*Review* **The Role of the Human Microbiome in the Pathogenesis of Pain**

**Klaudia Ustianowska 1, Łukasz Ustianowski 1, Filip Machaj 1,2, Anna Gor ˛acy 3, Jakub Rosik 1,4, Bartosz Szostak 1, Joanna Szostak <sup>5</sup> and Andrzej Pawlik 1,\***


**Abstract:** Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut–brain axis. The signals in the gut–brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut–brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut–brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome's role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain.

**Keywords:** microbiome; pain; IBS; neuropathy
