Microbiome-Targeted Biotics and Migraine: Mechanistic and Clinical Signals

A narrative review in migraine and the gut–brain axis synthesizes proposed mechanistic links between gut microbial ecology and migraine biology, while collating human trial signals for microbiome-targeted “biotics.” The authors outline how gastrointestinal features, immune and oxidative pathways, and neuroinflammatory signaling have been discussed in relation to migraine. They also summarize interventional reports spanning probiotic supplementation and earlier-stage work on other microbiome-directed strategies. Overall, the review is presented as a narrative synthesis of mechanistic pathways, reported probiotic trial outcomes, and remaining evidence gaps.

The review describes observational and translational literature in which migraine has been associated with intestinal dysbiosis, increased intestinal permeability (barrier disruption), and low-grade systemic inflammation. These associations are discussed alongside migraine’s frequent co-occurrence with gastrointestinal symptoms and comorbid gastrointestinal diseases, with gut barrier integrity presented as a recurring theme in proposed pathophysiology. Immune activation is described in parallel as a plausible bridge between gut perturbations and migraine-relevant signaling, with inflammation framed as “low-grade” rather than overt systemic illness. In the review’s framing, these reported associations underpin interest in studying microbiome-targeted approaches in migraine populations.

Against this background, the authors discuss probiotic and “psychobiotic” pathways, emphasizing interventions that include Lactobacillus and Bifidobacterium taxa. In their narrative, these probiotics are described as potential modulators of cytokine and inflammatory signaling, including downstream effects that could intersect with neuroinflammatory pathways along the gut–brain axis. The authors also highlight gut epithelial tight-junction integrity as a mechanistic node and cite oxidative stress as another repeatedly discussed pathway in the mechanistic literature they summarize. Neurotransmitter-related pathways are presented as part of the “brain” side of this axis, linking microbial activity and metabolites to neurotransmitter-related signaling along the gut–brain axis. These pathways are framed as biologically plausible links assembled from mechanistic evidence rather than definitive causal explanations.

Human probiotic supplementation trials summarized in the review are described as heterogeneous across designs, populations, and assessed outcomes, spanning both adult and pediatric migraine cohorts. At a high level, the authors report that some studies observed improvements in migraine frequency, severity, disability scores, and analgesic use, while other studies reported more limited or variable findings. The review notes that, although probiotics, prebiotics, and postbiotics are described as having potential benefits with favorable safety profiles, evidence remains limited on strain-, formulation-, and population-specific characteristics. Overall, the trial literature is characterized in the review as mixed, with sometimes favorable signals in certain studies but without uniform effects across the body of evidence.

Beyond probiotics, the review describes emerging but limited evidence for prebiotics, including inulin-type fructans, and for microbiota-derived metabolites such as short-chain fatty acids, noting that direct clinical data in migraine remain limited. In discussing translation, the authors state that well-powered, placebo-controlled trials with standardized migraine endpoints and integrated microbiome and metabolomic analyses are needed to define responders, optimal interventions, and clinical relevance. This future-work framing is presented as a way to link proposed mechanisms to more interpretable human data while addressing current heterogeneity. The review closes by juxtaposing mechanistic hypotheses with the stated need for more definitive clinical evidence.

Key Takeaways:

• The review reports associations between migraine and intestinal dysbiosis, increased gut permeability/barrier disruption, and low-grade systemic inflammation.
• The authors describe probiotic-related pathways along the gut–brain axis that include cytokine/inflammatory signaling, tight-junction integrity, oxidative stress, and neurotransmitter-related mechanisms.
• The review summarizes heterogeneous probiotic trial findings alongside limited prebiotic/postbiotic data and highlights the authors’ call for standardized, placebo-controlled studies with integrated microbiome and metabolomic analyses.