• Connection Between Stress, Neuroinflammation, and Irritable Bowel Syndrome: Positive Impact of Probiotic Therapy
  • Maryam Azarfarin,1 Nasrollah Moradikor,2 Somaieh Matin,3 Masoomeh Dadkhah,4,*
    1. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran/Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
    2. International Center for Neuroscience Research, Institute for Intelligent Research, Tbilisi, Georgia
    3. Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
    4. Lung Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran


  • Introduction: Stress is a physiological response to environmental challenges, aimed at maintaining bodily homeostasis. Prolonged activation of the hypothalamic–pituitary– adrenal (HPA) axis under chronic stress conditions triggers robust inflammatory responses. This chronic stress is implicated in the development and exacerbation of irritable bowel syndrome (IBS), a prevalent gastrointestinal disorder. IBS is characterized by a compromised gut barrier, often referred to as ”leaky gut,” which allows microbiota to enter the bloodstream, leading to low-grade systemic inflammation. This inflammation is increasingly recognized as a contributor to the pathophysiology of neuropsychiatric disorders. The interplay between stress, neuroinflammation, and IBS underscores the need to explore underlying mechanisms and potential therapeutic interventions, such as probiotics. This review aims to elucidate how stress influences the risk and severity of IBS, its association with neuroinflammation, and the therapeutic potential of probiotics in managing IBS under chronic stress conditions.
  • Methods: This review synthesizes findings from peer-reviewed studies published in scientific databases, including PubMed, Scopus, and Web of Science, up to August 2025. Search terms included ”stress,” ”neuroinflammation,” ”irritable bowel syndrome,” ”leaky gut,” ”HPA axis,” and ”probiotics.” Studies were selected based on their relevance to the mechanisms linking stress and IBS, the role of neuroinflammation, and the efficacy of probiotic interventions. Both preclinical and clinical studies were included, with a focus on those exploring gut-brain axis dysregulation, microbiota alterations, and inflammatory markers. Data were analyzed qualitatively to identify common pathways and therapeutic outcomes, with an emphasis on the modulatory effects of probiotics on gut permeability and systemic inflammation.
  • Results: Chronic stress activates the HPA axis, leading to elevated cortisol levels and heightened inflammatory responses, which disrupt gut barrier integrity and contribute to IBS development. Leaky gut in IBS facilitates microbial translocation into the bloodstream, promoting low-grade systemic inflammation and neuroinflammation, which are linked to neuropsychiatric comorbidities. Probiotics, particularly strains of Lactobacillus and Bifidobacterium, have shown promise in restoring gut barrier function, reducing inflammation, and modulating the gut-brain axis. Clinical studies demonstrate that probiotic therapy can alleviate IBS symptoms, such as abdominal pain and irregular bowel movements, while also mitigating stress-related neuroinflammatory markers. These effects are attributed to probiotics’ ability to enhance gut microbiota diversity and suppress pro-inflammatory cytokine
  • Conclusion: The interplay between chronic stress, neuroinflammation, and IBS highlights the critical role of the gut-brain axis in gastrointestinal and neuropsychiatric health. Stress-induced HPA axis activation exacerbates gut permeability and systemic inflammation, key features of IBS, which in turn contribute to neuroinflammatory processes. Probiotic therapy offers a promising approach to mitigate these effects by restoring gut barrier integrity, reducing inflammation, and improving IBS symptoms. Future research should focus on optimizing probiotic strains and dosages to maximize therapeutic outcomes in patients with IBS and chronic stress, potentially offering a non-invasive strategy to manage both gastrointestinal and neuropsychiatric symptoms.
  • Keywords: irritable bowel syndrome, microbiota–gut–brain axis, neuroinflammation, probiotic, stress