immune system by enhancing the immune response. Initial applications of HMOs in adults have supported these findings.

Therefore, this study aims to investigate how daily administration of 5.5 g of an HMO mixture during hibernation at Concordia Station in Antarctica affects:

  • glucose tolerance
  • inflammatory processes
  • immune function
  • fat and bone metabolism and
  • Well-being

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 65 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Physically and mentally healthy subjects
  • Volunteers that are able and declare their willingness to participate in the entire study
  • Fasting blood glucose concentration: <120 mg/dL
  • Willing to be assigned randomly either to the treatment or the control group
  • Successfully pass the medical screening
  • Signed informed consent
  • Social insurance

排除标准

  • Medication that may interfere with the interpretation of the results
  • Recent sub-standard nutritional status
  • Abuse of drugs, medicine or alcohol
  • Participation in another study up to two months before study onset
  • Cannot clear a criminal background check
  • No signed consent form before the onset of the experiment
  • Blood donors in the past three months before the onset of the experiment
  • Vegetarian and Vegans

结局指标

主要结局

Insulin resistance

时间窗: baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica

Area under the serum insulin concentration curve (2 hours) over time

Glucose tolerance

时间窗: baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica

Area under the serum glucose concentration curve (2 hours) over time

次要结局

  • Saliva DHEA(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Fecal calprotectin(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Fecal short chain fatty acids(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Fecal zonulin(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • GLP-1(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Saliva cortisol(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Lipid metabolism(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • CRP changes in blood(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Fetuin-A(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Gut microbiota profiling(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Inflammation markers in blood(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)
  • Glycated albumin(baseline, pre-Antarctica; every 1-2 month from month 4 to 10 during the stay in Antarctica (total stay about 12 month); about 6-7 month after return from Antarctica)

研究者

发起方
IU University of Applied Sciences
申办方类型
Other
责任方
Principal Investigator
主要研究者

Martina Heer

Program Direction Nutritional Sciences

IU University of Applied Sciences

研究点 (2)

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