BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3. The clinical manifestations are influenced by genetic and environmental factors that may include gut microbiome. RESULTS: We investigated the fecal metagenome, fecal metabolome, serum metabolome, neurotransmitters, and cytokines in a cohort of 24 CADASIL patients with 28 healthy household controls. The integrated-omics study showed CADASIL patients harbored an altered microbiota composition and functions. The abundance of bacterial coenzyme A, thiamin, and flavin-synthesizing pathways was depleted in patients. Neurotransmitter balance, represented by the glutamate/GABA (4-aminobutanoate) ratio, was disrupted in patients, which was consistent with the increased abundance of two major GABA-consuming bacteria, Megasphaera elsdenii and Eubacterium siraeum. Essential inflammatory cytokines were significantly elevated in patients, accompanied by an increased abundance of bacterial virulence gene homologs. The abundance of patient-enriched Fusobacterium varium positively correlated with the levels of IL-1β and IL-6. Random forest classification based on gut microbial species, serum cytokines, and neurotransmitters showed high predictivity for CADASIL with AUC = 0.89. Targeted culturomics and mechanisms study further showed that patient-derived F. varium infection caused systemic inflammation and behavior disorder in Notch3R170C/+ mice potentially via induction of caspase-8-dependent noncanonical inflammasome activation in macrophages. CONCLUSION: These findings suggested the potential linkage among the brain-gut-microbe axis in CADASIL. Video Abstract.

BACKGROUND: The influence of microbiota in ecological interactions, and in particular competition, is poorly known. We studied competition between two insect species, the invasive pest Drosophila suzukii and the model Drosophila melanogaster, whose larval ecological niches overlap in ripe, but not rotten, fruit. RESULTS: We discovered D. suzukii females prevent costly interspecific larval competition by avoiding oviposition on substrates previously visited by D. melanogaster. More precisely, D. melanogaster association with gut bacteria of the genus Lactobacillus triggered D. suzukii avoidance. However, D. suzukii avoidance behavior is condition-dependent, and D. suzukii females that themselves carry D. melanogaster bacteria stop avoiding sites visited by D. melanogaster. The adaptive significance of avoiding cues from the competitor's microbiota was revealed by experimentally reproducing in-fruit larval competition: reduced survival of D. suzukii larvae only occurred if the competitor had its normal microbiota. CONCLUSIONS: This study establishes microbiotas as potent mediators of interspecific competition and reveals a central role for context-dependent behaviors under bacterial influence. Video Abstract.

BACKGROUND AND AIMS: At the West Antarctic Peninsula, snow algae blooms are composed of complex microbial communities dominated by green microalgae and bacteria. During their progression, the assembly of these microbial communities occurs under harsh environmental conditions and variable nutrient content due to fast snow melting. To date, it is still unclear what are the ecological mechanisms governing the composition and abundance of microorganisms during the formation of snow algae blooms. In this study, we aim to examine the main ecological mechanisms governing the assembly of snow algae blooms from early stages to colorful stages blooms. METHODS: The composition of the microbial communities within snow algae blooms was recorded in the West Antarctic Peninsula (Isabel Riquelme Islet) during a 35-day period using 16S rRNA and 18S rRNA metabarcoding. In addition, the contribution of different ecological processes to the assembly of the microbial community was quantified using phylogenetic bin-based null model analysis. RESULTS: Our results showed that alpha diversity indices of the eukaryotic communities displayed a higher variation during the formation of the algae bloom compared with the bacterial community. Additionally, in a macronutrients rich environment, the content of nitrate, ammonium, phosphate, and organic carbon did not play a major role in structuring the community. The quantification of ecological processes showed that the bacterial community assembly was governed by selective processes such as homogenous selection. In contrast, stochastic processes such as dispersal limitation and drift, and to a lesser extent, homogenous selection, regulate the eukaryotic community. CONCLUSIONS: Overall, our study highlights the differences in the microbial assembly between bacteria and eukaryotes in snow algae blooms and proposes a model to integrate both assembly processes. Video Abstract.

BACKGROUND: The microbiota of the upper respiratory tract is increasingly recognized as a gatekeeper of respiratory health. Despite this, the microbiota of healthy adults remains understudied. To address this gap, we investigated the composition of the nasopharyngeal and oropharyngeal microbiota of healthy adults, focusing on the effect of Streptococcus pneumoniae carriage, smoking habits, and contact with children. RESULTS: Differential abundance analysis indicated that the microbiota of the oropharynx was significantly different from that of the nasopharynx (P < 0.001) and highly discriminated by a balance between the classes Negativicutes and Bacilli (AUC of 0.979). Moreover, the oropharynx was associated with a more homogeneous microbiota across individuals, with just two vs. five clusters identified in the nasopharynx. We observed a shift in the nasopharyngeal microbiota of carriers vs. noncarriers with an increased relative abundance of Streptococcus, which summed up to 30% vs. 10% in noncarriers and was not mirrored in the oropharynx. The oropharyngeal microbiota of smokers had a lower diversity than the microbiota of nonsmokers, while no differences were observed in the nasopharyngeal microbiota. In particular, the microbiota of smokers, compared with nonsmokers, was enriched (on average 16-fold) in potential pathogenic taxa involved in periodontal diseases of the genera Bacillus and Burkholderia previously identified in metagenomic studies of cigarettes. The microbiota of adults with contact with children resembled the microbiota of children. Specifically, the nasopharyngeal microbiota of these adults had, on average, an eightfold increase in relative abundance in Streptococcus sp., Moraxella catarrhalis, and Haemophilus influenzae, pathobionts known to colonize the children's upper respiratory tract, and a fourfold decrease in Staphylococcus aureus and Staphylococcus lugdunensis. CONCLUSIONS: Our study showed that, in adults, the presence of S. pneumoniae in the nasopharynx is associated with a shift in the microbiota and dominance of the Streptococcus genus. Furthermore, we observed that smoking habits are associated with an increase in bacterial genera commonly linked to periodontal diseases. Interestingly, our research also revealed that adults who have regular contact with children have a microbiota enriched in pathobionts frequently carried by children. These findings collectively contribute to a deeper understanding of how various factors influence the upper respiratory tract microbiota in adults. Video Abstract.

BACKGROUND: Aging is a significant risk factor for ischemic stroke and worsens its outcome. However, the mechanisms for this worsened neurological outcome with aging are not clearly defined. RESULTS: Old C57BL/6J male mice (18 to 20 months old) had a poorer neurological outcome and more severe inflammation after transient focal brain ischemia than 8-week-old C57BL/6J male mice (young mice). Young mice with transplantation of old mouse gut microbiota had a worse neurological outcome, poorer survival curve, and more severe inflammation than young mice receiving young mouse gut microbiota transplantation. Old mice and young mice transplanted with old mouse gut microbiota had an increased level of blood valeric acid. Valeric acid worsened neurological outcome and heightened inflammatory response including blood interleukin-17 levels after brain ischemia. The increase of interleukin-17 caused by valeric acid was inhibited by a free fatty acid receptor 2 antagonist. Neutralizing interleukin-17 in the blood by its antibody improved neurological outcome and attenuated inflammatory response in mice with brain ischemia and receiving valeric acid. Old mice transplanted with young mouse feces had less body weight loss and better survival curve after brain ischemia than old mice transplanted with old mouse feces or old mice without fecal transplantation. CONCLUSIONS: These results suggest that the gut microbiota-valeric acid-interleukin-17 pathway contributes to the aging-related changes in the outcome after focal brain ischemia and response to stimulus. Valeric acid may activate free fatty acid receptor 2 to increase interleukin-17.

BACKGROUND: Gypsum Hill Spring, located in Nunavut in the Canadian High Arctic, is a rare example of a cold saline spring arising through thick permafrost. It perennially discharges cold (~ 7 °C), hypersaline (7-8% salinity), anoxic (~ 0.04 ppm O2), and highly reducing (~ - 430 mV) brines rich in sulfate (2.2 g.L-1) and sulfide (9.5 ppm), making Gypsum Hill an analog to putative sulfate-rich briny habitats on extraterrestrial bodies such as Mars. RESULTS: Genome-resolved metagenomics and metatranscriptomics were utilized to describe an active microbial community containing novel metagenome-assembled genomes and dominated by sulfur-cycling Desulfobacterota and Gammaproteobacteria. Sulfate reduction was dominated by hydrogen-oxidizing chemolithoautotrophic Desulfovibrionaceae sp. and was identified in phyla not typically associated with sulfate reduction in novel lineages of Spirochaetota and Bacteroidota. Highly abundant and active sulfur-reducing Desulfuromusa sp. highly transcribed non-coding RNAs associated with transcriptional regulation, showing potential evidence of putative metabolic flexibility in response to substrate availability. Despite low oxygen availability, sulfide oxidation was primarily attributed to aerobic chemolithoautotrophic Halothiobacillaceae. Low abundance and transcription of photoautotrophs indicated sulfur-based chemolithoautotrophy drives primary productivity even during periods of constant illumination. CONCLUSIONS: We identified a rare surficial chemolithoautotrophic, sulfur-cycling microbial community active in a unique anoxic, cold, hypersaline Arctic spring. We detected Mars-relevant metabolisms including hydrogenotrophic sulfate reduction, sulfur reduction, and sulfide oxidation, which indicate the potential for microbial life in analogous S-rich brines on past and present Mars. Video Abstract.

BACKGROUND: Improving feed efficiency is the most important goal for modern animal production. The regulatory mechanisms of controlling feed efficiency traits are extremely complex and include the functions related to host genetics and gut microbiota. Short-chain fatty acids (SCFAs), as significant metabolites of microbiota, could be used to refine the combined effect of host genetics and gut microbiota. However, the association of SCFAs with the gut microbiota and host genetics for regulating feed efficiency is far from understood. RESULTS: In this study, 464 broilers were housed for RFI measuring and examining the host genome sequence. And 300 broilers were examined for cecal microbial data and SCFA concentration. Genome-wide association studies (GWAS) showed that four out of seven SCFAs had significant associations with genome variants. One locus (chr4: 29414391-29417189), located near or inside the genes MAML3, SETD7, and MGST2, was significantly associated with propionate and had a modest effect on feed efficiency traits and the microbiota. The genetic effect of the top SNP explained 8.43% variance of propionate. Individuals with genotype AA had significantly different propionate concentrations (0.074 vs. 0.131 μg/mg), feed efficiency (FCR: 1.658 vs. 1.685), and relative abundance of 14 taxa compared to those with the GG genotype. Christensenellaceae and Christensenellaceae_R-7_group were associated with feed efficiency, propionate concentration, the top SNP genotypes, and lipid metabolism. Individuals with a higher cecal abundance of these taxa showed better feed efficiency and lower concentrations of caecal SCFAs. CONCLUSION: Our study provides strong evidence of the pathway that host genome variants affect the cecal SCFA by influencing caecal microbiota and then regulating feed efficiency. The cecal taxa Christensenellaceae and Christensenellaceae_R-7_group were identified as representative taxa contributing to the combined effect of host genetics and SCFAs on chicken feed efficiency. These findings provided strong evidence of the combined effect of host genetics and gut microbial SCFAs in regulating feed efficiency traits. Video Abstract.