Exploring Midgut NETs Through the Lens of the Microbiome

Midgut neuroendocrine tumors (NETs), such as small intestinal NETs, originate in the neuroendocrine cells of the midgut, a part of the digestive system, and have witnessed a dramatic increase in incidence over the past four decades. This phenomenon is partially attributed to enhanced diagnostic methods and increased awareness, but environmental factors may also play a role, as evidenced by the primary site distribution of NETs varying globally, with different regions showing differing prevalences of foregut, midgut, and hindgut NETs.

Midgut NETs can have variable clinical behavior, sometimes producing hormones that can lead to distinct clinical syndromes. One of these syndromes is carcinoid syndrome (CS), which affects approximately one-third of patients. This syndrome, characterized by symptoms like chronic diarrhea and flushing, is linked to elevated levels of serotonin. CS severely affects patients’ quality of life, yet there is a gap in understanding CS and midgut NETs, leading to limited progress in treatment options.

Recent advancements in medical research have brought the gut microbiome into focus as a potential player in the development and progression of midgut NETs. Our gut hosts a complex ecosystem of microbes that have been shown to influence various health conditions, including cancer. Dr. Hans Hofland, of Erasmus Medical Center and Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, received a 2019 NETRF Pilot Award to study the midgut NET microbiome and its associations with clinical outcomes.

Dr. Hofland and his team recently published their findings in the European Journal of Cancer. They found that in midgut NET patients, the gut microbiome was less diverse and rich when compared to controls (individuals without a diagnosed NET). They did not find a difference in microbial composition between patients with CS and those without CS. However, they believe that more research is needed to see if a link between the microbiome and CS can be found.

Interestingly, they identified a microbial signature comprising 17 species that was predictive of midgut NETs. The discovery of a microbial signature specific to midgut NETs paves the way for potentially developing non-invasive diagnostic tools to empower early detection and treatment strategies. However, these findings must be validated in broader studies to avoid biases and ensure specificity, especially considering the influence of other diseases on the microbiome.

This research marks an important step in understanding midgut NETs and their relationship with the gut microbiome. The altered microbiome in midgut NET patients opens the door to potential new diagnostic and therapeutic strategies and underscores the necessity of collaborative, multi-center research to validate and apply these findings in clinical practice. The Neuroendocrine Tumor Research Foundation remains committed to advancing our understanding of NETs, aiming to improve outcomes and quality of life for patients with midgut NETs.

Read the full publication here.