Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is associated with alterations of the fecal and tissue-associated microbiome. Preclinical models support a pathogenic role of the microbiome in CRC, including in promoting metastasis and modulating antitumor immune responses. To investigate whether the microbiome is associated with lymph node metastasis and T cell infiltration in human CRC, we performed 16S rRNA gene sequencing of feces, tumor core, tumor surface, and healthy adjacent tissue collected from 34 CRC patients undergoing surgery (28 fecal samples and 39 tissue samples). Tissue microbiome profiles—including increased Fusobacterium—were significantly associated with mesenteric lymph node (MLN) involvement. Fecal microbes were also associated with MLN involvement and accurately classified CRC patients into those with or without MLN involvement. Tumor T cell infiltration was assessed by immunohistochemical staining of CD3 and CD8 in tumor tissue sections. Tumor core microbiota, including members of the Blautia and Faecalibacterium genera, were significantly associated with tumor T cell infiltration. Abundance of specific fecal microbes including a member of the Roseburia genus predicted high vs. low total and cytotoxic T cell infiltration in random forests classifiers. These findings support a link between the microbiome and antitumor immune responses that may influence prognosis of locally advanced CRC.

The multispecies microbial cluster of Fusobacterium, Parvimonas, Bacteroides and Faecalibacterium as a precision biomarker for colorectal cancer diagnosis

“…Moreover, a consistent depletion of Faecalibacterium and Blautia genera was observed in CRC individuals when compared to the non‐CRC group. Both genera are producers of short‐chain fatty acids (SCFAs) and have been described in previous studies as beneficial groups in the gut, exhibiting important immunemodulatory, anti‐inflammatory, and anti‐tumorigenic effects in host cells [ 97 , 98 , 99 , 100 ]. These genera have also been found to exhibit reduced abundance in the colon of patients diagnosed with different bowel diseases, including cirrhosis and obesity, as detailed in multiple scientific reports [ 47 , 101 , 102 , 103 , 104 ].…”

Effects of dietary metabolizable energy level on hepatic lipid metabolism and cecal microbiota in aged laying hens

“…It can be assumed that the enrichment of Lactobacillus_crispatus at low energy levels stimulates the potential for glycogen utilization by the organism, thus providing the required energy. Blautia caecimuris , as the dominant bacteria in the intestinal microbiota, has a significant correlation with the physiological dysfunction of the host, such as obesity, diabetes, cancer and various inflammatory diseases ( Luu et al, 2023 ). Parabacteroides spp.…”

Distinct gut microbiomes in Thai patients with colorectal polyps

“…B. caecimuris is a commensal bacterium in the human gut, and there is no evidence linking it to colorectal polyps[ 68 ]. However, B. caecimuris has been detected in fecal samples from CRC patients[ 69 ]. The abundance of C. symbiosum is increased in colorectal adenoma, making it a promising biomarker for the noninvasive detection of colorectal adenoma[ 70 , 71 ] .…”