Intestinal dysmotility is common in many diseases and is correlated with gut microbiota dysbiosis and systemic inflammation. Functional constipation (FC) is the most typical manifestation of intestinal hypomotility and reduces patients’ quality of life. Some studies have reported that fecal micriobiota transplantation (FMT) may be an effective and safe therapy for FC as it corrects intestinal dysbiosis. This study was conducted to evaluate how FMT remodels the gut microbiome and to determine a possible correlation between certain microbes and clinical symptoms in constipated individuals. Data were retrospectively collected on 18 patients who underwent FMT between January 1, 2019 and June 30, 2020. The fecal bacterial genome was detected by sequencing the V3–V4 hypervariable regions of the 16S rDNA gene. Fecal short chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry, and serum inflammatory factor concentrations were detected via enzyme-linked immunosorbent assay. Comparing the changes in fecal microbiome compositions before and after FMT revealed a significant augmentation in the alpha diversity and increased abundances of some flora such as Clostridiales, Fusicatenibacter, and Paraprevotella. This was consistent with the patients experiencing relief from their clinical symptoms. Abundances of other flora, including Lachnoanaerobaculum, were decreased, which might correlate with the severity of patients’ constipation. Although no differences were found in SCFA production, the butyric acid concentration was correlated with both bacterial alterations and clinical symptoms. Serum IL-8 levels were significantly lower after FMT than at baseline, but IL-4, IL-6, IL-10, and IL-12p70 levels were not noticeably changed. This study showed how FMT regulates the intestinal microenvironment and affects systemic inflammation in constipated patients, providing direction for further research on the mechanisms of FMT. It also revealed potential microbial targets for precise intervention, which may bring new breakthroughs in treating constipation.

Background: The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer. Results: Se-MnP NPs had an organic–inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn²⁺). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice. Conclusions: OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR.

Colorectal cancer (CRC)-associated senescent fibroblasts may play a crucial role in tumor progression, but the mechanism remains unclear. In order to solve this complicated problem, we randomly collected 16 patients with CRC, who had been treated with oxaliplatin and capecitabine (XELOX). Hematoxylin-eosin (HE) staining revealed that the tumor-stroma ratio (TSR) of CRC was affected by XELOX treatment. Immunohistochemistry (IHC) and senescence-associated β-galactosidase (SAβG) staining were used to verify a stable model of senescent fibroblasts. IHC analysis showed that high expression levels of galactosylceramidase (GALC) and significant senescence-associated β-galactosidase (SAβG) staining were associated with CRC patient survival. We observed that fibroblasts overexpressing GALC underwent cell cycle arrest. Changes in cell morphology and cell cycle characteristics were accompanied by the upregulation of the p16, p21, and p53 gene, and the downregulation of hTERT expression. In a co-culture system, fibroblasts overexpressing GALC significantly increased the proliferation of CRC cells. Transmission electron microscopy (TEM) analysis confirmed that GALC overexpression fibroblasts co-cultured with CRC caused changes in CRC cell morphology. The aging fibroblast co-culture group (70%) had a higher migration ability. In vivo experiments and transcriptomics analysis were performed to verify the effect of senescent fibroblasts on tumor formation and to identify the potential mechanisms for the above results. We found that a high expression of ATF3 was related to good survival rates. However, a high expression of KIAA0907 was bad for survival rates (p < 0.05). The knockdown of ATF3 can promote cell proliferation, migration, and clonogenic assays, while downregulation of KIAA0907 inhibits cell proliferation, migration, and clonogenic assays. The results demonstrate that senescent fibroblasts with a high level of GALC regulated several aspects of the tumor growth process, including migration and invasion.

Enterococcus gallinarum, a gut pathobiont, is an opportunistic pathogen that carries the risk of antibiotic resistance in the clinic and has been proven to drive autoimmunity in both mice and humans. Screening for novel bacteriophages targeting Enterococcus gallinarum is expected to provide a promising strategy for controlling such infections or regulating related chronic diseases. In the present study, we isolated a novel lytic Enterococcus gallinarum phage, Phi_Eg_SY1, which presents favourable thermostability and pH stability. Further assays indicated that Phi_Eg_SY1 can efficiently adsorb and lyse the host bacteria in vitro. Genomic and phylogenetic analyses suggested that Phi_Eg_SY1 does not contain virulence or lysogeny genes and presents a novel unassigned evolutionary lineage among the related dsDNA phages. Phi_Eg_SY1 is therefore considered to be suitable for further applications.