Depression Promotes the Onset of Irritable Bowel Syndrome through Unique Dysbiosis in Rats

BACKGROUND/AIMS: Although studies using conventional animal models have shown that specific stressors cause irritable bowel syndrome (IBS), it is unclear whether depression itself causes IBS. Our aim was to establish a rat model to determine if depression itself promotes the onset of IBS and to elucidate the role of gut microbiota in brain-gut axis pathogenesis during coincident depression and IBS. METHODS: Rat models of depression were induced using our shuttle box method of learned helplessness. Visceral hypersensitivity was evaluated by colorectal distension (CRD) to diagnose IBS. Gut microbiota compositions were analyzed using high-throughput sequencing. In the subanalysis of rats without depression-like symptoms, rats with posttraumatic stress disorder (PTSD) were also examined. RESULTS: The threshold value of CRD in depressed rats was significantly lower than that in control rats. Microbial community analysis of cecal microbiota showed that the relative abundance of Clostridiales incertae sedis, the most prevalent microbe, was significantly lower in depressed rats than in control rats. The distribution pattern of the microbiota clearly differed between depressed rats and control rats. Neither visceral hypersensitivity nor the composition of gut microbiota was altered in rats with PTSD-like phenotypes. CONCLUSIONS: Our rat model of depression is useful for clarifying the effect of depression on IBS and suggests that depression itself, rather than specific stressors, promotes the onset of IBS. Further, we provided evidence that various psychiatric diseases, viz., depression and PTSD, are associated with unique gut microbiota profiles, which could differentially affect the onset and progression of coincident IBS.

Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan

BACKGROUND/AIMS: Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines. METHODS: This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines. RESULTS: Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037). CONCLUSIONS: Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.

Asian Consensus Report on Functional Dyspepsia

BACKGROUND/AIMS: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared to the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. METHODS: Consensus team members were selected from Asian experts and consensus development was carried out using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using keypad voting system. A grade of evidence and a strength of recommendation were applied to each statement according to the method of the GRADE Working Group. RESULTS: Twenty-nine consensus statements were finalized, including 7 for definition and diagnosis, 5 for epidemiology, 9 for pathophysiology and 8 for management. Algorithms for diagnosis and management of functional dyspepsia were added. CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.