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Despite the importance of FD in terms of decreased quality of life and recurrence, treatment modalities have been unsatisfactory, mainly because of their complex and heterogeneous nature. A link between microbiome dysbiosis and low-grade inflammation, along with mucosal barrier disruption of the duodenal mucosa, has been suggested and may be a potential target for FD treatment. This link supports the gut-brain (overactive visceral signaling and pain modulation) and the brain-gut (abnormal central processing) axes in FD. A definite increase in Streptococcus and a reduced abundance of Prevotella, Veillonella, and Actinomyces have also been observed. In addition, bacterial overgrowth is frequently observed in the small intestine, and rifaximin treatment improves the symptoms of FD, especially in women. This evidence highlights the importance of bacterial ecology in the development of FD symptoms. 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