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Purpose Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disorder. Probiotics and synbiotics have been shown to improve symptoms of IBS, although mechanisms of action are currently not understood. Methods We investigated the effects of a 4-week oral synbiotic treatment (OMNi-BiOTiC® Stress Repair) in ten IBS-D patients on gastrointestinal mucosal and fecal microbiota, mucosa-associated immune cells, and fecal short-chain fatty acids. The upper and lower gastrointestinal tracts were compared before and after a 4-week synbiotic treatment using endoscopic evaluation to collect mucosal specimens for FACS analysis and mucosal 16S rRNA gene analysis. In stool samples, analysis for fecal SCFAs using GC–MS, fecal zonulin using ELISA, and fecal 16S rRNA gene analysis was performed. Results Synbiotics led to an increased microbial diversity in gastric (p = 0.008) and duodenal (p = 0.025) mucosal specimens. FACS analysis of mucosal immune cells showed a treatment-induced reduction of CD4+ T cells (60 vs. 55%, p = 0.042) in the ascending colon. Short-chain fatty acids (acetate 101 vs. 202 µmol/g; p = 0.007) and butyrate (27 vs. 40 µmol/g; p = 0.037) were elevated in fecal samples after treatment. Furthermore, treatment was accompanied by a reduction of fecal zonulin concentration (67 vs. 36 ng/ml; p = 0.035) and disease severity measured by IBS-SSS (237 vs. 54; p = 0.002). Conclusions Our findings indicate that a short-course oral synbiotic trial may influence the human gastrointestinal tract in IBS-D patients on different levels which are region specific. Electronic supplementary material The online version of this article (10.1007/s00394-018-1826-7) contains supplementary material, which is available to authorized users.

Obesity is associated with one-third of colon cancer. This is related to altered adipocyte-secreted factors including increased leptin and decreased adiponectin levels [3]. These risk factors cause increased signal pathways important in the carcinogenesis of colon cancer. We read with great interest the paper ‘‘Effects of adipocyte-secreted factors on cell cycle progression in HT29 cells’’ published in your journal [8]. The author screened 30 conditional adipocyte media on HT29 cell growth. In 11 of these, positive responses were found. Furthermore, the author also demonstrated that leptin upregulates ERK pathway, which was inhibited by genistein [6, 7]. In addition to ERK, leptin can also stimulate Src/PI3K/ Akt signal pathway [5]. Src/PI3K/Akt is also an important signal pathway in the carcinogenesis of colon cancer. Activation of the pathway can cause increased cell proliferation and decreased apoptosis in colon cancer as well as cytoskeleton change. Inhibition of this pathway has great potential for the treatment of colon cancer [2]. In Jaffe’s study, leptin is shown to form lamellipodia via Src/rac and this is related to invasion of colon cancer. Thus, two carcinogenic signal pathways MAPK and Src/PI3K/Akt may have synergistic effect in leptin-causing carcinogenesis. Usually, these multiple signal pathways are necessary for the carcinogenesis [4]. Genistein also inhibits PI3K/Akt pathway except MAPK [1, 7]. In conclusion, leptin may cause colon cancer through both PI3K/Akt and ERK pathways. Combinational inhibition could provide better therapy for the disease.