Impact of chronic stress on intestinal mucosal immunity in colorectal cancer progression. Cytokine & growth factor reviews Chronic stress is a significant risk factor that contributes to the progression of colorectal cancer (CRC) and has garnered considerable attention in recent research. It influences the distribution and function of immune cells within the intestinal mucosa through the "brain-gut" axis, altering cytokine and chemokine secretion and creating an immunosuppressive tumor microenvironment. The intestine, often called the "second brain," is particularly susceptible to the effects of chronic stress. Cytokines and chemokines in intestinal mucosal immunity（IMI） are closely linked to CRC cells' proliferation, metastasis, and drug resistance under chronic stress. Recently, antidepressants have emerged as potential therapeutic agents for CRC, possibly by modulating IMI to restore homeostasis and exert anti-tumor effects. This article reviews the role of chronic stress in promoting CRC progression via its impact on intestinal mucosal immunity, explores potential targets within the intestinal mucosa under chronic stress, and proposes new approaches for CRC treatment. 10.1016/j.cytogfr.2024.10.007

Dietary and metabolic effects on intestinal stem cells in health and disease. Nature reviews. Gastroenterology & hepatology Diet and nutritional metabolites exhibit wide-ranging effects on health and disease partly by altering tissue composition and function. With rapidly rising rates of obesity, there is particular interest in how obesogenic diets influence tissue homeostasis and risk of tumorigenesis; epidemiologically, these diets have a positive correlation with various cancers, including colorectal cancer. The gastrointestinal tract is a highly specialized, continuously renewing tissue with a fundamental role in nutrient uptake and is, in turn, influenced by diet composition and host metabolic state. Intestinal stem cells are found at the base of the intestinal crypt and can generate all mature lineages that comprise the intestinal epithelium and are uniquely influenced by host diet, metabolic by-products and energy dynamics. Similarly, tumour growth and metabolism can also be shaped by nutrient availability and host diet. In this Review, we discuss how different diets and metabolic changes influence intestinal stem cells in homeostatic and pathological conditions, as well as tumorigenesis. We also discuss how dietary changes and composition affect the intestinal epithelium and its surrounding microenvironment. 10.1038/s41575-024-00980-7

A distinct Fusobacterium nucleatum clade dominates the colorectal cancer niche. Nature Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals, is enriched in human colorectal cancer (CRC) tumours. High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis. Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche. 10.1038/s41586-024-07182-w