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Bijvank, E.

Publications and source records attributed to Bijvank, E..

2 recordsLinked to original sources

Associations and recovery dynamics of the nasopharyngeal microbiota during influenza-like illness in the aging population

BackgroundOlder adults are more susceptible to respiratory pathogens, several of which have been associated with an altered respiratory microbiota. Influenza-like illness (ILI), a disease caused by respiratory pathogens including but not exclusively by influenza virus, is a major health concern in this population. However, there is little information on changes in the nasopharyngeal (NP) microbiota of older adults associated with respiratory infections identified by/ reported as ILI, as well as its dynamics during recovery. Here, we compared the NP microbiota in older adults who presented with ILI (n= 240) to the NP microbiota in older adults not reporting an ILI event (n= 157) during the 2014-2015 influenza season. To investigate the dynamics of the microbiota from the acute phase to the recovery phase of the infection, participants reporting an ILI event were sampled at onset of infection (<72 hours), at 14 days and at 7-9 weeks after infection (recovery sample). ResultsCross-sectional analysis of the microbiota at the different time-points showed no differences in alpha diversity between the groups. A small but significant effect of the ILI was observed on the microbiota community and structure when compared to controls and recovery samples. Furthermore, the NP microbiota exhibited inter-individual differences in dynamics from onset of ILI to recovery. Corynebacterium, one of the keystone species in the upper respiratory tract, was negatively associated with ILI and its abundance increased after recovery. Potential pathobionts such as Haemophilus, Porphyromonas and Gemella had higher abundances during acute-ILI. Stability and changes in the NP microbial community showed individual dynamics. Key core genera, Corynebacterium, Moraxella and Dolosigranulum exhibited higher inter-individual variability in acute-ILI, but showed comparable variability to controls after recovery. Participants in the ILI group with higher core microbiota abundances at the acute phase showed higher microbiota stability after recovery. ConclusionsOur findings demonstrate that acute-ILI is associated with small but significant alterations in the phylogenetic structure of the NP microbiota in older adults. The observed variation in the core microbiota suggests potential imbalances in the ecosystem, which could play a role in the recovery of the NP microbiota after an ILI event.

microbiology↗

Distinct pathogenic genes causing intellectual disability and autism exhibit overlapping effects on neuronal network development

An intriguing question in medical biology is how mutations in functionally distinct genes can lead to similar clinical phenotypes. For example, patients with mutations in distinct epigenetic regulators EHMT1, MBD5, MLL3 or SMARCB1 share the core clinical features of intellectual disability (ID), autism spectrum disorder (ASD) and facial dysmorphisms. To elucidate how these phenotypic similarities are reflected by convergence at the molecular, cellular and neuronal network level, we directly compared the effects of their loss of function in neurons. Interestingly, knockdown of each gene resulted in hyperactive neuronal networks with altered patterns of synchronized activity. At the single-cell level, we found genotype-specific changes in intrinsic excitability and excitatory-inhibitory balance, but in all cases leading to increased excitability. Congruent with our physiological findings, we identified dysregulated genes that converge on biological and cellular pathways related to neuronal excitability and synaptic function, including genes previously implicated in ID/ASD. Yet, our data suggests that the common cellular phenotypes depend on the ensemble of dysregulated genes engaged in neuronal excitability rather than the direction of transcriptional changes of individual genes. The demonstration of increasing convergence from molecular pathways to neuronal networks may be a paradigm for other types of ID/ASD.

neuroscience↗