Colorectal cancer (CRC) is one of the most common malignant tumors and is associated with Fusobacterium nucleatum ( F. nucleatum, Fn ) infection. In this study, we explored the role of F. nucleatum in the CRC metastasis. Our results showed that the abundance of F. nucleatum was enriched in the feces and tumors of patients with CRC and tended to increase in stage IV compared to stage I in patients with metastatic CRC. Tumor-derived CCL20 activated by F. nucleatum not only increases CRC metastasis, but also participates in the reprograming of the tumor microenvironment. F. nucleatum promoted macrophage infiltration through CCL20 activation and simultaneously induced M2 macrophage polarization, enhancing the metastasis of CRC. In addition, we identified using database prediction and luciferase activity hat miR-1322, a candidate regulatory micro-RNA, could bind to CCL20 directly. F. nucleatum infection decreased the expression of miR-1322 by activating the NF-κB signaling pathway in CRC cells. In conclusion, F. nucleatum promotes CRC metastasis through the miR-1322/CCL20 axis and M2 polarization.

Aims To explore the potential relationships among gut microbiota (GM), local brain spontaneous activity, and neuropsychological characteristics in amnestic mild cognitive impairment (aMCI) patients. Methods Twenty aMCI and 22 healthy control (HC) subjects were recruited. The GM composition was determined by 16S ribosomal RNA gene sequencing. Resting‐state functional magnetic resonance imaging scans were performed, and fractional amplitude of low‐frequency fluctuations (fALFF) was calculated across different frequencies. The Spearman or Pearson correlation analysis was used to analyze the relationship between spontaneous brain activity and cognitive function, and GM composition. Results aMCI patients had altered GM state and local spontaneous brain activity as compared with HC subjects. Correlation analysis showed that aMCI and HC groups had different “GM‐intrinsic brain activity interaction” patterns. In aMCI group, at the typical band (0.01‐0.08 Hz), the relative abundance (RA) of Bacteroides from phylum to genus level was negatively correlated with fALFF value of cerebellar vermis IV‐V, and the Ruminococcaceae RA was negatively correlated with fALFF values of left lenticular nucleus and pallidum. The Clostridiaceae RA and Blautia RA were positively correlated with the left cerebellum lobules IV‐V at the slow‐4 band (0.027‐0.073 Hz). The Veillonellaceae RA was positively correlated with fALFF values of left precentral gyrus at the slow‐5 band (0.073‐0.08 Hz). Correlation analysis showed that Clostridium members (Lachnospiraceae and Blautia) were positively, while Veillonellaceae was negatively, correlated with cognition test. Bacteroides was positively correlated with attention and computation, and negatively correlated with the three‐stage command score. Conclusions aMCI patients have a specific GM‐intrinsic brain activity‐cognitive function interaction pattern.

The interplay between gut microbiota and the host immune system is emerging as a factor in the pathogenesis of colorectal cancer. Here, we set out to identify the effect of Akkermansia muciniphila (A. muciniphila) on colorectal cancer pathogenesis. A. muciniphila abundance was significantly reduced in patients with colorectal cancer from two independent clinical cohorts and the GMrepo dataset. Supplementation with A. muciniphila suppressed colonic tumorigenesis in ApcMin/+ mice and the growth of implanted HCT116 or CT26 tumors in nude mice. Mechanistically, A. muciniphila facilitated enrichment of M1-like macrophages in an NLRP3-dependent manner in vivo and in vitro. As a consequence, NLRP3 deficiency in macrophages attenuated the tumor-suppressive effect of A. muciniphila. In addition, we revealed that TLR2 was essential for the activation of the NF-κB/NLRP3 pathway and A. muciniphila induced M1-like macrophage response. We observed positive correlations between M1-like macrophages, NLRP3/TLR2 and A. muciniphila in patients with colorectal cancer, which corroborated these findings. In summary, A. muciniphila–induced M1-like macrophages provide a therapeutic target in the colorectal cancer tumor microenvironment.