Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the intestine. The incidence of IBD is increasing worldwide, including Japan, and in approximately 25% of all affected patients it is diagnosed before 18 years of age. For the health maintenance of such patients, planned transition to adult care systems is essential. Previous Japanese surveys have revealed gaps between adult and pediatric gastroenterologists with regard to their knowledge and perception of health‐care transition for patients with childhood‐onset IBD. In 2021–2022, several Web workshops to discuss issues related to the transitional care of IBD patients were held by the Ministry of Health, Labour and Welfare of Japan as part of their program for research on intractable diseases. Clinicians experienced in IBD treatment for pediatric and adult patients participated. As a result, this panel of adult and pediatric gastroenterologists developed five consensus statements on the issue of “transfer from pediatric to adult care” and nine statements on the issue of “addressing transitional care (transition program).” To address current gaps in health‐care transition for childhood‐onset IBD patients, a programmed approach to transition, and better partnerships between pediatric and adult gastroenterologists are indicated. It is hoped that this consensus statement will provide a basis for the development of appropriate guidelines for clinical practice.
Intestinal ultrasound (IUS) is a promising modality for the management of inflammatory bowel disease (IBD) and has the potential to particularly contribute in monitoring disease activity, an advantage crucial for optimizing the therapeutic strategy. While many IBD physicians appreciate and are interested in the use of IUS for IBD, currently only a limited number of facilities can employ this examination in daily clinical practice. A lack of guidance is one of the major barriers to introducing this procedure. Standardized protocols and assessment criteria are needed such that IUS for IBD can be considered a feasible, reliable examination in clinical practice, and multicenter clinical studies can be conducted for further clinical evidence of the application of IUS in IBD for best patient care. In this article, we provide an overview of how to start IUS for IBD and introduce basic procedures. Furthermore, IUS images from our practice are provided as a color atlas for understanding sonographic findings and scoring systems. We anticipate this “first aid” article will be helpful to promote IUS for IBD in daily practice.
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of metabolic syndrome and major indications for liver transplantation. Western diet contributes to disease pathogenesis, partially mediated through the gut microbiome, yet mechanisms remain elusive. Human epidemiological studies identified high dietary cholesterol intake as a NAFLD risk factor and it is essential to drive disease in murine models, yet little is known about its role in reshaping gut microbiota. Using the fast food (FF) diet murine model in germ‐free (GF) mice completely devoid of all microbes and their conventionally‐raised (control) counterparts harboring complex microbiomes, we hypothesized high dietary cholesterol‐induced gut microbiota impact NAFLD onset, progression, and severity. Male C57Bl/6 age‐matched GF and control mice were fed 1 of 4 semi‐purified diets: low‐fat (LF); high fat (HF); FF + 0.2% high cholesterol (FFHC); FF + 2% very high cholesterol (FFVHC) for 8 or 24 weeks. Fecal gut microbiota profiles were tracked over time via Illumina MiSeq 16S rRNA gene amplicon sequencing. Serum alanine transaminase (ALT) and lipopolysaccharide binding protein (LBP, an indicator of gut barrier function) were measured throughout the study. Livers were collected for histology and Illumina NovaSeq RNA‐sequencing. Despite equal caloric intake between GF and controls across diets, significant weight gain and increased liver weight to body weight ratios (P<0.05) were observed only in control mice fed FF diets. GF mice were largely protected from disease, with no elevation in plasma ALT, LBP, or histology‐based NAFLD activity score (NAS) regardless of treatment. Conversely, FFVHC control mice exhibited significantly elevated plasma ALT after 8 weeks on diet, which was exacerbated at 24 weeks relative to LF control and all GF groups. FF diets significantly increased (FFHC: P<0.05; FFVHC: P<0.01) plasma LBP after 24 weeks. Control mice fed FF diets exhibited severe steatosis, where FFVHC significantly increased NAS at 8 (P<0.05) and 24 (P<0.001) weeks relative to LF control and all GF groups. Microbiota profiling revealed no change in α‐diversity regardless of diet in control mice. β‐diversity analysis showed HF and FF diets, particularly FFVHC, rapidly shifted gut microbiota community membership after only 4 weeks, preceding disease onset and was further exacerbated over time. Liver RNA‐seq revealed FFVHC diet in control, but not GF, mice significantly enriched genes involved in the KEGG pathway, “antigen processing and presentation” (Bonferroni P<0.001) relative to HF‐fed counterparts at 24 weeks. Taken together, FF diet‐induced shifts in gut microbes are both a prerequisite for and precede NAFLD/NASH disease onset, which is exacerbated by increased dietary cholesterol, driving liver inflammation. These data provide unique insights into how Western diet components impact host‐microbe interactions in complex liver diseases, which may aid in identifying novel therapeutic interventions.
Objectives An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients with a Mayo endoscopic subscore (MES) ≤1 who underwent colonoscopy for UC in clinical remission were included. LCI index was defined as redness (R) (grade 0–2), area of inflammation (A) (grade 0–3), and lymphoid follicles (L) (grade 0–3). Histological healing was defined as Geboes score <2B.1. Endoscopic and histopathological scores were determined by central judgment. Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. There were 22/117/30 cases of grade 0/1/2 in LCI index-R, 113/34/17/5 cases of grade 0/1/2/3 in LCI index-A, and 124/27/14/4 cases of grade 0/1/2/3 in LCI index-L. Histological healing was achieved in 84.0% (142/169) of the cases, and there were significant associations with histological healing/non-healing in LCI index-R (P=0.013) and A (P=0.0014). Conclusions A new LCI index is useful for predicting histological healing in UC patients with MES ≤1 and clinical remission.
Background Circadian rhythms are ubiquitous in nature, driving many bodily processes and behaviors, including sleep‐wake cycles and feeding patterns over 24 hours. We and others revealed gut microbes and their functional outputs also exhibit diurnal rhythms that are responsive to how much, what, and when food is consumed. These microbial cues are integrated into host circadian networks, serving as key regulators of metabolism. High fat (HF) diet disrupts diurnal microbial oscillations, impacting diet‐induced obesity (DIO). Apart from feeding, host factors that drive microbial oscillations, specifically in the small intestine, are complex and remain poorly understood. We hypothesized that HF diet disrupts coordination of diurnal rhythms between host‐derived antimicrobial peptides, particularly the host C‐type lectin Regenerating islet‐derived 3 gamma(Reg3γ), and gut microbial community membership, contributing to DIO and metabolic dysfunction. Results Distal ileal tissue and luminal contents were collected every 4 hours over a 12:12 LD cycle from regular chow (RC) vs. HF‐fed germ‐free (GF) and conventionally raised (CONV) C57Bl/6 age and sex‐matched mice. Ileal tissue gene expression analysis reveals diurnal Reg3γ expression is only observed in RC‐fed, but not HF‐fed, CONV mice. Illumina MiSeq 16S rRNA gene amplicon sequencing of ileal luminal contents indicates that HF diet significantly shifts microbial community membership with a corresponding reduction in oscillations relative to RC. Specific Lactobacillaceae bacteria selected by RC oscillate and exhibit positive correlation with Reg3γ expression, while HF promotes expansion of Clostridiales bacteria that negatively correlate with Reg3γ. Using both in vitro intestinal organoid and in vivomonoassociation of GF mice, we identified that exposure to bacterial strains representative of those selected by RC or HF diet elicit a bi‐directional interaction with Reg3γ; only RC‐driven Lactobacillus rhamnosus GG (LGG) induces diurnal Reg3γ expression, suggesting a bacteria‐specific effect. While dietary composition remains the primary driver of microbial oscillators, host factors such as Reg3γ provide secondary cues to drive abundance and oscillation of key gut microbes that are essential for host metabolic homeostasis. Conclusions Together, these results demonstrate transkingdom co‐evolved biological rhythms that are primarily influenced by diet, and reciprocal sensor‐effector signals between host and microbial components. The diurnal dynamics of host innate immune factors and specific diet‐induced ileal gut microbes are key for the maintenance of regional intestinal host‐microbe interactions and metabolic homeostasis.
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