Malnutrition is a major contributor to muscle loss and muscle dysfunction, known as sarcopenia. Malnutrition is common in patients with inflammatory bowel disease (IBD). IBD includes ulcerative colitis (UC) and Crohn’s disease (CD). The number of patients with IBD has recently been increasing. More severe malnutrition is often seen in CD compared to UC, probably due to CD affecting the main site of nutrient absorption, extensive mucosal lesions, fistulas, short bowel syndrome after resection, or obstruction of the gastrointestinal tract. A recent meta-analysis showed the high prevalence of sarcopenia in patients with IBD, and thus sarcopenia is a very important problem for IBD. Although IBD is more common in younger patients, sarcopenia can develop through a variety of mechanisms, including malnutrition, chronic inflammation, increased inflammatory status in adipose tissue, vitamin deficiency, and imbalance of the muscle–gut axis. In addition, sarcopenia has a negative impact on postoperative complications and hospital stay in patients with IBD. Appropriate intervention for sarcopenia may be important, in addition to clinical remission and endoscopic mucosal healing in patients with IBD. Much more attention will thus be paid to sarcopenia in patients with IBD. In this review, we outline IBD and sarcopenia, based on the current evidence.

The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide.

Background and Aim: Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome. Methods: We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis. Results: Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group. Conclusion: Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs.

The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and anti-diarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogs, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.

Background and Aims: The calcineurin inhibitor tacrolimus is reportedly effective for moderate/severe ulcerative colitis (UC); however, it is also reportedly associated with nephrotoxicity. We investigated the risk factors for tacrolimus-induced nephrotoxicity and whether renal impairment adversely affected the outcomes of tacrolimus treatment in patients with UC. Methods: We conducted a retrospective study of 93 patients with UC who were administered tacrolimus leading to high trough levels (10–15 ng/mL) for 2 weeks and low trough levels (5–10 ng/mL) for 3 months. Results: Acute kidney injury (AKI) occurred in 44 patients (47.3%) during tacrolimus treatment. Of these patients, 34 (36.6%) developed AKI during the high trough phase and 17 (18.3%) developed AKI when the trough value exceeded the original target value of 15 ng/mL. Multivariate logistic regression analysis revealed that the male sex was significantly associated with AKI (p = 0.002, AOR = 4.38, 95% CI [1.69–11.3]). Clinical remission rate after 4, 8, 12, and 24 weeks of tacrolimus treatment in patients with AKI was lower than that in patients without AKI. Six patients (6.5%) had chronic kidney disease (CKD) after tacrolimus treatment completion, and all patients with CKD developed AKI during treatment. The median duration of treatment with no improvement in AKI was significantly longer in patients with CKD than in those without CKD (p = 0.016). Conclusion: We revealed the risk factors for tacrolimus-induced nephrotoxicity. Renal impairment occurrence adversely affected the tacrolimus treatment outcome; therefore, it is important to carefully administer tacrolimus to prevent renal impairment.

Background: In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. Methods: Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. Results: Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. Conclusions: Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.