Search

Midgut neuroendocrine tumors (NET) derive from enterochromaffin cells, which have a close interrelationship with intestinal microbiota. Recently, we have utilized 16S rRNA sequencing to uncover that midgut NET patients have a depleted gut microbiome and a specific fecal microbial signature. This study aims to validate these findings and to further characterize the role of microbes and microbial metabolic pathways in midgut NET patients with and without carcinoid syndrome (CS). Fecal samples from 60 midgut NET patients and 20 household-matched controls were subjected to whole metagenome sequencing. The gut microbial community composition of midgut NET patients differed from that of controls, with 2 genera, 17 species and 9 microbial pathways showing differential abundance (P < 0.001). No differences in the microbial composition were observed between midgut NET patients with and without CS (P > 0.05). However, we did observe changes in inter-genus correlations of Bacteroides, Odoribacter, Parasutterella, Klebsiella, Ruminococcus and Proteobacteria when comparing these two patient groups. A signature of 16 microbial species (area under the receiver operating characteristics (AUROC) curve 0.892) or 18 microbial pathways (AUROC 0.909) accurately predicted the presence of a midgut NET. Furthermore, a microbial signature consisting of 14 functional microbial pathways distinguished CS patients from non-CS patients (AUROC 0.807). Thus, this study confirms that the gut microbiome of midgut NET patients is altered at the metagenomic level, which is not related to the presence of CS. A fecal microbial signature could constitute a novel biomarker for the diagnosis of midgut NET or CS.

Introduction: Neuroendocrine tumors (NETs) are a heterogeneous group of epithelial tumors originating from different anatomical sites, and identifying the gut microbiota and metabolic mechanisms involved in the onset of NETs may help to develop appropriate disease prevention and monitoring strategies., Methods: We employed a mediated two-sample Mendelian randomization (MR) approach, analyzing gut microbiota from German studies and NET datasets from the 10th round of the FinnGen project. Mediation analyses were conducted using the metabolites dataset from the Canadian Longitudinal Study of Aging (CLSA) and the TwinsUK study. Instrumental variables were chosen according to established MR criteria and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. To ensure robustness, sensitivity analyses were performed using Cochrane's Q, Egger's intercept, MR-PRESSO, and leave-one-out methods., Results: Causal relationships were identified between the genetic determinants of 6, 5, 2, 1, 2, 3 gut microbiotas and the risk of colorectal, lung, pancreatic, rectum, small intestine, and stomach NETs. Similarly, the genetic determinants of 4, 6, 1, 5, 10, and 7 metabolites were found to be causally related to the risk of colorectal, lung, pancreatic, rectum, small intestine, and stomach NETs, respectively. Through Wald ratio and IVW methods, we preliminarily identified 957 microbiota-metabolite pairs with significant causal associations and formed 13 mediated relationships between the impact of gut microbiotas on NETs., Conclusion: Our study suggests that gut microbiotas and its derived metabolites may contribute to the onset of NET, offering a novel insight into the disease's pathogenesis., (© 2024 S. Karger AG, Basel.)

Gastric neuroendocrine carcinomas (NEC) are very rare, aggressive tumors of the stomach that are distinct from the more benign neuroendocrine tumors, sometimes referred to as "gastric carcinoids." We present 3 cases of gastric NEC representing various histological subtypes that were successfully staged and followed with F-FDG PET/CT, impacting therapeutic management in each case.

Background: The aims were to comparatively investigate the biostructure of colonic microbiota in patients with neuroendocrine tumors and Crohn's disease (CD) and to study the response of the microbiota to therapy., Methods: Sections of fecal cylinders from 66 patients with neuroendocrine tumors (NET; 25 foregut, 30 midgut, 11 hindgut), 50 patients with CD (Crohn's Disease Activity Index [CDAI] ≥150), and 30 patients with chronic idiopathic diarrhea seen at the Charité Hospital and 25 healthy controls were investigated using fluorescence in situ hybridization with probes specific for five bacterial groups: Faecalibacterium prausnitzii, Clostridium group XIVa / Roseburia group, Bacteroides, Enterobacteriaceae, and Bifidobacteriaceae., Results: We found a striking F. prausnitzii (Fprau) depletion in the stool of patients with NET of the midgut and patients with CD. The changes of the microbiota in the two other NET groups were uncharacteristic and similar to those observed in patients with chronic idiopathic diarrhea. Fprau depletion was reversible with chemotherapy and with interferon alpha-2b treatment in patients with midgut NET. Somatostatin analogs had no influence on Fprau concentrations., Conclusions: Patients with NET and CD show similarities in their abnormalities of the fecal biostructure. Interferon alpha and systemic chemotherapy significantly improved the fecal biostructure in patients with midgut NET., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Helicobacter pylori (HP) has been associated with neuroendocrine tumors of the stomach and duodenum. Gastric enterochromaffin-like (ECL) cell tumors and duodenal gastrinomas have also been associated with HP gastritis in separate series but have not been reported together. With other possible causes excluded, we present a patient with HP-associated atrophy of the oxyntic mucosa that ultimately resulted in stimulation and reactive hyperplasia of gastrin-producing cells in both the antrum and proximal duodenum, the latter progressing to formation of a gastrin-producing cell nodule (gastrinoma). Both of these sources of gastrin resulted in ECL hyperplasia in the atrophied oxyntic mucosa with progression to microcarcinoids and well-differentiated neuroendocrine tumors, along with hypertrophy of residual proximal gastric parietal cells. As atrophy tends to spread from the antrum proximally, residual oxyntic mucosa was still infected with HP and offers 1 explanation for the apparent paradox of atrophic gastritis with ECL hyperplasia and neoplasia in the distal oxyntic mucosa, with proximal oxyntic mucosa showing mild hypertrophic changes in a background of typical HP gastritis.