Project description:Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This study found that age-associated changes of the gut microbiome of BALB/c and C57BL/6 mice could be reverted by co-housing of aged (22 months old) and adult (3 months old) mice for 30-40 days or faecal microbiota transplantation (FMT) from adult into aged mice. This was demonstrated using high-throughput sequencing of the V3-V4 hypervariable region of bacterial 16S rRNA gene isolated from faecal pellets collected from 3-4 months old adult and 22-23 months old aged mice before and after co-housing or FMT.
Project description:To further decipher the alteration of gene expression profile of irradiated mice with or without faecal microbiota transplantation (FMT), we performed FMT for 10 days following total body irradiaton (6.5 Gy gamma ray). Twenty-one days after irradiation, the mice were euthanized and the small intestine tissues excised.
Project description:In this randomised placebo-controlled trial, irritable bowel syndrome (IBS) patients were treated with faecal material from a healthy donor (n=8, allogenic FMT) or with their own faecal microbiota (n=8, autologous FMT). The faecal transplant was administered by whole colonoscopy into the caecum (30 g of stool in 150 ml sterile saline). Two weeks before the FMT (baseline) as well as two and eight weeks after the FMT, the participants underwent a sigmoidoscopy, and biopsies were collected at a standardised location (20-25 cm from the anal verge at the crossing with the arteria iliaca communis) from an uncleansed sigmoid. In patients treated with allogenic FMT, predominantly immune response-related genes sets were induced, with the strongest response two weeks after FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected.
Project description:Necrotizing enterocolitis (NEC) is an acute and life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventative therapy, but potential bacterial infection raise concern. Removal of bacteria from donor feces may reduce this risk while maintaining the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of bacteria-free fecal filtrate transfer (FFT). Using fecal material from healthy suckling piglets, we administered FMT rectally, or cognate FFT either rectally or oro-gastrically to formula-fed preterm, cesarean-delivered piglets as a model for preterm infants, We compared gut pathology and related safety parameters with saline controls, and analyzed ileal mucosal transcriptome to gauge the host e response to FMT and FFT treatments relative to control. Results showed that oro-gastric FFT prevented NEC, whereas FMT did not perform better than control. Moreover, FFT but not FMT reduced intestinal permeability, whereas FMT animals had reduced body weight increase and intestinal growth. Global gene expression of host mucosa responded to FMT but not FFT with increased and decreased bacterial and viral defense mechanisms, respectively. In conclusion, as preterm infants are extremely vulnerable to enteric bacterial infections, rational NEC-preventive strategies need incontestable safety profiles. Here we show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects. If translatable to preterm infants, this could lead to a change of practice and in turn a reduction in NEC burden.
2021-10-01 | GSE158878 | GEO
Project description:Collection of multiresistant Gram negative bacilli of clinical origin
Project description:Guanidine DNA quadruplex (G4-DNA) structures convey a distinctive layer of epigenetic information that is critical for the regulation of key biological activities and processes as genome transcription regulation, replication and repair. Despite several works that have been published recently, the information regarding their role and possible use as therapeutic drug targets in bacteria is still scarce. Here, we tested the biological activity of a small G4-DNA ligand library based on the naphthalene diimide (NDI) pharmacophore, against both Gram-positive and Gram-negative bacteria. For the best compound identified, NDI-10, the action mechanism was further characterized. Gram-negative bacteria were more resistant altogether due to the presence of the outer membrane, although the activity of the G4-Ligand was generally bactericidal, while it was bacteriostatic for Gram-positive bacteria. This asymmetric activity could be related to the different prevalence of putative G4-DNA structures in each group, the influence that they can exert on the gene expression (which was found more severe for the Gram-negative bacteria) and the role of the G4 structures in these bacteria, that seems to be more related to promote transcription in Gram-positive bacteria and repress transcription in Gram-negative.