Highlights d Thousands of gut bacterial genomes from worldwide human populations were sequenced d HGT occurs at high frequency in the gut microbiome of individual persons d HGT occurs more frequently in the microbiome of industrialized and urban populations d Transferred gene functions in the microbiome reflect the lifestyle of the host

The research on neurodegenerative disorders has long focused on neuronal pathology and used transgenic mice as disease models. However, our understanding of the chronic neurodegenerative process in the human brain is still very limited. It is increasingly recognized that neuronal loss is not caused solely by intrinsic degenerative processes but rather via impaired interactions with surrounding glia and other brain cells. Dysfunctional astrocytes do not provide sufficient nutrients and antioxidants to the neurons, while dysfunctional microglia cannot efficiently clear pathogens and cell debris from extracellular space, thus resulting in chronic inflammatory processes in the brain. Importantly, human glia, especially the astrocytes, differ significantly in morphology and function from their mouse counterparts, and therefore more human‐based disease models are needed. Recent advances in stem cell technology make it possible to reprogram human patients' somatic cells to induced pluripotent stem cells (iPSC) and differentiate them further into patient‐specific glia and neurons, thus providing a virtually unlimited source of human brain cells. This review summarizes the recent studies using iPSC‐derived glial models of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis and discusses the applicability of these models to drug testing. This line of research has shown that targeting glial metabolism can improve the survival and function of cocultured neurons and thus provide a basis for future neuroprotective treatments.

COVID-19 is a disease caused by the coronavirus SARS-CoV-2. Millions of patients display neurological symptoms, including headache, impairment of memory, seizures, and encephalopathy, as well as anatomical abnormalities, such as changes in brain morphology.

The PSEN1 ΔE9 mutation causes a familial form of Alzheimer’s disease (AD) by shifting the processing of amyloid precursor protein (APP) towards the generation of highly amyloidogenic Aβ42 peptide. We have previously shown that the PSEN1 ΔE9 mutation in human-induced pluripotent stem cell (iPSC)-derived astrocytes increases Aβ42 production and impairs cellular responses. Here, we injected PSEN1 ΔE9 mutant astrosphere-derived glial progenitors into newborn mice and investigated mouse behavior at the ages of 8, 12, and 16 months. While we did not find significant behavioral changes in younger mice, spatial learning and memory were paradoxically improved in 16-month-old PSEN1 ΔE9 glia-transplanted male mice as compared to age-matched isogenic control-transplanted animals. Memory improvement was associated with lower levels of soluble, but not insoluble, human Aβ42 in the mouse brain. We also found a decreased engraftment of PSEN1 ΔE9 mutant cells in the cingulate cortex and significant transcriptional changes in both human and mouse genes in the hippocampus, including the extracellular matrix-related genes. Overall, the presence of PSEN1 ΔE9 mutant glia exerted a more beneficial effect on aged mouse brain than the isogenic control human cells likely as a combination of several factors.