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To the Editor: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder that presents as abdominal pain with altered bowel habits. The pathophysiologic mechanism of IBS is not well understood, although many hypotheses have been proposed, including visceral hypersensitivity, gastrointestinal dysmotility, low-grade inflammation of the intestinal mucosa, and dysfunction of the brain-gut interaction. Dysfunction of the brain-gut interaction is thought to be involved in IBS because a considerable proportion of patients with IBS have some form of psychologic comorbidity, such as depression or anxiety. In addition, mental and psychologic problems increase the risk for IBS and the symptom severity of IBS. Recently, changes in the gut microbiota have also been suggested to contribute to both IBS and depression. Our previous study demonstrated significant altered gut microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and depression.Therapies that intend to manipulate the gut microbiota can effectively alleviate IBS symptoms. Probiotics are the most frequently used of these kinds of agents, and can shift the composition of the gut microbiota while relieving IBS symptoms. Shifts in the composition of gut microbiota and short-chain fatty acids (SCFAs) levels (the main metabolic products of gut bacteria) can result in the regulation of host immune function, which is essential in the pathogenesis of IBS. Antidepressants are often employed when patients with IBS have psychologic comorbidities, and are highly effective for the alleviation of both psychologic and IBS symptoms. However, whether probiotics or antibiotics can relieve the severity of psychologic comorbidities in IBS, in addition to the effect of antidepressants on the gut microbiota, are still unknown. Therefore, to investigate the interaction between the gut microbiota and the brain-gut axis, Duloxetine or probiotics were applied on patients with IBS-D with depression to identify the shifts in gut microbiota profiles and fecal SCFA levels, systematic inflammatory responses, and clinical responses of those patients to both therapies to clarify the potential mechanisms of the microbiota-gut-brain axis.The protocol was approved by Peking University Third Hospital Medical Ethics Committee (No. 2013-112) and all the methods were carried out in accordance with the approved guidelines of the committee and with the Declaration of Helsinki. All patients provided written informed consent to participate. The present study has been registered on Chinese Clinical Trial Registry (No. ChiCTR-COC-17011176).Patients with IBS-D (diagnosed according to the Rome III criteria) and depression (according to the Mini-International Neuropsychiatric Interview [MINI] DSM-IV version 5.0.0) comorbidity between 18 and 65 years were recruited from Department of Gastroenterology, Peking University Third Hospital and the Outpatient Department, Institute of Mental Health of Peking University. After endocrine, metabolic, infectious diseases and organic intestinal diseases were excluded, eligible participants were randomized (random number table) to receive probiotics (Bifico® [SINE, Shanghai, China], 20 mg 3 times daily, Bifico contains 3 strains: Bifidobacterium longum, Lactobacillus acidophilus, Enterococcus faecalis, and the number of bacteria is no less than 1.0 × 107 colony-forming units (CFUs) or antidepressants (Duloxetine [Cymbalta®, Eli Lilly and Company, USA] 30 mg once daily for the first 4 days, and raise to 60 mg once daily if it was well tolerated) for 8 weeks. Data on the severity of IBS symptoms and depression, in addition to fecal and blood samples were collected before colonoscopy and at the end of treatment. The severity of IBS symptoms and depression was assessed using the IBS-severity scoring system (IBS-SSS) and the validated Zung self-rating depression scale (SDS), respectively and plasma cytokines, fecal SCFAs, gut microbiota composition were assessed before and after treatment.