BackgroundPeople living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed... Show moreBackgroundPeople living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls.ResultsPLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid.ConclusionsWe identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications.1fCw832AZENtKENNTh8vkGVideo AbstractConclusionsWe identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications.1fCw832AZENtKENNTh8vkGVideo Abstract Show less
Salicylic acid (SA) is a signal molecule that plays an important role in plant defense against pests and diseases. Introducing the gene(s) that overexpressed SA would be an advantage where the crop... Show moreSalicylic acid (SA) is a signal molecule that plays an important role in plant defense against pests and diseases. Introducing the gene(s) that overexpressed SA would be an advantage where the crop performance could be improved by enhancing its resistance to pathogen attack. This thesis aimed at developing transgenic Brassica rapa plants with a bacterial SA pathway gene, the entC gene (encoding for isochorismate synthase) and subsequently investigating the effect of introducing this gene on the B. rapa secondary metabolite profile. The transgenic B. rapa carrying the entC gene was developed by using Agrobacterium tumefaciens-mediated transformation. The level of SA and its glucosides (SAG) were increased in transgenic plants which means that the bacterial entC gene was functional in B. rapa. In contrast, the introduction of the gene was expected to have an effect on other isochorismate derived products, but did not have a significant effect on the phylloquinone accumulation. However, the glucosinolate profiles particularly for indole and aliphatic glucosinolates was altered. The altered profile of the glucosinolates might be due to the increased level of SA produced via isochorismate that leads to activation of plant defense. Metabolome analysis of the transgenic plants showed that some phenylpropanoid compounds and indole glucosinolate (neoglucobrassicin) were increased in comparison to the control plants. These results suggest that the expression of the bacterial entC gene in B. rapa did not affect fluxes into pathways to the other groups of secondary metabolites through competition for the same precursor (chorismate). On the contrary, the biosynthesis of chorismate derived products (SA) seems to induce the competitive pathways via phenylalanine and tryptophan, pathways that are known to play a role in plant resistance. Future studies on the resistance of the transgenic plants are required to proof an increased resistance as it previously has been reported for tobacco plants overproducing salicylic acid Show less
