Search Results for: GUT

This review in the Translational Science series summarizes current evidence regarding the human microbiome and cancer, including how the microbiota in the gut and other anatomical locations affect cancer outcomes and response to cancer therapy.

Introduction
As a disorder of gut–brain interaction, irritable bowel syndrome (IBS) is a common reason for patient visits in primary and specialist care settings. IBS is associated with recurrent abdominal pain, altered bowel habit, resulting in alternating constipation and diarrhoea, bloating, without serious organic diseases. The bidirectional relationship between IBS and psychological factor is also complex. Studies have suggested that tricyclic antidepressants can effectively control the concomitant symptoms of IBS, especially some severe and refractory symptoms. At present, the conventional treatment of IBS remains somewhat unsatisfactory. Studies have shown that the antidepressant effects of esketamine are rapid and significant, whether a single low dose of esketamine is effective in IBS deserves further investigation. In this study, we hypothesise that a single low dose of esketamine will be effective for IBS.

Methods and analysis
This is a single-centre, randomised, double-blind, placebo-controlled trial. Patients with IBS are divided into three levels according to the severity of IBS: mild, moderate and severe. 92 patients in the esketamine group and 92 patients in the control group who are scheduled for colonoscopy will be prospectively recruited in each level. The primary outcome is the IBS Severity Scoring System at baseline and at 3 days, 1 week, 3 weeks, 6 weeks after colonoscopy. The secondary outcome includes IBS-Quality of Life, Bristol Stool Form scale, Hospital Anxiety and Depression Scale, Patient Health Questionnaire-12 Somatic Symptom Score and adverse events. The allocation sequence is assigned by a random number table using a block randomisation method by SPSS (Version 26, IBM Inc., USA) Statistics software. All enrolled patients, anaesthesiologist B and researchers responsible for follow-up and data collection and analysis are therefore fully blinded. All data will be performed using SPSS Statistics software, and a p value

Introduction
Concurrent with infants’ progression in dietary complexity and gut microbiome diversity, infants gradually change their defecation patterns during the first year of life. However, the links between bowel habits, the gut microbiota and early life nutrition remain unclear. The primary outcome is to characterise the gut microbiome development from birth to 1 year of age. Second, to investigate how bowel habits and nutrition in early life relate to the gut microbiome and metabolome during this period of life, and to explore how the development of the gut microbiome associates with host development.

Methods and analysis
The MOTILITY Mother-Child Cohort (MOTILITY) is a Danish prospective longitudinal cohort study enrolling up to 125 mother–infant dyads. Assessments occur at 36 weeks gestation (visit 1), birth (screening of infant) and 3, 6, 9 and 12 months (±2 weeks) post partum (visits 2–5). At visit 1, maternal anthropometrics, self-collected faecal and urine samples, and questionnaires on bowel habits and lifestyle are obtained. Between visits, infant faecal (biweekly), urine (monthly) and maternal breast milk (monthly until 6 months of age) samples are collected at home, and bowel habits and dietary intake are assessed biweekly by self-reported questionnaires. At visits 2–5, infant blood and saliva samples are collected, and anthropometric measurements are obtained. In addition, dietary intake is recorded thrice throughout the study period for mother and infant, respectively, and infant whole-gut transit time is estimated by sweet corn tests at 9 and 12 months of age. Birth, growth, motor development, sleep patterns, tooth development, overall health and well-being are assessed using questionnaires. Univariate and multivariate statistics will be applied to identify associations between the gut microbiome, early life nutrition and host physiology including bowel habits during the first year of life.

Ethics and dissemination
The MOTILITY study has been approved by the Research Ethics Committee for the Capital Region of Denmark (reference number: H-21063016). Selected results will be made available to the participants in the form of a summary document. Results will be published in peer-review journals and by means of national and international conferences.

Trial registration number
NCT05491161.

Inflammatory bowel disease (IBD) has emerged as a global disease, affecting individuals of every ethnicity and age groups worldwide.1 It is broadly accepted that the greatest single risk factor for the development of IBD is having an affected family member.2 First-degree relatives (FDRs) of patients with IBD have approximately a 10-fold greater likelihood of developing the disease than the general population. Despite the fact that numerous studies have been deliciated towards exploring the possible determinants that participated in, the underlying aetiology remains elusive. Amalgamation of both genetic predisposition and environmental exposures have been widely recognised as the predominant factors that instigate and drive the course of IBD. On this basis, they may also serve as contributing factors to the familial occurrence of IBD. Given that the family members of patients with IBD represent a specific population enduring this dual challenges over an extended period, it…

Basic scienceSensing pain in the gut: new insights into enterochromaffin cells Touhara K, Rossen N, Deng F et al Topological segregation of stress sensors along the gut crypt-villus axis. Nature 2025; 640(8059): 732-742. doi: 10.1038/s41586-024-08581-9. The gut barrier is monitored by enterochromaffin (EC) cells, epithelial sensory enteroendocrine cells which release serotonin in response to stimuli. TRPA1 (transient receptor potential cation channel, subfamily A, member 1—also known as the wasabi receptor), which detects electrophilic irritants, is present in the crypts. TRPM2 (transient receptor potential cation channel, subfamily M, member 2), which measures oxidative stress, is in the villi. The EC-pain circuit is not well understood. Touhara et al used a new mouse model to study this. Serotonin receptors were labelled in a way that fluorescence intensity increased after serotonin release. Tonic (low-level) serotonin release was observed in crypts where TRPA1 was expressed. This activated metabotropic 5-HT4 (5-hydroxytryptamine receptor…

We read with great interest the article by Cai et al,1 titled ‘Construction of exosome non-coding RNA feature for non-invasive, early detection of gastric cancer patients by machine learning: a multi-cohort study’, published in Gut. The study presents a novel approach for the early detection of gastric cancer (GC) using serum exosome non-coding RNAs (ncRNAs) and machine learning, which is a significant step forward in the field of liquid biopsy for cancer diagnostics. The study by Cai et al has several notable strengths. First, the comprehensive multi-cohort design, including both training and external validation cohorts, provides robust evidence for the diagnostic potential of the identified exosome ncRNA feature. The use of machine learning algorithms, particularly LASSO-logistic regression, to develop the combined diagnostic model (cd-score) is innovative and demonstrates high diagnostic accuracy with an area under the curve of 0.959 in the training cohort and 0.949 in the…

Hepatocellular carcinoma (HCC) is often diagnosed at the unresectable stage with limited treatment options.1 Immunotherapy with immune checkpoint blockade (ICB) has been shown to provide significant survival benefit for HCC patients with advanced disease. Two combination therapies of anti-PD-L1 plus anti-VEGF or anti-PD1 plus anti-CTLA4 represent the current first-line treatments for unresectable HCC.2 3 However, only about one-third of patients respond to therapy, typically in the context of immune-enriched (‘hot’) tumour microenvironments.4 5 Therefore, there is a major need for treatment strategies that overcome ICB resistance. In Gut, Tu et al observe a correlation of poor prognostic outcomes by anti-PD-1-treated patients with high expression of major histone deacetylases (HDACs) by HCC tumours.6 They, therefore, test the potential of epigenetic immunotherapy combining HDAC inhibitors with ICB therapy in preclinical animal models and provide evidence that the epigenetic immunotherapy…

The gut microbiota is pivotal for maintaining health through beneficial symbiotic interaction with the host supporting the homeostasis of the gastrointestinal tract but also of the majority of extraintestinal organs. Alterations in the gut microbiome have been linked to the pathogenesis of various diseases, including cancer, which remains a leading cause of mortality worldwide. The colonisation or overgrowth of certain bacterial species at the expense of others has been implicated in tumorigenesis. For instance, Helicobacter pylori infection is known to cause chronic inflammation and significantly increases the risk of developing gastric cancer, while Bacteroides fragilis and Fusobacterium nucleatum overgrowth have been associated with colorectal cancer (CRC). Consequently, several microbiota-based strategies have been developed to regulate cancer progression, enhance immune responses towards tumorous cells and improve the effectiveness of current anticancer therapies.1 Among the most abundant bacteria in the healthy human gut microbiota, Faecalibacterium prausnitzii, an anaerobic member…

Li M, Xu C, Shi J, et al. et al Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway. Gut 2018;67:2169–80.
This article has been corrected since it was first published. During the integration of data and preparation of final figures, the incorrect image was mistakenly included for figure 6, panel C. In the online version of the article, this has now been replaced with the correct image from the same experiment involving treatments with F+NC, F+siMPST, F+siMPST+NC, and F+siMPST+siCSE, respectively.

The prevalence of Crohn disease (CD) is rising globally and therefore is of increasing relevance in the dermatology clinic. Between 14% and 44% of patients with CD demonstrate mucocutaneous involvement, which has been postulated to result from abnormal homing of gut lymphocytes to the skin.

Introduction
Type 1 diabetes (T1D) mellitus is caused by autoimmune destruction of insulin-producing beta-cells, requiring exogenous insulin to sustain life. Achieving near normal blood glucose levels with insulin, a primary goal of diabetes management, carries a significant risk of hypoglycaemia. There is compelling evidence that an abnormal gut microbiota or dysbiosis can increase intestinal permeability (IP) and contribute to dysglycaemia seen in T1D. Given that prebiotic fibre can mitigate dysbiosis, reduce IP and improve glycaemic control, we hypothesise that microbial changes induced by prebiotics contribute to gut and endocrine adaptations that reduce glucose fluctuations, including less hypoglycaemia. In a pilot study, we showed that in children who had T1D for at least 1 year, a 3-month course of prebiotic fibre significantly reduced the frequency of hypoglycaemia. The prebiotic group had an increase in Bifidobacterium with a moderate improvement in IP. Importantly, the prebiotic group maintained their serum C peptide level (marker of residual beta cell function) while the placebo group saw a drop. Given that preserving endogenous beta cell function in patients with T1D, particularly in the first year of diagnosis, reduces hypoglycaemia and glycaemic variability, we propose to examine the effect of prebiotic supplementation in patients with T1D.

Methods and analysis
This is a multicentre, randomised, double-blind, placebo-controlled study. Individuals (n=144) with T1D will be randomised 1:1 for 6 months to prebiotic (oligofructose-enriched inulin) or placebo (isocaloric maltodextrin). Participants will have three in-person study visits at baseline, 3 months and 6 months. The primary outcome, frequency of hypoglycaemia, will be determined from continuous glucose monitor (CGM) reports and patient blood glucose logs. Secondary outcomes will include glycaemic variability, time-in-range, glycated haemoglobin, stimulated C peptide, IP, serum inflammatory markers, quality of life and fear of hypoglycaemia ratings, as well as gut microbiome and metabolomics analysis. At 9 months, participant CGM data will be used to assess frequency of hypoglycaemia and glycaemic variability at 3 months postintervention.

Ethics and dissemination
The study received ethical approval from the University of Calgary Conjoint Health Research Ethics Board (REB21-0852). The University of Alberta subsite was granted ethical approval under the province of Alberta’s research ethics reciprocity agreement as a participating site (REB21-0852; pSite00000066). The University of Saskatchewan subsite was granted ethical approval by the Biomedical Research Ethics Board (#4149). Trial findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number
clinicaltrials.gov NCT04963777.

In Reply Dr Trocheris-Fumery and colleagues are correct to highlight the uncertainties and variation in practice in IV lidocaine dosage in the context of perioperative infusion in colorectal and other abdominal surgery. Our clinical trial was a pragmatic evaluation of an intervention that has gained credence despite an absence of robust dose-response studies for perioperative recovery end points. The relationship between infusion rate and serum lidocaine levels is affected by many variables as well as body weight; available data suggest that lidocaine infusion rates between 1.5 and 3 mg/kg/h appear to achieve similar serum lidocaine concentrations. Although our loading dose and infusion schedule was within accepted practice for this intervention, to prioritize safety we used ideal body weight rather than total body weight, given data suggesting increased serum levels in patients with obesity using total body weight. The currently recruiting VAPOR-C and LOLLIPOP trials evaluating perioperative IV lidocaine also use a dosage schedule modified for excess weight (adjusted body weight and ideal body weight, respectively).

To the Editor Dr Paterson and colleagues conducted a randomized clinical trial to evaluate the effect of perioperative IV lidocaine on return of gut function after elective minimally invasive colon resection. I was surprised by the lack of discussion regarding the observed difference in postoperative opioid consumption between the lidocaine and placebo groups and its potential impact on the study’s findings.

To the Editor Dr Paterson and colleagues evaluated the effect of intravenous (IV) lidocaine on gut function recovery after colonic surgery. They did not observe a beneficial effect of IV lidocaine on recovery of intestinal function.