The primary objective of this study is to evaluate the effect of daily oral administration of the probiotic supplement OMNi-BiOTiC® SR-9 for 90 days, compared to placebo, on gut microbiome beta diversity in patients aged 60 years or older with acute ischemic stroke.
Ischemic stroke induces a rapid and sustained systemic inflammatory response that contributes to secondary brain injury, post-stroke complications, and long-term functional outcome. In addition to well-characterized neuroinflammatory mechanisms, increasing evidence indicates that stroke profoundly alters the gut microbiota through autonomic dysfunction, reduced intestinal motility, altered permeability, and frequent exposure to antibiotics and hospital-related stressors. This stroke-induced dysbiosis has been linked to systemic immune activation, impaired immune homeostasis, and increased susceptibility to infections, all of which negatively affect recovery after stroke. Experimental studies have demonstrated that the composition and functional capacity of the gut microbiota influence ischemic brain injury and post-stroke inflammation. Alterations in microbial community structure can modulate peripheral immune responses, including myeloid cell activation and cytokine production, and affect levels of microbiota-derived metabolites such as short-chain fatty acids (SCFAs). SCFAs, including acetate, propionate, and butyrate, exert immunomodulatory effects by regulating innate and adaptive immune responses and maintaining intestinal barrier integrity. Reduced SCFA availability has been associated with enhanced systemic inflammation and adverse neurological outcomes in experimental stroke models. Clinical observations further support the relevance of the gut-brain axis in stroke. Patients with acute ischemic stroke exhibit rapid changes in gut microbiome composition, reduced microbial diversity, and shifts in specific taxa that correlate with stroke severity, systemic inflammation, and functional outcome. However, whether targeted modulation of the gut microbiota after stroke can reproducibly alter microbial community structure and downstream biological processes in humans remains unclear. Existing clinical studies of probiotics and synbiotics have shown anti-inflammatory effects in various non-neurological conditions, but data from adequately powered randomized controlled trials in acute ischemic stroke are lacking. The probiotic formulation OMNi-BiOTiC® SR-9 contains multiple well-characterized bacterial strains combined with a prebiotic matrix designed to support bacterial viability and metabolic activity. This formulation has demonstrated immunomodulatory properties and a favorable safety profile in previous clinical applications. Administered early after stroke, probiotic supplementation represents a low-risk, non-invasive strategy to counteract stroke-associated dysbiosis, stabilize gut microbial community structure, and potentially restore microbiota-derived metabolic and immune signaling. Given the complexity and inter-individual variability of the human gut microbiome, global measures of microbial community composition, such as beta diversity, represent sensitive and biologically meaningful endpoints to capture probiotic-induced changes. Assessing microbiome beta diversity at 90 days allows sufficient time for microbial ecosystem restructuring and stabilization following acute stroke and hospitalization, while still reflecting effects initiated during the early post-stroke phase. Therefore, this randomized, placebo-controlled phase 2 trial is designed to evaluate whether daily oral administration of OMNi-BiOTiC® SR-9 for 90 days can induce measurable changes in gut microbiome beta diversity in patients with acute ischemic stroke. Secondary objectives address clinical outcome, specific microbial taxa, and circulating SCFAs to provide complementary mechanistic insights and inform the design of future outcome-driven trials.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
220
Each sachet contains approximately 7.5 × 10\^9 live bacteria. Administered orally twice daily.
Identical in appearance, packaging, and administration method to the probiotic preparation, with no active ingredients.
Beta diversity of gut microbiota at Day 90±3 (treatment vs. placebo)
Beta diversity assessed using stool samples at Day 90±3. PERMANOVA will be used to evaluate differences in microbial community composition between treatment arms. This endpoint captures global, community-level alterations of gut microbiota reflecting probiotic-induced ecosystem restructuring in the post-stroke setting, rather than changes in individual taxa alone.
Time frame: Day 90 ± 3 days
Modified Rankin Scale (mRS) score at Day 90±3
The mRS evaluates degree of disability or dependence in daily activities post-stroke. Scores range from 0 to 6, with higher scores indicating worse outcome.
Time frame: Day 90 ± 3 days
Change in modified Rankin Scale (mRS) score from baseline to Day 90±3
Calculated as change of mRS at Day 90±3 compared with mRS at baseline. The mRS is a 7-point scale from 0 to 6, with higher scores indicating worse outcome.
Time frame: Baseline to Day 90 ± 3 days
Changes in gut microbiota diversity and relative abundance of Prevotella copri at Day 90±3
Temporal beta diversity indices (TBI) will assess changes in beta diversity from baseline to Day 90±3. Changes in alpha diversity will be calculated using Abundance-based Coverage Estimator (ACE), expressed as ACE at Day 90±3 minus ACE at baseline. Relative abundance of Prevotella copri in stool samples at Day 90±3 will be compared between verum and placebo groups.
Time frame: Baseline to Day 90 ± 3 days
Serum concentrations of short-chain fatty acids (SCFAs) at Day 90±3
Measured SCFAs include acetate, butyrate, and propionate. Evaluates metabolic changes associated with gut microbiota modulation.
Time frame: Baseline and Day 90 ± 3 days
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EQ-5D-5L at day 90
EQ-5D-5L assesses health-related quality of life across 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), higher scores indicate better health. EQ-VAS ranges from 0 to 100, higher scores indicate better self-perceived health.
Time frame: Day 90 ± 3 days
Barthel Index at day 90
The Barthel Index is an ordinal scale consisting of 10 activities of daily living (including feeding, bathing, grooming, dressing, bowel and bladder control, toilet use, bed-to-chair transfer, ambulation, and stair climbing). Total scores range from 0 to 100, with higher scores indicating greater functional independence and better prognosis.
Time frame: Day 90 ± 3 days
Safety Outcomes
The safety outcome is the number of reported adverse events (AEs) and serious adverse events (SAEs) in the verum group compared to the placebo group. All events will be assessed for severity, causality, and relevance, and reported in accordance with regulatory guidelines.
Time frame: Baseline to Day 90 ± 3 days