Gut microbes shape microglia and cognitive function during malnutrition

Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG model was analyzed in comparison to malnourished (MAL mice) and healthy (CON mice) controls. Malnourished mice display poor spatial memory and learning plasticity, as well as altered microglia, non-neuronal CNS cells that regulate neuroimmune responses and brain plasticity. Chronic fecal-oral exposures shaped microglial morphology and transcriptional profile, promoting phagocytic features in MAL-BG mice. Unexpectedly, these changes occurred independently from significant cytokine-induced inflammation or blood-brain barrier (BBB) disruption, key gut-brain pathways. Metabolomic profiling of the MAL-BG cortex revealed altered polyunsaturated fatty acid (PUFA) profiles and systemic lipoxidative stress. In contrast, supplementation with an ω3 PUFA/antioxidant-associated diet (PAO) mitigated cognitive deficits within the MAL-BG model. These findings provide valued insight into the malnourished gut microbiota-brain axis, highlighting PUFA metabolism as a potential therapeutic target

Optical properties of exfoliated MoS2 coaxial nanotubes - analogues of graphene

We report on the first exfoliation of MoS2 coaxial nanotubes. The single-layer flakes, as the result of exfoliation, represent the transition metal dichalcogenides' analogue of graphene. They show a very low degree of restacking in comparison with exfoliation of MoS2 plate-like crystals. MoS2 monolayers were investigated by means of electron and atomic force microscopies, showing their structure, and ultraviolet-visible spectrometry, revealing quantum confinement as the consequence of the nanoscale size in the z-direction

The role of gut microbiota in Parkinson's disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. Non-motor symptoms including gastrointestinal (GI) dysfunction and mood disorders (such as depression) are also particularly common. GI symptoms include constipation, and PD patients display altered gut microbiota composition. Evidence in animal models points towards a potential causal role for the microbiota in mediating PD pathology. However, the constipation, medication use, and lifestyle habits of PD patients can also be expected to change microbiota composition. In this thesis, I explore the role of the gut microbiota in PD, in terms of the degree that it is shaped by the disease state and its ability to mediate disease symptoms. Using a transgenic mouse model of PD that displays motor deficits, GI dysfunction, and behavioral alterations, I assessed how broad alterations to the gut microbiota impacted the motor and non-motor phenotype. I found that both depletion of the microbiota through antibiotics, and a shift towards a healthy wild-type mouse microbiota, had a minimal impact on the PD-like symptoms. This suggested that the PD-like transgenic state of this model may drive the disease phenotype to a greater extent than the microbiota. Similarly, I demonstrated that the decreased abundance of Lachnospiraceae and decreased abundance of Ruminococcaceae and Oscillospira observed in PD patients may be a result of constipation by treating PD mice with laxatives that reversed these shifts. Lachnospiraceae abundance was also found to be decreased by treatment of this model with the PD medications L-DOPA and carbidopa. Conversely, different antibiotic treatment regimens were able to shift the microbial community and alter GI transit time in PD mice. Specific bacterial taxa, such as Lachnospiraceae (Ruminococcus), were associated with transit time – indicating a potential to treat PD constipation via the microbiota. Furthermore, treatment of PD mice with PD medications had a beneficial effect on constipation and depression-like behavior, potentially through increasing the abundance of Turicibacter and promoting butyrate production. This thesis demonstrates that certain PD-associated microbiota alterations may be a result of slowed GI transit or the presence of medications. However, specific shifts to the gut microbiota may in turn mediate non-motor symptoms in PD.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat