A new article published in Clinical and Experimental Gastroenterology discussed that irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by abdominal pain that occurs with defecation or alterations in bowel habits. Classification of this condition is based on the predominant bowel habit - constipation-predominant; diarrhea-predominant (IBS-D); or mixed IBS. The authors stated that the pathogenesis of IBS is unclear and is considered multifactorial in nature. Gastrointestinal (GI) dysbiosis has been reported in patients with IBS. Alterations in the gut microbiota has been noted in patients with small intestinal bacterial overgrowth, while overgrowth may occur in a subset of patients with IBS. This article further reported on the management of IBS, which includes therapies targeting the commonly known factors involved in the pathogenesis of this condition. But, many of these interventions, like eluxadoline and alosetron require long-term, daily administration and have important safety considerations. Meanwhile, agents that modulate the gut microbiota, such as antibiotics and probiotics, have shown potential benefits in clinical studies. However, probiotics lack uniformity in composition and consistency of response in patients. On the other hand, rifaximin - a nonsystemic antibiotic, when administered as a 2-week course, has demonstrated safety and efficacy in the treatment of IBS-D. Moreover, rifaximin exhibits a favorable benefit-to-harm ratio when compared to daily therapies of IBS-D, for instance, alosetron and tricyclic antidepressants, and is not associated with the emergence of bacterial antibiotic resistance. Hence, a short-course therapy with rifaximin is an appropriate treatment option for IBS-D.