Search Results for: GUT

Basic ScienceUnderstanding further gut motility: a RET story Shepherd A, Feinstein L, Sabel S, et al. RET signaling persists in the adult intestine and stimulates motility by limiting PYY release from enteroendocrine cells. Gastroenterology 2024; 166(3): 437–449. doi: 10.1053/j.gastro.2023.11.020. The role of rearranged during transfection (RET) tyrosine kinase in enteric nervous system (ENS) development is known. Its effect on mature intestine is unclear. GI symptoms are common in conditions where RET signalling is disrupted. Using murine models, Shepherd et al, evaluated the impact on gut motility of RET signalling within neurons, epithelial and entero-endocrine cells. RET was measured in neurons at different stages of mice’s lives along the gut, demonstrating stable expression with age and location. Shepherd et al, generated the mice line (RETcko) where RET is depleted after ENS development on Tamoxifen administration. RETcko and control mice had same ENS density at 4 weeks from Tamoxifen…

Objective
Selective decontamination of the digestive tract (SDD) is a well-studied but hotly contested medical intervention of enhanced infection control. Here, we aim to characterise the changes to the microbiome and antimicrobial resistance (AMR) gene profiles in critically ill children treated with SDD-enhanced infection control compared with conventional infection control.

Design
We conducted shotgun metagenomic microbiome and resistome analysis on serial oropharyngeal and faecal samples collected from critically ill, mechanically ventilated patients in a pilot multicentre cluster randomised trial of SDD. The microbiome and AMR profiles were compared for longitudinal and intergroup changes. Of consented patients, faecal microbiome baseline samples were obtained in 89 critically ill children. Additionally, samples collected during and after critical illness were collected in 17 children treated with SDD-enhanced infection control and 19 children who received standard care.

Results
SDD affected the alpha and beta diversity of critically ill children to a greater degree than standard care. At cessation of treatment, the microbiome of SDD patients was dominated by Actinomycetota, specifically Bifidobacterium, at the end of mechanical ventilation. Altered gut microbiota was evident in a subset of SDD-treated children who returned late longitudinal samples compared with children receiving standard care. Clinically relevant AMR gene burden was unaffected by the administration of SDD-enhanced infection control compared with standard care. SDD did not affect the composition of the oral microbiome compared with standard treatment.

Conclusion
Short interventions of SDD caused a shift in the microbiome but not of the AMR gene pool in critically ill children at the end mechanical ventilation, compared with standard antimicrobial therapy.

We read with great interest the review by Tranah et al,1 which highlighted that alcohol consumption, alterations in the gut microbiome and impairment of the gut barrier function were linked to the development of alcohol-related liver disease (ALD). However, the impact of acute alcohol consumption on the circulating microbiome in patients with ALD remains unclear. To address this gap, we conducted a controlled acute alcohol intervention in healthy controls (n=8), individuals with ALD (n=14) and non-alcoholic fatty liver disease (NAFLD) (n=14). Ethanol (2.5 mL of 40% EtOH per kg body weight) was instilled via a nasogastric tube over 30 min by infusion pump. To sample hepatic and systemic venous blood simultaneously, we placed a catheter in a hepatic vein via a transjugular access and another catheter in the right internal jugular vein. Blood was sampled at eight time points over 3 hours (figure 1A).2 3

The microbial ecosystem of the human gut (‘the gut microbiome’) plays an important role in human health through a variety of mechanisms, including the degradation of complex carbohydrates, the production of vitamins and other beneficial compounds and by providing a barrier to invading pathogens.1 The gut can also be the source of pathobionts, including the Gram-negatives Escherichia coli, Klebsiella spp and other members of the family Enterobacteriaceae. These bacteria can be carried asymptomatically by the host but can also cause urinary tract or bloodstream infections, particularly in immunocompromised individuals. Specific hospital-adapted Enterobacteriaceae clones are circulating in healthcare systems and have acquired resistance to multiple classes of antibiotics.2 These multidrug-resistant strains are thus importantly selected for when patients are treated with antibiotics, while susceptible bacteria are simultaneously eradicated.3 The combined impacts of critical illness, antibiotic therapy and other factors associated with intensive care unit…

We have read with interest several recent papers in Gut that have reported novel insights about the potential consequences of reduced gastric acid secretion. These include reports that proton pump inhibitor (PPI) use increases the risks of developing diverse diseases including gastric adenocarcinoma1 2 and severe COVID-19 infection.3 An intriguing recent paper has also shown that pathological suppression of gastric acid secretion in people with autoimmune atrophic gastritis does not predispose to gastric adenocarcinoma development unless they are also infected with Helicobacter pylori.4 These patients are, however, more prone to developing type 1 gastric neuroendocrine (carcinoid) tumours (NETs). Interestingly, gastric NETs do not develop in people who have H. pylori induced atrophic gastritis or following long term drug-induced acid inhibition. These observations highlight the complexity of the regulation of gastric acid secretion and suggest that the underlying cause of hypochlorhydria is…

The progression of cirrhosis with clinically significant portal hypertension towards decompensated cirrhosis remains clinically challenging and the evolution towards acute-on-chronic liver failure (ACLF), with one or more extrahepatic organ failures, is associated with very high mortality. In the last decade, significant progress has been made in the understanding of the mechanisms leading to decompensation and ACLF. As portal hypertension advances, bacterial translocation across an impaired gut barrier culminates in endotoxaemia, systemic inflammation and cirrhosis-associated immune dysfunction (CAID). Gut-derived systemic inflammation and CAID have become the logical targets for innovative therapies that prevent hepatic decompensation episodes and the progression to ACLF.
Furthermore, classification of disease and biomarker discovery to personalise care have advanced in the field. This review discusses progress in biomarker discovery and personalisation of treatment in decompensated cirrhosis and ACLF.

Putative anion transporter-1 (PAT1, SLC26A6) plays a key role in intestinal oxalate and bicarbonate secretion. PAT1 knockout (PKO) mice exhibit hyperoxaluria and nephrolithiasis. Notably, diseases such as inflammatory bowel diseases (IBD) are also associated with higher risk of hyperoxaluria and nephrolithiasis. However, the potential role of PAT1 deficiency in gut barrier integrity and susceptibility to colitis is currently elusive.