The incidence of Idiopathic Recurrent Pregnancy Loss (RPL) is doubled in patients suffering from Celiac Disease (CD) compared to healthy populations. CD genetic components are HLA class II genes known as HLA-DQ2 and DQ8. Genetically susceptible women can remain asymptomatic even though they are exposed to a doubled risk of RPL compared to the general population. Furthermore, CD has been associated with microbiota alterations. The aim of this study is to evaluate endometrial and vaginal microbiota in HLA-DQ2/DQ8 positive and negative RPL patients compared to healthy pregnant women. Endometrial and vaginal microbiota of 3 subgroups were evaluated: 15 HLA-DQ2/DQ8 positive RPL women, 25 HLA DQ2/DQ8 negative RPL women (for a total of 40 RPL women) and 7 healthy fertile controls with previous uncomplicated pregnancies (all HLA-DQ2/DQ8 negative). The 2 RPL subgroups (HLA-DQ2/DQ8 positive and negative) showed a different endometrial and vaginal composition in the Lactobacillacae family compared to controls: Lactobacillus acidophilus was absent both in the vaginal and endometrial samples of RPL women, while Lactobaciluus iners, which can favor a less stable vaginal microbiota, was found only in RPL women (26.4% in HLA DQ2/DQ8 positive and 22.1% HLA DQ2/DQ8 negative) in both the vaginal and endometrial districts. In conclusion, both HLA DQ2/DQ8 positive-RPL and HLA DQ2/DQ8 negative-RPL women showed different endometrial and vaginal microbiota composition compared to healthy controls.

Even though Everolimus has been investigated in a phase II randomized trial as a host-directed therapy (HDT) to treat tuberculosis (TB), an oncological patient treated with Everolimus for a neuroendocrine pancreatic neoplasia developed active TB twice and a non-tuberculous mycobacterial (NTM) infection in a year and a half time span. To investigate this interesting case, we isolated and genotypically characterized the Mycobacterium tuberculosis (Mtb) clinical strain from the patient and tested the effect of Everolimus on its viability in an axenic culture and in a peripheral blood mononuclear cell (PBMCs) infection model. To exclude strain-specific resistance, we tested the activity of Everolimus against Mtb strains of ancient and modern lineages. Furthermore, we investigated the Everolimus effect on ROS production and autophagy modulation during Mtb infection. Everolimus did not have a direct effect on mycobacteria viability and a negligible effect during Mtb infection in host cells, although it stimulated autophagy and ROS production. Despite being a biologically plausible HDT against TB, Everolimus does not exert a direct or indirect activity on Mtb. This case underlines the need for a careful approach to drug repurposing and implementation and the importance of pre-clinical experimental studies.

The human bladder has been long thought to be sterile until that, only in the last decade, advances in molecular biology have shown that the human urinary tract is populated with microorganisms. The relationship between the urobiota and the development of urinary tract disorders is now of great interest. Patients with spina bifida (SB) can be born with (or develop over time) neurological deficits due to damaged nerves that originate in the lower part of the spinal cord, including the neurogenic bladder. This condition represents a predisposing factor for urinary tract infections so that the most frequently used approach to treat patients with neurogenic bladder is based on clean intermittent catheterization (CIC). In this study, we analyzed the urobiota composition in a pediatric cohort of patients with SB compared to healthy controls, as well as the urobiota characteristics based on whether patients received CIC or not.

Graphene Oxide has been proposed as a potential adjuvant to develop improved anti-TB treatment, thanks to its activity in entrapping mycobacteria in the extracellular compartment limiting their entry in macrophages. Indeed, when administered together with linezolid, Graphene Oxide significantly enhanced bacterial killing due to the increased production of Reactive Oxygen Species. In this work, we evaluated Graphene Oxide toxicity and its anti-mycobacterial activity on human peripheral blood mononuclear cells. Our data show that Graphene Oxide, different to what is observed in macrophages, does not support the clearance of Mycobacterium tuberculosis in human immune primary cells, probably due to the toxic effects of the nano-material on monocytes and CD4+ lymphocytes, which we measured by cytometry. These findings highlight the need to test GO and other carbon-based nanomaterials in relevant in vitro models to assess the cytotoxic activity while measuring antimicrobial potential.

A diverse and well-functioning gut microbiota normally serves as a protective shield against the invasion of harmful bacteria or the proliferation of opportunistic pathogens. Clostridioides difficile infection (CDI) is predominantly associated with the overuse of antibiotics, resulting in a significant alteration in the gut’s microbial balance. Unfortunately, the lack of global standardization does not allow for the identification of a set of biomarkers associated with the onset and progression of this disease. In this study, we examined the composition of the gut microbiota in patients at the time of the initial detection of CDI compared to a control group of CDI-negative individuals, with a focus on identifying potential CDI biomarkers for diagnosis. While no significant differences in the alpha and beta diversity between CDI-negative and CDI-positive individuals were found, we found that certain genera (such as Clostridium XIVa and Clostridium XVIII) showed different abundance patterns in the two groups, indicating potential differences in gut microbiota balance. In conclusion, am enrichment in Clostridium XI and a decrease in Faecalibacterium emerged in the CDI-positive patients and following antibiotic treatment, indicating that changes in the Clostridium/Faecalibacterium ratio may be a promising biomarker that warrants further investigation for CDI diagnosis.