Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.

Background: Microdeletion of the human chromosomal region 16p11.2 (16p11.2 $${}^{+/-}$$ + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 $${}^{+/-}$$ + / - syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 $${}^{+/-}$$ + / - are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 $${}^{+/-}$$ + / - , as well as the underlying molecular mechanisms. Results: Mice with the 16p11.2 $${}^{+/-}$$ + / - showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. Conclusions: Our study reveals that 16p11.2 $${}^{+/-}$$ + / - leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 $${}^{+/-}$$ + / - mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome.

We show that the G protein‐coupled receptor GPR37‐like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1^–/– mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1‐mediated signalling inhibited astrocyte glutamate transporters and – surprisingly, given its lack of expression in neurons – reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia. This effect on NMDAR signalling was not mediated by a change in the release of D‐serine or TNF‐α, two astrocyte‐derived agents known to modulate NMDAR function. After middle cerebral artery occlusion, Gpr37l1 expression was increased around the lesion. Neuronal death was increased by ∼40% in Gpr37l1^–/– brain compared to wild type in an in vitro model of ischemia. Thus, GPR37L1 protects neurons during ischemia, presumably by modulating extracellular glutamate concentration and NMDAR activation.

Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender. In the validating cohort, we affirm the GABA/Glu ratio as an ASD diagnostic indicator after adjusting for geography, age, gender, and specific food-consuming frequency. Integrated analysis of metabolomics, 16S rRNA sequencing, and metagenomics reveals a correlation between overrepresented Escherichia and disrupted GABA metabolism. Furthermore, we observe social behavioral impairments in weaning mice transplanted with E. coli, suggesting a potential link to ASD symptomatology. Collectively, these findings provide insights into potential diagnostic and therapeutic strategies aimed at evaluating and restoring gut microbial neurotransmitter homeostasis.

This new decade has started with a global pandemic of COVID‐19 caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID‐19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID‐19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS‐CoV‐2 in chickens and extracted IgY (called IgY‐S) from egg yolk. IgY‐S exhibited high immunoreactivity against SARS‐CoV‐2 S, and by epitope mapping, we found five linear epitopes of IgY‐S in SARS‐CoV‐2 S, two of which are cross‐reactive with SARS‐CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS‐CoV‐2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus‐cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY‐S or epitope SIIAYTMS‐specific IgY as neutralizing antibody for preventing or treating SARS‐CoV‐2 infection is worth exploring.