The gut is an immune-microbiome-epithelial complex. Gut microbiome-host interactions have widespread biological implications, and the role of this complex system extends beyond the digestion of food and nutrient absorption. Dietary nutrients can affect this complex and play a key role in determining gut homeostasis to maintain host health. In this article, we review various dietary nutrients and their contribution to the pathogenesis and treatment of various intestinal diseases including inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, and diverticulitis, among other such disorders. A better understanding of diet-host-gut microbiome interactions is essential to provide beneficial nutrients for gut health and to limit nutritional hazards to ensure successful nutritional management of gastrointestinal conditions in clinical practice. (Intest Res 2019;17:443-454)

Cancer is a catabolic inflammatory disease that causes patients to often experience weight loss, or even cachexia in severe cases. Undernourishment in patients with cancer impairs the quality of life and therapeutic response, further leading to poor prognosis. Active and frequent nutritional screening and assessment using valid tools are important for fast and appropriate nutritional intervention. Additionally, a suitable individualized nutritional intervention strategy should be established based on the nutritional assessment result. In general, nutritional intervention begins with nutritional counseling of patients diagnosed with cancer, and a well-planned nutritional counseling improves the treatment adherence and nutritional status. When planning nutritional supplementation for cancer patients, specific nutrients, including amino acids and fatty acids, should be considered. However, there has been no consistent result showing that any particular nutrient significantly improves the prognosis of cancer patients. Hence, continuous attention from clinical physicians is needed to plan nutritional improvement in patients with cancer. (Intest Res 2019;17:455-462)

Malnutrition is observed more frequently in patients with inflammatory bowel disease (IBD) than in the general population and associated with adverse clinical outcomes. This study aimed to review the current knowledge regarding the efficacy of dietary and nutritional intervention in IBD patients. Exclusive enteral nutrition might be inferior to corticosteroid treatment in adults with active Crohn's disease (CD) but might even be superior considering the adverse effects of corticosteroid treatment in children. Total parenteral nutrition has no advantage over enteral nutrition, which is considered a more physiologic modality in organ function. Current guidelines do not yet recommend ω3-polyunsaturated fatty acid supplementation for the prevention and maintenance of remission in IBD patients. Dietary fiber supplementation could be effective in the relief of symptoms and maintenance of remission in ulcerative colitis (UC). Although vitamin D may be favorable to clinical course of IBD and bone density. Probiotic supplementation has proven to be effective in preventing and treating pouchitis for UC but is less effective in treating CD. Nutritional interventions not only correct nutritional deficiencies but also improve symptoms and clinical courses of the disease. Hence, nutritional approaches need to be developed to significantly evaluate the effectiveness of dietary interventions used to treat IBD. (Intest Res 2019;17:463-475)

Background/Aims: Tacrolimus is effective for refractory ulcerative colitis in adults, while data for children is sparse. We aimed to evaluate the effectiveness and safety of tacrolimus for induction and maintenance therapy in Japanese children with ulcerative colitis. Methods: We retrospectively reviewed the multicenter survey data of 67 patients with ulcerative colitis aged <17 years treated with tacrolimus between 2000 and 2012. Patients' characteristics, disease activity, Pediatric Ulcerative Colitis Activity Index (PUCAI) score, initial oral tacrolimus dose, short-term (2-week) and long-term (1-year) outcomes, steroid-sparing effects, and adverse events were evaluated. Clinical remission was defined as a PUCAI score <10; treatment response was defined as a PUCAI score reduction of ≥20 points compared with baseline. Results: Patients included 35 boys and 32 girls (median [interquartile range] at admission: 13 [11-15] years). Thirty-nine patients were steroid-dependent and 26 were steroid-refractory; 20 had severe colitis and 43 had moderate colitis. The initial tacrolimus dose was 0.09 mg/kg/day (range, 0.05-0.12 mg/kg/day). The short-term clinical remission rate was 47.8%, and the clinical response rate was 37.3%. The mean prednisolone dose was reduced from 19.2 mg/day at tacrolimus initiation to 5.7 mg/day at week 8 (P<0.001). The adverse event rate was 53.7%; 6 patients required discontinuation of tacrolimus therapy. Conclusions: Tacrolimus was a safe and effective second-line induction therapy for steroid-dependent and steroid-refractory ulcerative colitis in Japanese children. (Intest Res 2019;17:476-485)

Background/Aims: Information about familial aggregation of inflammatory bowel disease (IBD) in Asia is limited. We aimed to analyze the prevalence and risk of familial IBD in an Indian cohort and compare familial and sporadic cases. Methods: Familial IBD cases were identified from a large prospectively maintained IBD registry. The prevalence of IBD in first- and second-degree relatives of index cases was evaluated. The disease behavior was compared to that of sporadic cases. Results: Total 3,553 patients (ulcerative colitis [UC], 2,053; Crohn's disease [CD], 1,500) were included. Familial IBD was noted in 4.13% of CD and 4.34% of UC patients. Family history was commoner in pediatric group (<18 years) (P=0.0002; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6-4.8). Majority had paternal transmission (UC, 67.42%; CD, 70.97%). Concordance of disease type was higher in UC (79.7%) compared to CD (37.1%). Familial IBD was associated with higher cumulative relapse rate (CD, P<0.001; UC, P<0.001), higher cumulative rate of surgery (CD, P<0.001; UC, P<0.001) and higher rate of biologic use (CD, P=0.010; UC, P=0.015). Pan-colitis was higher in familial UC (P=0.003; OR, 1.935; 95% CI, 1.248-3.000). Fistulizing disease was commoner in familial CD (P=0.041; OR, 2.044; 95% CI, 1.030-4.056). Conclusions: The prevalence of familial IBD in India appears comparable to rest of Asia but lower than the West. It is associated with a younger age of onset, higher incidence of pan-colitis in UC and fistulizing complications in CD. Familial IBD has higher cumulative relapse, surgery and biologic use rates. Hence, family history of IBD could have important prognostic implications. (Intest Res 2019;17:486-495)

Background/Aims: Polypharmacy is a common clinical problem with chronic diseases that can be associated with adverse patient outcomes. The present study aimed to determine the prevalence and patient-specific characteristics associated with polypharmacy in an ulcerative colitis (UC) population and to assess the impact of polypharmacy on disease outcomes. Methods: A retrospective chart review of patients with UC who visited a tertiary medical center outpatient clinic between 2006 and 2011 was performed. Polypharmacy was defined as major (≥5 non-UC medications) or minor (2-4 non-UC medications). UC medications were excluded in the polypharmacy grouping to minimize the confounding between disease severity and polypharmacy. Outcomes of interest include disease flare, therapy escalation, UC-related hospitalization, and surgery within 5 years of the initial visit. Results: A total of 457 patients with UC were eligible for baseline analysis. Major polypharmacy was identified in 29.8% of patients, and minor polypharmacy was identified in 40.9% of the population. Polypharmacy at baseline was associated with advanced age (P<0.001), female sex (P=0.019), functional gastrointestinal (GI) disorders (P<0.001), and psychiatric disease (P<0.001). Over 5 years of follow-up, 265 patients remained eligible for analysis. After adjusting for age, sex, functional GI disorders, and psychiatric disease, major polypharmacy was found to be significantly associated with an increased risk of disease flare (odds ratio, 4.00; 95% confidence interval, 1.66-9.62). However, major polypharmacy was not associated with the risk of therapy escalation, hospitalization, or surgery. Conclusions: Polypharmacy from non-inflammatory bowel disease medications was present in a substantial proportion of adult patients with UC and was associated with an increased risk of disease flare. (Intest Res 2019;17:496-503)

Background/Aims: An interim analysis of post-marketing surveillance of CT-P13, an infliximab biosimilar, was performed to evaluate its safety and efficacy in Japanese patients with inflammatory bowel disease. Methods: Patients were prospectively enrolled between November 2014 and March 2017, after the launch of CT-P13 in Japan, and case report forms of patients followed for at least 4 months were analyzed as of July 2018. Results: Of 523 patients in the analysis set, 372 remained on CT-P13 therapy, while 54 (20.2%) of 267 patients with Crohn's disease, and 97 (37.9%) of 256 patients with ulcerative colitis were withdrawn during follow-up. A total of 144 adverse drug reactions (ADRs) were reported in 106 patients (20.3%). Infusion reaction was the most frequent ADR observed in 49 patients (9.4%). Efficacy parameters decreased immediately after the start of treatment in naïve patients to anti-tumor necrosis factor-α antibody. In the patients switched from originator infliximab for nonmedical reasons, the decreased parameters due to proceeded treatment with the originator were maintained in low ranges, and the treatment continuation rate was high with low ADR incidence. In contrast, in patients switched for medical reasons such as adverse event or loss of response, the incidence of ADRs was high. However, the efficacy parameters were improved, and the treatment continuation rate was not significantly different from that of the naïve patient group. Conclusions: In this interim analysis, CT-P13 was comparable to the originator infliximab with respect to ADRs and efficacy, and is therefore considered to be a cost-efficient interchangeable biosimilar for Japanese patients with inflammatory bowel disease. (Intest Res 2019;17:504-515)

Background/Aims: When determining the subsequent management after endoscopic resection of the early colon cancer (ECC), various factors including the margin status should be considered. This study assessed the subsequent management and outcomes of ECCs according to margin status. Methods: We examined the data of 223 ECCs treated by endoscopic mucosal resection (EMR) from 215 patients during 2004 to 2014, and all patients were followed-up at least for 2 years. Results: According to histological analyses, the margin statuses of all lesions after EMR were as follows: 138 cases (61.9%) were negative, 65 cases (29.1%) were positive for dysplastic cells on the resection margins, and 20 cases (8.9%) were uncertain. The decision regarding subsequent management was affected not only by pathologic outcomes but also by the endoscopist's opinion on whether complete resection was obtained. Surgery was preferred if the lesion extended to the submucosa (odds ratio [OR], 25.46; 95% confidence interval [CI], 7.09-91.42), the endoscopic resection was presumed incomplete (OR, 15.55; 95% CI, 4.28-56.56), or the lymph system was invaded (OR, 13.69; 95% CI, 1.76-106.57). Fourteen patients (6.2%) had residual or recurrent malignancies at the site of the previous ECC resection and were significantly associated with presumed incomplete endoscopic resection (OR, 4.59; 95% CI, 1.21-17.39) and submucosal invasion (OR, 5.14; 95% CI, 1.18-22.34). Conclusions: Subsequent surgery was associated with submucosa invasion, lymphatic invasion, and cancer-positive margins. Presumed completeness of the resection may be helpful for guiding the subsequent management of patients who undergo endoscopic resection of ECC. (Intest Res 2019;17:516-526)

Background/Aims: Transforming growth factor-β1 (TGF-β1) induction of epithelial-mesenchymal transition (EMT) is one of the mechanisms by which colorectal cancer (CRC) cells acquire migratory and invasive capacities, and subsequently metastasize. Parthenolide (PT) expresses multiple anti-cancer and anti-inflammatory activities that inhibit nuclear factor κB by targeting the IκB kinase complex. In the present study, we aimed to investigate whether PT can inhibit TGF-β1-induced EMT in CRC cell lines. Methods: HT-29 and SW480 cell lines were used in the experiment. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and sub-G1 analysis was measured by flow cytometry. The induction of EMT by TGF-β1 and inhibition of the process by PT was analyzed by phase contrast microscopy, wounding healing, cellular migration and invasion assays, and Western blotting. Results: TGF-β1 inhibits HT-29 cell proliferation, but has no effect on SW480 cell proliferation; different concentrations of TGF-β1 did not induce apoptosis in HT-29 and SW480 cells. PT attenuates TGF-β1-induced elongated, fibroblast-like shape changing in cells. PT inhibits TGF-β1-induced cell migration and cell invasion. In addition, other EMT markers such as β-catenin, Vimentin, Snail, and Slug were suppressed by PT, while E-cadherin was increased by PT. Conclusions: Our findings show that PT inhibits TGF-β1-induced EMT by suppressing the expression of the mesenchymal protein and increasing expression of the epithelial protein. These findings suggest a novel approach for CRC treatment by suppression of TGF-β1-induced EMT. (Intest Res 2019;17:527-536)

Background/Aims: Despite the evidence of a modest to high prevalence of gastrointestinal (GI) symptoms in recreational runners and endurance athletes, the frequency and intensity of GI symptoms in exercisers, but nonathletes, individuals from different modalities have been less investigated. Therefore, the present study aimed to assess the prevalence of GI symptoms in individuals that practice moderate or vigorous physical exercise, at rest and during physical exercise training session. Methods: The sample consisted of 142 exercisers individuals (64 women and 78 men with mean age of 32.9±10.7 years). Out of the 142 participants, 71 reported to perform moderate physical exercise and 71 reported to perform vigorous physical exercise. Participants were assessed by an internet-based questionnaire designed to assess the frequency and intensity (at rest and during physical exercise training session) of 18 GI symptoms. Results: The GI symptoms most frequently reported by the respondents (during rest and physical exercise training session, respectively) were flatulence (90.8% and 69.7%), abdominal noise (77.5% and 41.5%), and eructation (73.9% and 52.1%). Overall, the frequency and intensity of symptoms were higher (P<0.050) during rest than physical exercise training session for who perform moderate and vigorous physical exercise. Conclusions: It can be concluded that GI symptoms in exercisers, but nonathletes, individuals are more prevalent during rest than during physical exercise training session, suggesting that moderate and vigorous physical exercise may act as a regulator of the GI tract. (Intest Res 2019;17:537-545)