Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

Background: The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD. Methods: Thirty-one CD patients and 7 controls were enrolled. Circulating CD133+ and CD34+ HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3+ lymphoid cells) and the putative ISC compartment (CD133+ and Lgr5+ epithelial cells). Results: At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal. Conclusions: In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission

Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach

Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response

Endoscopic submucosal dissection in colorectal neoplasia performed with a waterjet system-assisted knife: higher resection rate than conventional technique

Background/Aims Colorectal endoscopic submucosal dissection (ESD) is burdened by its associated high risk of adverse events and long procedure time. Recently, a waterjet-assisted knife was introduced to simplify and speed up the procedure. The aim of this study was to evaluate the efficacy and safety of waterjet-assisted ESD (WESD) compared to that of the conventional ESD (CESD) technique. Methods The charts of 254 consecutive patients who underwent colorectal ESD between January 2014 and February 2021 for colorectal neoplasms were analyzed. The primary outcome was the en-bloc resection rate. Secondary outcomes were complete and curative resection rates, the need to switch to a hybrid ESD, procedure speed, the adverse event rates, and the recurrence rates. Results Approximately 174 neoplasias were considered, of which, 123 were removed by WESD and 51 by CESD. The en-bloc resection rate was higher in the WESD group (94.3% vs. 84.3%). Complete resection rates and curative resection rates were similar. The need to switch to a hybrid ESD was greater during CESD (39.2% vs. 13.8%). Procedure speed and adverse event rates were similar. During follow-up, one recurrence occurred after a WESD. Conclusions WESD allows a high rate of en-bloc resections and less frequently requires a rescue switch to the hybrid ESD compared to CESD

Stem cell-based therapies for liver diseases: state of the art and new perspectives.

Millions of patients worldwide suffer from end-stage liver pathologies, whose only curative therapy is liver transplantation (OLT). Given the donor organ shortage, alternatives to OLT have been evaluated, including cell therapies. Hepatocyte transplantation has been attempted to cure metabolic liver disorders and end-stage liver diseases. The evaluation of its efficacy is complicated by the shortage of human hepatocytes and their difficult expansion and cryopreservation. Recent advances in cell biology have led to the concept of "regenerative medicine", based on the therapeutic potential of stem cells (SCs). Different types of SCs are theoretically eligible for liver cell replacement. These include embryonic and fetal SCs, induced pluripotent cells, annex SCs, endogenous liver SCs, and extrahepatic adult SCs. Aim of this paper is to critically analyze the possible sources of SCs suitable for liver repopulation and the results of the clinical trials that have been published until now