A Study of Probiotics in Patients With Acute Ischemic Stroke

Placebo-Controlled, Double-Blind, Phase 2 Trial of Probiotic Supplementation in Acute Ischemic Stroke

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.

Inclusion Criteria:

1. Age ≥ 60 years;
2. Diagnosis of ischemic stroke; (1)Ischemic stroke is defined as clinically manifest acute neurological deficits linked to an acute cerebral infarct in the anterior circulation; (2)Central retinal artery occlusion or likely central retinal artery occlusion are not considered ischemic strokes in the context of this trial;
3. Randomization within 72 hours of symptom onset;
4. Ability to provide written informed consent;
5. Baseline NIHSS >=4;
6. Pre-stroke mRS <=2;

Exclusion Criteria:

1. Suspected lack of compliance;
2. Presence of moderate to severe dysphagia;
3. Current participation in other interventional trials or recent participation (within the last 30 days) in an interventional trial;
4. Known allergy or hypersensitivity to trial compounds components or placebo;
5. No known history before randomization of imminently life-shortening medical conditions or any other reason, including any physical, psychological, or psychiatric condition that in the investigator's opinion would compromise the safety or interfere with the subject's participation in this study, or would make the subject an unsuitable candidate to receive study drug, or would put the subject at risk by participating in the study;
6. Malignant diseases including active malignancies with a life expectancy of less than 3 months;
7. Major gastro-intestinal (GI) surgery, chronic inflammatory diseases of the gut and significant GI-neoplasms;