Parkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

Shunying Yu, Yibin Sun, Xinyu Shao, Yuqing Zhou, Yang Yu, Xiaoyi Kuai, and Chunli Zhou. J. Microbiol. Biotechnol. 2022;32:825-34. https://doi.org/10.4014/jmb.2203.03022

Background: Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5‐year survival rate. The glycolytic enzyme α-enolase (ENO1) is overexpressed in multiple cancers and is involved in tumor cell proliferation and metastasis. However, its clinical significance, biological role, and underlying molecular mechanisms in CRC are still unclear. The aim of the present study was to investigate the potential role of ENO1 in the initiation and development of CRC. Patients and methods: The in situ expression of ENO1 in CRC and adjacent normal tissues was examined by immunohistochemistry. The effects of ENO1 on the in vitro proliferation and migration of CRC cell lines were investigated by MTT, colony formation, and Transwell assays. Finally, the in vivo tumorigenic capacity of ENO1 was assessed in a mouse model. Results: ENO1 was overexpressed in CRC tissues and significantly correlated with the clinicopathological parameters. Furthermore, Rab1A was also overexpressed in CRC tissues and was positively correlated to that of ENO1. The high expression levels of both ENO1 and Rab1A led to significantly worse prognosis of CRC patients compared to either alone. Furthermore, knockdown of ENO1 significantly inhibited CRC cells proliferation and migration in vitro and reduced xenograft growth in vivo via the concomitant downregulation of Rab1A. Conclusion: The ENO1/Rab1A signaling axis is involved in CRC progression and is a potential biomarker for the treatment of CRC.

Background: Nucleotide-binding domain Leucine-rich Repeat Protein 3 (NLRP3) plays a regulatory role in the immune and inflammatory responses, and has been implicated in Colorectal Cancer (CRC) progression and metastasis. However, the underlying molecular mechanisms have not been fully elucidated. Methods: In this study, we analyzed the expression levels of NLRP3 in human CRC tissues, and performed functional assays in CRC cell lines and a subcutaneous tumor model to elucidate its role in the development and progression of CRC. Results: In this study, we found that NLRP3 was significantly upregulated in human CRC tissues and was associated with tumor size and invasion, lymph node metastasis, venous invasion, neural invasion and TNM staging. Furthermore, knockdown of NLRP3 in CRC cells inhibited their migration and growth in vitro and in vivo, and reversed Epithelial-Mesenchymal Transition (EMT) in vitro. Conclusion: Our findings indicate that NLRP3 likely regulates CRC metastasis by activating the EMT program, and is a potential therapeutic target.

Colorectal carcinoma (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer-related deaths in the US. Recently, Rab1A has been reported to be an activator of mTORC1 and p-S6K1, which is downstream of mTORC1. However, the association between Rab1A and p-S6K1 in CRC remains elusive. In the present study, we first demonstrated that Rab1A was overexpressed in CRC tissues and Rab1A overexpression was positively related to lymph node invasion, degree of differentiation, venous invasion and tumor-node-metastasis (TNM) stage. In both TNM stage I-II and III-IV patients, Rab1A-positive patients had a shorter survival time than Rab1A-negative patients. Furthermore, in univariate and multivariate analyses, only Rab1A expression was verified as an independent prognostic factor for survival in CRC patients. The level of p-S6K1 was markedly high in CRC tissues and Rab1A expression level had a positive association with p-S6K1 level. In addition, high levels of both Rab1A and p-S6K1 were associated with a poorer prognosis compared with low expression of either Rab1A or p-S6K1 level. Moreover, high levels of both Rab1A and p-S6K1 were associated with a poorer prognosis than patients with high levels of either Rab1A or p-S6K1 alone. Finally, knockdown of Rab1A expression inhibited migration and proliferation of SW480 and HCT116 cell lines by targeting regulation of p-S6K1. Thus, our findings indicate that Rab1A plays an important role in CRC and may provide a therapeutic target for CRC, particularly for mTORC1-targeted therapy-resistant cancers.