Modulating the Gut Microbiota to Target Neuroinflammation, Cognition and Mood: A Systematic Review of Human Studies with Relevance to Fibromyalgia

Aim: This systematic review aims to evaluate the effectiveness of microbiota-modulating interventions (such as probiotics, prebiotics, and fecal microbiota transplantation) in reducing cognitive symptoms, pain, and neuroinflammation in human studies relevant to fibromyalgia (FM). The review will investigate the role of gut–brain axis modulation through these interventions and explore the potential therapeutic benefits for FM management. Materials and Methods: A comprehensive search was conducted in electronic databases including PubMed, Scopus, and the Cochrane Library for studies published from 1 January 2015 to 30 April 2025. Studies were eligible if they were randomized controlled trials (RCTs), pilot studies, or observational studies assessing the impact of microbiota-targeted interventions (probiotics, prebiotics, fecal microbiota transplantation) on cognitive function, pain, or neuroinflammation in patients with FM. Studies were excluded if they involved animal models, lacked relevant outcome measures, or were not peer-reviewed. Although only a subset of the included studies directly involved FM patients, all were selected for their relevance to symptom domains (e.g., pain, cognition, mood) and mechanisms (e.g., neuroinflammation, gut–brain axis dysfunction) that are central to FM. A total of 11 human studies were included in the final qualitative synthesis. Results: Preliminary findings from the included studies suggest that microbiota-targeted interventions, particularly probiotics and prebiotics, show promise in reducing cognitive symptoms, pain, and neuroinflammation in FM patients. Improvements in mood and quality of life were also reported, indicating potential benefits for overall well-being. However, heterogeneity in study designs, sample sizes, and outcome measures limit the ability to draw definitive conclusions. Conclusions: This systematic review highlights the potential of microbiota modulation as a therapeutic strategy for managing FM symptoms, particularly cognitive dysfunction and neuroinflammation.