Acromegaly and colorectal cancer risk: emerging roles of the gut microbiota

Acromegaly is a rare endocrine disorder characterized by chronic growth hormone (GH) hypersecretion, usually due to a pituitary neuroendocrine tumor, leading to persistently elevated insulin-like growth factor 1 (IGF-1) levels. Although improved biochemical control reduces complications, cancer-related mortality remains a growing concern. Patients with acromegaly exhibit an increased prevalence of colorectal neoplasia, likely driven by sustained GH/IGF-1-mediated epithelial proliferation, reduced apoptosis, and activation of pro-tumorigenic signaling pathways. Concurrently, gut microbiota has emerged as a key modulator of intestinal homeostasis and carcinogenesis. Dysbiosis contributes to colorectal cancer development through chronic inflammation, production of genotoxins, disruption of epithelial barrier, and altered microbial metabolite profiles, including reduced short-chain fatty acids (SCFAs). Increasing evidence supports a bidirectional relationship between the gut microbiota and the GH/IGF-1 axis: microbial composition and SCFAs production can influence systemic and local IGF-1 levels, while GH and IGF-1 modulate microbial diversity, intestinal barrier function, and immune responses. Recent studies suggest that acromegalic patients display distinct oral and fecal microbial signatures, characterized by reduced alpha diversity, altered Firmicutes/Bacteroidetes ratio, and increased abundance of taxa potentially associated with colorectal carcinogenesis. Although causality has not been established, these alterations may interact with hormonal excess, insulin resistance, and systemic inflammation to create a permissive microenvironment for neoplastic transformation. This review provides an integrated clinical and pathophysiological synthesis of current evidence linking acromegaly, gut microbiota alterations, and colorectal cancer risk. Understanding this complex interplay may refine colorectal cancer risk stratification and open avenues for microbiota-targeted preventive or therapeutic strategies alongside endocrine disease control.