Modulation of Gut Microbiota in Early Sepsis: A Pilot Study
Condition: Sepsis
MeSH terms: Sepsis; Toxemia
Study type: Interventional

Summary: 
      Background Sepsis is a common disease leading to high morbidity and mortality. Gut microbiota
      and/or gut permeability may play a crucial role in the development of organ dysfunction.

      Hypothesis The ingestion of a multispecies probiotic in early sepsis is able to modulate gut
      microbiota and/or gut permeability.
    

Detailed description: 
      Sepsis is a systemic deleterious host response to infection causing major healthcare
      problems. Sepsis affects millions of people around the world each year, with a lethality of
      25%-50%. The incidence is increasing partly because of a raise in average age and occurrence
      of predisposing diseases in the population, and partly because of shifts in causative
      pathogens. Effectiveness of therapy administered in the initial hours of severe sepsis
      critically influences the clinical outcome of the patient.

      Lacking reliable biomarkers for early stages, the diagnosis of (severe) sepsis relies on a
      combination of surrogate parameters indicating end organ dysfunction.

      Recently, gut wall integrity has been identified as a key feature in protecting the body
      against potentially harmful compounds such as bacteria, toxins and antigens. The gut barrier
      consists of the mucus barrier, antimicrobial peptides, secretory IgA, the epithelial barrier,
      and the gut immune system. Gut permeability is reported to increase in sepsis and to play a
      key role in the development of multi-organ dysfunction. Therefore, gut permeability markers
      might have the potential to predict the risk of progression from sepsis to severe sepsis. The
      mechanisms leading to increased gut permeability are not completely clear, yet. Direct and
      indirect interactions of pathogens, hormonal imbalances, beta-adrenergic activity,
      hyperglycemia and cytokine activation as well as individual predisposition have been
      proposed. It seems that increased gut permeability is the common final pathway of a multitude
      of influencing factors.

      Furthermore, the importance of gut microbiota composition has recently been recognized in
      several diseases; however, not much is known about the role of the microbiome in sepsis to
      date. Available data suggest, that disturbances in microbiome homeostasis are present in
      sepsis, but it is yet unknown if these changes are cause or consequence of sepsis. Changes in
      gut barrier and/or gut microbiota can lead to an increase in microbial products in
      circulation, contributing to (inadequate) activation and later "paralysis" of immune cells.
      It is not yet known if the gut microbiome of a patient in early stages of sepsis differs from
      the healthy microbiome or from the microbiome of a patient in late stages of sepsis. Also,
      the possibility to modulate the gut microbiome in early sepsis has not been studied yet.

      A typical strategy to modulate the gut microbiome is the use of probiotic bacteria. In
      sepsis, the use of probiotics is well established for specific indications, such as
      necrotising enterocolitis in neonates, however, studies in adults are scarce. Therefore the
      aim of this study is to investigate if the ingestion of a multispecies probiotic in early
      sepsis is able to modulate gut microbiota and/or gut permeability and observe the clinical
      outcome of treated patients.
    

Intervention name(s): Winclove 607; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): multispecies probiotic; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention