Search Results for: GUT

Introduction
Differences in the profile of the vaginal microbiota (VMB) have been associated with pregnancy rates after medical assisted reproduction (MAR) such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Monitoring the VMB profile of IVF patients creates an opportunity to identify the best window for IVF treatment and embryo transfer. The ReceptIVFity test is a predictive test that assesses the chances of becoming pregnant in women undergoing IVF treatment based on the VMB composition. A VMB profile dominated by beneficial strains, most notably Lactobacillus species, is associated with increased pregnancy chances. However, to date, limited evidence is available on the effect of active modification strategies to facilitate the modulation of the VMB profile to help restore a VMB dominated by Lactobacillus species.

Methods and analysis
This is a randomised, placebo-controlled, double-blind intervention study. The study will involve 1:1 randomisation to one of the two arms: oral probiotic or placebo. Vaginal and rectal swabs will be collected at intake and 4, 6 and 8 weeks after the start of the treatment. Our objective is to determine if oral probiotic treatment improves the VMB profile of IVF patients from a low to a medium/high ReceptIVFity score, compared with placebo treatment. Secondary outcomes are: the potential of the bacterial strains in the oral probiotic to be detected in the vaginal tract and/or in the gut, and if the treatment leads to an increased ongoing pregnancy rate after IVF.

Ethics and dissemination
Ethical approval was obtained by the local medical ethical review committee at the Maastricht University Medical Centre. Findings from this study will be published in a peer-reviewed scientific journal and presented at one or more scientific conferences.

Trial registration number
CCMO NL81210.068.22, registered 25 September 2023.

Lin Y, Pu S, Wang J et al. Pancreatic STAT5 activation promotes KrasG12D-induced and inflammation-induced acinar-to-ductal metaplasia and pancreatic cancer. Gut 2024;73:1831–3.
A magnified version of figure 3E was incorrectly used for figure 7L. The article has been amended to show the correct version of figure 7L.
A magnified version of figure 2D was incorrectly used for figure 4A. The article has been amended to show the correct version of figure 4A.
In the view of the editor, these errors and their corrections do not alter the findings of the article.

Gisbert JP, Donday MG, Riestra S, et al. Withdrawal of antitumour necrosis factor in inflammatory bowel disease patients in remission: a randomised placebo-controlled clinical trial of GETECCU. Gut 2025;74:387–396.
There is an error in table 1 in the number of patients with CD. The correct number should be 31 (44%) in each column.

Zeng X. Unleashing the potential of exosome ncRNAs for early gastric cancer detection—a critical appraisal of machine learning approaches. Gut 2025;74:1191–1192.
This letter1 has been retracted by Gut due to apparent peer review manipulation.
BMJ has evidence that this letter’s peer review process was compromised. Two reviewers, recommended by the authors, used the same computer to submit their peer review comments as the submitting author used to submit the article to the journal. The authors and reviewers were asked to respond to these concerns and provide an explanation, but did not provide a satisfactory response.

Alcohol-associated liver disease (ALD) is a leading cause of chronic liver disease and liver-related mortality worldwide. The progression of ALD can range from simple fatty liver (steatosis) to severe liver damage, including alcohol-associated hepatitis (AH), liver fibrosis or cirrhosis, and hepatocellular carcinoma.1 Research over the past few decades has shown that the mechanisms behind the development of ALD are complex, involving multiple cellular factors and interactions between different organs. At the cellular level, alcohol and its metabolites, such as acetaldehyde, can lead to the production of reactive oxygen species, increase in endoplasmic reticulum stress, mitochondrial damage and megamitochondria formation, impaired autophagy-lysosomal functions, and the accumulation of Mallory-Denk bodies resulting in hepatocyte death and degeneration, as well as increased infiltration of immune cells, particularly neutrophils with high IL-8 expression.1 2 Consequently, these changes also contribute to an increased ductular reaction (DR) and cholestasis, fibrosis,…

Acute severe ulcerative colitis (ASUC) remains one of the challenging presentations in inflammatory bowel disease (IBD) where progress on therapeutic approaches has been limited since 1955 when corticosteroids revolutionised care 1 to reduce the mortality associated with ASUC. Despite the advent of rescue therapy options, short- and long-term colectomy rates remain stubbornly high2 . While newer strategies to reduce the need for in-hospital colectomy during an index admission are being considered with variable success, there is limited data guiding the management of steroid-responsive patients with ASUC. In GUT, Amiot et al 3 aimed to address this gap in knowledge by randomising ASUC patients responding to intravenous steroids (IV) to infliximab with azathioprine (IFX+AZA) or azathioprine (AZA) alone. The results indicate a 28% reduction in treatment failure at week 52, defined as the composite of the absence of steroid-free clinical remission and endoscopic response…

Background
The gut microbiome and diet are important factors in the pathogenesis and management of Crohn’s disease (CD). However, the role of the gut phageome under dietary influences is unknown.

Objective
We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.

Design
We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.

Results
On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.

Conclusion
Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.

In 1996, a landmark study from Kelly et al demonstrated that placement of children with oesophageal eosinophilia on an elemental diet, that is, a diet devoid of all food antigens, led to histological and symptomatic normalisation.1 Over the past three decades, this simple understanding of eosinophilic oesophagitis (EoE) has evolved from a one-act play to a highly complex drama involving multiple scenes and actors. Recently in Gut, Santacroce et al2 carefully and elegantly illustrated an understandable and exciting view of the pathogenesis of EoE. Roughly, three acts were presented to advance the pathobiology of EoE: barrier dysfunction, inflammation and tissue remodelling. The observation that large protein antigens and pathogens can penetrate the oesophageal epithelium is a novel concept.3 Dysfunction of this barrier leading to antigen penetration is manifest pathologically by dilation of intracellular spaces, physiologically by methods that demonstrate increased permeability and mechanistically…

We read with interest the Australian inflammatory bowel disease (IBD) consensus statements for pregnancy by Laube et al, which highlights that patients with IBD in the active stage have reduced fertility with unclear reasons.1 IBD, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), involves gut microbiota and metabolites as key players in its development.2 A recent study revealed ovarian impairment in CD, while polycystic ovary syndrome (PCOS) is a common cause of ovarian dysfunction and infertility in women.3 4 Mounting evidence supported an association between gut microbiota and ovarian function,5 and our recent work revealed that gut microbiota was involved in the pathogenesis of PCOS.6 7 Therefore, we speculated that IBD may induce PCOS by disrupting gut microbiota, leading to alterations in plasma metabolites. Initially, we performed a phenome-wide Mendelian randomisation (MR) analysis based on…

Basic scienceComing out of my (glyco)cage Ma W, Wang C, Kothandapani J, et al. Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting. Science 2025; eadk7633. doi: 10.1126/science.adk7633. Targeted drug delivery to the colon is somewhat of a ‘holy grail’ in gastrointestinal medicine. The need to get the right drug to the right place at the right time to treat intestinal inflammation without the collateral damage of unwanted systemic uptake has led to several novel solutions over the years. These include multimatrix delivery systems, administration of prodrugs and pH-dependent and time-dependent carriers. Our ever-increasing knowledge of the human gut microbiota is allowing us to harness its activity to achieve the same ends. Xyloglucans (XyG) are polysaccharides found in fruit and vegetables. While humans lack enzymes to degrade XyG, human gut microbiomes all contain genes coding for these enzymes in abundant bacteria such as Bacteroides sp. In this study,…

Background
Gut-liver crosstalk plays an important role in alcohol-associated liver disease (ALD) pathogenesis; but underlying mechanisms remain obscure.

Objective
We examined the regulation of intestinal and intrahepatic CD8+ T lymphocytes and their contribution to ALD.

Design
ALD patients were recruited for evaluation of intestinal and liver T cells. Single-cell RNA sequencing (scRNA seq) was performed to analyse intrahepatic and peripheral T cells in ALD. Wildtype, CD8-specific Bcl2 transgenic (Cd8 Bcl-2), and Cd8 –/– mice were subjected to chronic-plus-binge ethanol feeding.

Results
In ALD patients, duodenal CD8+ T cells were selectively reduced and negatively correlated with liver injury and bacterial translocation markers, while intrahepatic CD8+ T cells were markedly increased. ScRNA seq analysis of ALD patient livers revealed several populations of CD8+ T cells expressing activation and survival genes (eg, Bcl2). Transcriptomics and functional studies revealed a key role of prosurvival BCL2 in this opposite regulation of CD8+ T cells. Mechanistically, chronic-plus-binge ethanol feeding reduced CD8+ T cells specifically in the duodenum where ethanol levels are high. Inducing BCL2 in CD8+ T cells reversed ethanol-induced loss of duodenal CD8+ T cells, improved gut barrier function and ameliorated ALD, while CD8 deficiency was linked to enhanced neutrophil and macrophage infiltration in the liver, exacerbating ALD in mice.

Conclusions
ALD is associated with loss of duodenal CD8+ T cells but elevation of intrahepatic CD8+ T cells, which aggravates and ameliorates ALD, respectively. Restoration of survival and functions of intestinal and intrahepatic CD8+ T cells may represent a novel therapeutic strategy for ALD patients.

Background
Gut microbial metabolites are recognised as critical effector molecules that influence the development of colorectal cancer (CRC). Peptidoglycan fragments (PGFs) produced by microbiota play a crucial role in maintaining intestinal homeostasis, but their role in CRC remains unclear.

Objective
Here, we aimed to explore the potential contribution of PGFs in intestinal tumourigenesis.

Design
The relative abundance of peptidoglycan synthase and hydrolase genes was assessed by metagenomic analysis. Specific PGFs in the faeces and serum of CRC patients were quantified using targeted mass spectrometry. The effects of PGF on intestinal tumourigenesis were systematically evaluated using various murine models of CRC and organoids derived from CRC patients. Downstream molecular targets were screened and evaluated using proteome microarray, transcriptome sequencing and rescue assays.

Results
Metagenomic analysis across seven independent cohorts (n=1121) revealed a comprehensive reduction in peptidoglycan synthase gene relative abundance in CRC patients. Targeted mass spectrometry identified significant depletion of a specific PGF, N-acetylmuramic acid (NAM) in CRC patients, which decreased as tumours progressed (p

Introduction
Pain is one of the most bothersome symptoms that affects patients with inflammatory bowel disease (IBD) but is often inadequately treated. Inadequate pain control in the inpatient setting not only impacts patients’ experience but increases opioid use and hospital length of stay. Opioids are often considered first-line treatment for severe pain but are associated with significant morbidity and mortality in IBD. Non-steroidal anti-inflammatory drugs are a non-opioid analgesic option, but concerns regarding their contribution to IBD flares have limited their use. Brain-gut behavioural therapies (BGBT), such as cognitive behavioural therapy, meditation and gut-directed hypnotherapy, are effective for pain management and have a role in the treatment of IBD symptoms. However, the use of BGBT in IBD is challenging, given limited access to behavioural health specialists, especially in the inpatient setting. Virtual reality (VR)-directed BGBT programmes can bridge this gap and enhance pain treatment for inpatients with IBD. Therefore, in this study, we aim to establish feasibility and acceptability for a VR-directed BGBT inpatient programme for patients with IBD.

Methods and analysis
We will recruit 40 patients with IBD who are hospitalised at Michigan Medicine and who endorse IBD-related pain. We will assess patient-reported outcomes (pain rating, IBD-specific symptoms, perceived stress, mood) before and after treatment, cumulative inpatient analgesic requirements and hospital length of stay. Our primary objective will be to establish intervention feasibility defined by the frequency and percentage of enrolled participants that use the VR-directed BGBT inpatient intervention in any capacity. Our secondary objective will be to evaluate intervention acceptability by conducting semistructured interviews with study participants. We will also explore the preliminary effectiveness of VR-directed BGBT on patient-reported outcomes and healthcare utilisation as compared with historic controls.

Ethics and dissemination
The study was approved by the institutional review board of the University of Michigan Medical School on 10 October 2023 (HUM00240999). All human subjects will be required to sign an informed consent document prior to study participation. Study findings will be reported through peer-reviewed publication.

Trial registration number
NCT06188793.

The production of autoantibodies against the enzyme transglutaminase 2 (TG2) in celiac disease likely results from TG2-specific B cells receiving help from gluten-specific CD4+ T cells in gut-associated lymphoid tissues (GALT) via the formation of transient enzyme-substrate complexes formed between TG2 and gluten. Where in the body enzymatically active TG2 encounters gluten peptides remains unknown.

Chronic gastrointestinal (GI) diseases, including functional, inflammatory, and neoplastic conditions, are rising globally, partly due to modern lifestyles. The circadian rhythm, regulated by the central clock in the hypothalamus and synchronized with peripheral clocks in the gastrointestinal organs, orchestrates GI functions in response to environmental cycles. This clock is influenced by cues such as light, sleep, and eating times. The circadian machinery prepares the host to cope with environmental conditions to adjust cellular and organ function accordingly.

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.